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## Complete Summary

#### GUIDELINE TITLE

Long-term follow-up guidelines for survivors of childhood, adolescent,
and young adult cancers. Sections 6-37: chemotherapy.

#### BIBLIOGRAPHIC SOURCE(S)

Children\'s Oncology Group. Long-term follow-up guidelines for survivors
of childhood, adolescent, and young adult cancers. Sections 6-37:
chemotherapy. Bethesda (MD): Children\'s Oncology Group; 2006 Mar. 37 p.
\[191 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Children\'s Oncology Group.
Long-term follow-up guidelines for survivors of childhood, adolescent,
and young adult cancers. Version 1.2. 2004 Mar.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse**: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [May 23, 2007, Gadolinium-based Contrast
    Agents](http://www.fda.gov/medwatch/safety/2007/safety07.htm#Gadolinium):
    The addition of a boxed warning and new warnings about the risk of
    nephrogenic systemic fibrosis (NSF) to the full prescribing
    information for all gadolinium-based contrast agents (GBCAs).

-   [May 2, 2007, Antidepressant
    drugs](http://www.fda.gov/medwatch/safety/2007/safety07.htm#Antidepressant):
    Update to the existing black box warning on the prescribing
    information on all antidepressant medications to include warnings
    about the increased risks of suicidal thinking and behavior in young
    adults ages 18 to 24 years old during the first one to two months of
    treatment.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Late effects resulting from therapeutic exposures to chemotherapy used
during treatment of pediatric malignancies. Effects include sensory
(dental, ocular, otologic), reproductive (testicular, ovarian)
pulmonary, urologic (urinary, renal), dermatologic, neurologic (central,
peripheral, cognitive), hepatic, vascular, and skeletal sequelae;
dyslipidemia; and secondary malignancies.

**Note**: These guidelines are intended for use beginning two or more
years following the completion of cancer therapy, and provide a
framework for ongoing late effects monitoring in childhood cancer
survivors; however, these guidelines are not intended to provide
guidance for follow-up of the pediatric cancer survivor\'s primary
disease.

#### GUIDELINE CATEGORY

Counseling\
Evaluation\
Management\
Prevention\
Screening

#### CLINICAL SPECIALTY

Cardiology\
Dentistry\
Dermatology\
Endocrinology\
Family Practice\
Gastroenterology\
Internal Medicine\
Nephrology\
Neurology\
Obstetrics and Gynecology\
Oncology\
Ophthalmology\
Otolaryngology\
Pediatrics\
Pulmonary Medicine\
Urology

#### INTENDED USERS

Advanced Practice Nurses\
Dentists\
Nurses\
Physician Assistants\
Physicians\
Psychologists/Non-physician Behavioral Health Clinicians

#### GUIDELINE OBJECTIVE(S)

-   To provide recommendations for screening and management of late
    effects in survivors of pediatric malignancies

-   To increase quality of life and decrease complication-related
    healthcare costs for pediatric cancer survivors by providing
    standardized and enhanced follow-up care throughout the life-span
    that (a) promotes healthy lifestyles, (b) provides for ongoing
    monitoring of health status, (c) facilitates early identification of
    late effects, and (d) provides timely intervention for late effects

#### TARGET POPULATION

Asymptomatic survivors of childhood, adolescent, or young adult cancers
who were treated with chemotherapy and who present for routine
exposure-related medical follow-up

#### INTERVENTIONS AND PRACTICES CONSIDERED

Thorough history and physical examination, including targeted screening
evaluations

#### MAJOR OUTCOMES CONSIDERED

Not stated

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Hand-searches of Published Literature (Secondary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

Pertinent information from the published medical literature over the
past 20 years (updated as of October 2005) was retrieved and reviewed
during the development and updating of these guidelines. For each
therapeutic exposure, a complete search was performed via MEDLINE
(National Library of Medicine, Bethesda, MD). Keywords included
\"childhood cancer therapy,\" \"complications,\" and \"late effects,\"
combined with keywords for each therapeutic exposure. References from
the bibliographies of selected articles were used to broaden the search.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Expert Consensus (Committee)\
Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

\"High-level evidence\" (recommendation category 1) was defined as
evidence derived from high quality case control or cohort studies.

\"Lower-level evidence\" (recommendation categories 2A and 2B) was
defined as evidence derived from non-analytic studies, case reports,
case series, and clinical experience.

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review with Evidence Tables

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

The guidelines were scored by the multidisciplinary panel of experts
using a modified version of the National Criteria: Comprehensive Cancer
Network \"Categories of Consensus\" system. Each score reflects the
expert panel\'s assessment of the strength of data from the literature
linking a specific late effect with a therapeutic exposure, coupled with
an assessment of the appropriateness of the screening recommendation
based on the expert panel\'s collective clinical experience.
\"High-level evidence\" (category 1) was defined as evidence derived
from high quality case control or cohort studies. \"Lower-level
evidence\" (categories 2A and 2B) was defined as evidence derived from
non-analytic studies, case reports, case series and clinical experience.
Rather than submitting recommendations representing major disagreements,
items scored as \"Category 3\" were either deleted or revised by the
panel of experts to provide at least a \"Category 2B\" score for all
recommendations included in the guidelines.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

In 2002, the leadership of the Children\'s Oncology Group Late Effects
Committee and Nursing Discipline appointed a 7-member task force, with
representation from the Late Effects Committee, Nursing Discipline, and
Patient Advocacy Committee. The task force was convened to review and
summarize the medical literature and develop a draft of clinical
practice guidelines to direct long-term follow-up care for pediatric
cancer survivors. The task force followed a modified version of the
guideline development process established by the National Comprehensive
Cancer Network (NCCN), integrating available literature with expert
opinion using reiterative feedback loops.

The original draft went through several iterations within the task force
prior to initial review. Multidisciplinary experts in the field,
including nurses, physicians (pediatric oncologists and other
subspecialists), patient advocates, behavioral specialists, and other
healthcare professionals, were then recruited by the task force to
provide an extensive, targeted review of the draft, including focused
review of selected guideline sections. Revisions were made based on
these recommendations. The revised draft was then sent out to additional
multidisciplinary experts for further review. A total of 62 individuals
participated in the review process. The guidelines subsequently
underwent comprehensive review and scoring by a panel of experts in the
late effects of pediatric malignancies, comprised of multidisciplinary
representatives from the COG Late Effects Committee.

**Revisions**

In order to keep the guidelines current and clinically meaningful, the
COG Late Effects Committee organized 18 multi-disciplinary task forces
in March 2004. These task forces were charged with the responsibility
for monitoring the medical literature in regard to specific
system-related clinical topics relevant to the guidelines (e.g.,
cardiovascular, neurocognitive, fertility/reproductive), providing
periodic reports to the Late Effects Committee, and recommending
revisions to the guidelines and their associated health education
materials and references (including the addition of therapeutic
exposures) as new information became available. Task force members were
assigned according to their respective areas of expertise and clinical
interest. A list of these task forces and their membership is included
in the \"Contributors\" section of the original guideline document. The
revisions incorporated into the current release of these guidelines
(Version 2.0 -- March 2006) reflect the contributions and
recommendations of these task forces.

All revisions proposed by the task forces were evaluated by a panel of
experts, and if accepted, assigned a score (see \"Rating Scheme for the
Strength of the Evidence\"). Proposed revisions that were rejected by
the expert panel were returned with explanation to the relevant task
force chair. If desired, task force chairs were given an opportunity to
respond by providing additional justification and resubmitting the
rejected task force recommendation(s) for further consideration by the
expert panel. A total of 34 sections and 9 Health Links were added to
Version 2.0 of these guidelines.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Each score relates to the strength of the association of the identified
late effect with the specific therapeutic exposure based on current
literature, and is coupled with a recommendation for periodic health
screening based on the collective clinical experience of the panel of
experts. This is due to the fact that there are no randomized clinical
trials (and none forthcoming in the foreseeable future) on which to base
recommendations for periodic screening evaluations in this population;
therefore, the guidelines should not be misconstrued as representing
conventional \"evidence-based clinical practice guidelines\" or
\"standards of care\".

Each item was scored based on the level of evidence currently available
to support it. Scores were assigned according to a modified version of
the National Comprehensive Cancer Network \"Categories of Consensus,\"
as follows:

1  There is uniform consensus of the panel that (1) there is high-level
evidence linking the late effect with the therapeutic exposure, and (2)
the screening recommendation is appropriate based on the collective
clinical experience of panel members.

2A  There is uniform consensus of the panel that (1) there is
lower-level evidence linking the late effect with the therapeutic
exposure, and (2) the screening recommendation is appropriate based on
the collective clinical experience of panel members.

2B  There is non-uniform consensus of the panel that (1) there is
lower-level evidence linking the late effect with the therapeutic
exposure, and (2) the screening recommendation is appropriate based on
the collective clinical experience of panel members.

3  There is major disagreement that the recommendation is appropriate.

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

External Peer Review\
Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

The initial version of the guidelines (Version 1.0 -- Children\'s
Oncology Group Late Effects Screening Guidelines) was released to the
Children\'s Oncology Group (COG) membership in March 2003 for a
six-month trial period. This allowed for initial feedback from the COG
membership, resulting in additional review and revision of the
guidelines by the Late Effects Committee prior to public release.

**Revisions**

All revisions proposed by the task forces were evaluated by a panel of
experts, and if accepted, assigned a score (see \"Rating Scheme for the
Strength of the Evidence\"). Proposed revisions that were rejected by
the expert panel were returned with explanation to the relevant task
force chair. If desired, task force chairs were given an opportunity to
respond by providing additional justification and resubmitting the
rejected task force recommendation(s) for further consideration by the
expert panel.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

Grades of recommendations (1, 2A, 2B, 3) are defined at the end of the
\"Major Recommendations\" field.

***Note from the Children\'s Oncology Group and the National Guideline
Clearinghouse (NGC):*** The *Children\'s Oncology Group Long-Term
Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young
Adult Cancers* (COG LTFU) are organized according to therapeutic
exposures; this guideline has been divided into individual summaries. In
addition to the current summary, the following are available:

-   [Sections 1-2: Any Cancer
    Experience](http://www.guideline.gov/summary/summary.aspx?doc_id=10246&nbr=005395)

-   [Sections 3--5: Blood/Serum
    Products](http://www.guideline.gov/summary/summary.aspx?doc_id=10768&nbr=005596)

-   [Sections 38--91:
    Radiation](http://www.guideline.gov/summary/summary.aspx?doc_id=10771&nbr=005599)

-   [Sections 92--106: Hematopoietic Cell
    Transplant](http://www.guideline.gov/summary/summary.aspx?doc_id=10772&nbr=005600)

-   [Sections 107--132:
    Surgery](http://www.guideline.gov/summary/summary.aspx?doc_id=10773&nbr=005601)

-   [Sections 133--136: Other Therapeutic
    Modalities](http://www.guideline.gov/summary/summary.aspx?doc_id=10774&nbr=005602)

-   [Sections 137--146: Cancer and General Health
    Screening](http://www.guideline.gov/summary/summary.aspx?doc_id=10775&nbr=005603)

In order to accurately derive individualized screening recommendations
for a specific childhood cancer survivor using this guideline, see
\"Using the COG LTFU Guidelines to Develop Individualized Screening
Recommendations\" in the [original guideline
document](http://www.survivorshipguidelines.org/pdf/LTFUGuidelines.pdf).
(Note: For ease of use, a Patient-Specific Guideline Identification Tool
has been developed to streamline the process and is included in
[Appendix
I](http://www.survivorshipguidelines.org/pdf/GuidelinesAppendixI.pdf) of
the original guideline document.)

**Guideline Organization**

The *Children\'s Oncology Group Long-Term Follow-Up Guidelines for
Survivors of Childhood, Adolescent, and Young Adult Cancers* are
organized according to therapeutic exposures, arranged by column as
follows:

  ------------------ -------------------------------------------------------------------------
  **System**         Body system (e.g., auditory, musculoskeletal) most relevant to each
                     guideline section.

  **Score**          Score assigned by expert panel representing the strength of data from the
                     literature linking a specific late effect with a therapeutic exposure
                     coupled with an assessment of the appropriateness of the screening
                     recommendation based on collective clinical experience.

  **Section Number** Unique identifier for each guideline section corresponding with listing
                     in Index.

  **Therapeutic      Therapeutic intervention for malignancy, including chemotherapy,
  Agent**            radiation, surgery, blood/serum products, hematopoietic cell transplant,
                     and other therapeutic modalities.

  **Risk Factors**   Host factors (e.g., age, sex, race, genetic predisposition), treatment
                     factors (e.g., cumulative dose of therapeutic agent, mode of
                     administration, combinations of agents), medical conditions (e.g.,
                     pre-morbid or co-morbid conditions), and health behaviors (e.g., diet,
                     smoking, alcohol use) that may increase risk of developing the
                     complication.

  **Highest Risk     Conditions (host factors, treatment factors, medical conditions and/or
  Factors**          health behaviors) associated with the highest risk for developing the
                     complication.

  **Periodic         Recommended screening evaluations, including health history, physical
  Evaluations**      examination, laboratory evaluation, imaging, and psychosocial assessment.
                     Recommendation for minimum frequency of periodic evaluations is based on
                     risk factors and magnitude of risk, as supported by the medical
                     literature and/or the combined clinical experience of the reviewers and
                     panel of experts.

  **Health           ***Health Links***: Health education materials developed specifically to
  Counseling/\       accompany these guidelines. Title(s) of Health Link(s) relevant to each
  Further            guideline section are referenced in this column. Health Link documents
  Considerations**   are included in [Appendix
                     II](http://www.survivorshipguidelines.org/pdf/GuidelinesAppendixII.pdf)
                     of the original guideline document.\
                     **Counseling**: Suggested patient counseling regarding measures to
                     prevent/reduce risk or promote early detection of the potential treatment
                     complication.\
                     **Resources**: See the original guideline document for lists of books and
                     web sites that may provide the clinician with additional relevant
                     information.\
                     **Considerations for Further Testing and Intervention**: Recommendations
                     for further diagnostic evaluations beyond minimum screening for
                     individuals with positive screening tests, recommendations for
                     consultation and/or referral, and recommendations for management of
                     exacerbating or predisposing conditions.

  **References**     References are listed immediately following each guideline section in the
                     original guideline document. Included are medical citations that provide
                     evidence for the association of the therapeutic intervention with the
                     specific treatment complication and/or evaluation of predisposing risk
                     factors. In addition, some general review articles have been included in
                     the Reference section of the original guideline document for clinician
                     convenience.
  ------------------ -------------------------------------------------------------------------

**Note**: See the end of the \"Major Recommendations\" field for
explanations of [abbreviations](#Abbreviations) included in the summary.

**System = Dental\
Score = 1**

  --------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic    **Potential Late       **Risk        **Highest    **Periodic       **Health
  \#**    Agent(s)**       Effects**              Factors**     Risk         Evaluation**     Counseling Further
                                                                Factors**                     Considerations**
  ------- ---------------- ---------------------- ------------- ------------ ---------------- ------------------
  6       **Any            **Dental               **Host        **Host       **Physical**\    **Health Links**\
          Chemotherapy**   Abnormalities**\       Factors**\    Factors**\   \                \
                           \                      \             \            **Oral exam**\   **See \"Patient
                           Tooth/root agenesis\   Any patient   Younger age  \                Resources\"
                           Root                   who had not   at           (Yearly)\        field**\
                           thinning/shortening\   developed     treatment,   \                \
                           Enamel dysplasia       permanent     especially   **Screening**\   Dental Health\
                                                  dentition at  \<5 years    \                \
                                                  time of       old          **Dental exam    **Considerations
                                                  cancer                     and cleaning**\  for Further
                                                  therapy\                   \                Testing and
                                                  \                          (Every six       Intervention**\
                                                  **Treatment                months)          \
                                                  Factors**\                                  Regular dental
                                                  \                                           care including
                                                  Any radiation                               fluoride
                                                  treatment                                   applications.
                                                  involving the                               Baseline panorex
                                                  oral cavity                                 prior to dental
                                                  or salivary                                 procedures to
                                                  glands                                      evaluate root
                                                                                              development.

  --------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Male reproductive**

**Scores = Alkylating agents: 1\
Heavy metals: 2A\
Non-classical alkylators: 2A**

+---+---------+--------+-------------+----------+--------+------------+
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+===+=========+========+=============+==========+========+============+
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|   |         |        |             |          | infert | h          |
|   |         |        |             |          | ility. | ypogonadal |
|   |         |        |             |          | Pe     | patients.  |
|   |         |        |             |          | riodic | Re         |
|   |         |        |             |          | eval   | productive |
|   |         |        |             |          | uation | e          |
|   |         |        |             |          | over   | ndocrinolo |
|   |         |        |             |          | time   | gy/urology |
|   |         |        |             |          | is     | referral   |
|   |         |        |             |          | recom  | for        |
|   |         |        |             |          | mended | i          |
|   |         |        |             |          | as     | nfertility |
|   |         |        |             |          | resu   | evaluation |
|   |         |        |             |          | mption | and        |
|   |         |        |             |          | of     | co         |
|   |         |        |             |          | spe    | nsultation |
|   |         |        |             |          | rmatog | regarding  |
|   |         |        |             |          | enesis | assisted   |
|   |         |        |             |          | can    | re         |
|   |         |        |             |          | occur  | productive |
|   |         |        |             |          | up to  | tec        |
|   |         |        |             |          | 10     | hnologies. |
|   |         |        |             |          | years  |            |
|   |         |        |             |          | post   |            |
|   |         |        |             |          | th     |            |
|   |         |        |             |          | erapy) |            |
+---+---------+--------+-------------+----------+--------+------------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Female reproductive**

**Scores = Alkylating agents: 1\
Heavy metals: 2A\
Non-classical alkylators: 2A**

+---+---------+--------+-------------+---------+-----------+-----------+
| * | **Ther  | **Pot  | **Risk      | **      | *         | **Health  |
| * | apeutic | ential | Factors**   | Highest | *Periodic | C         |
| S | Age     | Late   |             | Risk    | Eva       | ounseling |
| e | nt(s)** | Eff    |             | Fa      | luation** | Further   |
| c |         | ects** |             | ctors** |           | Conside   |
| \ |         |        |             |         |           | rations** |
| # |         |        |             |         |           |           |
| * |         |        |             |         |           |           |
| * |         |        |             |         |           |           |
+===+=========+========+=============+=========+===========+===========+
| 7 | **Alk   | **G    | **Treatment | **Tr    | **H       | **Health  |
| b | ylating | onadal | Factors**\  | eatment | istory**\ | Links**\  |
|   | Ag      | dysfu  | \           | Fac     | \         | \         |
|   | ents**\ | nction | Higher      | tors**\ | *         | **See     |
|   | \       | (ovari | cumulative  | \       | *Pubertal | \"Patient |
|   | Bu      | an)**\ | doses of    | MOPP    | (onset,   | Re        |
|   | sulfan\ | \      | alkylators  | [\>     | tempo)**\ | sources\" |
|   | Car     | Dela   | or          | ]{.unde | \         | field**\  |
|   | mustine | yed/ar | c           | rline}3 | **M       | \         |
|   | (BCNU)\ | rested | ombinations | cycles\ | enstrual/ | Female    |
|   | Chlora  | pu     | of          | B       | pregnancy | Health    |
|   | mbucil\ | berty\ | alkylators\ | usulfan | h         | Issues\   |
|   | Cyc     | Pre    | Combined    | [\>]{   | istory**\ | \         |
|   | lophosp | mature | with        | .underl | \         | **Res     |
|   | hamide\ | meno   | radiation   | ine}600 | **Sexual  | ources**\ |
|   | Ifos    | pause\ | to:         | m       | function  | \         |
|   | famide\ | Infer  |             | g/m^2^\ | (vaginal  | Extensive |
|   | Lo      | tility | -   Abd     | Cy      | dryness,  | in        |
|   | mustine |        | omen/pelvis | clophos | l         | formation |
|   | (CCNU)\ |        |             | phamide | ibido)**\ | regarding |
|   | Me      |        | -   Lumbar  | cum     | \         | in        |
|   | chloret |        |     or      | ulative | **M       | fertility |
|   | hamine\ |        |     sacral  | dose    | edication | for       |
|   | Mel     |        |     spine   | [\>]{   | use       | patients  |
|   | phalan\ |        |     (from   | .underl | impacting | and       |
|   | Procar  |        |     ovarian | ine}7.5 | sexual    | h         |
|   | bazine\ |        |             | g/m^2^  | fu        | ealthcare |
|   | Th      |        |    scatter) | or as   | nction**\ | prof      |
|   | iotepa\ |        |             | condi   | \         | essionals |
|   | \       |        | -   Brain,  | tioning | (Yearly)\ | is        |
|   | **Heavy |        |     cranium | for     | \         | available |
|   | Me      |        |     (neu    | HCT\    | **Ph      | on the    |
|   | tals**\ |        | roendocrine | Any     | ysical**\ | following |
|   | \       |        |     axis)   | alk     | \         | w         |
|   | Carbo   |        |             | ylators | **Tanner  | ebsites:\ |
|   | platin\ |        | **Health    | c       | stage**\  | \         |
|   | Cis     |        | B           | ombined | \         | American  |
|   | platin\ |        | ehaviors**\ | with:   | (Yearly   | Society   |
|   | \       |        | \           |         | until     | for       |
|   | *       |        | Smoking\    | -       | sexually  | Rep       |
|   | *Non-Cl |        | \           |  Pelvic | mature)\  | roductive |
|   | assical |        | **Info      |     ra  | \         | Medicine  |
|   | Alkyla  |        | Link**\     | diation | **Scr     | ([w       |
|   | tors**\ |        | \           |         | eening**\ | ww.asrm.o |
|   | \       |        | Doses that  | -   TBI | \         | rg](http: |
|   | Daca    |        | cause       |         | **FSH\    | //www.asr |
|   | rbazine |        | gonadal     |         | \         | m.org/))\ |
|   | (DTIC)\ |        | dysfunction |         | LH\       | Fertile   |
|   | Temoz   |        | show        |         | \         | Hope      |
|   | olomide |        | individual  |         | Est       | ([www.fe  |
|   |         |        | variation.  |         | radiol**\ | rtilehope |
|   |         |        | Females can |         | \         | .org](htt |
|   |         |        | typically   |         | (Baseline | p://www.f |
|   |         |        | maintain    |         | at age 13 | ertilehop |
|   |         |        | gonadal     |         | **and**   | e.org/))\ |
|   |         |        | function at |         | as        | \         |
|   |         |        | higher      |         | c         | **Coun    |
|   |         |        | cumulative  |         | linically | seling**\ |
|   |         |        | doses than  |         | indicated | \         |
|   |         |        | males.      |         | in        | Counsel   |
|   |         |        |             |         | patients  | currently |
|   |         |        |             |         | with      | men       |
|   |         |        |             |         | delayed   | struating |
|   |         |        |             |         | puberty,  | women at  |
|   |         |        |             |         | irregular | increased |
|   |         |        |             |         | menses,   | risk of   |
|   |         |        |             |         | primary   | early     |
|   |         |        |             |         | or        | menopause |
|   |         |        |             |         | secondary | to be     |
|   |         |        |             |         | am        | cautious  |
|   |         |        |             |         | enorrhea, | about     |
|   |         |        |             |         | and/or    | delaying  |
|   |         |        |             |         | clinical  | chil      |
|   |         |        |             |         | signs and | dbearing. |
|   |         |        |             |         | symptoms  | Counsel   |
|   |         |        |             |         | of        | regarding |
|   |         |        |             |         | estrogen  | the need  |
|   |         |        |             |         | de        | for       |
|   |         |        |             |         | ficiency) | contr     |
|   |         |        |             |         |           | aception, |
|   |         |        |             |         |           | since     |
|   |         |        |             |         |           | there is  |
|   |         |        |             |         |           | t         |
|   |         |        |             |         |           | remendous |
|   |         |        |             |         |           | i         |
|   |         |        |             |         |           | ndividual |
|   |         |        |             |         |           | va        |
|   |         |        |             |         |           | riability |
|   |         |        |             |         |           | in        |
|   |         |        |             |         |           | gonadal   |
|   |         |        |             |         |           | toxicity  |
|   |         |        |             |         |           | after     |
|   |         |        |             |         |           | exposure  |
|   |         |        |             |         |           | to        |
|   |         |        |             |         |           | a         |
|   |         |        |             |         |           | lkylating |
|   |         |        |             |         |           | agents.   |
|   |         |        |             |         |           | Recovery  |
|   |         |        |             |         |           | of        |
|   |         |        |             |         |           | fertility |
|   |         |        |             |         |           | may occur |
|   |         |        |             |         |           | years     |
|   |         |        |             |         |           | after     |
|   |         |        |             |         |           | therapy.\ |
|   |         |        |             |         |           | \         |
|   |         |        |             |         |           | **Consi   |
|   |         |        |             |         |           | derations |
|   |         |        |             |         |           | for       |
|   |         |        |             |         |           | Further   |
|   |         |        |             |         |           | Testing   |
|   |         |        |             |         |           | and       |
|   |         |        |             |         |           | Interv    |
|   |         |        |             |         |           | ention**\ |
|   |         |        |             |         |           | \         |
|   |         |        |             |         |           | Bone      |
|   |         |        |             |         |           | density   |
|   |         |        |             |         |           | e         |
|   |         |        |             |         |           | valuation |
|   |         |        |             |         |           | for       |
|   |         |        |             |         |           | osteo     |
|   |         |        |             |         |           | penia/ost |
|   |         |        |             |         |           | eoporosis |
|   |         |        |             |         |           | in        |
|   |         |        |             |         |           | hy        |
|   |         |        |             |         |           | pogonadal |
|   |         |        |             |         |           | patients. |
|   |         |        |             |         |           | Refer to  |
|   |         |        |             |         |           | endocr    |
|   |         |        |             |         |           | inologist |
|   |         |        |             |         |           | for       |
|   |         |        |             |         |           | delayed   |
|   |         |        |             |         |           | puberty   |
|   |         |        |             |         |           | or        |
|   |         |        |             |         |           | per       |
|   |         |        |             |         |           | sistently |
|   |         |        |             |         |           | abnormal  |
|   |         |        |             |         |           | hormone   |
|   |         |        |             |         |           | levels.   |
|   |         |        |             |         |           | Hormonal  |
|   |         |        |             |         |           | re        |
|   |         |        |             |         |           | placement |
|   |         |        |             |         |           | therapy   |
|   |         |        |             |         |           | for       |
|   |         |        |             |         |           | hy        |
|   |         |        |             |         |           | pogonadal |
|   |         |        |             |         |           | patients. |
|   |         |        |             |         |           | Rep       |
|   |         |        |             |         |           | roductive |
|   |         |        |             |         |           | endo      |
|   |         |        |             |         |           | crinology |
|   |         |        |             |         |           | referral  |
|   |         |        |             |         |           | for       |
|   |         |        |             |         |           | in        |
|   |         |        |             |         |           | fertility |
|   |         |        |             |         |           | e         |
|   |         |        |             |         |           | valuation |
|   |         |        |             |         |           | and       |
|   |         |        |             |         |           | con       |
|   |         |        |             |         |           | sultation |
|   |         |        |             |         |           | regarding |
|   |         |        |             |         |           | assisted  |
|   |         |        |             |         |           | rep       |
|   |         |        |             |         |           | roductive |
|   |         |        |             |         |           | tech      |
|   |         |        |             |         |           | nologies. |
|   |         |        |             |         |           | Consider  |
|   |         |        |             |         |           | 2 months  |
|   |         |        |             |         |           | off       |
|   |         |        |             |         |           | hormonal  |
|   |         |        |             |         |           | re        |
|   |         |        |             |         |           | placement |
|   |         |        |             |         |           | in women  |
|   |         |        |             |         |           | with      |
|   |         |        |             |         |           | ovarian   |
|   |         |        |             |         |           | failure   |
|   |         |        |             |         |           | to assess |
|   |         |        |             |         |           | ovarian   |
|   |         |        |             |         |           | recovery. |
+---+---------+--------+-------------+---------+-----------+-----------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = SMN**

**Scores = Alkylating agents: 1\
Heavy metals: 2A\
Non-classical alkylators: 2A**

  ---------------------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic       **Potential Late     **Risk Factors**    **Highest   **Periodic Evaluation** **Health
  \#**    Agent(s)**          Effects**                                Risk                                Counseling Further
                                                                       Factors**                           Considerations**
  ------- ------------------- -------------------- ------------------- ----------- ----------------------- ------------------
  8       **Alkylating        **Acute myeloid      **Treatment                     **History**\            **Health Links**\
          Agents**\           leukemia**\          Factors**\                      \                       \
          \                   \                    \                               **Fatigue\              **See \"Patient
          Busulfan\           **Myelodysplasia**   Less than 10 years              \                       Resources\"
          Carmustine (BCNU)\                       since exposure to               Bleeding\               field**\
          Chlorambucil\                            agent\                          \                       \
          Cyclophosphamide\                        Higher cumulative               Easy bruising**\        Reducing the Risk
          Ifosfamide\                              alkylator dose or               \                       of Second Cancers\
          Lomustine (CCNU)\                        combination of                  (Yearly, up to 10 years \
          Mechlorethamine\                         alkylators\                     after exposure to       **Counseling**\
          Melphalan\                               \                               agent)\                 \
          Procarbazine\                            *Note*: Melphalan               \                       Counsel to
          Thiotepa\                                and mechlorethamine             **Physical**\           promptly report
          \                                        are more potent                 \                       fatigue, pallor,
          **Heavy Metals**\                        leukemogens than                **Dermatologic exam     petechiae, or bone
          \                                        cyclophosphamide\               (pallor, petechiae,     pain.\
          Carboplatin\                             \                               purpura)**\             \
          Cisplatin\                               **Medical                       \                       **Considerations
          \                                        Conditions**\                   (Yearly, up to 10 years for Further
          **Non-Classical                          \                               after exposure to       Testing and
          Alkylators**\                            Splenectomy                     agent)\                 Intervention**\
          \                                        (conflicting                    \                       \
          Dacarbazine (DTIC)\                      evidence)                       **Screening**\          Bone marrow exam
          Temozolomide                                                             \                       as clinically
                                                                                   **CBC/differential**\   indicated
                                                                                   \                       
                                                                                   (Yearly, up to 10 years 
                                                                                   after exposure to       
                                                                                   agent)                  

  ---------------------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Pulmonary\
Score = 1**

+---+---------+--------+--------+-----------+---------+--------------+
| * | **Ther  | **Pot  | **Risk | **Highest | **P     | **Health     |
| * | apeutic | ential | Fac    | Risk      | eriodic | Counseling   |
| S | Age     | Late   | tors** | Factors** | Evalu   | Further      |
| e | nt(s)** | Eff    |        |           | ation** | Cons         |
| c |         | ects** |        |           |         | iderations** |
| \ |         |        |        |           |         |              |
| # |         |        |        |           |         |              |
| * |         |        |        |           |         |              |
| * |         |        |        |           |         |              |
+===+=========+========+========+===========+=========+==============+
| 9 | **Alk   | **Pul  | **Tre  | **        | **His   | **Health     |
|   | ylating | monary | atment | Treatment | tory**\ | Links**\     |
|   | Ag      | fibr   | fact   | F         | \       | \            |
|   | ents**\ | osis** | ors**\ | actors**\ | *       | **See        |
|   | \       |        | \      | \         | *Cough\ | \"Patient    |
|   | Bu      |        | Higher | BCNU      | \       | Resources\"  |
|   | sulfan\ |        | cumu   | [         | SOB\    | field**\     |
|   | Car     |        | lative | \>]{.unde | \       | \            |
|   | mustine |        | doses\ | rline}600 | DOE\    | Pulmonary    |
|   | (BCNU)\ |        | Co     | mg/m^2^\  | \       | Health\      |
|   | Lo      |        | mbined | Busulfan  | \       | \            |
|   | mustine |        | with   | [         | Whee    | **           |
|   | (CCNU)  |        | bleo   | \>]{.unde | zing**\ | Resources**\ |
|   |         |        | mycin\ | rline}500 | \       | \            |
|   |         |        | \      | mg        | (Y      | Extensive    |
|   |         |        | **M    | (t        | early)\ | information  |
|   |         |        | edical | ransplant | \       | regarding    |
|   |         |        | C      | doses)\   | **Phys  | smoking      |
|   |         |        | onditi | Combined  | ical**\ | cessation is |
|   |         |        | ons**\ | with:     | \       | available    |
|   |         |        | \      |           | **Pu    | for patients |
|   |         |        | Atopic | -   Chest | lmonary | on the       |
|   |         |        | hi     |           | exam**\ | NCI\'s       |
|   |         |        | story\ | radiation | \       | website:     |
|   |         |        | \      |           | (Y      | [www.smokefr |
|   |         |        | **     | -   TBI   | early)\ | ee.gov](http |
|   |         |        | Health |           | \       | ://www.smoke |
|   |         |        | Behavi |           | **Scree | free.gov/).\ |
|   |         |        | ors**\ |           | ning**\ | \            |
|   |         |        | \      |           | \       | **C          |
|   |         |        | S      |           | **Chest | ounseling**\ |
|   |         |        | moking |           | x       | \            |
|   |         |        |        |           | -ray**\ | Counsel      |
|   |         |        |        |           | \       | regarding    |
|   |         |        |        |           | **PFTs  | tobacco      |
|   |         |        |        |           | (in     | avoid        |
|   |         |        |        |           | cluding | ance/smoking |
|   |         |        |        |           | DLCO    | cessation.   |
|   |         |        |        |           | and     | Due to the   |
|   |         |        |        |           | spirome | potential    |
|   |         |        |        |           | try)**\ | pulmonary    |
|   |         |        |        |           | \       | toxicity of  |
|   |         |        |        |           | (B      | this         |
|   |         |        |        |           | aseline | therapy,     |
|   |         |        |        |           | at      | patients who |
|   |         |        |        |           | entry   | desire to    |
|   |         |        |        |           | into    | SCUBA dive   |
|   |         |        |        |           | lo      | should be    |
|   |         |        |        |           | ng-term | advised to   |
|   |         |        |        |           | fo      | obtain       |
|   |         |        |        |           | llowup. | medical      |
|   |         |        |        |           | Repeat  | clearance    |
|   |         |        |        |           | as      | from a       |
|   |         |        |        |           | cli     | diving       |
|   |         |        |        |           | nically | medicine     |
|   |         |        |        |           | in      | specialist.\ |
|   |         |        |        |           | dicated | \            |
|   |         |        |        |           | in      | **Co         |
|   |         |        |        |           | p       | nsiderations |
|   |         |        |        |           | atients | for Further  |
|   |         |        |        |           | with    | Testing and  |
|   |         |        |        |           | a       | Int          |
|   |         |        |        |           | bnormal | ervention**\ |
|   |         |        |        |           | results | \            |
|   |         |        |        |           | or      | In patients  |
|   |         |        |        |           | prog    | with         |
|   |         |        |        |           | ressive | abnormal     |
|   |         |        |        |           | pu      | PFTs and/or  |
|   |         |        |        |           | lmonary | CXR,         |
|   |         |        |        |           | dysfun  | consider     |
|   |         |        |        |           | ction.) | repeat       |
|   |         |        |        |           |         | evaluation   |
|   |         |        |        |           |         | prior to     |
|   |         |        |        |           |         | general      |
|   |         |        |        |           |         | anesthesia.  |
|   |         |        |        |           |         | Pulmonary    |
|   |         |        |        |           |         | consultation |
|   |         |        |        |           |         | for          |
|   |         |        |        |           |         | symptomatic  |
|   |         |        |        |           |         | pulmonary    |
|   |         |        |        |           |         | dysfunction. |
|   |         |        |        |           |         | Influenza    |
|   |         |        |        |           |         | and          |
|   |         |        |        |           |         | pneumococcal |
|   |         |        |        |           |         | vaccines.    |
+---+---------+--------+--------+-----------+---------+--------------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Ocular\
Score = 2B**

  ------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic   **Potential     **Risk Factors**  **Highest     **Periodic        **Health
  \#**    Agent(s)**      Late Effects**                    Risk          Evaluation**      Counseling Further
                                                            Factors**                       Considerations**
  ------- --------------- --------------- ----------------- ------------- ----------------- ------------------
  10      **Alkylating    **Cataracts**   **Treatment       **Treatment   **History**\      **Health Links**\
          Agents**\                       factors**\        Factors**\    \                 \
          \                               \                 \             **Visual          **See \"Patient
          Busulfan                        Combined with     Combined with difficulties**\   Resources\"
                                          corticosteroids   cranial,      \                 field**\
                                                            orbital, or   (Yearly)\         \
                                                            eye           \                 Cataracts\
                                                            radiation\    **Physical**\     \
                                                            TBI\          \                 **Considerations
                                                            Longer        **Eye exam        for Further
                                                            interval      (visual acuity,   Testing and
                                                            since         funduscopic exam  Intervention**\
                                                            treatment     for lens          \
                                                                          opacity)**\       Ophthalmology
                                                                          \                 consultation if
                                                                          (Yearly)          problem
                                                                                            identified. Refer
                                                                                            patients with
                                                                                            visual deficits to
                                                                                            school liaison in
                                                                                            community or
                                                                                            cancer center
                                                                                            (psychologist,
                                                                                            social worker,
                                                                                            school counselor)
                                                                                            to facilitate
                                                                                            acquisition of
                                                                                            educational
                                                                                            resources.

  ------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Urinary\
Score = 1**

  ---------------------------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic       **Potential Late **Risk         **Highest Risk       **Periodic Evaluation**     **Health Counseling
  \#**    Agent(s)**          Effects**        Factors**      Factors**                                        Further
                                                                                                               Considerations**
  ------- ------------------- ---------------- -------------- -------------------- --------------------------- --------------------
  11      **Alkylating        **Urinary tract  **Treatment    **Treatment          **History**\                **Health Links**\
          Agents**\           toxicity**\      Factors**\     Factors**\           \                           \
          Cyclophosphamide\   \                \              \                    **Hematuria**\              **See \"Patient
          Ifosfamide          Hemorrhagic      Higher         Cyclophosphamide     \                           Resources\" field**\
                              cystitis\        cumulative     dose                 **Urinary                   \
                              Bladder          doses          [\>]{.underline}3    urgency/frequency**\        Bladder Health\
                              fibrosis\        (decreased     g/m^2^\              \                           \
                              Dysfunctional    incidence with Pelvic radiation     **Urinary                   **Counseling**\
                              voiding\         Mesna)\        dose                 incontinence/retention**\   \
                              Vesicoureteral   Combined with: [\>]{.underline}30   \                           Counsel to promptly
                              reflux\          pelvic         Gy                   **Dysuria**\                report dysuria or
                              Hydronephrosis   radiation\                          \                           gross hematuria\
                                               \                                   **Nocturia**\               \
                                               **Health                            \                           **Considerations for
                                               Behaviors**\                        **Abnormal urinary          Further Testing and
                                               \                                   stream**\                   Intervention**\
                                               Alcohol use\                        \                           \
                                               Smoking                             (Yearly)\                   Urine culture, spot
                                                                                   \                           urine
                                                                                   **Screening**\              calcium/creatinine
                                                                                   \                           ratio, and
                                                                                   **Urinalysis**\             ultrasound of
                                                                                   \                           kidneys and bladder
                                                                                   (Yearly)                    for patients with
                                                                                                               microscopic
                                                                                                               hematuria (defined
                                                                                                               as [\>]{.underline}5
                                                                                                               RBC/HPF on at least
                                                                                                               2 occasions).
                                                                                                               Nephrology or
                                                                                                               urology referral for
                                                                                                               patients with
                                                                                                               culture-negative
                                                                                                               microscopic
                                                                                                               hematuria AND
                                                                                                               abnormal ultrasound
                                                                                                               and/or abnormal
                                                                                                               calcium/creatinine
                                                                                                               ratio. Urology
                                                                                                               referral for
                                                                                                               patients with
                                                                                                               culture negative
                                                                                                               macroscopic
                                                                                                               hematuria.

  ---------------------------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = SMN\
Score = 2A**

  ---------------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic      **Potential    **Risk         **Highest   **Periodic Evaluation**     **Health Counseling
  \#**    Agent(s)**         Late Effects** Factors**      Risk                                    Further
                                                           Factors**                               Considerations**
  ------- ------------------ -------------- -------------- ----------- --------------------------- --------------------
  12      **Alkylating       **Bladder      **Treatment                **History**\                **Health Links**\
          Agents**\          malignancy**   Factors**\                 \                           \
          \                                 \                          **Hematuria**\              **See \"Patient
          Cyclophosphamide                  Combined with:             \                           Resources\" field**\
                                            pelvic                     **Urinary                   \
                                            radiation\                 urgency/frequency**\        Bladder Health\
                                            \                          \                           \
                                            **Health                   **Urinary                   **Counseling**\
                                            Behaviors**\               incontinence/retention**\   \
                                            \                          \                           Counsel to promptly
                                            Alcohol use\               **Dysuria**\                report dysuria or
                                            Smoking                    \                           gross hematuria\
                                                                       **Nocturia**\               \
                                                                       \                           **Considerations for
                                                                       **Abnormal urinary          Further Testing and
                                                                       stream**\                   Intervention**\
                                                                       \                           \
                                                                       (Yearly)\                   Urine culture, spot
                                                                       \                           urine
                                                                       **Screening**\              calcium/creatinine
                                                                       \                           ratio, and
                                                                       **Urinalysis**\             ultrasound of
                                                                       \                           kidneys and bladder
                                                                       (Yearly)                    for patients with
                                                                                                   microscopic
                                                                                                   hematuria (defined
                                                                                                   as [\>]{.underline}5
                                                                                                   RBC/HPF on at least
                                                                                                   2 occasions).
                                                                                                   Nephrology or
                                                                                                   urology referral for
                                                                                                   patients with
                                                                                                   culture-negative
                                                                                                   microscopic
                                                                                                   hematuria AND
                                                                                                   abnormal ultrasound
                                                                                                   and/or abnormal
                                                                                                   calcium/creatinine
                                                                                                   ratio. Urology
                                                                                                   referral for
                                                                                                   patients with
                                                                                                   culture negative
                                                                                                   macroscopic
                                                                                                   hematuria.

  ---------------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Urinary\
Score = 1**

+---+-------+-----------+-------------------+-------+-------+---------+
| * | **T   | **        | **Risk Factors**  | **Hi  | **Per | *       |
| * | herap | Potential |                   | ghest | iodic | *Health |
| S | eutic | Late      |                   | Risk  | Ev    | Cou     |
| e | Agent | Effects** |                   | Fact  | aluat | nseling |
| c | (s)** |           |                   | ors** | ion** | Further |
| \ |       |           |                   |       |       | Co      |
| # |       |           |                   |       |       | nsidera |
| * |       |           |                   |       |       | tions** |
| * |       |           |                   |       |       |         |
+---+-------+-----------+-------------------+-------+-------+---------+
| 1 | **    | **Renal   | **Host Factors**\ | *     | **P   | *       |
| 3 | Alkyl | to        | \                 | *Host | hysic | *Health |
|   | ating | xicity**\ | Younger age at    | Facto | al**\ | L       |
|   | Agen  | \         | treatment\        | rs**\ | \     | inks**\ |
|   | ts**\ | G         | Mononephric\      | \     | **    | \       |
|   | \     | lomerular | \                 | Age   | Blood | **See   |
|   | Ifosf | toxicity\ | **Treatment       | \<5   | p     | \"      |
|   | amide | Tubular   | Factors**\        | years | ressu | Patient |
|   |       | toxicity  | \                 | at    | re**\ | Reso    |
|   |       | (renal    | Higher cumulative | time  | \     | urces\" |
|   |       | tubular   | dose\             | of    | (Yea  | f       |
|   |       | acidosis, | Combined with     | treat | rly)\ | ield**\ |
|   |       | F         | other nephrotoxic | ment\ | \     | \       |
|   |       | anconi\'s | agents, such as:  | \     | **Sc  | Kidney  |
|   |       | syndrome, |                   | *     | reeni | Health\ |
|   |       | hypopho   | -   Cisplatin     | *Trea | ng**\ | See     |
|   |       | sphatemic |                   | tment | \     | also:   |
|   |       | rickets)  | -   Carboplatin   | Facto | *     | Single  |
|   |       |           |                   | rs**\ | *BUN\ | Kidney  |
|   |       |           | -                 | \     | \     | Health\ |
|   |       |           |   Aminoglycosides | Ifosf | C     | \       |
|   |       |           |                   | amide | reati | **      |
|   |       |           | -   Amphotericin  | dose  | nine\ | Conside |
|   |       |           |                   | [\>   | \     | rations |
|   |       |           | -   I             | ]{.un | Na,   | for     |
|   |       |           | mmunosuppressants | derli | K,    | Further |
|   |       |           |                   | ne}60 | Cl,   | Testing |
|   |       |           | -   Methotrexate  | g/    | C     | and     |
|   |       |           |                   | m^2^\ | O~2~\ | I       |
|   |       |           | -   Radiation     | Renal | \     | nterven |
|   |       |           |     impacting the | radi  | Ca,   | tion**\ |
|   |       |           |     kidney        | ation | Mg,   | \       |
|   |       |           |                   | dose  | PO~   | Elec    |
|   |       |           | **Medical         | [\>   | 4~**\ | trolyte |
|   |       |           | Conditions**\     | ]{.un | \     | supp    |
|   |       |           | \                 | derli | (Bas  | lements |
|   |       |           | Tumor             | ne}15 | eline | for     |
|   |       |           | infiltration of   | Gy    | at    | p       |
|   |       |           | kidney(s)\        |       | entry | atients |
|   |       |           | Pre-existing      |       | into  | with    |
|   |       |           | renal impairment\ |       | long  | per     |
|   |       |           | Nephrectomy       |       | -term | sistent |
|   |       |           |                   |       | foll  | elec    |
|   |       |           |                   |       | owup. | trolyte |
|   |       |           |                   |       | If    | w       |
|   |       |           |                   |       | abno  | asting. |
|   |       |           |                   |       | rmal, | Nep     |
|   |       |           |                   |       | r     | hrology |
|   |       |           |                   |       | epeat | consu   |
|   |       |           |                   |       | as    | ltation |
|   |       |           |                   |       | clini | for     |
|   |       |           |                   |       | cally | p       |
|   |       |           |                   |       | in    | atients |
|   |       |           |                   |       | dicat | with    |
|   |       |           |                   |       | ed.)\ | hypert  |
|   |       |           |                   |       | \     | ension, |
|   |       |           |                   |       | **Uri | prote   |
|   |       |           |                   |       | nalys | inuria, |
|   |       |           |                   |       | is**\ | or      |
|   |       |           |                   |       | \     | prog    |
|   |       |           |                   |       | (Ye   | ressive |
|   |       |           |                   |       | arly) | renal   |
|   |       |           |                   |       |       | insuff  |
|   |       |           |                   |       |       | iciency |
+---+-------+-----------+-------------------+-------+-------+---------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Auditory\
Score = 1**

+---+--------+--------+-------------+--------+-----------+----------+
| * | *      | **Pot  | **Risk      | **H    | *         | **Health |
| * | *Thera | ential | Factors**   | ighest | *Periodic | Co       |
| S | peutic | Late   |             | Risk   | Eva       | unseling |
| e | Agen   | Eff    |             | Fac    | luation** | Further  |
| c | t(s)** | ects** |             | tors** |           | Consider |
| \ |        |        |             |        |           | ations** |
| # |        |        |             |        |           |          |
| * |        |        |             |        |           |          |
| * |        |        |             |        |           |          |
+===+========+========+=============+========+===========+==========+
| 1 | *      | **Ot   | **Host      | **Host | **H       | **Health |
| 4 | *Heavy | otoxic | Factors**\  | Fact   | istory**\ | Links**\ |
|   | Met    | ity**\ | \           | ors**\ | \         | \        |
|   | als**\ | \      | Age \<4     | \      | **Hearing | **See    |
|   | \      | S      | years at    | CNS    | dif       | \        |
|   | Carbop | ensori | treatment\  | neo    | ficulties | "Patient |
|   | latin\ | neural | \           | plasm\ | (wit      | Res      |
|   | (in    | h      | **Treatment | \      | h/without | ources\" |
|   | m      | earing | Factors**\  | **Tre  | b         | field**\ |
|   | yeloab | loss\  | \           | atment | ackground | \        |
|   | lative | Tin    | Combined    | Fact   | noise)**\ | Hearing  |
|   | doses  | nitus\ | with:       | ors**\ | \         | Loss\    |
|   | only)\ | V      |             | \      | **Ti      | Edu      |
|   | Cisp   | ertigo | -           | Cumu   | nnitus**\ | cational |
|   | latin\ |        | Cranial/ear | lative | \         | Issues\  |
|   | \      |        |             | cis    | **V       | \        |
|   | **Info |        |   radiation | platin | ertigo**\ | **Consid |
|   | L      |        |             | dose   | \         | erations |
|   | ink**: |        | -           | [      | (Yearly)\ | for      |
|   | Pa     |        |    Ototoxic | \>]{.u | \         | Further  |
|   | tients |        |     drugs   | nderli | **Ph      | Testing  |
|   | who    |        |     (e.g.,  | ne}360 | ysical**\ | and      |
|   | re     |        |     amino   | mg     | \         | Interve  |
|   | ceived |        | glycosides, | /m^2^\ | **        | ntion**\ |
|   | carbo  |        |     loop    | High   | Otoscopic | \        |
|   | platin |        |             | dose   | exam**\   | A        |
|   | in     |        |  diuretics) | cis    | \         | udiology |
|   | non-m  |        |             | platin | (Yearly)\ | cons     |
|   | yeloab |        | **Medical   | (i.e., | \         | ultation |
|   | lative |        | Co          | 40     | **Scr     | for      |
|   | doses  |        | nditions**\ | m      | eening**\ | ampli    |
|   | do not |        | \           | g/m^2^ | \         | fication |
|   | appear |        | Chronic     | per    | *         | in       |
|   | to be  |        | otitis\     | day x  | *Complete | patients |
|   | at     |        | Cerumen     | 5 days | pure tone | with     |
|   | risk   |        | impaction\  | per    | audiogram | pro      |
|   | for    |        | Renal       | co     | or        | gressive |
|   | clin   |        | dysfunction | urse)\ | brainstem | hearing  |
|   | ically |        |             | Cis    | auditory  | loss.    |
|   | signi  |        |             | platin | evoked    | Speech   |
|   | ficant |        |             | admini | response  | and      |
|   | ototo  |        |             | stered | \[BAER,   | language |
|   | xicity |        |             | after  | ABR\]**\  | therapy  |
|   | based  |        |             | crani  | \         | for      |
|   | on     |        |             | al/ear | (Baseline | children |
|   | r      |        |             | radi   | at entry  | with     |
|   | esults |        |             | ation\ | into      | hearing  |
|   | of     |        |             | Carbo  | long-term | loss.    |
|   | cur    |        |             | platin | followup. | Otolar   |
|   | rently |        |             | condit | If        | yngology |
|   | ava    |        |             | ioning | hearing   | cons     |
|   | ilable |        |             | for    | loss is   | ultation |
|   | st     |        |             | HCT\   | detected, | in       |
|   | udies. |        |             | Rad    | test at   | patients |
|   |        |        |             | iation | least     | with     |
|   |        |        |             | inv    | yearly,   | chronic  |
|   |        |        |             | olving | or as     | in       |
|   |        |        |             | ear    | re        | fection, |
|   |        |        |             | [\>]{. | commended | cerumen  |
|   |        |        |             | underl | by        | im       |
|   |        |        |             | ine}30 | aud       | paction, |
|   |        |        |             | Gy     | iologist. | or other |
|   |        |        |             |        | For       | an       |
|   |        |        |             |        | patients  | atomical |
|   |        |        |             |        | who also  | problems |
|   |        |        |             |        | received  | exac     |
|   |        |        |             |        | cr        | erbating |
|   |        |        |             |        | anial/ear | or       |
|   |        |        |             |        | r         | cont     |
|   |        |        |             |        | adiation, | ributing |
|   |        |        |             |        | test      | to       |
|   |        |        |             |        | yearly    | hearing  |
|   |        |        |             |        | after     | loss.    |
|   |        |        |             |        | c         | Refer    |
|   |        |        |             |        | ompletion | patients |
|   |        |        |             |        | of        | with     |
|   |        |        |             |        | therapy   | auditory |
|   |        |        |             |        | for 5     | deficits |
|   |        |        |             |        | years     | to       |
|   |        |        |             |        | \[for     | school   |
|   |        |        |             |        | patients  | liaison  |
|   |        |        |             |        | \<10      | in       |
|   |        |        |             |        | years     | c        |
|   |        |        |             |        | old,      | ommunity |
|   |        |        |             |        | continue  | or       |
|   |        |        |             |        | yearly    | cancer   |
|   |        |        |             |        | until age | center   |
|   |        |        |             |        | 10\],     | (psych   |
|   |        |        |             |        | then      | ologist, |
|   |        |        |             |        | every 5   | social   |
|   |        |        |             |        | years. If | worker,  |
|   |        |        |             |        | clinical  | school   |
|   |        |        |             |        | suspicion | co       |
|   |        |        |             |        | of        | unselor) |
|   |        |        |             |        | hearing   | to       |
|   |        |        |             |        | loss at   | fa       |
|   |        |        |             |        | any time, | cilitate |
|   |        |        |             |        | test as   | p        |
|   |        |        |             |        | c         | rovision |
|   |        |        |             |        | linically | of       |
|   |        |        |             |        | i         | edu      |
|   |        |        |             |        | ndicated. | cational |
|   |        |        |             |        | If        | re       |
|   |        |        |             |        | audiogram | sources. |
|   |        |        |             |        | is        | Consider |
|   |        |        |             |        | inc       | specific |
|   |        |        |             |        | onclusive | needs    |
|   |        |        |             |        | or        | and/or   |
|   |        |        |             |        | une       | pref     |
|   |        |        |             |        | valuable, | erential |
|   |        |        |             |        | refer to  | c        |
|   |        |        |             |        | au        | lassroom |
|   |        |        |             |        | diologist | seating, |
|   |        |        |             |        | for       | FM       |
|   |        |        |             |        | cons      | ampli    |
|   |        |        |             |        | ideration | fication |
|   |        |        |             |        | of        | system,  |
|   |        |        |             |        | electroph | and      |
|   |        |        |             |        | ysiologic | other    |
|   |        |        |             |        | testing   | edu      |
|   |        |        |             |        | e.g.,     | cational |
|   |        |        |             |        | OAEs.)\   | as       |
|   |        |        |             |        | \         | sistance |
|   |        |        |             |        | **Info    | as       |
|   |        |        |             |        | Link**:\  | in       |
|   |        |        |             |        | \         | dicated. |
|   |        |        |             |        | Complete  |          |
|   |        |        |             |        | pure tone |          |
|   |        |        |             |        | audiogram |          |
|   |        |        |             |        | should    |          |
|   |        |        |             |        | include   |          |
|   |        |        |             |        | testing   |          |
|   |        |        |             |        | of both   |          |
|   |        |        |             |        | ears:     |          |
|   |        |        |             |        |           |          |
|   |        |        |             |        | 1.  Air   |          |
|   |        |        |             |        |     c     |          |
|   |        |        |             |        | onduction |          |
|   |        |        |             |        |     from  |          |
|   |        |        |             |        |     250   |          |
|   |        |        |             |        |     to    |          |
|   |        |        |             |        |     8000  |          |
|   |        |        |             |        |     Hz    |          |
|   |        |        |             |        |           |          |
|   |        |        |             |        | 2.  Bone  |          |
|   |        |        |             |        |     c     |          |
|   |        |        |             |        | onduction |          |
|   |        |        |             |        |     if    |          |
|   |        |        |             |        |     air   |          |
|   |        |        |             |        |     c     |          |
|   |        |        |             |        | onduction |          |
|   |        |        |             |        |     t     |          |
|   |        |        |             |        | hresholds |          |
|   |        |        |             |        |           |          |
|   |        |        |             |        |    exceed |          |
|   |        |        |             |        |     bone  |          |
|   |        |        |             |        |     by 15 |          |
|   |        |        |             |        |     dB at |          |
|   |        |        |             |        |     any   |          |
|   |        |        |             |        |           |          |
|   |        |        |             |        | frequency |          |
|   |        |        |             |        |           |          |
|   |        |        |             |        | 3         |          |
|   |        |        |             |        | .  Speech |          |
|   |        |        |             |        |     discr |          |
|   |        |        |             |        | imination |          |
|   |        |        |             |        |     e     |          |
|   |        |        |             |        | valuation |          |
|   |        |        |             |        |           |          |
|   |        |        |             |        | OAEs      |          |
|   |        |        |             |        | measure   |          |
|   |        |        |             |        | outer     |          |
|   |        |        |             |        | hair cell |          |
|   |        |        |             |        | function  |          |
|   |        |        |             |        | only.     |          |
|   |        |        |             |        | Because   |          |
|   |        |        |             |        | ca        |          |
|   |        |        |             |        | rboplatin |          |
|   |        |        |             |        | se        |          |
|   |        |        |             |        | lectively |          |
|   |        |        |             |        | damages   |          |
|   |        |        |             |        | inner     |          |
|   |        |        |             |        | hair      |          |
|   |        |        |             |        | cells,    |          |
|   |        |        |             |        | patients  |          |
|   |        |        |             |        | treated   |          |
|   |        |        |             |        | with      |          |
|   |        |        |             |        | ca        |          |
|   |        |        |             |        | rboplatin |          |
|   |        |        |             |        | should    |          |
|   |        |        |             |        | not be    |          |
|   |        |        |             |        | evaluated |          |
|   |        |        |             |        | with      |          |
|   |        |        |             |        | OAEs.     |          |
+---+--------+--------+-------------+--------+-----------+----------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = PNS\
Scores = 2A**

+---+---------+--------+---------------+--------+--------+-----------+
| * | **Ther  | **Pot  | **Risk        | **H    | **Pe   | **Health  |
| * | apeutic | ential | Factors**     | ighest | riodic | C         |
| S | Age     | Late   |               | Risk   | Evalua | ounseling |
| e | nt(s)** | Eff    |               | Fac    | tion** | Further   |
| c |         | ects** |               | tors** |        | Conside   |
| \ |         |        |               |        |        | rations** |
| # |         |        |               |        |        |           |
| * |         |        |               |        |        |           |
| * |         |        |               |        |        |           |
+===+=========+========+===============+========+========+===========+
| 1 | **Heavy | **Peri | **Treatment   | **Tre  | **Hist | **Health  |
| 5 | Me      | pheral | Factors**\    | atment | ory**\ | Links**\  |
|   | tals**\ | s      | \             | Fact   | \      | \         |
|   | \       | ensory | Combined      | ors**\ | **Peri | **See     |
|   | Carbo   | n      | with:         | \      | pheral | \"Patient |
|   | platin\ | europa |               | Cumu   | n      | Re        |
|   | Ci      | thy**\ | -             | lative | europa | sources\" |
|   | splatin | \      |   Vincristine | cis    | thy**\ | field**\  |
|   |         | **Info |               | platin | \      | \         |
|   |         | L      | -   Taxanes   | dose   | (      | P         |
|   |         | ink**: |               | [      | Yearly | eripheral |
|   |         | Neur   | -             | \>]{.u | until  | Ne        |
|   |         | opathy |   Gemcitabine | nderli | 2 to 3 | uropathy\ |
|   |         | pr     |               | ne}300 | years  | \         |
|   |         | esents |               | m      | after  | **Consi   |
|   |         | as     |               | g/m^2^ | th     | derations |
|   |         | pers   |               |        | erapy. | for       |
|   |         | istent |               |        | M      | Further   |
|   |         | effect |               |        | onitor | Testing   |
|   |         | after  |               |        | yearly | and       |
|   |         | t      |               |        | if     | Interv    |
|   |         | herapy |               |        | sy     | ention**\ |
|   |         | and is |               |        | mptoms | \         |
|   |         | typ    |               |        | pers   | Physical  |
|   |         | ically |               |        | ist.)\ | therapy   |
|   |         | not    |               |        | \      | referral  |
|   |         | late   |               |        | *      | for       |
|   |         | in     |               |        | *Physi | patients  |
|   |         | onset  |               |        | cal**\ | with      |
|   |         |        |               |        | \      | sy        |
|   |         |        |               |        | **Neur | mptomatic |
|   |         |        |               |        | ologic | ne        |
|   |         |        |               |        | e      | uropathy. |
|   |         |        |               |        | xam**\ | Physical  |
|   |         |        |               |        | \      | and       |
|   |         |        |               |        | (      | occ       |
|   |         |        |               |        | Yearly | upational |
|   |         |        |               |        | until  | therapy   |
|   |         |        |               |        | 2 to 3 | a         |
|   |         |        |               |        | years  | ssessment |
|   |         |        |               |        | after  | of hand   |
|   |         |        |               |        | th     | function. |
|   |         |        |               |        | erapy. | Consider  |
|   |         |        |               |        | M      | treatment |
|   |         |        |               |        | onitor | with      |
|   |         |        |               |        | yearly | agent     |
|   |         |        |               |        | if     | effective |
|   |         |        |               |        | sy     | for       |
|   |         |        |               |        | mptoms | ne        |
|   |         |        |               |        | per    | uropathic |
|   |         |        |               |        | sist.) | pain      |
|   |         |        |               |        |        | (e.g.,    |
|   |         |        |               |        |        | g         |
|   |         |        |               |        |        | abapentin |
|   |         |        |               |        |        | or        |
|   |         |        |               |        |        | amitri    |
|   |         |        |               |        |        | ptyline). |
+---+---------+--------+---------------+--------+--------+-----------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Urinary\
Score = 1**

+---+--------+-------+--------------------+-------+-------+----------+
| * | *      | *     | **Risk Factors**   | **Hi  | **Per | **Health |
| * | *Thera | *Pote |                    | ghest | iodic | Co       |
| S | peutic | ntial |                    | Risk  | Ev    | unseling |
| e | Agen   | Late  |                    | Fact  | aluat | Further  |
| c | t(s)** | Effe  |                    | ors** | ion** | Consider |
| \ |        | cts** |                    |       |       | ations** |
| # |        |       |                    |       |       |          |
| * |        |       |                    |       |       |          |
| * |        |       |                    |       |       |          |
+===+========+=======+====================+=======+=======+==========+
| 1 | *      | **    | **Host Factors**\  | *     | **P   | **Health |
| 6 | *Heavy | Renal | \                  | *Trea | hysic | Links**\ |
|   | Met    | t     | Mononephric\       | tment | al**\ | \        |
|   | als**\ | oxici | \                  | Facto | \     | **See    |
|   | \      | ty**\ | **Treatment        | rs**\ | **    | \        |
|   | Carbop | \     | Factors**\         | \     | Blood | "Patient |
|   | latin\ | Glome | \                  | Cisp  | p     | Res      |
|   | Cis    | rular | Combined with      | latin | ressu | ources\" |
|   | platin | in    | other nephrotoxic  | dose  | re**\ | field**\ |
|   |        | jury\ | agents such as:    | [\>]  | \     | \        |
|   |        | Tu    |                    | {.und | (Yea  | Kidney   |
|   |        | bular | -   Ifosfamide     | erlin | rly)\ | Health\  |
|   |        | in    |                    | e}200 | \     | See      |
|   |        | jury\ | -                  | mg/   | **Sc  | also:    |
|   |        | Renal |    Aminoglycosides | m^2^\ | reeni | Single   |
|   |        | ins   |                    | Renal | ng**\ | Kidney   |
|   |        | uffic | -   Amphotericin   | radi  | \     | Health\  |
|   |        | iency |                    | ation | *     | \        |
|   |        |       | -                  | dose  | *BUN\ | **Couns  |
|   |        |       | Immunosuppressants | [\>   | \     | eling**\ |
|   |        |       |                    | ]{.un | C     | \        |
|   |        |       | -   Methotrexate   | derli | reati | In       |
|   |        |       |                    | ne}15 | nine\ | patients |
|   |        |       | -   Radiation      | Gy    | \     | with     |
|   |        |       |     impacting the  |       | Na,   | salt     |
|   |        |       |     kidney         |       | K,    | -wasting |
|   |        |       |                    |       | Cl,   | tubular  |
|   |        |       | **Medical          |       | C     | dysf     |
|   |        |       | Conditions**\      |       | O~2~\ | unction, |
|   |        |       | \                  |       | \     | educate  |
|   |        |       | Diabetes mellitus\ |       | Ca,   | that low |
|   |        |       | Hypertension\      |       | Mg,   | m        |
|   |        |       | Nephrectomy        |       | PO~   | agnesium |
|   |        |       |                    |       | 4~**\ | levels   |
|   |        |       |                    |       | \     | po       |
|   |        |       |                    |       | (Bas  | tentiate |
|   |        |       |                    |       | eline | coronary |
|   |        |       |                    |       | at    | a        |
|   |        |       |                    |       | entry | theroscl |
|   |        |       |                    |       | into  | erosis.\ |
|   |        |       |                    |       | long  | \        |
|   |        |       |                    |       | -term | **Consid |
|   |        |       |                    |       | foll  | erations |
|   |        |       |                    |       | owup. | for      |
|   |        |       |                    |       | If    | Further  |
|   |        |       |                    |       | abno  | Testing  |
|   |        |       |                    |       | rmal, | and      |
|   |        |       |                    |       | r     | Interve  |
|   |        |       |                    |       | epeat | ntion**\ |
|   |        |       |                    |       | as    | \        |
|   |        |       |                    |       | clini | Ele      |
|   |        |       |                    |       | cally | ctrolyte |
|   |        |       |                    |       | in    | sup      |
|   |        |       |                    |       | dicat | plements |
|   |        |       |                    |       | ed.)\ | for      |
|   |        |       |                    |       | \     | patients |
|   |        |       |                    |       | **Uri | with     |
|   |        |       |                    |       | nalys | pe       |
|   |        |       |                    |       | is**\ | rsistent |
|   |        |       |                    |       | \     | ele      |
|   |        |       |                    |       | (Ye   | ctrolyte |
|   |        |       |                    |       | arly) | wasting. |
|   |        |       |                    |       |       | Ne       |
|   |        |       |                    |       |       | phrology |
|   |        |       |                    |       |       | cons     |
|   |        |       |                    |       |       | ultation |
|   |        |       |                    |       |       | for      |
|   |        |       |                    |       |       | patients |
|   |        |       |                    |       |       | with     |
|   |        |       |                    |       |       | hyper    |
|   |        |       |                    |       |       | tension, |
|   |        |       |                    |       |       | prot     |
|   |        |       |                    |       |       | einuria, |
|   |        |       |                    |       |       | or       |
|   |        |       |                    |       |       | pro      |
|   |        |       |                    |       |       | gressive |
|   |        |       |                    |       |       | renal    |
|   |        |       |                    |       |       | insuf    |
|   |        |       |                    |       |       | ficiency |
+---+--------+-------+--------------------+-------+-------+----------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Cardiovascular\
Score = 2B**

  -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic   **Potential Late   **Risk Factors**     **Highest   **Periodic Evaluation**                                                        **Health
  \#**    Agent(s)**      Effects**                               Risk                                                                                       Counseling Further
                                                                  Factors**                                                                                  Considerations**
  ------- --------------- ------------------ -------------------- ----------- ------------------------------------------------------------------------------ ------------------
  17      **Heavy         **Dyslipidemia**   **Host Factors**\                **Screening**\                                                                 **Health Links**\
          Metals**\                          \                                \                                                                              \
          \                                  Family history of                **Fasting lipid profile**\                                                     **See \"Patient
          Carboplatin\                       dyslipidemia\                    \                                                                              Resources\"
          Cisplatin                          \                                (Baseline at entry into long-term followup, then as per United States          field**\
                                             **Medical                        Preventive Task Force Recommendations:                                         \
                                             Conditions**\                    [www.ahrq.gov/clinic/prevenix.htm](http://www.ahrq.gov/clinic/prevenix.htm))   Diet and Physical
                                             \                                                                                                               Activity\
                                             Overweight/Obesity                                                                                              \
                                                                                                                                                             **Counseling**\
                                                                                                                                                             \
                                                                                                                                                             Counsel regarding
                                                                                                                                                             lipid lowering
                                                                                                                                                             strategies
                                                                                                                                                             including diet,
                                                                                                                                                             exercise, and
                                                                                                                                                             weight loss in
                                                                                                                                                             patients with
                                                                                                                                                             dyslipidemia.\
                                                                                                                                                             \
                                                                                                                                                             **Considerations
                                                                                                                                                             for Further
                                                                                                                                                             Testing and
                                                                                                                                                             Intervention**\
                                                                                                                                                             \
                                                                                                                                                             Consider
                                                                                                                                                             pharmacologic
                                                                                                                                                             therapy (e.g.,
                                                                                                                                                             statins) in
                                                                                                                                                             patients with
                                                                                                                                                             dyslipidemia.

  -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = CNS\
Score = 2A**

+---+---------+-----------+--------------+------+-----------+----------+
| * | **Ther  | **        | **Risk       | *    | *         | **Health |
| * | apeutic | Potential | Factors**    | *Hig | *Periodic | Co       |
| S | Age     | Late      |              | hest | Eva       | unseling |
| e | nt(s)** | Effects** |              | Risk | luation** | Further  |
| c |         |           |              | F    |           | Consider |
| \ |         |           |              | acto |           | ations** |
| # |         |           |              | rs** |           |          |
| * |         |           |              |      |           |          |
| * |         |           |              |      |           |          |
+===+=========+===========+==============+======+===========+==========+
| 1 | **Anti  | **Neuro   | **Host       | **   | **H       | **Health |
| 8 | metabol | cognitive | Factors**\   | Host | istory**\ | Links**\ |
|   | ites**\ | de        | \            | Fa   | \         | \        |
|   | Cyta    | ficits**\ | Younger age  | ctor | **Ed      | **See    |
|   | rabine\ | \         | at           | s**\ | ucational | \        |
|   | (high   | F         | treatment\   | \    | and/or    | "Patient |
|   | dose    | unctional | CNS          | Age  | v         | Res      |
|   | IV)\    | deficits  | leukem       | \<3  | ocational | ources\" |
|   | \       | in:       | ia/lymphoma\ | y    | pr        | field**\ |
|   | **Info  |           | Relapsed     | ears | ogress**\ | \        |
|   | Link**: | -         | leuke        | old  | \         | Edu      |
|   | Hi      | Executive | mia/lymphoma | at   | (Yearly)\ | cational |
|   | gh-dose |           | treated with | time | \         | Issues\  |
|   | IV is   |  function | CNS-directed | of   | **Scr     | \        |
|   | defined |           | therapy\     | tr   | eening**\ | **Consid |
|   | as any  | (planning | \            | eatm | \         | erations |
|   | single  |     and   | **Treatment  | ent\ | *         | for      |
|   | dose    |     orga  | Factors**\   | Fe   | *Referral | Further  |
|   | [\>]{.  | nization) | \            | male | for       | Testing  |
|   | underli |           | In           | sex\ | formal    | and      |
|   | ne}1000 | -         | combination  | P    | neuropsyc | Interve  |
|   | m       | Sustained | with:        | remo | hological | ntion**\ |
|   | g/m^2^. |           |              | rbid | eval      | \        |
|   |         | attention | -   D        | or   | uation**\ | Formal   |
|   |         |           | examethasone | fa   | \         | ne       |
|   |         | -         |              | mily | (Baseline | uropsych |
|   |         |    Memory | -   TBI      | his  | at entry  | ological |
|   |         |     (par  |              | tory | into      | ev       |
|   |         | ticularly | -   Cranial  | of   | long-term | aluation |
|   |         |           |              | lear | f         | to       |
|   |         |   visual, |    radiation | ning | ollow-up, | include  |
|   |         |     se    |              | or   | then      | tests of |
|   |         | quencing, | -            | a    | per       | pr       |
|   |         |           | Methotrexate | tten | iodically | ocessing |
|   |         |  temporal |     (IT, IO, | tion | as        | speed,   |
|   |         |           |              | p    | c         | comput   |
|   |         |   memory) |    high-dose | robl | linically | er-based |
|   |         |           |     IV)      | ems\ | indicated | at       |
|   |         | -   P     |              | \    | for       | tention, |
|   |         | rocessing | -   Longer   | **T  | patients  | visual   |
|   |         |     speed |     elapsed  | reat | with      | motor    |
|   |         |           |     time     | ment | evidence  | inte     |
|   |         | -   Vis   |     since    | Fa   | of        | gration, |
|   |         | ual-motor |     therapy  | ctor | impaired  | memory,  |
|   |         |     in    |              | s**\ | ed        | compr    |
|   |         | tegration | **Info       | \    | ucational | ehension |
|   |         |           | Link**\      | R    | or        | of       |
|   |         | Learning  | \            | adia | v         | verbal   |
|   |         | deficits  | Acute        | tion | ocational | instr    |
|   |         | in math   | toxicity     | dose | progress) | uctions, |
|   |         | and       | predominates | [\   |           | verbal   |
|   |         | reading   | if           | >]{. |           | fluency, |
|   |         | (par      | administered | unde |           | e        |
|   |         | ticularly | systemically | rlin |           | xecutive |
|   |         | reading   | as a single  | e}24 |           | function |
|   |         | compre    | agent. May   | Gy\  |           | and      |
|   |         | hension)\ | contribute   | Si   |           | p        |
|   |         | D         | to late      | ngle |           | lanning. |
|   |         | iminished | n            | frac |           | Refer    |
|   |         | IQ\       | eurotoxicity | tion |           | patients |
|   |         | B         | if combined  | TBI  |           | with     |
|   |         | ehavioral | with high    | (10  |           | neuroc   |
|   |         | change\   | dose or      | Gy)  |           | ognitive |
|   |         | \         | intrathecal  |      |           | deficits |
|   |         | **Info    | methotrexate |      |           | to       |
|   |         | Link**:   | and/or       |      |           | school   |
|   |         | Neuro     | cranial      |      |           | liaison  |
|   |         | cognitive | radiation.   |      |           | in       |
|   |         | deficits  |              |      |           | c        |
|   |         | in        |              |      |           | ommunity |
|   |         | survivors |              |      |           | or       |
|   |         | of        |              |      |           | cancer   |
|   |         | leukemia  |              |      |           | center   |
|   |         | and       |              |      |           | (psych   |
|   |         | lymphoma  |              |      |           | ologist, |
|   |         | are more  |              |      |           | social   |
|   |         | f         |              |      |           | worker,  |
|   |         | requently |              |      |           | school   |
|   |         | related   |              |      |           | co       |
|   |         | to        |              |      |           | unselor) |
|   |         | in        |              |      |           | to       |
|   |         | formation |              |      |           | fa       |
|   |         | p         |              |      |           | cilitate |
|   |         | rocessing |              |      |           | acq      |
|   |         | (e.g.,    |              |      |           | uisition |
|   |         | learning  |              |      |           | of       |
|   |         | dis       |              |      |           | edu      |
|   |         | ability). |              |      |           | cational |
|   |         | Neuro     |              |      |           | r        |
|   |         | cognitive |              |      |           | esources |
|   |         | deficits  |              |      |           | and/or   |
|   |         | in brain  |              |      |           | social   |
|   |         | tumor     |              |      |           | skills   |
|   |         | survivors |              |      |           | t        |
|   |         | treated   |              |      |           | raining. |
|   |         | with      |              |      |           | Consider |
|   |         | higher    |              |      |           | use of   |
|   |         | doses of  |              |      |           | psyc     |
|   |         | cranial   |              |      |           | hotropic |
|   |         | radiation |              |      |           | me       |
|   |         | are more  |              |      |           | dication |
|   |         | global    |              |      |           | (e.g.,   |
|   |         | (si       |              |      |           | sti      |
|   |         | gnificant |              |      |           | mulants) |
|   |         | decline   |              |      |           | or       |
|   |         | in IQ).   |              |      |           | eviden   |
|   |         | Extent of |              |      |           | ce-based |
|   |         | deficit   |              |      |           | rehabi   |
|   |         | depends   |              |      |           | litation |
|   |         | on age at |              |      |           | t        |
|   |         | t         |              |      |           | raining. |
|   |         | reatment, |              |      |           | Caution  |
|   |         | intensity |              |      |           | ---lower |
|   |         | of        |              |      |           | starting |
|   |         | t         |              |      |           | dose and |
|   |         | reatment, |              |      |           | as       |
|   |         | and time  |              |      |           | sessment |
|   |         | since     |              |      |           | of       |
|   |         | t         |              |      |           | i        |
|   |         | reatment. |              |      |           | ncreased |
|   |         | New       |              |      |           | sen      |
|   |         | deficits  |              |      |           | sitivity |
|   |         | may       |              |      |           | when     |
|   |         | emerge    |              |      |           | in       |
|   |         | over      |              |      |           | itiating |
|   |         | time.     |              |      |           | therapy  |
|   |         |           |              |      |           | is       |
|   |         |           |              |      |           | reco     |
|   |         |           |              |      |           | mmended. |
|   |         |           |              |      |           | Refer to |
|   |         |           |              |      |           | c        |
|   |         |           |              |      |           | ommunity |
|   |         |           |              |      |           | services |
|   |         |           |              |      |           | for      |
|   |         |           |              |      |           | vo       |
|   |         |           |              |      |           | cational |
|   |         |           |              |      |           | rehabi   |
|   |         |           |              |      |           | litation |
|   |         |           |              |      |           | or for   |
|   |         |           |              |      |           | services |
|   |         |           |              |      |           | for      |
|   |         |           |              |      |           | develop  |
|   |         |           |              |      |           | mentally |
|   |         |           |              |      |           | d        |
|   |         |           |              |      |           | isabled. |
+---+---------+-----------+--------------+------+-----------+----------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = CNS\
Score = 2A**

+---+---------+------------+--------------+------+-------+------------+
| * | **Ther  | *          | **Risk       | *    | **Per | **Health   |
| * | apeutic | *Potential | Factors**    | *Hig | iodic | Counseling |
| S | Age     | Late       |              | hest | Ev    | Further    |
| e | nt(s)** | Effects**  |              | Risk | aluat | Consid     |
| c |         |            |              | F    | ion** | erations** |
| \ |         |            |              | acto |       |            |
| # |         |            |              | rs** |       |            |
| * |         |            |              |      |       |            |
| * |         |            |              |      |       |            |
+===+=========+============+==============+======+=======+============+
| 1 | **Anti  | **Clinical | **Host       | **T  | **    | **Cons     |
| 9 | metabol | le         | Factors**\   | reat | Histo | iderations |
|   | ites**\ | ukoencepha | \            | ment | ry**\ | for        |
|   | \       | lopathy**\ | Younger age  | Fa   | \     | Further    |
|   | Cyta    | \          | at           | ctor | **    | Testing    |
|   | rabine\ | S          | treatment\   | s**\ | Cogni | and        |
|   | (high   | pasticity\ | CNS          | \    | tive, | Inter      |
|   | dose    | Ataxia\    | leukem       | R    | m     | vention**\ |
|   | IV)\    | D          | ia/lymphoma\ | adia | otor, | \          |
|   | \       | ysarthria\ | Relapsed     | tion | a     | Brain MRI, |
|   | **Info  | Dysphagia\ | leuke        | dose | nd/or | Brain CT   |
|   | Link**: | He         | mia/lymphoma | [\   | se    | with MR    |
|   | Hi      | miparesis\ | treated with | >]{. | nsory | a          |
|   | gh-dose | Seizures\  | CNS-directed | unde | d     | ngiography |
|   | IV is   | \          | therapy\     | rlin | efici | as         |
|   | defined | **Info     | \            | e}24 | ts**\ | clinically |
|   | as any  | Link**:    | **Treatment  | Gy   | \     | indicated; |
|   | single  | Clinical   | Factors**\   |      | **S   | preferred  |
|   | dose    | leukoence  | \            |      | eizur | study      |
|   | [\>]{.  | phalopathy | Combined     |      | es**\ | based on   |
|   | underli | may        | with:        |      | \     | in         |
|   | ne}1000 | present    |              |      | **    | tracranial |
|   | m       | with or    | -            |      | Other | lesion to  |
|   | g/m^2^. | without    | Methotrexate |      | neuro | be         |
|   |         | imaging    |     (IT, IO, |      | logic | evaluated: |
|   |         | abn        |              |      | s     |            |
|   |         | ormalities |    high-dose |      | ympto | -   MRI:   |
|   |         | (e.g.,     |     IV)      |      | ms**\ |     White  |
|   |         | leukoencep |              |      | \     |     matter |
|   |         | halopathy, | -   D        |      | (Yea  |            |
|   |         | cerebral   | examethasone |      | rly)\ | -          |
|   |         | lacunes,   |              |      | \     |  Gadoliniu |
|   |         | cerebral   | -   Cranial  |      | **P   | m-enhanced |
|   |         | atrophy,   |              |      | hysic |     MRI:   |
|   |         | dystrophic |    radiation |      | al**\ |     Mic    |
|   |         | calci      |              |      | \     | rovascular |
|   |         | fications, |              |      | **Spa |     injury |
|   |         | mi         |              |      | stici |            |
|   |         | neralizing |              |      | ty**\ | -   CT:    |
|   |         | microan    |              |      | \     |     Calc   |
|   |         | giopathy). |              |      | *     | ifications |
|   |         | Transient  |              |      | *Atax |            |
|   |         | white      |              |      | ia**\ | Neurology  |
|   |         | matter     |              |      | \     | co         |
|   |         | anomalies  |              |      | **Dys | nsultation |
|   |         | may follow |              |      | arthr | and        |
|   |         | ra         |              |      | ia**\ | follow-up  |
|   |         | diotherapy |              |      | \     | as         |
|   |         | and        |              |      | *     | clinically |
|   |         | high-dose  |              |      | *Hemi | indicated. |
|   |         | ch         |              |      | pares |            |
|   |         | emotherapy |              |      | is**\ |            |
|   |         | for        |              |      | \     |            |
|   |         | m          |              |      | (Ye   |            |
|   |         | edulloblas |              |      | arly) |            |
|   |         | toma/PNET, |              |      |       |            |
|   |         | may mimic  |              |      |       |            |
|   |         | tumor      |              |      |       |            |
|   |         | r          |              |      |       |            |
|   |         | ecurrence, |              |      |       |            |
|   |         | and        |              |      |       |            |
|   |         | signify    |              |      |       |            |
|   |         | risk of    |              |      |       |            |
|   |         | persistent |              |      |       |            |
|   |         | neurologic |              |      |       |            |
|   |         | sequelae.  |              |      |       |            |
|   |         | Ne         |              |      |       |            |
|   |         | uroimaging |              |      |       |            |
|   |         | changes do |              |      |       |            |
|   |         | not always |              |      |       |            |
|   |         | correlate  |              |      |       |            |
|   |         | with       |              |      |       |            |
|   |         | degree of  |              |      |       |            |
|   |         | cognitive  |              |      |       |            |
|   |         | dy         |              |      |       |            |
|   |         | sfunction. |              |      |       |            |
|   |         | P          |              |      |       |            |
|   |         | rospective |              |      |       |            |
|   |         | studies    |              |      |       |            |
|   |         | are needed |              |      |       |            |
|   |         | to define  |              |      |       |            |
|   |         | the        |              |      |       |            |
|   |         | d          |              |      |       |            |
|   |         | ose/effect |              |      |       |            |
|   |         | re         |              |      |       |            |
|   |         | lationship |              |      |       |            |
|   |         | of         |              |      |       |            |
|   |         | neurotoxic |              |      |       |            |
|   |         | agents.    |              |      |       |            |
|   |         | *Note: new |              |      |       |            |
|   |         | deficits   |              |      |       |            |
|   |         | may emerge |              |      |       |            |
|   |         | over       |              |      |       |            |
|   |         | time.*     |              |      |       |            |
+---+---------+------------+--------------+------+-------+------------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = N/A\
Score = 1**

  -------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic          **Potential    **Risk      **Highest   **Periodic     **Health
  \#**    Agent(s)**             Late Effects** Factors**   Risk        Evaluation**   Counseling Further
                                                            Factors**                  Considerations**
  ------- ---------------------- -------------- ----------- ----------- -------------- ------------------
  20      **Antimetabolites**\   **No known                                             
          \                      late                                                  
          Cytarabine\            effects**\                                            
          (low dose IV)\         \                                                     
          Cytarabine IO\         **Info Link**:                                        
          Cytarabine IT\         Acute                                                 
          Cytarabine SQ\         toxicities                                            
          \                      predominate,                                          
          **Info Link**:         from which the                                        
          Low-dose IV is defined majority of                                           
          as any single dose     patients                                              
          \<1000 mg/m^2^.        recover                                               
                                 without                                               
                                 sequelae.                                             

  -------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = GI/Hepatic\
Score = 2A**

  ---------------------------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic          **Potential Late **Risk          **Highest Risk  **Periodic          **Health Counseling Further
  \#**    Agent(s)**             Effects**        Factors**       Factors**       Evaluation**        Considerations**
  ------- ---------------------- ---------------- --------------- --------------- ------------------- -----------------------------
  21      **Antimetabolites**\   **Hepatic        **Medical       **Medical       **Physical**\       **Health Links**\
          \                      dysfunction**\   Conditions**\   Conditions**\   \                   \
          Mercaptopurine (6MP)\  \                \               \               **Scleral           **See \"Patient Resources\"
          \                      **VOD**\         Viral           Chronic viral   icterus**\          field**\
          Thioguanine (6TG)\     \                hepatitis\      hepatitis       \                   \
          \                      **Info Link**:   Previous VOD\                   **Jaundice**\       Liver Health\
          **Info Link**: Acute   Acute toxicities Siderosis                       \                   \
          hepatotoxicity         predominate from                                 **Ascites**\        **Considerations for Further
          reported with          which the                                        \                   Testing and Intervention**\
          thioguanine used in    majority of                                      **Hepatomegaly**\   \
          CCG 1952 (regimens B1  patients recover                                 \                   Prothrombin time for
          and B2) for ALL        without                                          **Splenomegaly**\   evaluation of hepatic
          maintenance therapy    sequelae.                                        \                   synthetic function in
          requires longer        Delayed hepatic                                  (Yearly)\           patients with abnormal liver
          follow-up to determine dysfunction may                                  \                   screening tests. Screen for
          long-term sequelae.    occur after a                                    **Screening**\      viral hepatitis in patients
          See COG Website (CCG   history of acute                                 \                   with persistently abnormal
          1952 protocol page)    VOD, presenting                                  **ALT**\            liver function or any patient
          for updated            as portal                                        \                   transfused prior to 1993.
          advisories.            hypertension                                     **AST**\            Gastroenterology/hepatology
                                 with liver                                       \                   consultation in patients with
                                 biopsy                                           **Bilirubin**\      persistent liver dysfunction.
                                 indicating                                       \                   Hepatitis A and B
                                 nodular                                          (Baseline at entry  immunization in patients
                                 regenerative                                     into long-term      lacking immunity.
                                 hyperplasia,                                     followup. Repeat as 
                                 fibrosis, or                                     clinically          
                                 siderosis.                                       indicated.)         

  ---------------------------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Musculoskeletal\
Score = 2B**

  -------------------------------------------------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic          **Potential Late      **Risk Factors**       **Highest Risk       **Periodic       **Health Counseling Further
  \#**    Agent(s)**             Effects**                                    Factors**            Evaluation**     Considerations**
  ------- ---------------------- --------------------- ---------------------- -------------------- ---------------- -------------------------------------
  22      **Antimetabolites**\   **Osteopenia**\       **Host Factors**\      **Host Factors**\    **Screening**\   **Health Links**\
          \                      \                     \                      \                    \                \
          Methotrexate (high     **Osteoporosis**\     Both genders are at    Older age at time of **Bone density   **See \"Patient Resources\" field**\
          dose IV)\              \                     risk\                  treatment\           evaluation (DEXA \
          Methotrexate (low dose Osteopenia is defined \                      \                    or quantitative  Bone Health\
          IV)\                   as BMD                **Treatment Factors**\ **Treatment          CT)**\           \
          Methotrexate IM\       [\>]{.underline}1 and \                      Factors**\           \                **Resources**\
          Methotrexate PO\       \<2.5 SD below mean\  Corticosteroids\       \                    (Baseline at     \
          \                      \                     Cranial radiation\     Methotrexate         entry into       National Osteoporosis Foundation
          **Info Link**:         Osteoporosis is       HCT/TBI\               cumulative dose      long-term        Website:
          High-dose IV is        defined as BMD        \                      [\>]{.underline}40   followup. Repeat [www.nof.org](http://www.nof.org/)\
          defined as any single  [\>]{.underline}2.5   **Medical              gm/m^2^\             as clinically    \
          dose                   SD below mean\        Conditions**\          Prolonged            indicated.)\     **Considerations for Further Testing
          [\>]{.underline}1000   \                     \                      corticosteroid       \                and Intervention**\
          mg/m^2^.               **Info Link**: The    Growth hormone         therapy (e.g., for   **Info Link**:   \
                                 World Health          deficiency\            chronic GVHD)        The optimal      Nutritional supplements in cases of
                                 Organization          Hypogonadism/delayed                        method of        osteopenia unresponsive to behavioral
                                 definition of         puberty\                                    measuring bone   and dietary management: Calcium 1000
                                 osteoporosis in       Hyperthyroidism\                            health in        to 1500 mg daily plus RDA for vitamin
                                 adults is based on    \                                           children is      D. Use caution regarding calcium
                                 comparison of a       **Health Behaviors**\                       controversial.   supplementation in patients with
                                 measured BMD of young \                                           Existing         history of renal lithiasis. Treatment
                                 adults at peak bone   Inadequate intake of                        technologies     of exacerbating or predisposing
                                 age and defined as a  calcium and vitamin D\                      have             conditions (e.g., hormonal
                                 T-score. A T-score is Lack of weight bearing                      limitations.     replacement therapy for hypogonadism,
                                 the number of         exercise\                                   DEXA provides an growth hormone deficiency, correction
                                 standard deviations   Smoking\                                    estimate of      of chronic metabolic acidosis that
                                 the BMD measurement   Alcohol use                                 total bone mass  could accelerate bone loss).
                                 is above or below the                                             at a given site. Endocrine consultation for patients
                                 mean. A T-score of                                                Quantitative CT  with osteoporosis or history of
                                 [\>]{.underline}2.5                                               provides         multiple fractures for pharmacologic
                                 standard deviations                                               distinct         interventions (e.g., bisphosphonates,
                                 BELOW the mean is                                                 measures of      calcitonin, selective estrogen
                                 consistent with a                                                 trabecular and   receptor modulators).
                                 diagnosis of                                                      cortical bone    
                                 osteoporosis.                                                     dimension and    
                                 T-scores are not                                                  density.         
                                 appropriate to assess                                                              
                                 skeletal health in                                                                 
                                 pediatric patients                                                                 
                                 who have not achieved                                                              
                                 peak adult bone mass.                                                              
                                 Instead, pediatric                                                                 
                                 BMD reference data                                                                 
                                 sets calculate                                                                     
                                 Z-scores based on age                                                              
                                 and gender. A Z-score                                                              
                                 is the number of                                                                   
                                 standard deviations                                                                
                                 the measurement is                                                                 
                                 above or below the                                                                 
                                 AGE-MATCHED MEAN BMD.                                                              
                                 There are no defined                                                               
                                 standards for                                                                      
                                 referral or treatment                                                              
                                 of low BMD in                                                                      
                                 children.                                                                          

  -------------------------------------------------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Urinary\
Score = 2A**

+---+----------+--------+-------------------+-------+-------+----------+
| * | **The    | **Pot  | **Risk Factors**  | **Hi  | **Per | **Health |
| * | rapeutic | ential |                   | ghest | iodic | Co       |
| S | Ag       | Late   |                   | Risk  | Ev    | unseling |
| e | ent(s)** | Eff    |                   | Fact  | aluat | Further  |
| c |          | ects** |                   | ors** | ion** | Consider |
| \ |          |        |                   |       |       | ations** |
| # |          |        |                   |       |       |          |
| * |          |        |                   |       |       |          |
| * |          |        |                   |       |       |          |
+===+==========+========+===================+=======+=======+==========+
| 2 | **An     | *      | **Host Factors**\ | *     | **P   | **Health |
| 3 | timetabo | *Renal | \                 | *Trea | hysic | Links**\ |
|   | lites**\ | toxic  | Mononephric\      | tment | al**\ | \        |
|   | \        | ity**\ | \                 | Facto | \     | **See    |
|   | Meth     | \      | **Treatment       | rs**\ | **    | \        |
|   | otrexate | **Info | Factors**\        | \     | Blood | "Patient |
|   | (high    | L      | \                 | Trea  | p     | Res      |
|   | dose     | ink**: | Combined with     | tment | ressu | ources\" |
|   | IV)\     | Acute  | other nephrotoxic | b     | re**\ | field**\ |
|   | Meth     | toxi   | agents such as:   | efore | \     | \        |
|   | otrexate | cities |                   | 1970  | (Yea  | Kidney   |
|   | (low     | predom | -   Cisp          |       | rly)\ | Health\  |
|   | dose     | inate, | latin/carboplatin |       | \     | See      |
|   | IV)\     | from   |                   |       | **Sc  | also:    |
|   | Meth     | which  | -   Ifosfamide    |       | reeni | Single   |
|   | otrexate | the    |                   |       | ng**\ | Kidney   |
|   | IM\      | ma     | -                 |       | \     | Health\  |
|   | Meth     | jority |   Aminoglycosides |       | **B   | \        |
|   | otrexate | of     |                   |       | UN**\ | **Consid |
|   | PO\      | pa     | -   Amphotericin  |       | \     | erations |
|   | \        | tients |                   |       | **Cre | for      |
|   | **Info   | r      | -   I             |       | atini | Further  |
|   | Link**:  | ecover | mmunosuppressants |       | ne**\ | Testing  |
|   | H        | w      |                   |       | \     | and      |
|   | igh-dose | ithout | -   Radiation     |       | **Na, | Interve  |
|   | IV is    | se     |     impacting the |       | K,    | ntion**\ |
|   | defined  | quelae |     kidney        |       | Cl,   | \        |
|   | as any   |        |                   |       | CO~   | Ne       |
|   | single   |        | **Medical         |       | 2~**\ | phrology |
|   | dose     |        | Conditions**\     |       | \     | cons     |
|   | [\>]     |        | \                 |       | **Ca, | ultation |
|   | {.underl |        | Diabetes          |       | Mg,   | for      |
|   | ine}1000 |        | mellitus\         |       | P0~   | patients |
|   | mg/m^2^. |        | Hypertension\     |       | 4~**\ | with     |
|   |          |        | Nephrectomy       |       | \     | hyper    |
|   |          |        |                   |       | (Bas  | tension, |
|   |          |        |                   |       | eline | prot     |
|   |          |        |                   |       | at    | einuria, |
|   |          |        |                   |       | entry | or       |
|   |          |        |                   |       | into  | pro      |
|   |          |        |                   |       | long  | gressive |
|   |          |        |                   |       | -term | renal    |
|   |          |        |                   |       | foll  | insuf    |
|   |          |        |                   |       | owup. | ficiency |
|   |          |        |                   |       | If    |          |
|   |          |        |                   |       | abno  |          |
|   |          |        |                   |       | rmal, |          |
|   |          |        |                   |       | r     |          |
|   |          |        |                   |       | epeat |          |
|   |          |        |                   |       | as    |          |
|   |          |        |                   |       | clini |          |
|   |          |        |                   |       | cally |          |
|   |          |        |                   |       | in    |          |
|   |          |        |                   |       | dicat |          |
|   |          |        |                   |       | ed.)\ |          |
|   |          |        |                   |       | \     |          |
|   |          |        |                   |       | **Uri |          |
|   |          |        |                   |       | nalys |          |
|   |          |        |                   |       | is**\ |          |
|   |          |        |                   |       | \     |          |
|   |          |        |                   |       | (Ye   |          |
|   |          |        |                   |       | arly) |          |
+---+----------+--------+-------------------+-------+-------+----------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = GI/Hepatic\
Score = 2A**

  ---------------------------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic          **Potential Late **Risk          **Highest Risk  **Periodic          **Health Counseling Further
  \#**    Agent(s)**             Effects**        Factors**       Factors**       Evaluation**        Considerations**
  ------- ---------------------- ---------------- --------------- --------------- ------------------- -----------------------------
  24      **Antimetabolites**\   **Hepatic        **Treatment     **Treatment     **Physical**\       **Health Links**\
          \                      dysfunction**\   Factors**\      Factors**\      \                   \
          Methotrexate (high     \                \               \               **Scleral           **See \"Patient Resources\"
          dose IV)\              **Info Link**:   Abdominal       Treatment       icterus**\          field**\
          Methotrexate (low dose Acute toxicities radiation\      before 1970\    \                   \
          IV)\                   predominate,     \               \               **Jaundice**\       Liver Health\
          Methotrexate IM\       from which the   **Medical       **Medical       \                   \
          Methotrexate PO\       majority of      Conditions**\   Conditions**\   **Ascites**\        **Considerations for Further
          \                      patients recover \               \               \                   Testing and Intervention**\
          **Info Link**:         without sequelae Viral hepatitis Chronic viral   **Hepatomegaly**\   \
          High-dose IV is                                         hepatitis       \                   Prothrombin time for
          defined as any single                                                   **Splenomegaly**\   evaluation of hepatic
          dose                                                                    \                   synthetic function in
          [\>]{.underline}1000                                                    (Yearly)\           patients with abnormal liver
          mg/m^2^.                                                                \                   screening tests. Screen for
                                                                                  **Screening**\      viral hepatitis in patients
                                                                                  \                   with persistently abnormal
                                                                                  **ALT**\            liver function or any patient
                                                                                  \                   transfused prior to 1993.
                                                                                  **AST**\            Gastroenterology/hepatology
                                                                                  \                   consultation in patients with
                                                                                  **Bilirubin**\      persistent liver dysfunction.
                                                                                  \                   Hepatitis A and B
                                                                                  (Baseline at entry  immunization in patients
                                                                                  into long-term      lacking immunity.
                                                                                  follow-up. Repeat   
                                                                                  as clinically       
                                                                                  indicated.)         

  ---------------------------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = CNS\
Score = 1**

+---+---------+-----------+--------------+------+-----------+----------+
| * | **Ther  | **        | **Risk       | *    | *         | **Health |
| * | apeutic | Potential | Factors**    | *Hig | *Periodic | Co       |
| S | Age     | Late      |              | hest | Eva       | unseling |
| e | nt(s)** | Effects** |              | Risk | luation** | Further  |
| c |         |           |              | F    |           | Consider |
| \ |         |           |              | acto |           | ations** |
| # |         |           |              | rs** |           |          |
| * |         |           |              |      |           |          |
| * |         |           |              |      |           |          |
+===+=========+===========+==============+======+===========+==========+
| 2 | **Anti  | **Neuro   | **Host       | **   | **H       | **Health |
| 5 | metabol | cognitive | Factors**\   | Host | istory**\ | Links**\ |
|   | ites**\ | de        | \            | Fa   | \         | \        |
|   | \       | ficits**\ | Younger age  | ctor | **Ed      | **See    |
|   | Metho   | \         | at           | s**\ | ucational | \        |
|   | trexate | F         | treatment\   | \    | and/or    | "Patient |
|   | (high   | unctional | CNS          | Age  | v         | Res      |
|   | dose    | deficits  | leukem       | \<3  | ocational | ources\" |
|   | IV)\    | in:       | ia/lymphoma\ | y    | pr        | field**\ |
|   | Metho   |           | Relapsed     | ears | ogress**\ | \        |
|   | trexate | -         | leuke        | old  | \         | Edu      |
|   | IO\     | Executive | mia/lymphoma | at   | (Yearly)\ | cational |
|   | \       |           | treated with | time | \         | Issues\  |
|   | Metho   |  function | CNS-directed | of   | **Scr     | \        |
|   | trexate |           | therapy\     | tr   | eening**\ | **Consid |
|   | IT\     | (planning | \            | eatm | \         | erations |
|   | \       |     and   | **Treatment  | ent\ | *         | for      |
|   | **Info  |     orga  | Factors**\   | Fe   | *Referral | Further  |
|   | Link**: | nization) | \            | male | for       | Testing  |
|   | Hi      |           | In           | sex\ | formal    | and      |
|   | gh-dose | -         | combination  | P    | neuropsyc | Interve  |
|   | IV is   | Sustained | with:        | remo | hological | ntion**\ |
|   | defined |           |              | rbid | eval      | \        |
|   | as any  | attention | -   D        | or   | uation**\ | Formal   |
|   | single  |           | examethasone | fa   | \         | ne       |
|   | dose    | -         |              | mily | (Baseline | uropsych |
|   | [\>]{.  |    Memory | -   TBI      | his  | at entry  | ological |
|   | underli |     (par  |              | tory | into      | ev       |
|   | ne}1000 | ticularly | -   Cranial  | of   | long-term | aluation |
|   | m       |           |              | lear | f         | to       |
|   | g/m^2^. |   visual, |    radiation | ning | ollow-up, | include  |
|   |         |     se    |              | or   | then      | tests of |
|   |         | quencing, | -            | a    | per       | pr       |
|   |         |           |   Cytarabine | tten | iodically | ocessing |
|   |         |  temporal |              | tion | as        | speed,   |
|   |         |           |   (high-dose | p    | c         | comput   |
|   |         |   memory) |     IV)      | robl | linically | er-based |
|   |         |           |              | ems\ | indicated | at       |
|   |         | -   P     | Longer       | \    | for       | tention, |
|   |         | rocessing | elapsed time | **T  | patients  | visual   |
|   |         |     speed | since        | reat | with      | motor    |
|   |         |           | therapy      | ment | evidence  | inte     |
|   |         | -   Vis   |              | Fa   | of        | gration, |
|   |         | ual-motor |              | ctor | impaired  | memory,  |
|   |         |     in    |              | s**\ | ed        | compr    |
|   |         | tegration |              | \    | ucational | ehension |
|   |         |           |              | R    | or        | of       |
|   |         | Learning  |              | adia | v         | verbal   |
|   |         | deficits  |              | tion | ocational | instr    |
|   |         | in math   |              | dose | progress) | uctions, |
|   |         | and       |              | [\   |           | verbal   |
|   |         | reading   |              | >]{. |           | fluency, |
|   |         | (par      |              | unde |           | e        |
|   |         | ticularly |              | rlin |           | xecutive |
|   |         | reading   |              | e}24 |           | function |
|   |         | compre    |              | Gy\  |           | and      |
|   |         | hension)\ |              | Si   |           | p        |
|   |         | D         |              | ngle |           | lanning. |
|   |         | iminished |              | frac |           | Refer    |
|   |         | IQ\       |              | tion |           | patients |
|   |         | B         |              | TBI  |           | with     |
|   |         | ehavioral |              | (10  |           | neuroc   |
|   |         | change\   |              | Gy)  |           | ognitive |
|   |         | \         |              |      |           | deficits |
|   |         | **Info    |              |      |           | to       |
|   |         | Link**:   |              |      |           | school   |
|   |         | Neuro     |              |      |           | liaison  |
|   |         | cognitive |              |      |           | in       |
|   |         | deficits  |              |      |           | c        |
|   |         | in        |              |      |           | ommunity |
|   |         | survivors |              |      |           | or       |
|   |         | of        |              |      |           | cancer   |
|   |         | leukemia  |              |      |           | center   |
|   |         | and       |              |      |           | (psych   |
|   |         | lymphoma  |              |      |           | ologist, |
|   |         | are more  |              |      |           | social   |
|   |         | f         |              |      |           | worker,  |
|   |         | requently |              |      |           | school   |
|   |         | related   |              |      |           | co       |
|   |         | to        |              |      |           | unselor) |
|   |         | in        |              |      |           | to       |
|   |         | formation |              |      |           | fa       |
|   |         | p         |              |      |           | cilitate |
|   |         | rocessing |              |      |           | acq      |
|   |         | (e.g.,    |              |      |           | uisition |
|   |         | learning  |              |      |           | of       |
|   |         | dis       |              |      |           | edu      |
|   |         | ability). |              |      |           | cational |
|   |         | Neuro     |              |      |           | r        |
|   |         | cognitive |              |      |           | esources |
|   |         | deficits  |              |      |           | and/or   |
|   |         | in brain  |              |      |           | social   |
|   |         | tumor     |              |      |           | skills   |
|   |         | survivors |              |      |           | t        |
|   |         | treated   |              |      |           | raining; |
|   |         | with      |              |      |           | Consider |
|   |         | higher    |              |      |           | use of   |
|   |         | doses of  |              |      |           | psyc     |
|   |         | cranial   |              |      |           | hotropic |
|   |         | radiation |              |      |           | me       |
|   |         | are more  |              |      |           | dication |
|   |         | global    |              |      |           | (e.g.,   |
|   |         | (si       |              |      |           | sti      |
|   |         | gnificant |              |      |           | mulants) |
|   |         | decline   |              |      |           | or       |
|   |         | in IQ).   |              |      |           | eviden   |
|   |         | Extent of |              |      |           | ce-based |
|   |         | deficit   |              |      |           | rehabi   |
|   |         | depends   |              |      |           | litation |
|   |         | on age at |              |      |           | t        |
|   |         | t         |              |      |           | raining. |
|   |         | reatment, |              |      |           | C        |
|   |         | intensity |              |      |           | aution - |
|   |         | of        |              |      |           | lower    |
|   |         | t         |              |      |           | starting |
|   |         | reatment, |              |      |           | dose and |
|   |         | and time  |              |      |           | as       |
|   |         | since     |              |      |           | sessment |
|   |         | t         |              |      |           | of       |
|   |         | reatment. |              |      |           | i        |
|   |         | New       |              |      |           | ncreased |
|   |         | deficits  |              |      |           | sen      |
|   |         | may       |              |      |           | sitivity |
|   |         | emerge    |              |      |           | when     |
|   |         | over      |              |      |           | in       |
|   |         | time.     |              |      |           | itiating |
|   |         |           |              |      |           | therapy  |
|   |         |           |              |      |           | is       |
|   |         |           |              |      |           | reco     |
|   |         |           |              |      |           | mmended. |
|   |         |           |              |      |           | Refer to |
|   |         |           |              |      |           | c        |
|   |         |           |              |      |           | ommunity |
|   |         |           |              |      |           | services |
|   |         |           |              |      |           | for      |
|   |         |           |              |      |           | vo       |
|   |         |           |              |      |           | cational |
|   |         |           |              |      |           | rehabi   |
|   |         |           |              |      |           | litation |
|   |         |           |              |      |           | or for   |
|   |         |           |              |      |           | services |
|   |         |           |              |      |           | for      |
|   |         |           |              |      |           | develop  |
|   |         |           |              |      |           | mentally |
|   |         |           |              |      |           | d        |
|   |         |           |              |      |           | isabled. |
+---+---------+-----------+--------------+------+-----------+----------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = CNS\
Score = 1**

+---+---------+------------+--------------+------+-------+------------+
| * | **Ther  | *          | **Risk       | *    | **Per | **Health   |
| * | apeutic | *Potential | Factors**    | *Hig | iodic | Counseling |
| S | Age     | Late       |              | hest | Ev    | Further    |
| e | nt(s)** | Effects**  |              | Risk | aluat | Consid     |
| c |         |            |              | F    | ion** | erations** |
| \ |         |            |              | acto |       |            |
| # |         |            |              | rs** |       |            |
| * |         |            |              |      |       |            |
| * |         |            |              |      |       |            |
+===+=========+============+==============+======+=======+============+
| 2 | **Anti  | **Clinical | **Host       | **T  | **    | **Cons     |
| 6 | metabol | le         | Factors**\   | reat | Histo | iderations |
|   | ites**\ | ukoencepha | \            | ment | ry**\ | for        |
|   | \       | lopathy**\ | Younger age  | Fa   | \     | Further    |
|   | Metho   | \          | at           | ctor | **    | Testing    |
|   | trexate | S          | treatment\   | s**\ | Cogni | and        |
|   | (high   | pasticity\ | CNS          | \    | tive, | Inter      |
|   | dose    | Ataxia\    | leukem       | R    | m     | vention**\ |
|   | IV)\    | D          | ia/lymphoma\ | adia | otor, | \          |
|   | Metho   | ysarthria\ | Relapsed     | tion | a     | Brain MRI, |
|   | trexate | Dysphagia\ | leuke        | dose | nd/or | Brain CT   |
|   | IO\     | He         | mia/lymphoma | [\   | se    | with MR    |
|   | \       | miparesis\ | treated with | >]{. | nsory | a          |
|   | Metho   | Seizures\  | CNS-directed | unde | d     | ngiography |
|   | trexate | \          | therapy\     | rlin | efici | as         |
|   | IT\     | **Info     | \            | e}24 | ts**\ | clinically |
|   | \       | Link**:    | **Treatment  | Gy   | \     | indicated; |
|   | **Info  | Clinical   | Factors**\   |      | **S   | preferred  |
|   | Link**: | leukoence  | \            |      | eizur | study      |
|   | Hi      | phalopathy | In           |      | es**\ | based on   |
|   | gh-dose | may        | combination  |      | \     | in         |
|   | IV is   | present    | with:        |      | **    | tracranial |
|   | defined | with or    |              |      | Other | lesion to  |
|   | as any  | without    | -            |      | neuro | be         |
|   | single  | imaging    |  Cytarabine\ |      | logic | evaluated: |
|   | dose    | abn        |              |      | s     |            |
|   | [\>]{.  | ormalities |   (high-dose |      | ympto | -   MRI:   |
|   | underli | (e.g.,     |     IV)      |      | ms**\ |     White  |
|   | ne}1000 | leukoencep |              |      | \     |     matter |
|   | m       | halopathy, | -   D        |      | (Yea  |            |
|   | g/m^2^. | cerebral   | examethasone |      | rly)\ | -          |
|   |         | lacunes,   |              |      | \     |  Gadoliniu |
|   |         | cerebral   | -   Cranial  |      | **P   | m-enhanced |
|   |         | atrophy,   |              |      | hysic |     MRI:   |
|   |         | dystrophic |    radiation |      | al**\ |     Mic    |
|   |         | calci      |              |      | \     | rovascular |
|   |         | fications, |              |      | **Spa |     injury |
|   |         | mi         |              |      | stici |            |
|   |         | neralizing |              |      | ty**\ | -   CT:    |
|   |         | microan    |              |      | \     |     Calc   |
|   |         | giopathy). |              |      | *     | ifications |
|   |         | Transient  |              |      | *Atax |            |
|   |         | white      |              |      | ia**\ | Neurology  |
|   |         | matter     |              |      | \     | co         |
|   |         | anomalies  |              |      | **Dys | nsultation |
|   |         | may follow |              |      | arthr | and        |
|   |         | ra         |              |      | ia**\ | follow-up  |
|   |         | diotherapy |              |      | \     | as         |
|   |         | and        |              |      | *     | clinically |
|   |         | high-dose  |              |      | *Hemi | indicated  |
|   |         | ch         |              |      | pares |            |
|   |         | emotherapy |              |      | is**\ |            |
|   |         | for        |              |      | \     |            |
|   |         | m          |              |      | (Ye   |            |
|   |         | edulloblas |              |      | arly) |            |
|   |         | toma/PNET, |              |      |       |            |
|   |         | may mimic  |              |      |       |            |
|   |         | tumor      |              |      |       |            |
|   |         | r          |              |      |       |            |
|   |         | ecurrence, |              |      |       |            |
|   |         | and        |              |      |       |            |
|   |         | signify    |              |      |       |            |
|   |         | risk of    |              |      |       |            |
|   |         | persistent |              |      |       |            |
|   |         | neurologic |              |      |       |            |
|   |         | sequelae.  |              |      |       |            |
|   |         | Ne         |              |      |       |            |
|   |         | uroimaging |              |      |       |            |
|   |         | changes do |              |      |       |            |
|   |         | not always |              |      |       |            |
|   |         | correlate  |              |      |       |            |
|   |         | with       |              |      |       |            |
|   |         | degree of  |              |      |       |            |
|   |         | cognitive  |              |      |       |            |
|   |         | dy         |              |      |       |            |
|   |         | sfunction. |              |      |       |            |
|   |         | P          |              |      |       |            |
|   |         | rospective |              |      |       |            |
|   |         | studies    |              |      |       |            |
|   |         | are needed |              |      |       |            |
|   |         | to define  |              |      |       |            |
|   |         | the        |              |      |       |            |
|   |         | d          |              |      |       |            |
|   |         | ose/effect |              |      |       |            |
|   |         | re         |              |      |       |            |
|   |         | lationship |              |      |       |            |
|   |         | of         |              |      |       |            |
|   |         | neurotoxic |              |      |       |            |
|   |         | agents.    |              |      |       |            |
|   |         | *Note: new |              |      |       |            |
|   |         | deficits   |              |      |       |            |
|   |         | may emerge |              |      |       |            |
|   |         | over       |              |      |       |            |
|   |         | time.*     |              |      |       |            |
+---+---------+------------+--------------+------+-------+------------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = SMN\
Score = 1**

  ------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic     **Potential   **Risk        **Highest   **Periodic Evaluation** **Health
  \#**    Agent(s)**        Late          Factors**     Risk                                Counseling Further
                            Effects**                   Factors**                           Considerations**
  ------- ----------------- ------------- ------------- ----------- ----------------------- ------------------
  27      **Anthracycline   **Acute       **Treatment               **History**\            **Health Links**\
          Antibiotics**\    myeloid       Factors**\                \                       \
          \                 leukemia**    \                         **Fatigue**\            **See \"Patient
          Daunorubicin\                   Less than 5               \                       Resources\"
          Doxorubicin\                    years since               **Bleeding**\           field**\
          Epirubicin\                     exposure to               \                       \
          Idarubicin\                     agent                     **Easy bruising**\      Reducing the Risk
          Mitoxantrone\*\                                           \                       of Second Cancers\
          \                                                         (Yearly up to 10 years  \
          \*Although                                                after exposure to       **Counseling**\
          Mitoxantrone                                              agent)\                 \
          technically                                               \                       Counsel to
          belongs to the                                            **Physical**\           promptly report
          anthracenedione                                           \                       fatigue, pallor,
          class of                                                  **Dermatologic exam     petechiae, or bone
          anti-tumor                                                (pallor, petechiae,     pain\
          antibiotics, it                                           purpura)**\             \
          is related to the                                         \                       **Considerations
          anthracycline                                             (Yearly up to 10 years  for Further
          family.                                                   after exposure to       Testing and
                                                                    agent)\                 Intervention**\
                                                                    \                       \
                                                                    **Screening**\          Bone marrow exam
                                                                    \                       as clinically
                                                                    **CBC/differential**\   indicated
                                                                    \                       
                                                                    (Yearly up to 10 years  
                                                                    after exposure to       
                                                                    agent)                  

  ------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Cardiovascular\
Score = 1**

+---+-------------+---------+---------------+---------+------+--------+
| * | **          | **Po    | **Risk        | **      | **   | **     |
| * | Therapeutic | tential | Factors**     | Highest | Peri | Health |
| S | Agent(s)**  | Late    |               | Risk    | odic | Coun   |
| e |             | Ef      |               | Fa      | Eval | seling |
| c |             | fects** |               | ctors** | uati | F      |
| \ |             |         |               |         | on** | urther |
| # |             |         |               |         |      | Cons   |
| * |             |         |               |         |      | iderat |
| * |             |         |               |         |      | ions** |
+===+=============+=========+===============+=========+======+========+
| 2 | **An        | **      | **Treatment   | **Host  | **Hi | **     |
| 8 | thracycline | Cardiac | Factors**\    | Fac     | stor | Health |
|   | Ant         | toxi    | \             | tors**\ | y**\ | Li     |
|   | ibiotics**\ | city**\ | Combined with | \       | \    | nks**\ |
|   | \           | \       | radiation     | Female  | **SO | \      |
|   | Da          | **Car   | involving the | sex\    | B**\ | **See  |
|   | unorubicin\ | diomyop | heart\        | B       | \    | \"P    |
|   | D           | athy**\ | Combined with | lack/of | **DO | atient |
|   | oxorubicin\ | \       | other         | African | E**\ | Resou  |
|   | Epirubicin\ | **      | cardiotoxic   | d       | \    | rces\" |
|   | Idarubicin\ | Arrhyth | chemotherapy: | escent\ | **   | fi     |
|   | Mito        | mias**\ |               | Younger | Orth | eld**\ |
|   | xantrone\*\ | \       | -   Cyc       | than    | opne | \      |
|   | \           | **Subc  | lophosphamide | age 5   | a**\ | Heart  |
|   | \*Although  | linical |               | years   | \    | H      |
|   | M           | left    |  conditioning | at time | **C  | ealth\ |
|   | itoxantrone | vent    |     for HCT   | of      | hest | \      |
|   | technically | ricular |               | tre     | pai  | **C    |
|   | belongs to  | dysfun  | -   Amsacrine | atment\ | n**\ | ounsel |
|   | the         | ction** |               | \       | \    | ing**\ |
|   | anth        | (s      | **Medical     | **Tr    | *    | \      |
|   | racenedione | ystolic | Conditions**\ | eatment | *Pal | C      |
|   | class of    | dysf    | \             | Fac     | pita | ounsel |
|   | anti-tumor  | unction | Obesity\      | tors**\ | tion | pa     |
|   | a           | as      | Congenital    | \       | s**\ | tients |
|   | ntibiotics, | a       | heart         | Higher  | \    | with   |
|   | it is       | ssessed | disease\      | cum     | **If | pro    |
|   | related to  | by ECHO | Febrile       | ulative | u    | longed |
|   | the         | or      | illness\      | anthra  | nder | QTc    |
|   | an          | MUGA)\  | Pregnancy\    | cycline | 25   | in     |
|   | thracycline | \       | \             | doses:  | yea  | terval |
|   | family.\    | **Info  | **Health      |         | rs:\ | about  |
|   | \           | Link**: | Behaviors**\  | -   P   | A    | use of |
|   | **Info      | Dose    | \             | atients | bdom | medic  |
|   | Link**: Use | levels  | Isometric     |     18  | inal | ations |
|   | the         | corr    | exercise\     |         | symp | that   |
|   | following   | elating | Smoking\      |   years | toms | may    |
|   | formulas to | with    | Drug use      |     or  | (nau | f      |
|   | convert to  | cardiot | (e.g.,        |         | sea, | urther |
|   | do          | oxicity | cocaine, diet |   older | vomi | p      |
|   | xorubicin/d | are     | pills,        |     at  | ting | rolong |
|   | aunorubicin | derived | ephedra,      |         | )**\ | the    |
|   | isotoxic    | from    | mahuang)      |    time | \    | QTc    |
|   | equivalents | adult   |               |     of  | (    | in     |
|   | prior to    | s       |               |     tre | Year | terval |
|   | calculating | tudies. |               | atment: | ly)\ | (e.g., |
|   | total       | Ch      |               |         | \    | tri    |
|   | cumulative  | ildhood |               |   [\>]{ | **   | cyclic |
|   | an          | cancer  |               | .underl | Info | anti-  |
|   | thracycline | p       |               | ine}550 | Lin  | depres |
|   | dose.       | atients |               |         | k**: | sants, |
|   |             | exhibit |               | mg/m^2^ | Ex   | antifu |
|   | -           | c       |               |         | erti | ngals, |
|   | Epirubicin: | linical |               | -   P   | onal | mac    |
|   |             | and     |               | atients | int  | rolide |
|   |    Multiply | subc    |               |         | oler | antibi |
|   |     total   | linical |               | younger | ance | otics, |
|   |     dose x  | t       |               |         | is   | met    |
|   |     0.67    | oxicity |               |    than | unco | ronida |
|   |             | at      |               |     18  | mmon | zole). |
|   | -           | lower   |               |         | in   | C      |
|   | Idarubicin: | levels. |               |   years | y    | ounsel |
|   |             | Certain |               |     at  | oung | reg    |
|   |    Multiply | con     |               |         | pati | arding |
|   |     total   | ditions |               |    time | ents | maint  |
|   |     dose x  | (such   |               |     of  | (    | aining |
|   |     5       | as      |               |     tre | \<25 | appro  |
|   |             | is      |               | atment: | yea  | priate |
|   | -   Mi      | ometric |               |         | rs). | w      |
|   | toxantrone: | ex      |               |   [\>]{ | A    | eight, |
|   |             | ercise, |               | .underl | bdom | blood  |
|   |    Multiply | pre     |               | ine}300 | inal | pre    |
|   |     total   | gnancy, |               |         | symp | ssure, |
|   |     dose x  | and     |               | mg/m^2^ | toms | and    |
|   |     3.5     | viral   |               |         | (nau | h      |
|   |             | infe    |               | -   Any | sea, | eart-h |
|   | *Note:      | ctions) |               |         | eme  | ealthy |
|   | There is a  | have    |               |    dose | sis) | diet.  |
|   | paucity of  | been    |               |     in  | may  | C      |
|   | literature  | anec    |               |         | be   | ounsel |
|   | to support  | dotally |               |  infant | obse | reg    |
|   | isotoxic    | r       |               |         | rved | arding |
|   | dose        | eported |               | Chest   | more | appro  |
|   | conversion; | to      |               | ra      | fr   | priate |
|   | however,    | prec    |               | diation | eque | exe    |
|   | the above   | ipitate |               | [\>]    | ntly | rcise. |
|   | conversion  | cardiac |               | {.under | than | A      |
|   | factors may | d       |               | line}30 | ex   | erobic |
|   | be used for | ecompen |               | Gy\     | erti | ex     |
|   | convenience | sation. |               | Longer  | onal | ercise |
|   | in order to | Pros    |               | time    | dys  | is     |
|   | gauge       | pective |               | elapsed | pnea | gen    |
|   | screening   | studies |               | since   | or   | erally |
|   | frequency.  | are     |               | tr      | c    | safe   |
|   | Clinical    | needed  |               | eatment | hest | and    |
|   | judgment    | to      |               |         | pain | should |
|   | should      | define  |               |         | in   | be     |
|   | ultimately  | risk    |               |         | y    | enco   |
|   | be used to  | f       |               |         | oung | uraged |
|   | determine   | actors. |               |         | pa   | for    |
|   | indicated   | *Note:  |               |         | tien | most   |
|   | screening   | Pe      |               |         | ts.\ | pat    |
|   | for         | diatric |               |         | \    | ients. |
|   | individual  | studies |               |         | *    | Int    |
|   | patients.*  | of      |               |         | *Phy | ensive |
|   |             | anthra  |               |         | sica | iso    |
|   |             | cycline |               |         | l**\ | metric |
|   |             | cardiot |               |         | \    | acti   |
|   |             | oxicity |               |         | *    | vities |
|   |             | ty      |               |         | *Car | (e.g., |
|   |             | pically |               |         | diac | heavy  |
|   |             | d       |               |         | m    | weight |
|   |             | escribe |               |         | urmu | li     |
|   |             | risks   |               |         | r**\ | fting, |
|   |             | based   |               |         | \    | wres   |
|   |             | on      |               |         | *    | tling) |
|   |             | c       |               |         | *S3, | should |
|   |             | ombined |               |         | S    | gen    |
|   |             | cum     |               |         | 4**\ | erally |
|   |             | ulative |               |         | \    | be     |
|   |             | doses   |               |         | **I  | av     |
|   |             | of      |               |         | ncre | oided. |
|   |             | dau     |               |         | ased | L      |
|   |             | nomycin |               |         | P2   | imited |
|   |             | and     |               |         | soun | high   |
|   |             | doxor   |               |         | d**\ | repe   |
|   |             | ubicin, |               |         | \    | tition |
|   |             | a       |               |         | *    | weight |
|   |             | ssuming |               |         | *Per | l      |
|   |             | an      |               |         | icar | ifting |
|   |             | equ     |               |         | dial | (i.e., |
|   |             | ivalent |               |         | ru   | l      |
|   |             | r       |               |         | b**\ | ifting |
|   |             | elative |               |         | \    | a      |
|   |             | cardiot |               |         | **   | l      |
|   |             | oxicity |               |         | Rale | ighter |
|   |             | per mg  |               |         | s**\ | weight |
|   |             | dose.   |               |         | \    | with   |
|   |             | Ida     |               |         | **Wh | ease   |
|   |             | rubicin |               |         | eeze | no     |
|   |             | and     |               |         | s**\ | more   |
|   |             | mitox   |               |         | \    | than   |
|   |             | antrone |               |         | *    | 15 to  |
|   |             | are     |               |         | *Jug | 20     |
|   |             | more    |               |         | ular | times  |
|   |             | card    |               |         | ve   | in a   |
|   |             | iotoxic |               |         | nous | row)   |
|   |             | than    |               |         | d    | is     |
|   |             | doxo    |               |         | iste | much   |
|   |             | rubicin |               |         | nsio | less   |
|   |             | or      |               |         | n**\ | str    |
|   |             | dauno   |               |         | \    | essful |
|   |             | rubicin |               |         | **Pe | to the |
|   |             | on a mg |               |         | riph | heart  |
|   |             | per mg  |               |         | eral | and is |
|   |             | dose    |               |         | edem | more   |
|   |             | basis.  |               |         | a**\ | likely |
|   |             | In      |               |         | \    | to be  |
|   |             | limited |               |         | (    | safe.  |
|   |             | s       |               |         | Year | Pa     |
|   |             | tudies, |               |         | ly)\ | tients |
|   |             | epi     |               |         | \    | who    |
|   |             | rubicin |               |         | **   | choose |
|   |             | has     |               |         | Scre | to     |
|   |             | similar |               |         | enin | engage |
|   |             | dose    |               |         | g**\ | in     |
|   |             | equi    |               |         | \    | str    |
|   |             | valency |               |         | **   | enuous |
|   |             | to      |               |         | ECHO | or     |
|   |             | dau     |               |         | or   | v      |
|   |             | nomycin |               |         | MUGA | arsity |
|   |             | and     |               |         | for  | team   |
|   |             | doxoru  |               |         | ev   | sports |
|   |             | bicin.* |               |         | alua | should |
|   |             |         |               |         | tion | d      |
|   |             |         |               |         | of   | iscuss |
|   |             |         |               |         | syst | appro  |
|   |             |         |               |         | olic | priate |
|   |             |         |               |         | fun  | guid   |
|   |             |         |               |         | ctio | elines |
|   |             |         |               |         | n**\ | and a  |
|   |             |         |               |         | \    | plan   |
|   |             |         |               |         | (    | for    |
|   |             |         |               |         | Base | o      |
|   |             |         |               |         | line | ngoing |
|   |             |         |               |         | at   | moni   |
|   |             |         |               |         | e    | toring |
|   |             |         |               |         | ntry | with a |
|   |             |         |               |         | to   | ca     |
|   |             |         |               |         | l    | rdiolo |
|   |             |         |               |         | ong- | gist.\ |
|   |             |         |               |         | term | \      |
|   |             |         |               |         | fo   | **Co   |
|   |             |         |               |         | llow | nsider |
|   |             |         |               |         | -up, | ations |
|   |             |         |               |         | then | for    |
|   |             |         |               |         | p    | F      |
|   |             |         |               |         | erio | urther |
|   |             |         |               |         | dica | T      |
|   |             |         |               |         | lly, | esting |
|   |             |         |               |         | b    | and    |
|   |             |         |               |         | ased | Int    |
|   |             |         |               |         | on   | ervent |
|   |             |         |               |         | age  | ion**\ |
|   |             |         |               |         | at   | \      |
|   |             |         |               |         | tr   | Card   |
|   |             |         |               |         | eatm | iology |
|   |             |         |               |         | ent, | consul |
|   |             |         |               |         | his  | tation |
|   |             |         |               |         | tory | in     |
|   |             |         |               |         | of   | pa     |
|   |             |         |               |         | c    | tients |
|   |             |         |               |         | hest | with   |
|   |             |         |               |         | r    | subcl  |
|   |             |         |               |         | adia | inical |
|   |             |         |               |         | tion | a      |
|   |             |         |               |         | and  | bnorma |
|   |             |         |               |         | cu   | lities |
|   |             |         |               |         | mula | on     |
|   |             |         |               |         | tive | scr    |
|   |             |         |               |         | a    | eening |
|   |             |         |               |         | nthr | evalua |
|   |             |         |               |         | acyc | tions, |
|   |             |         |               |         | line | left   |
|   |             |         |               |         | do   | ventr  |
|   |             |         |               |         | se - | icular |
|   |             |         |               |         | *see | dysfun |
|   |             |         |               |         | next | ction, |
|   |             |         |               |         | t    | dysrhy |
|   |             |         |               |         | able | thmia, |
|   |             |         |               |         | .*)\ | or     |
|   |             |         |               |         | \    | pro    |
|   |             |         |               |         | **E  | longed |
|   |             |         |               |         | KG** | QTc    |
|   |             |         |               |         | (inc | int    |
|   |             |         |               |         | lude | erval. |
|   |             |         |               |         | ev   | Co     |
|   |             |         |               |         | alua | nsider |
|   |             |         |               |         | tion | excess |
|   |             |         |               |         | of   | risk   |
|   |             |         |               |         | QTc  | of     |
|   |             |         |               |         | in   | iso    |
|   |             |         |               |         | terv | metric |
|   |             |         |               |         | al)\ | ex     |
|   |             |         |               |         | \    | ercise |
|   |             |         |               |         | (    | p      |
|   |             |         |               |         | Base | rogram |
|   |             |         |               |         | line | in any |
|   |             |         |               |         | at   | high   |
|   |             |         |               |         | e    | risk   |
|   |             |         |               |         | ntry | p      |
|   |             |         |               |         | into | atient |
|   |             |         |               |         | l    | (d     |
|   |             |         |               |         | ong- | efined |
|   |             |         |               |         | term | as     |
|   |             |         |               |         | f    | n      |
|   |             |         |               |         | ollo | eeding |
|   |             |         |               |         | wup. | scr    |
|   |             |         |               |         | Re   | eening |
|   |             |         |               |         | peat | every  |
|   |             |         |               |         | as   | 1 or 2 |
|   |             |         |               |         | cl   | y      |
|   |             |         |               |         | inic | ears). |
|   |             |         |               |         | ally | F      |
|   |             |         |               |         | ind  | emales |
|   |             |         |               |         | icat | only:  |
|   |             |         |               |         | ed.) | Addi   |
|   |             |         |               |         |      | tional |
|   |             |         |               |         |      | card   |
|   |             |         |               |         |      | iology |
|   |             |         |               |         |      | eval   |
|   |             |         |               |         |      | uation |
|   |             |         |               |         |      | in     |
|   |             |         |               |         |      | pa     |
|   |             |         |               |         |      | tients |
|   |             |         |               |         |      | who    |
|   |             |         |               |         |      | re     |
|   |             |         |               |         |      | ceived |
|   |             |         |               |         |      | [      |
|   |             |         |               |         |      | \>]{.u |
|   |             |         |               |         |      | nderli |
|   |             |         |               |         |      | ne}300 |
|   |             |         |               |         |      | m      |
|   |             |         |               |         |      | g/m^2^ |
|   |             |         |               |         |      | or     |
|   |             |         |               |         |      | \<300  |
|   |             |         |               |         |      | m      |
|   |             |         |               |         |      | g/m^2^ |
|   |             |         |               |         |      | plus   |
|   |             |         |               |         |      | chest  |
|   |             |         |               |         |      | rad    |
|   |             |         |               |         |      | iation |
|   |             |         |               |         |      | who    |
|   |             |         |               |         |      | are    |
|   |             |         |               |         |      | pr     |
|   |             |         |               |         |      | egnant |
|   |             |         |               |         |      | or     |
|   |             |         |               |         |      | pl     |
|   |             |         |               |         |      | anning |
|   |             |         |               |         |      | preg   |
|   |             |         |               |         |      | nancy. |
|   |             |         |               |         |      | Eval   |
|   |             |         |               |         |      | uation |
|   |             |         |               |         |      | to     |
|   |             |         |               |         |      | i      |
|   |             |         |               |         |      | nclude |
|   |             |         |               |         |      | an     |
|   |             |         |               |         |      | ECHO   |
|   |             |         |               |         |      | before |
|   |             |         |               |         |      | and    |
|   |             |         |               |         |      | period |
|   |             |         |               |         |      | ically |
|   |             |         |               |         |      | during |
|   |             |         |               |         |      | pre    |
|   |             |         |               |         |      | gnancy |
|   |             |         |               |         |      | (espe  |
|   |             |         |               |         |      | cially |
|   |             |         |               |         |      | during |
|   |             |         |               |         |      | third  |
|   |             |         |               |         |      | trim   |
|   |             |         |               |         |      | ester) |
|   |             |         |               |         |      | and    |
|   |             |         |               |         |      | moni   |
|   |             |         |               |         |      | toring |
|   |             |         |               |         |      | during |
|   |             |         |               |         |      | labor  |
|   |             |         |               |         |      | and    |
|   |             |         |               |         |      | de     |
|   |             |         |               |         |      | livery |
|   |             |         |               |         |      | due to |
|   |             |         |               |         |      | risk   |
|   |             |         |               |         |      | of     |
|   |             |         |               |         |      | c      |
|   |             |         |               |         |      | ardiac |
|   |             |         |               |         |      | fa     |
|   |             |         |               |         |      | ilure. |
+---+-------------+---------+---------------+---------+------+--------+

**Recommended Frequency of ECHO or MUGA Scan**

  -----------------------------------------------------------------------------
  **Age at            **Chest       **Anthracycline       **Recommended
  Treatment\***       Radiation**   Dose\*\***            Frequency**
  ------------------- ------------- --------------------- ---------------------
  \<1 year old        Yes           Any                   Every year

                      No            \<200 mg/m^2^         Every 2 years

                                    [\>]{.underline}200   Every year
                                    mg/m^2^               

  1--4 years old      Yes           Any                   Every year

                      No            \<100 mg/m^2^         Every 5 years

                                    [\>]{.underline}100   Every 2 years
                                    to \<300 mg/m^2^      

                                    [\>]{.underline}300   Every year
                                    mg/m^2^               

  [\>]{.underline}5   Yes           \<300 mg/m^2^         Every 2 years
  years old                                               

                                    [\>]{.underline}300   Every year
                                    mg/m^2^               

                      No            \<200 mg/m^2^         Every 5 years

                                    [\>]{.underline}200   Every 2 years
                                    to \<300 mg/m^2^      

                                    [\>]{.underline}300   Every year
                                    mg/m^2^               

  Any age with                                            Every year
  decrease in serial                                      
  function                                                
  -----------------------------------------------------------------------------

\*Age at time of first cardiotoxic therapy (anthracycline or chest
irradiation, whichever was given first)\
\*\*Based on equivalent mg of doxorubicin/daunorubicin

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Pulmonary**

**Scores = Interstitial pneumonitis: 1\
Pulmonary fibrosis: 1\
ARDS: 2B**

+---+--------+-------+--------------+----------+--------+-------------+
| * | *      | *     | **Risk       | *        | **Pe   | **Health    |
| * | *Thera | *Pote | Factors**    | *Highest | riodic | Counseling  |
| S | peutic | ntial |              | Risk     | Evalua | Further     |
| e | Agen   | Late  |              | F        | tion** | Consi       |
| c | t(s)** | Effe  |              | actors** |        | derations** |
| \ |        | cts** |              |          |        |             |
| # |        |       |              |          |        |             |
| * |        |       |              |          |        |             |
| * |        |       |              |          |        |             |
+===+========+=======+==============+==========+========+=============+
| 2 | **Anti | *     | **Host       | **T      | **Hist | **Health    |
| 9 | -Tumor | *Pulm | Factors**\   | reatment | ory**\ | Links**\    |
|   | An     | onary | \            | Fa       | \      | \           |
|   | tibiot | T     | Younger age  | ctors**\ | **Co   | **See       |
|   | ics**\ | oxici | at           | \        | ugh**\ | \"Patient   |
|   | \      | ty**\ | treatment\   | B        | \      | Resources\" |
|   | Ble    | \     | \            | leomycin | **     | field**\    |
|   | omycin | In    | **Treatment  | dose     | SOB**\ | \           |
|   |        | terst | Factors**\   | [\>      | \      | Pulmonary   |
|   |        | itial | \            | ]{.under | **     | Health\     |
|   |        | pn    | Higher       | line}400 | DOE**\ | Bleomycin   |
|   |        | eumon | cumulative   | U/m^2^   | \      | Alert\      |
|   |        | itis\ | dose\        | (injury  | *      | \           |
|   |        | Pulm  | \            | observed | *Wheez | **R         |
|   |        | onary | Combined     | in doses | ing**\ | esources**\ |
|   |        | fibr  | with:        | 60 to    | \      | \           |
|   |        | osis\ |              | 100      | (Ye    | Extensive   |
|   |        | Acute | -   Busulfan | U/m^2^   | arly)\ | information |
|   |        | r     |              | in       | \      | regarding   |
|   |        | espir | -            | ch       | *      | smoking     |
|   |        | atory |   Carmustine | ildren)\ | *Physi | cessation   |
|   |        | dis   |     (BCNU)   | \        | cal**\ | is          |
|   |        | tress |              | Combined | \      | available   |
|   |        | syn   | -            | with:    | **Pul  | for         |
|   |        | drome |    Lomustine |          | monary | patients on |
|   |        | (very |     (CCNU)   | -        | e      | the NCI\'s  |
|   |        | rare) |              |    Chest | xam**\ | website:    |
|   |        |       | **Medical    |     r    | \      | [www        |
|   |        |       | C            | adiation | (Ye    | .smokefree. |
|   |        |       | onditions**\ |          | arly)\ | gov](http:/ |
|   |        |       | \            | -   TBI  | \      | /www.smokef |
|   |        |       | Renal        |          | **     | ree.gov/).\ |
|   |        |       | dysfunction\ |          | Screen | \           |
|   |        |       | High dose    |          | ing**\ | **Co        |
|   |        |       | oxygen       |          | \      | unseling**\ |
|   |        |       | support such |          | *      | \           |
|   |        |       | as during    |          | *Chest | SCUBA       |
|   |        |       | general      |          | x-     | diving      |
|   |        |       | anesthesia\  |          | ray**\ | should be   |
|   |        |       | \            |          | \      | avoided     |
|   |        |       | **Health     |          | **     | (potential  |
|   |        |       | Behaviors**\ |          | PFTs** | e           |
|   |        |       | \            |          | (inc   | xacerbation |
|   |        |       | Smoking      |          | luding | of          |
|   |        |       |              |          | DLCO   | pulmonary   |
|   |        |       |              |          | and    | fibrosis as |
|   |        |       |              |          | spirom | a result of |
|   |        |       |              |          | etry)\ | increased   |
|   |        |       |              |          | \      | oxygen      |
|   |        |       |              |          | (Ba    | con         |
|   |        |       |              |          | seline | centrations |
|   |        |       |              |          | at     | associated  |
|   |        |       |              |          | entry  | with        |
|   |        |       |              |          | into   | underwater  |
|   |        |       |              |          | lon    | pressures). |
|   |        |       |              |          | g-term | Notify      |
|   |        |       |              |          | foll   | healthcare  |
|   |        |       |              |          | ow-up. | providers   |
|   |        |       |              |          | Repeat | of history  |
|   |        |       |              |          | as     | of          |
|   |        |       |              |          | clin   | bleomycin   |
|   |        |       |              |          | ically | therapy and |
|   |        |       |              |          | ind    | risk of     |
|   |        |       |              |          | icated | worsening   |
|   |        |       |              |          | in     | fibrosis    |
|   |        |       |              |          | pa     | with high   |
|   |        |       |              |          | tients | oxygen      |
|   |        |       |              |          | with   | exposure    |
|   |        |       |              |          | ab     | such as     |
|   |        |       |              |          | normal | during      |
|   |        |       |              |          | r      | general     |
|   |        |       |              |          | esults | anesthesia. |
|   |        |       |              |          | or     | Adm         |
|   |        |       |              |          | progr  | inistration |
|   |        |       |              |          | essive | of high     |
|   |        |       |              |          | pul    | con         |
|   |        |       |              |          | monary | centrations |
|   |        |       |              |          | d      | of oxygen   |
|   |        |       |              |          | ysfunc | may result  |
|   |        |       |              |          | tion.) | in chronic  |
|   |        |       |              |          |        | progressive |
|   |        |       |              |          |        | pulmonary   |
|   |        |       |              |          |        | fibrosis.   |
|   |        |       |              |          |        | Counsel     |
|   |        |       |              |          |        | regarding   |
|   |        |       |              |          |        | tobacco     |
|   |        |       |              |          |        | avoida      |
|   |        |       |              |          |        | nce/smoking |
|   |        |       |              |          |        | cessation.\ |
|   |        |       |              |          |        | \           |
|   |        |       |              |          |        | **Con       |
|   |        |       |              |          |        | siderations |
|   |        |       |              |          |        | for Further |
|   |        |       |              |          |        | Testing and |
|   |        |       |              |          |        | Inte        |
|   |        |       |              |          |        | rvention**\ |
|   |        |       |              |          |        | \           |
|   |        |       |              |          |        | In patients |
|   |        |       |              |          |        | with        |
|   |        |       |              |          |        | abnormal    |
|   |        |       |              |          |        | PFTs and/or |
|   |        |       |              |          |        | CXR,        |
|   |        |       |              |          |        | consider    |
|   |        |       |              |          |        | repeat      |
|   |        |       |              |          |        | evaluation  |
|   |        |       |              |          |        | prior to    |
|   |        |       |              |          |        | general     |
|   |        |       |              |          |        | anesthesia. |
|   |        |       |              |          |        | Pulmonary   |
|   |        |       |              |          |        | c           |
|   |        |       |              |          |        | onsultation |
|   |        |       |              |          |        | in patients |
|   |        |       |              |          |        | with        |
|   |        |       |              |          |        | symptomatic |
|   |        |       |              |          |        | or          |
|   |        |       |              |          |        | progressive |
|   |        |       |              |          |        | pulmonary   |
|   |        |       |              |          |        | d           |
|   |        |       |              |          |        | ysfunction. |
|   |        |       |              |          |        | Influenza   |
|   |        |       |              |          |        | and         |
|   |        |       |              |          |        | p           |
|   |        |       |              |          |        | neumococcal |
|   |        |       |              |          |        | vaccines.   |
+---+--------+-------+--------------+----------+--------+-------------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = N/A\
Score = 1**

  -------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic    **Potential    **Risk      **Highest   **Periodic     **Health
  \#**    Agent(s)**       Late Effects** Factors**   Risk        Evaluation**   Counseling Further
                                                      Factors**                  Considerations**
  ------- ---------------- -------------- ----------- ----------- -------------- ------------------
  30      **Anti-Tumor     **No known                                             
          Antibiotics**\   late                                                  
          \                effects**\                                            
          Dactinomycin     \                                                     
                           **Info Link**:                                        
                           Dactinomycin                                          
                           has been                                              
                           associated                                            
                           with acute                                            
                           VOD, from                                             
                           which the                                             
                           majority of                                           
                           patients                                              
                           recover                                               
                           without                                               
                           sequelae.                                             

  -------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Musculoskeletal\
Score = 1**

  --------------------------------------------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic          **Potential Late      **Risk Factors**   **Highest Risk      **Periodic       **Health Counseling Further
  \#**    Agent(s)**             Effects**                                Factors**           Evaluation**     Considerations**
  ------- ---------------------- --------------------- ------------------ ------------------- ---------------- -------------------------------------
  31      **Corticosteroids**\   **Osteopenia**\       **Host Factors**\  **Host Factors**\   **Screening**\   **Health Links**\
          \                      \                     \                  \                   \                \
          Dexamethasone\         **Osteoporosis**\     Both genders are   Older age at time   **Bone density   **See \"Patient Resources\" field**\
          Prednisone             \                     at risk\           of treatment\       evaluation (DEXA \
                                 Osteopenia is defined \                  \                   or quantitative  Bone Health\
                                 as BMD                **Treatment        **Treatment         CT)**\           \
                                 [\>]{.underline}1 and Factors**\         Factors**\          \                **Resources**\
                                 \<2.5 SD below mean\  \                  \                   (Baseline at     \
                                 Osteoporosis is       Methotrexate\      Glucocorticoid      entry into       National Osteoporosis Foundation
                                 defined as BMD        Cranial radiation\ cumulative dose     long-term        Website:
                                 [\>]{.underline}2.5   HCT/TBI\           [\>]{.underline}9   followup. Repeat [www.nof.org](http://www.nof.org/)\
                                 SD below mean\        \                  gm/m^2^ prednisone  as clinically    \
                                 \                     **Medical          equivalent\         indicated.)\     **Considerations for Further Testing
                                 **Info Link**: The    Conditions**\      Dexamethasone       \                and Intervention**\
                                 World Health          \                  effect is more      **Info Link**:   \
                                 Organization          Growth hormone     potent than         The optimal      Nutritional supplements in cases of
                                 definition of         deficiency\        prednisone          method of        osteopenia unresponsive to behavioral
                                 osteoporosis in       Hypogonadism/                          measuring bone   and dietary management: Calcium 1000
                                 adults is based on    delayed puberty\                       health in        to 1500 mg daily plus RDA for vitamin
                                 comparison of a BMD   Hyperthyroidism\                       children is      D. Use caution regarding calcium
                                 of young adults at    \                                      controversial.   supplementation in patients with
                                 peak bone age and     **Health                               Existing         history of renal lithiasis. Treatment
                                 defined as a T-score. Behaviors**\                           technologies     of exacerbating or predisposing
                                 A T-score is the      \                                      have             conditions (e.g., hormonal
                                 number of standard    Inadequate intake                      limitations.     replacement therapy for hypogonadism,
                                 deviations the BMD    of calcium and                         DEXA provides an growth hormone deficiency, correction
                                 measurement is above  vitamin D\                             estimate of      of chronic metabolic acidosis that
                                 or below the mean. A  Lack of weight                         total bone mass  could accelerate bone loss).
                                 T-score of            bearing exercise\                      at a given site. Endocrine consultation for patients
                                 [\>]{.underline}2.5   Smoking\                               Quantitative CT  with osteoporosis or history of
                                 standard deviations   Alcohol use                            provides         multiple fractures for pharmacologic
                                 BELOW the mean is                                            distinct         interventions (e.g., bisphosphonates,
                                 consistent with a                                            measures of      calcitonin, selective estrogen
                                 diagnosis of                                                 trabecular and   receptor modulators).
                                 osteoporosis.                                                cortical bone    
                                 T-scores are not                                             dimension and    
                                 appropriate to assess                                        density.         
                                 skeletal health in                                                            
                                 pediatric patients                                                            
                                 who have not achieved                                                         
                                 peak adult bone mass.                                                         
                                 Instead, pediatric                                                            
                                 BMD reference data                                                            
                                 sets calculate                                                                
                                 Z-scores based on age                                                         
                                 and gender. A Z-score                                                         
                                 is the number of                                                              
                                 standard deviations                                                           
                                 the measurement is                                                            
                                 above or below the                                                            
                                 AGE-MATCHED MEAN BMD.                                                         
                                 There are no defined                                                          
                                 standards for                                                                 
                                 referral or treatment                                                         
                                 of low BMD in                                                                 
                                 children.                                                                     

  --------------------------------------------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Musculoskeletal\
Score = 1**

  ------- ---------------------- -------------------- --------------- -------------------- ------------------- -------------------
  **Sec   **Therapeutic          **Potential Late     **Risk          **Highest Risk       **Periodic          **Health Counseling
  \#**    Agent(s)**             Effects**            Factors**       Factors**            Evaluation**        Further
                                                                                                               Considerations**

  32      **Corticosteroids**\   **Osteonecrosis**\   **Host          **Host Factors**\    **History**\        **Health Links**\
          \                      (Avascular           Factors**\      \                    \                   \
          Dexamethasone\         Necrosis)\           \               Age                  **Joint pain**\     **See \"Patient
          Prednisone             \                    Both genders    [\>]{.underline}10   \                   Resources\"
                                 **Info Link**:       are at risk\    years at time of     **Swelling**\       field**\
                                 Osteonecrosis        Host            treatment\           \                   \
                                 typically occurs     polymorphisms   \                    **Immobility**\     Osteonecrosis\
                                 during the acute     may confer      **Treatment          \                   \
                                 treatment phase, may increased risk\ Factors**\           **Limited range of  **Considerations
                                 progress over time   \               \                    motion**\           for Further Testing
                                 or resolve.          **Treatment     Orthovoltage         \                   and Intervention**\
                                 Multifocal           Factors**\      radiation (commonly  (Yearly)\           \
                                 osteonecrosis is     \               used before 1970)    \                   MRI as clinically
                                 significantly more   Combined with   due to delivery of   **Physical**\       indicated in
                                 common (3:1) than    high-dose       greater dose to skin \                   patients with
                                 unifocal.            radiation to    and bones            **Musculoskeletal   history suggestive
                                                      any bone\                            exam**\             of osteonecrosis
                                                      Dexamethasone                        \                   (should be done
                                                      effect is more                       (Yearly)            soon after symptom
                                                      potent than                                              onset). Orthopedic
                                                      prednisone\                                              consultation in
                                                      \                                                        patients with
                                                      **Medical                                                positive imaging
                                                      Conditions**\                                            and/or symptoms of
                                                      \                                                        osteonecrosis.
                                                      Sickle cell                                              Physical therapy
                                                      disease                                                  evaluation (for
                                                                                                               non-pharmacologic
                                                                                                               pain management,
                                                                                                               range of motion,
                                                                                                               strengthening,
                                                                                                               stretching,
                                                                                                               functional
                                                                                                               mobility).
  ------- ---------------------- -------------------- --------------- -------------------- ------------------- -------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Ocular\
Score = 1**

+---+------------+-------+-------------+--------+--------+-----------+
| * | **T        | *     | **Risk      | **H    | **Pe   | **Health  |
| * | herapeutic | *Pote | Factors**   | ighest | riodic | C         |
| S | Agent(s)** | ntial |             | Risk   | Evalua | ounseling |
| e |            | Late  |             | Fac    | tion** | Further   |
| c |            | Effe  |             | tors** |        | Conside   |
| \ |            | cts** |             |        |        | rations** |
| # |            |       |             |        |        |           |
| * |            |       |             |        |        |           |
| * |            |       |             |        |        |           |
+===+============+=======+=============+========+========+===========+
| 3 | **Corticos | **C   | **Treatment | **Tre  | **Hist | **Health  |
| 3 | teroids**\ | atara | Factors**\  | atment | ory**\ | Links**\  |
|   | \          | cts** | \           | Fact   | \      | \         |
|   | Dexa       |       | Combined    | ors**\ | **     | **See     |
|   | methasone\ |       | with:       | \      | Visual | \"Patient |
|   | Prednisone |       |             | TBI\   | dif    | Re        |
|   |            |       | -   TBI     | Cr     | ficult | sources\" |
|   |            |       |             | anial, | ies**\ | field**\  |
|   |            |       | -           | or     | \      | \         |
|   |            |       |    Busulfan | bital, | (Ye    | C         |
|   |            |       |             | or eye | arly)\ | ataracts\ |
|   |            |       |             | radi   | \      | \         |
|   |            |       |             | ation\ | *      | **Consi   |
|   |            |       |             | Longer | *Physi | derations |
|   |            |       |             | in     | cal**\ | for       |
|   |            |       |             | terval | \      | Further   |
|   |            |       |             | since  | **Eye  | Testing   |
|   |            |       |             | tre    | exam** | and       |
|   |            |       |             | atment | (      | Interv    |
|   |            |       |             |        | visual | ention**\ |
|   |            |       |             |        | a      | \         |
|   |            |       |             |        | cuity, | Opht      |
|   |            |       |             |        | fundu  | halmology |
|   |            |       |             |        | scopic | con       |
|   |            |       |             |        | exam   | sultation |
|   |            |       |             |        | for    | if        |
|   |            |       |             |        | lens   | problem   |
|   |            |       |             |        | opa    | id        |
|   |            |       |             |        | city)\ | entified. |
|   |            |       |             |        | \      | Refer     |
|   |            |       |             |        | (Y     | patients  |
|   |            |       |             |        | early) | with      |
|   |            |       |             |        |        | visual    |
|   |            |       |             |        |        | deficits  |
|   |            |       |             |        |        | to school |
|   |            |       |             |        |        | liaison   |
|   |            |       |             |        |        | in        |
|   |            |       |             |        |        | community |
|   |            |       |             |        |        | or cancer |
|   |            |       |             |        |        | center    |
|   |            |       |             |        |        | (psyc     |
|   |            |       |             |        |        | hologist, |
|   |            |       |             |        |        | social    |
|   |            |       |             |        |        | worker,   |
|   |            |       |             |        |        | school    |
|   |            |       |             |        |        | c         |
|   |            |       |             |        |        | ounselor) |
|   |            |       |             |        |        | to        |
|   |            |       |             |        |        | f         |
|   |            |       |             |        |        | acilitate |
|   |            |       |             |        |        | ac        |
|   |            |       |             |        |        | quisition |
|   |            |       |             |        |        | of        |
|   |            |       |             |        |        | ed        |
|   |            |       |             |        |        | ucational |
|   |            |       |             |        |        | r         |
|   |            |       |             |        |        | esources. |
+---+------------+-------+-------------+--------+--------+-----------+

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = N/A\
Score = 1**

  ------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic   **Potential    **Risk      **Highest   **Periodic     **Health
  \#**    Agent(s)**      Late Effects** Factors**   Risk        Evaluation**   Counseling Further
                                                     Factors**                  Considerations**
  ------- --------------- -------------- ----------- ----------- -------------- ------------------
  34      **Enzymes**\    **No known                                             
          \               late                                                  
          Asparaginase    effects**\                                            
                          \                                                     
                          **Info Link**:                                        
                          Acute                                                 
                          toxicities                                            
                          predominate,                                          
                          from which the                                        
                          majority of                                           
                          patients                                              
                          recover                                               
                          without                                               
                          sequelae                                              

  ------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = PNS\
Score = 2A**

  ----------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic   **Potential     **Risk          **Highest Risk        **Periodic      **Health
  \#**    Agent(s)**      Late Effects**  Factors**       Factors**             Evaluation**    Counseling Further
                                                                                                Considerations**
  ------- --------------- --------------- --------------- --------------------- --------------- ------------------
  35      **Plant         **Peripheral    **Treatment     **Medical             **History**\    **Health Links**\
          Alkaloids**\    sensory or      Factors**\      Conditions**\         \               \
          \               motor           \               \                     **Peripheral    **See \"Patient
          Vinblastine\    neuropathy**\   Combined with   Charcot-Marie-Tooth   neuropathy**\   Resources\"
          Vincristine     \               platinum        disease               \               field**\
                          Areflexia\      chemotherapy,                         (Yearly, until  \
                          Weakness\       gemcitabine, or                       2 to 3 years    Peripheral
                          Foot drop\      taxanes\                              after therapy.  Neuropathy\
                          Paresthesias\   \                                     Monitor yearly  \
                          \               **Medical                             if symptoms     **Considerations
                          **Info Link**:  Conditions**\                         persist.)\      for Further
                          Acute           \                                     \               Testing and
                          toxicities most Anorexia\                             **Physical**\   Intervention**\
                          commonly occur  Severe weight                         \               \
                          and usually     loss                                  **Neurologic    Physical therapy
                          resolve prior                                         exam**\         referral for
                          to patients                                           \               patients with
                          entering                                              (Yearly, until  symptomatic
                          long-term                                             2 to 3 years    neuropathy.
                          follow-up.                                            after therapy;  Physical therapy
                          Neuropathy can                                        continue to     and occupational
                          persist after                                         monitor yearly  therapy assessment
                          treatment and                                         if symptoms     of hand function.
                          is typically                                          persist)        Consider treatment
                          not late in                                                           with an
                          onset.                                                                anticonvulsant
                                                                                                effective for
                                                                                                neuropathic pain
                                                                                                (e.g., gabapentin
                                                                                                and
                                                                                                amitriptyline).

  ----------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = Cardiovascular\
Score = 2A**

  -------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic   **Potential     **Risk         **Highest   **Periodic        **Health
  \#**    Agent(s)**      Late Effects**  Factors**      Risk        Evaluation**      Counseling Further
                                                         Factors**                     Considerations**
  ------- --------------- --------------- -------------- ----------- ----------------- ------------------
  36      **Plant         **Vasospastic   **Health                   **History**\      **Health Links**\
          Alkaloids**\    attacks**\      Behaviors**\               \                 \
          \               \               \                          **Vasospasms of   **See \"Patient
          Vinblastine\    (Raynaud\'s     Smoking\                   hands, feet,      Resources\"
          Vincristine     phenomenon)     Illicit drug               nose, lips,       field**\
                                          use                        cheeks, or        \
                                                                     earlobes related  Raynaud\'s
                                                                     to stress or cold Phenomenon\
                                                                     temperatures**\   \
                                                                     \                 **Counseling**\
                                                                     (Yearly)\         \
                                                                     \                 Counsel to wear
                                                                     **Physical**\     appropriate
                                                                     \                 protective
                                                                     **Physical exam   clothing in cold
                                                                     of affected       environments and
                                                                     area**\           not to use tobacco
                                                                     \                 or illicit drugs\
                                                                     (As Indicated)    \
                                                                                       **Considerations
                                                                                       for Further
                                                                                       Testing and
                                                                                       Intervention**\
                                                                                       \
                                                                                       Consider
                                                                                       vasodilating
                                                                                       medications
                                                                                       (calcium-channel
                                                                                       blockers, alpha
                                                                                       blockers) for
                                                                                       patients with
                                                                                       frequent, severe
                                                                                       vasospastic
                                                                                       attacks
                                                                                       unresponsive to
                                                                                       behavioral
                                                                                       management.

  -------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

**System = SNM\
Score = 1**

  ----------------------------------------------------------------------------------------------------------------------------
  **Sec   **Therapeutic Agent(s)**   **Potential   **Risk          **Highest Risk   **Periodic Evaluation** **Health
  \#**                               Late          Factors**       Factors**                                Counseling Further
                                     Effects**                                                              Considerations**
  ------- -------------------------- ------------- --------------- ---------------- ----------------------- ------------------
  37      **Epipodophyllotoxins**\   **Acute       **Medical       **Treatment      **History**\            **Health Links**\
          \                          myeloid       Conditions**\   Factors**\       \                       \
          Etoposide (VP16)\          leukemia**    \               \                **Fatigue**\            **See \"Patient
          Teniposide (VM26)\                       Splenectomy     Weekly or twice  \                       Resources\"
          \                                        (conflicting    weekly           **Bleeding**\           field**\
          **Info Link**:                           evidence)       administration   \                       \
          Administration schedules                                 Less than 5      **Easy bruising**\      Reducing the Risk
          since approximately 1990                                 years since      \                       of Second Cancers\
          have been modified to                                    exposure to      (Yearly, up to 10 years \
          reduce the risk of this                                  agent            after exposure to       **Counseling**\
          complication.                                                             agent)\                 \
                                                                                    \                       Counsel to
                                                                                    **Physical**\           promptly report
                                                                                    \                       fatigue, pallor,
                                                                                    **Dermatologic exam     petechiae, or bone
                                                                                    (pallor, petechiae,     pain\
                                                                                    purpura)**\             \
                                                                                    \                       **Considerations
                                                                                    (Yearly, up to 10 years for Further
                                                                                    after exposure to       Testing and
                                                                                    agent)\                 Intervention**\
                                                                                    \                       \
                                                                                    **Screening**\          Bone marrow exam
                                                                                    \                       as clinically
                                                                                    **CBC/differential**\   indicated
                                                                                    \                       
                                                                                    (Yearly, up to 10 years 
                                                                                    after exposure to       
                                                                                    agent)                  

  ----------------------------------------------------------------------------------------------------------------------------

**Note**: See a list of [Abbreviations](#Abbreviations) at the end of
the \"Major Recommendations\" field.

[]{#Abbreviations .anchor}**Abbreviations**

-   ABR, auditory brainstem response

-   ALT, alanine aminotransferase

-   AST, aspartate aminotransferase

-   BAER, brainstem auditory evoked responses

-   BMD, bone mineral density

-   BUN, blood urea nitrogen

-   Ca, calcium

-   CBC, complete blood count

-   CCG, Children\'s Cancer Group

-   Cl, chloride

-   CNS, central nervous system

-   CO~2~, carbon dioxide

-   COG, Children\'s Oncology Group

-   CT, computed tomography

-   CXR, chest x-ray

-   DEXA, dual energy x-ray absorptiometry

-   DLCO, diffusion capacity of carbon monoxide

-   DOE, dyspnea on exertion

-   ECHO, echocardiogram

-   EKG, electrocardiogram

-   FSH, follicle-stimulating hormone

-   GI, gastrointestinal

-   GVHD, graft versus host disease

-   Gy, gray

-   HCT, hematopoietic cell transplant

-   HPF, high power field

-   HZ, hertz

-   IM, intramuscular

-   IO, intraosseous

-   IQ, intelligence quotient

-   IT, intrathecal

-   IV, intravenous

-   K, potassium

-   LH, luteinizing hormone

-   Mg, magnesium

-   MOPP, mechlorethamine/Oncovin
    \[vincristine\]/procarbazine/prednisone

-   MR, magnetic resonance

-   MRI, magnetic resonance imaging

-   MUGA, multiple gated acquisition scan

-   N/A, not applicable

-   Na, sodium

-   NCI, National Cancer Institute

-   OAEs, otoacoustic emissions

-   PFTs, pulmonary function tests

-   PNET, primitive neuroectodermal tumor

-   PNS, peripheral neurosensory

-   PO, by mouth

-   PO~4~, phosphate

-   RBC, red blood cell

-   RDA, recommended daily allowance

-   SD, standard deviaion(s)

-   SMN, secondary malignant neoplasm

-   SOB, shortness of breath

-   SQ, subcutaneous

-   TBI, total body irradiation

-   VOD, veno-occlusive diseases

**Definitions**:

**Explanation of Scoring for the Long-Term Follow-Up Guidelines**

1  There is uniform consensus of the panel that (1) there is high-level
evidence linking the late effect with the therapeutic exposure, and (2)
the screening recommendation is appropriate based on the collective
clinical experience of panel members.

2A  There is uniform consensus of the panel that (1) there is
lower-level evidence linking the late effect with the therapeutic
exposure, and (2) the screening recommendation is appropriate based on
the collective clinical experience of panel members.

2B  There is non-uniform consensus of the panel that (1) there is
lower-level evidence linking the late effect with the therapeutic
exposure, and (2) the screening recommendation is appropriate based on
the collective clinical experience of panel members.

3  There is major disagreement that the recommendation is appropriate.

**Rating Scheme for the Strength of the Evidence**

\"High-level evidence\" (recommendation category 1) was defined as
evidence derived from high quality case control or cohort studies.

\"Lower-level evidence\" (recommendation categories 2A and 2B) was
defined as evidence derived from non-analytic studies, case reports,
case series, and clinical experience.

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of supporting evidence is identified and graded for each
recommendation (see \"Major Recommendations\").

Although several well-conducted studies on large populations of
childhood cancer survivors have demonstrated associations between
specific exposures and late effects, the size of the survivor population
and the rate of occurrence of late effects does not allow for clinical
studies that would assess the impact of screening recommendations on the
morbidity and mortality associated with the late effect. Therefore,
scoring of each exposure reflects the expert panel\'s assessment of the
level of literature support linking the therapeutic exposure with the
late effect coupled with an assessment of the appropriateness of the
recommended screening modality in identifying the potential late effect
based on the panel\'s collective clinical experience.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Potential benefits of implementing these guidelines into clinical
practice include earlier identification of and intervention for late
onset therapy-related complications in this at-risk population,
potentially reducing or ameliorating the impact of late complications on
the health status of survivors. In addition, ongoing healthcare that
promotes healthy lifestyle choices and provides ongoing monitoring of
health status is important for all cancer survivors.

#### POTENTIAL HARMS

Potential harms of guideline implementation include increased patient
anxiety related to enhanced awareness of possible complications, as well
as the potential for false-positive screening evaluations, leading to
unnecessary further workup. In addition, costs of long-term follow-up
care may be prohibitive for some patients, particularly those lacking
health insurance, or those with insurance that does not cover the
recommended screening evaluations.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   The information and contents of each document or series of documents
    made available by the Children\'s Oncology Group relating to late
    effects of cancer treatment and care or containing the title
    \"Long-Term Follow-Up Guidelines for Survivors of Childhood,
    Adolescent, and Young Adult Cancers\" or the title \"Health Link,\"
    whether available in print or electronic format (including any
    digital format, e-mail transmission, or download from the website),
    shall be known hereinafter as \"Informational Content.\" All
    Informational Content is for informational purpose only. The
    Informational Content is not intended to substitute for medical
    advice, medical care, diagnosis, or treatment obtained from a
    physician or healthcare provider.

-   *To cancer patients (if children, their parents or legal
    guardians)*: Please seek the advice of a physician or other
    qualified healthcare provider with any questions you may have
    regarding a medical condition and do not rely on the Informational
    Content. The Children\'s Oncology Group is a research organization
    and does not provide individualized medical care or treatment.

-   *To physicians and other healthcare providers*: The Informational
    Content is not intended to replace your independent clinical
    judgment, medical advice, or to exclude other legitimate criteria
    for screening, health counseling, or intervention for specific
    complications of childhood cancer treatment. Neither is the
    Informational Content intended to exclude other reasonable
    alternative follow-up procedures. The Informational Content is
    provided as a courtesy, but not intended as a sole source of
    guidance in the evaluation of childhood cancer survivors. The
    Children\'s Oncology Group recognizes that specific patient care
    decisions are the prerogative of the patient, family, and healthcare
    provider.

-   While the Children\'s Oncology Group has made every attempt to
    assure that the Informational Content is accurate and complete as of
    the date of publication, no warranty or representation, express or
    implied, is made as to the accuracy, reliability, completeness,
    relevance, or timeliness of such Informational Content.

-   No liability is assumed by the Children\'s Oncology Group or any
    affiliated party or member thereof for damage resulting from the
    use, review, or access of the Informational Content. You agree to
    the following terms of indemnification: (i) \"Indemnified Parties\"
    include authors and contributors to the Informational Content, all
    officers, directors, representatives, employees, agents, and members
    of the Children\'s Oncology Group and affiliated organizations; (ii)
    by using, reviewing, or accessing the Informational Content, you
    agree, at your own expense, to indemnify, defend and hold harmless
    Indemnified Parties from any and all losses, liabilities, or damages
    (including attorneys\' fees and costs) resulting from any and all
    claims, causes of action, suits, proceedings, or demands related to
    or arising out of use, review or access of the Informational
    Content.

-   Ultimately, as with all clinical guidelines, decisions regarding
    screening and clinical management for any specific patient should be
    individually tailored, taking into consideration the patient\'s
    treatment history, risk factors, co-morbidities, and lifestyle.
    These guidelines are therefore not intended to replace clinical
    judgment or to exclude other reasonable alternative follow-up
    procedures. The Children\'s Oncology Group recognizes that specific
    patient care decisions are the prerogative of the patient, family,
    and healthcare provider.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

Implementation of these guidelines is intended to standardize and
enhance follow-up care provided to survivors of pediatric malignancies
throughout the lifespan. Considerations in this regard include the
practicality and efficiency of applying these broad guidelines in
individual clinical situations. Studies to address guideline
implementation and refinement are a top priority of the Children\'s
Oncology Group (COG) Late Effects Committee, and proposals to study
feasibility of guideline use in limited institutions are currently
underway. Issues to be addressed include description of anticipated
barriers to application of the recommendations in the guidelines and
development of review criteria for measuring changes in care when the
guidelines are implemented. Additional concerns surround the lack of
current evidence establishing the efficacy of screening for late
complications in pediatric cancer survivors. While most clinicians
believe that ongoing surveillance for these late complications is
important in order to allow for early detection and intervention for
complications that may arise, development of studies addressing the
efficacy of this approach is imperative in order to determine which
screening modalities are optimal for asymptomatic survivors.

In addition, the clinical utility of this lengthy document has also been
a top concern of the COG Late Effects Committee. While recognizing that
the length and depth of these guidelines is important in order to
provide clinically-relevant, evidence-based recommendations and
supporting health education materials, clinician time limitations and
the effort required to identify the specific recommendations relevant to
individual patients have been identified as barriers to their clinical
application. Therefore, the COG Late Effects Committee is currently
partnering with the Baylor School of Medicine in order to develop a
web-based interface, known as \"Passport for Care,\" that will generate
individualized exposure-based recommendations from these guidelines in a
clinician-focused format for ease of patient-specific application of the
guidelines in the clinical setting. As additional information regarding
implementation of the Passport for Care web-based interface becomes
available, updates will be posted at
[www.survivorshipguidelines.org](http://www.survivorshipguidelines.org/).

#### IMPLEMENTATION TOOLS

Chart Documentation/Checklists/Forms\
Patient Resources\
Resources

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Living with Illness\
Staying Healthy

#### IOM DOMAIN

Effectiveness\
Patient-centeredness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Children\'s Oncology Group. Long-term follow-up guidelines for survivors
of childhood, adolescent, and young adult cancers. Sections 6-37:
chemotherapy. Bethesda (MD): Children\'s Oncology Group; 2006 Mar. 37 p.
\[191 references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2003 Sep (revised 2006 Mar)

#### GUIDELINE DEVELOPER(S)

Children\'s Oncology Group - Medical Specialty Society

#### SOURCE(S) OF FUNDING

This work was supported by the Children\'s Oncology Group grant U10
CA098543 from the National Cancer Institute.

#### GUIDELINE COMMITTEE

Children\'s Oncology Group Nursing Discipline and Late Effects Committee

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

Melissa M. Hudson, MD\
Vice-Chair -- COG Late Effects Committee\
Member, Department of Hematology-Oncology\
Director, After Completion of Therapy Clinic\
St. Jude Children\'s Research Hospital\
Memphis, Tennessee

Wendy Landier, RN, MSN, CPNP, CPON®\
Chair -- COG Nursing Clinical Practice Subcommittee\
Clinical Director - Survivorship Clinic\
City of Hope Comprehensive Cancer Center\
Duarte, California

Smita Bhatia, MD, MPH\
Chair -- COG Late Effects Committee\
Professor and Chair, Division of Population Sciences\
City of Hope Comprehensive Cancer Center\
Duarte, California

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

All Children\'s Oncology Group (COG) members have complied with the COG
conflict of interest policy, which requires disclosure of any potential
financial or other conflicting interests.

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Children\'s Oncology Group.
Long-term follow-up guidelines for survivors of childhood, adolescent,
and young adult cancers. Version 1.2. 2004 Mar.

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[Children\'s Oncology Group Web
site](http://www.survivorshipguidelines.org/).

#### AVAILABILITY OF COMPANION DOCUMENTS

The following are available:

-   Instructions for use. Long-term follow-up guidelines for survivors
    of childhood, adolescent, and young adult cancers. Version 2.0.
    Children\'s Oncology Group. 2006 March. 6 p.

-   Introductory material. Long-term follow-up guidelines for survivors
    of childhood, adolescent, and young adult cancers. Version 2.0.
    Children\'s Oncology Group. 2006 March. 9 p.

-   Summary of cancer treatment. Appendix I: Long-term follow-up
    guidelines for survivors of childhood, adolescent, and young adult
    cancers. Version 2.0. Children\'s Oncology Group. 2006 March.

-   Patient-specific guideline identification tool. Appendix I:
    Long-term follow-up guidelines for survivors of childhood,
    adolescent, and young adult cancers. Version 2.0. Children\'s
    Oncology Group. 2006 March.

Electronic copies: Available in Portable Document Format (PDF) from the
[Children\'s Oncology Group Web
site](http://www.survivorshipguidelines.org/).

#### PATIENT RESOURCES

In an effort led by the Nursing Clinical Practice Subcommittee,
complementary patient education materials (*Health Links*) were
developed and are available in Appendix II of the original guideline
document. The following Health Links are relevant to this summary:

**Section 6**

-   [Dental
    Health](http://www.survivorshipguidelines.org/pdf/DentalHealth.pdf)

**Section 7**

-   [Male Health
    Issues](http://www.survivorshipguidelines.org/pdf/MaleHealthIssues.pdf)

-   [Female Health
    Issues](http://www.survivorshipguidelines.org/pdf/FemaleHealthIssues.pdf)

**Sections 8, 27, 37**

-   [Reducing the Risk of Second
    Cancers](http://www.survivorshipguidelines.org/pdf/ReducingSecondCancerRisk.pdf)

**Sections 9, 29**

-   [Pulmonary
    Health](http://www.survivorshipguidelines.org/pdf/PulmonaryHealth.pdf)

**Sections 10, 33**

-   [Cataracts](http://www.survivorshipguidelines.org/pdf/Cataracts.pdf)

**Sections 11, 12**

-   [Bladder
    Health](http://www.survivorshipguidelines.org/pdf/BladderHealth.pdf)

**Sections 13, 16, 23**

-   [Kidney
    Health](http://www.survivorshipguidelines.org/pdf/KidneyHealth.pdf)

-   [Single Kidney Health (mononephric patients
    only)](http://www.survivorshipguidelines.org/pdf/SingleKidneyHealth.pdf)

**Section 14**

-   [Hearing
    Loss](http://www.survivorshipguidelines.org/pdf/HearingLoss.pdf)

**Sections 14, 18, 25**

-   [Educational
    Issues](http://www.survivorshipguidelines.org/pdf/EducationalIssues.pdf)

**Sections 15, 35**

-   [Peripheral
    Neuropathy](http://www.survivorshipguidelines.org/pdf/PeripheralNeuropathy.pdf)

**Section 17**

-   [Diet and Physical
    Activity](http://www.survivorshipguidelines.org/pdf/DietandPhysicalActivity.pdf)

**Sections 21, 24**

-   [Liver
    Health](http://www.survivorshipguidelines.org/pdf/LiverHealth.pdf)

**Sections 22, 31**

-   [Bone
    Health](http://www.survivorshipguidelines.org/pdf/BoneHealth.pdf)

**Section 28**

-   [Heart
    Health](http://www.survivorshipguidelines.org/pdf/HeartHealth.pdf)

**Section 29**

-   [Bleomycin
    Alert](http://www.survivorshipguidelines.org/pdf/BleomycinAlert.pdf)

**Section 32**

-   [Osteonecrosis](http://www.survivorshipguidelines.org/pdf/Osteonecrosis.pdf)

**Section 36**

-   [Raynaud\'s
    Phenomenon](http://www.survivorshipguidelines.org/pdf/RaynaudsPhenomenon.pdf)

Please note: This patient information is intended to provide health
professionals with information to share with their patients to help them
better understand their health and their diagnosed disorders. By
providing access to this patient information, it is not the intention of
NGC to provide specific medical advice for particular patients. Rather
we urge patients and their representatives to review this material and
then to consult with a licensed health professional for evaluation of
treatment options suitable for them as well as for diagnosis and answers
to their personal medical questions. This patient information has been
derived and prepared from a guideline for health care professionals
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The patient information is not reviewed by NGC to establish whether or
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#### NGC STATUS

This NGC summary was completed by ECRI Institute on May 8, 2007. The
information was verified by the guideline developer on June 11, 2007.
This summary was updated by ECRI Institute on November 9, 2007,
following the U.S. Food and Drug Administration advisory on
Antidepressant drugs.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions.

### DISCLAIMER

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Date Modified: 11/3/2008