A Pilot Study of High Dose Rate Brachytherapy in The Radiation Oncology Branch
Phase: PHASE2
Conditions: Cervical Cancer, Endometrial Cancer, Esophageal Cancer, Prostate Cancer, Biliary Cancer
Sponsor: National Cancer Institute (NCI)

Abbreviated Title: A Pilot Study of Brachytherapy
Version Date: 11/03/20200
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Abbreviated Title: A Pilot Study of Brachytherapy
CC Protocol # 09C0100 
Version Date: 11/03/2020
NCT Number: NCT00924027
Title: A Pilot Study High Dose Rate Brachytherapy in the Radiation Oncology Branch
NCI Principal Investigator:  Deborah Citrin, MD
Radiation Oncology Branch (ROB)
Center for Cancer Research (CCR)
National Cancer Institute (NCI)
Bldg 10/ Rm B2-3500
10 Center Drive
Bethesda, MD 20892
Phone: 240-760-6206
Email: citrind@mail.nih.gov
Commercial Devices:
Radiation

Abbreviated Title: A Pilot Study of Brachytherapy
Version Date: 11/03/20200
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PRECIS
BACKGROUND

High dose rate brachytherapy (HDR) is a challenging technique utilized in many 
malignancies in order to deliver a high dose of radiation therapy to tumor in a conformal 
fashion with a rapid dose fall-off with the objective of sparing normal surrounding tissue

HDR therapy has been targeted to particular subsites as an integral part of either 
definitive management of palliation for malignancy-related symptoms.
OBJECTIVES

The primary objective is to determine the quality of high dose rate brachytherapy 
implants performed in the radiation oncology branch.  An implant will be adequate if 
90% of the GTV receives 90% of the dose prescribed and 80% of the CTV receives 85% 
of the prescribed dose.  An implant will be inadequate if the above dose limitations are 
not met. 

To evaluate local control and late toxicity rates following brachytherapy at the NCI ROB

To increase the flow of oncology participants requiring brachytherapy to the NCI ROB, 
as these participants lend themselves to special study and have unique educational value 
for the purpose of educating nurses, medical students, residents, physicists, clinical 
fellows, and physicians.
ELIGIBILITY 

Participants with cancer who could potentially benefit from the use of high dose rate 
brachytherapy as a component of their treatment.
DESIGN 

Participants will undergo appropriate work-up and clinical evaluation to determine if 
high-dose brachytherapy would be beneficial in either primary treatment or palliation of 
their disease. Participants will be treated with high-dose brachytherapy appropriately 
sequenced with other modalities in their treatment regimen.  This treatment will be 
administered in accordance with standard radiation oncology practice and per the ABS 
(American Brachytherapy Society) guidelines.  

The participant’s disease status and toxicity outcomes will be documented for a 12- 
month period at 3 months intervals.

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TABLE OF CONTENTS
PRECIS............................................................................................................................................2
TABLE OF CONTENTS.................................................................................................................3
STATEMENT OF COMPLIANCE.................................................................................................6
1
INTRODUCTION....................................................................................................................7
1.1
Study Objectives..............................................................................................................7
1.1.1
Primary ........................................................................................................................7
1.1.2
Secondary ....................................................................................................................7
1.2
Background And Rationale..............................................................................................7
1.2.1
High Dose Rate Brachytherapy (HDR) .......................................................................7
1.2.2
Selection of HDR Sites................................................................................................7
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT ..........................................................9
2.1
Eligibility Criteria............................................................................................................9
2.1.1
Inclusion Criteria .........................................................................................................9
2.1.2
Exclusion Criteria ......................................................................................................10
2.1.3
Recruitment Strategies...............................................................................................11
2.2
Screening Evaluation.....................................................................................................11
2.2.1
Clinical Evaluation ....................................................................................................11
2.2.2
Laboratory Evaluation ...............................................................................................11
2.2.3
Radiographic Evaluation ...........................................................................................11
2.3
Participant Registration and Status Update Procedures.................................................12
2.3.1
Treatment Assignment Procedures............................................................................12
3
STUDY IMPLEMENTATION..............................................................................................12
3.1
Study Design..................................................................................................................12
3.2
Protocol Therapy Administration ..................................................................................12
3.2.1
Treatment Coordination.............................................................................................12
3.2.2
High Dose Rate Brachytherapy (HDR) .....................................................................13
3.3
Treatment Modifications ...............................................................................................14
3.4
On Study Evaluation......................................................................................................14
3.4.1
Active Treatment Phase.............................................................................................14
3.4.2
Post-Active Treatment Phase.....................................................................................14
3.5
Surgical Guidelines........................................................................................................14
3.6
Radiation Therapy Guidelines .......................................................................................15
3.7
Cost and Compensation .................................................................................................15

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3.7.1
Costs ..........................................................................................................................15
3.7.2
Compensation ............................................................................................................15
3.7.3
Reimbursement..........................................................................................................15
3.8
Criteria for Removal from Protocol Therapy and Off Study Criteria ...........................15
3.8.1
Criteria for removal from protocol therapy ...............................................................15
3.8.2
Off Study Criteria ......................................................................................................15
4
CONCOMITANT MEDICATIONS/MEASURES ...............................................................16
4.1
Supportive Care .............................................................................................................16
4.2
Concurrent Therapies.....................................................................................................16
5
DATA COLLECTION AND EVALUATION ......................................................................16
5.1
Data Collection ..............................................................................................................16
5.2
Response criteria............................................................................................................17
5.2.1
Evaluation of target lesions .......................................................................................17
5.3
Toxicity Criteria.............................................................................................................18
6
NIH  REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING PLAN ....18
6.1
Definitions .....................................................................................................................18
6.2
OHSRP Office of Compliance and Training / IRB Reporting ......................................18
6.2.1
Expedited Reporting ..................................................................................................18
6.2.2
IRB Requirements for PI Reporting at Continuing Review ......................................18
6.3
NCI Clinical Director Reporting ...................................................................................18
NIH Required ........................................................................................................................19
6.4
Data And Safety Monitoring Plan .................................................................................19
6.4.1
Principal Investigator/Research Team.......................................................................19
7
STATISTICAL CONSIDERATIONS...................................................................................19
8
HUMAN SUBJECTS PROTECTIONS.................................................................................20
8.1
Rationale For Subject Selection.....................................................................................20
8.2
Participation Of Children...............................................................................................20
8.3
Evaluation of Benefits and Risks/Discomforts..............................................................20
8.3.1
Radiation risk.............................................................................................................20
8.3.2
Imaging risk...............................................................................................................20
8.3.3
Contrast risk...............................................................................................................20
8.3.4
Blood draw risk..........................................................................................................21
8.3.5
Anesthesia risk...........................................................................................................21
8.3.6
High dose rate brachytherapy implants .....................................................................21

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8.4
Informed Consent Process And Documentation............................................................21
8.5
Participant Advocate......................................................................................................21
9
REGULATORY AND OPERATIONAL CONSIDERATIONS...........................................21
9.1
Study Discontinuation and Closure ...............................................................................21
9.2
Quality Assurance and Quality Control.........................................................................22
9.3
Conflict of Interest Policy..............................................................................................22
9.4
Confidentiality and Privacy ...........................................................................................22
10
COMMERCIAL DEVICE INFORMATION ........................................................................23
10.1
Radiation........................................................................................................................23
10.2
Source ............................................................................................................................23
10.3
Toxicity..........................................................................................................................23
10.4
Administration procedures.............................................................................................23
11
REFERENCES.......................................................................................................................24
12
APPENDICES........................................................................................................................26
12.1
Appendix A: Suggested Doses for Brachytherapy Administration per ABS Guidelines
26
12.2
Appendix B: Performance Status Criteria .....................................................................31

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STATEMENT OF COMPLIANCE
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following: 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812) 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training.
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; an 
IRB determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form.

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1
INTRODUCTION
1.1
STUDY OBJECTIVES
1.1.1
Primary
The primary objective is to determine the quality of high dose rate brachytherapy implants 
performed in the radiation oncology branch.  An implant will be adequate if 90% of the GTV 
receives 90% of the dose prescribed and 80% of the CTV receives 85% of the prescribed dose.  
An implant will be inadequate if the above dose limitations are not met. 
1.1.2
Secondary

To evaluate local control and late toxicity rates following brachytherapy at the NCI ROB

To increase the flow of oncology participants requiring brachytherapy to the NCI ROB, as 
these participants lend themselves to special study and have unique educational value for the 
purpose of educating nurses, medical students, residents, physicists, clinical fellows, and 
physicians 
1.2
BACKGROUND AND RATIONALE
1.2.1
High Dose Rate Brachytherapy (HDR)
This protocol is designed to treat participants with cancer who could potentially benefit from the 
use of high dose rate brachytherapy as a component of their treatment. Brachytherapy, the 
placement of a radioactive source close to a tumor, is a well-established part of the treatment of 
many malignancies, both for palliative and definitive applications.  High dose brachytherapy is 
useful in many malignancies in order to deliver a high dose of radiation therapy to tumor in a 
conformal fashion with a rapid dose fall-off with the objective of sparing normal surrounding 
tissue.  Typically, high dose rate is delivered after the applicators are properly secured, dose 
calculations are made and a remote afterloader is activated.
Here in the department of radiation oncology, our attending physicians have experience with a 
Nucletron afterloader in the treatment of cervical cancer, prostate cancer and 
cholangiocarcinoma and seek to train our residents in these procedures as well.
1.2.2
Selection of HDR Sites
HDR is a challenging technique that can be used alone or combined with external beam 
therapeutic irradiation in various settings.  HDR can be utilized for both definitive cases as well 
palliative setting for relief of obstructive symptoms or bleeding.  HDR can increase the quality of 
life or provide a potential avenue for re-treatment in those participants already treated with 
external beam regimens. In this regard, HDR brachytherapy can provide a unique opportunity to 
study and customize therapy to each individualized participant. Common sites of disease in 
which the role of brachytherapy has been well described include but are not limited to 
gynecological tract, (endometrial or cervical cancer), pulmonary, breast and prostate cancer.  
HDR can be potentially useful in any clinical situation in which a high-dose of radiation is 
needed for tumor control while potentially sparing sensitive-surrounding critical structures.

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For example, gynecologic brachytherapy has proven to be an integral treatment in curing even 
locally advanced malignancies while allowing sparing of the normal surrounding tissues. 
Gynecologic brachytherapy has proven very effective in curing even locally advanced 
malignancies while allowing sparing of the normal surrounding tissues. For cervical cancer, 
external beam radiation therapy (EBRT) and/or brachytherapy is used in the definitive 
management of locally advanced malignancies.  In large- scale randomized trials, brachytherapy 
has proven useful in decreasing the risk of local recurrence for certain high-risk endometrial 
cancers (1).  In cases of inoperable endometrial cancer, some reports have shown that this subset 
of participants can be treated with radiation therapy alone. Additionally, participants with 
potentially curable recurrences at the vaginal cuff are also possible candidates who benefit from 
high dose rate brachytherapy. (12)
Lung brachytherapy can be particularly helpful and may provide relatively quick relief to those 
who are suffering from severe local symptoms (hemoptysis, obstruction as a result of their 
cancer) secondary to endobronchial component or those who have received the maximum safely 
tolerated lung dose as a result of previous treatment with external beam radiotherapy (8).
Breast HDR brachytherapy provides a potential benefit to woman who may suffer from 
diminished cosmesis as a results of their larger breast size or those who are unable to travel the 
long distances daily for a conventional 6-week course of external radiation therapy. (6)
Prostate HDR has a long history in the radiation oncology branch in which there was significant 
accrual to the previous “phase II study of MR-guided high dose rate brachytherapy boosts for 
prostate cancer”.  Guidelines from this study represent a natural extension of the protocol that we 
are completing here. In general, clinical evidence has shown that dose escalation in organ 
confined prostate cancer improves local disease control (13, 14). HDR brachytherapy represents 
an elegant method of accomplishing dose escalation in prostate cancer (15) but precise evidence 
guiding dose and fractionation is lacking (16). HDR brachytherapy has three potentially 
significant roles in the curative intent treatment of prostate cancer: 1) as a boost in conjunction 
with supplemental EBRT for intermediate and high risk prostate cancer and 2) as monotherapy in 
low and low intermediate risk prostate cancer and 3) as salvage for localized recurrence after 
prior external beam irradiation or radical prostatectomy. The use of HDR brachytherapy as a 
boost as per 1) has significant evidence for the ability to dose escalate by way of 
hypofractionation with excellent biochemical relapse-free survival rates with a low incidence of 
severe late genitourinary or gastrointestinal toxicities (16,17) and this has been formalized in the 
NCCN guidelines. The use of HDR brachytherapy as monotherapy is supported by data from 
several institutions (18,19) and a recent systematic review (20). Prostate-specific antigen 
progression-free survival using monotherapy ranged from 79% to 100% and local control from 
97% to 100% with low toxicity rates. The use of HDR brachytherapy for localized recurrence 
while an exciting prospect remains investigational. As a whole, high dose rate brachytherapy is 
technically complicated but increasingly practiced in the United States with significant 
heterogeneity in terms of the doses and fractionations being employed. HDR for various body 
sites has so many advantages over low-dose rate or simple external radiation therapy which 
include but is not limited to: faster treatment times on an outparticipant basis resulting in less 
resources utilized on the participant and hospital’s behalf, better optimization secondary to the 
ability to vary dwell time versus low-dose rate therapy and a sharp dose fall-off allowing for 
decreased dose to adjacent critical organs

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We anticipate that the majority of participants treated will fall into one of these aforementioned 
subsites. However, almost all anatomic subsites have the ability to undergo HDR treatment with 
the objective of either primary cancer treatment or effective, expedited palliation of symptoms.
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT
2.1
ELIGIBILITY CRITERIA
2.1.1
Inclusion Criteria
2.1.1.1
Pathologically confirmed malignancy for which high-dose rate brachytherapy is 
appropriate as a component of their therapeutic regimen.
2.1.1.2
Age ≥ 18 years of age.
2.1.1.3
ECOG performance status of 0, 1, or 2 (see Appendix B)
2.1.1.4
Participant must have a primary medical or surgical oncologist in the community or at 
NCI who is willing to collaborate with the ROB staff in the clinical management of the 
participant.
2.1.1.5
Participants of childbearing or child- fathering potential must be willing to use a 
medically acceptable form of birth control, which includes abstinence, while they are 
being treated on this study.
2.1.1.6
Site-specific inclusion criteria (any one or more of the following):
2.1.1.6.1 Gynecologic cancers
2.1.1.6.1.1 Endometrial cancer

Participants at a higher risk of recurrence (because of either grade, myometrial invasion, 
lymphatic vascular space invasion, tumor size, lymph node status, tumor extension, 
presence or absence of surgical staging)

Participants who have suffered a recurrence at the vaginal cuff

Participants who are unable to undergo surgery and must have treatment for an 
inoperable primary endometrial cancer.
2.1.1.6.1.2 Cervical cancer

Participants who are unable to undergo surgery and must have treatment for an 
inoperable primary cervical cancer.

Participants with locally advanced cervical cancer in whom brachytherapy will be 
integrated as a boost to external beam radiation either a palliative or curative setting 
(definitive or post-operative setting).
2.1.1.6.2 Lung cancer 

Participants with a endobronchial component causing symptoms

Participants who cannot undergo resection because of poor lung function or distant lung 
metastasis
2.1.1.6.3 Breast cancer

Infiltrating ductal carcinoma or DCIS, stage T0, T1, and T2 ≤ 3.0 cm, N0 and M0, 

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
Participants benefiting from HDR as either as a boost or accelerated partial breast 
irradiation regimen.
2.1.1.6.4 Prostate Cancer 

Participants with localized prostate cancer (T1b-T3b) in whom brachytherapy will be 
integrated as a boost to external beam radiation or used as monotherapy for definitive 
management. 
2.1.2
Exclusion Criteria
2.1.2.1
Cognitively impaired participants who cannot give informed consent.
2.1.2.2
Participants receiving concurrent investigational chemotherapeutic agents.
2.1.2.3
Participants receiving concomitant chemotherapy administration in the 5 days preceding 
brachytherapy (except for gynecological cancer participants who may have received 
concurrent chemotherapy as a component of their treatment regimen)
2.1.2.4
Pregnant or breast-feeding females are excluded because of the potential mutagenic 
effects on a developing fetus or newborn.
2.1.2.5
Clinically significant unrelated systemic illness (serious infections or significant 
cardiac, pulmonary, hepatic or other organ dysfunction), which in the judgment of the 
Principal or Associate Investigator would compromise the participant’s ability to 
tolerate this therapy or are likely to interfere with the study procedures or results. 
2.1.2.6
Participants who are in the estimation of the PI, deemed unable or unlikely to adhere to 
protocol treatment.
2.1.2.7
Abnormal bleeding times or active anti-coagulation therapy.

platelets < 100,000 per mm³

PT/PTT>1.5 ULN
2.1.2.8
Any participant or tumor/anatomical factors that may prevent brachytherapy apparatus 
from being properly and safely inserted and positioned and from radiation therapy being 
administered per ABS guidelines (Appendix A) (5, 6, 8, 10, 11, 12)
2.1.2.9
Participants whose malignancy has one or more of the following site-specific criteria 
disqualifying them from the study:
2.1.2.9.1 Breast cancer:

Participants inappropriate for standard breast conservation therapy (Multicentric disease, 
inability to achieve clear margins);

male participants with breast cancer

autoimmune disorders, including SLE, Scleroderma, etc.

distant metastases; 
2.1.2.9.2 Prostate cancer:

distant metastases

lymph node metastases

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2.1.3
Recruitment Strategies
This protocol may be abstracted into a plain language announcement posted on NIH websites and 
on NIH social media platforms. 
2.2
SCREENING EVALUATION
Note:  Screening evaluation testing/procedures are conducted under the separate screening 
protocol, 01-C-0129 (Eligibility Screening and Tissue Procurement for the NIH Intramural 
Research Program Clinical Protocols). Assessments performed at outside facilities or on another 
NIH protocol within the timeframes below may also be used to determine eligibility once a 
participant has signed the consent.
2.2.1
Clinical Evaluation 

All participants will have a problem-based history and directed physical examination 
performed. This should include measurements of disease status, stage of disease, signs, 
and symptoms caused by the cancer, performance status, weight and concomitant 
medications. 

All pertinent medical records, pathology reports, and radiographic imaging studies will 
be reviewed. 

Vital signs, including ECOG

Anesthesia consult if sedation will be required
2.2.2
Laboratory Evaluation

Outside Pathology report confirming histological diagnosis of cancer. 

Pre- treatment blood tests should be performed within 72 hours prior to enrollment 

Urine Pregnancy required for females of childbearing potential

CBC, platelet count, PT/PTT
2.2.3
Radiographic Evaluation
2.2.3.1
For disease sites that can be imaged, imaging of target(s) will occur within 4 weeks of 
enrollment. 

The appropriate imaging modality will be chosen based on the site(s) of target however if 
the lesion is visible on CT imaging, this will be the preferred modality for this protocol. 
The selected imaging modality will be used at each follow-up to determine local control.

Additional radiographic studies will be obtained depending on the known sites of disease 
and as the clinical situation dictates (i.e. bone scan, plain films).

When deemed necessary (i.e. outdated or inadequate prior studies) MRI, CT, PET scans, 
may be obtained to complete clinical and pathologic staging.
2.2.3.2
Evaluation of target lesions

For disease sites that can be imaged, each lesion to be treated with HDR will be clearly 
identified in the medical record and will be measured at baseline.

The lesion(s) will be measured with margins defined as the largest measurement on CT, 
MRI, or other appropriate site-specific imaging dependent on the site of metastasis. 

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2.3
PARTICIPANT REGISTRATION AND STATUS UPDATE PROCEDURES
Registration and status updates (e.g., when a participant is taken off protocol therapy and when a 
participant is taken off-study) will take place per CCR SOP ADCR-2, CCR Participant 
Registration & Status Updates found here.
2.3.1
Treatment Assignment Procedures
Cohorts
Number
Name
Description
1
Gynecologic
Participants who have been diagnosed with gynecologic 
cancer
2
Pulmonary
Participants who have been diagnosed with pulmonary 
cancer
3
Breast
Participants who have been diagnosed with breast 
cancer
4
Prostate
Participants who have been diagnosed with prostate 
cancer
Arms
Number
Name
Description
1
Radiation therapy
Radiation therapy given as HDR Brachytherapy.
Arm Assignment
Participants in cohorts 1-4 will be directly assigned to arm 1.
3
STUDY IMPLEMENTATION
3.1
STUDY DESIGN
In this study, participants will undergo appropriate work-up and clinical evaluation to determine 
if high-dose brachytherapy would be beneficial in either primary treatment or palliation of their 
disease.  Participants will be treated with high-dose brachytherapy appropriately sequenced with 
other modalities in their treatment regimen.  This treatment will be administered in accordance 
with standard radiation oncology practice and per the ABS (American Brachytherapy Society) 
guidelines.   The participant’s disease status and toxicity outcomes will be documented for a 12-
month period at 3-month intervals.
3.2
PROTOCOL THERAPY ADMINISTRATION
3.2.1
Treatment Coordination
The participant will be evaluated by study investigators as to the appropriateness and feasibility 
of brachytherapy on an individual basis. This will necessitate close and continued collaboration 
with the participant’s referring oncologist.  Study investigators will coordinate the timing of 
brachytherapy session(s) with other modalities in the participant’s treatment regimen.

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3.2.2
High Dose Rate Brachytherapy (HDR)
3.2.2.1
Pre-plan

In diseases where targets can be imaged, volumes will be outlined based on CT or 
ultrasound images, which include (but are not limited to) a Gross Tumor Volume (GTV), 
Clinical Tumor Volume (CTV), and normal structures.  GTV will encompass the known 
tumor volume as seen clinically and on CT.  CTV includes a margin for areas of 
suspected microscopic disease based on Clinical and imaging data.  Treatment planning 
software will then be utilized to plan therapy in order to ensure maximum dose to the 
tumor while observing outlined dose constraints to the normal structures. For prostate 
brachytherapy, the pre-plan may be conducted prior to the brachytherapy procedure or 
integrated in the brachytherapy procedure as part of real-time planning.
3.2.2.2
Applicator/ Catheter Placement Procedure

If the participant is to receive sedation, instruction will be given per the anesthesia 
department.

The participant will arrive in the ROB clinic the morning of the procedure and be 
prepared for the HDR procedure by the ROB staff.   

In diseases where catheters have been previously placed at the time of surgery (i.e., breast 
cancer), the participant will arrive with catheters in place. Otherwise, the participant will 
be positioned, the area cleansed with an antimicrobial solution and draped according to 
standard sterile technique. Brachytherapy applicators or catheters are inserted in 
anatomical sites defined by the physician and secured by sutures or packing as needed.  

If the site can be imaged, ultrasound or CT images will again be obtained.  

The placement of the applicators may be adjusted as needed based on the images until the 
radiation oncologists are satisfied with applicator placements. 
3.2.2.3
Implant Dosimetry and Treatment Planning

In diseases where targets can be imaged, the final CT images are transferred to the 
treatment planning system, where optimization of dosimetry is performed.  For prostate 
cancer, planning is accomplished based on ultrasound imaging to which other imaging 
modalities may be fused.
3.2.2.4
Radiation Delivery

Participants will be transferred to the NRC approved brachytherapy treatment room in the 
ROB.  A radiographic film may be obtained on the treatment table and applicators may 
require a final adjustment at that time.  

Once a treatment plan has been completed, verified and accepted, the brachytherapy will 
be administered with a remote afterloading system using a stepping 192Ir source. 
(Nucletron Inc.)  

Radiation delivery will take approximately 10-30 minutes depending on the strength of 
the source and the dose to be delivered.

Suggested guidelines for proposed radiation doses are included in the Appendix A.
3.2.2.5 Device Removal

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
HDR applicator/ catheters will be removed by ROB investigators or the appropriate 
clinical staff.
3.3
TREATMENT MODIFICATIONS
Modifications to the radiation treatment plan will be made at the discretion of the radiation 
oncologist. Deviations from the planned treatment schedule may be required secondary to 
expected toxicity. 
3.4
ON STUDY EVALUATION  
3.4.1
Active Treatment Phase

Pre-plan obtained (3.2.2.1)

Applicator/ Catheter Placement Procedure (3.2.2.2)

Implant Dosimetry and Treatment Planning (3.2.2.3)

Radiation Delivery (3.2.2.4)

Device removal (3.2.2.5)
3.4.2
Post-Active Treatment Phase

Following completion of protocol therapy, participants will be seen in follow-up. Follow-
up evaluations should occur at NIH at one month after the completion of radiation 
therapy, at three months after completion of radiation therapy, followed by every 3 month 
intervals up to 12 months

Follow- up evaluations will include:
o
Clinical Evaluation- complete interval history and directed physical examination, 
notation of any ongoing or recently delivered systemic therapy 
o
Any medical procedures/tests will be based on the participant's diagnosis, 
treatment, and supporting clinical information.
o
Assessment of acute and long-term effects of radiation therapy using the RTOG 
and CTC 4.0
o
In diseases where targets can be imaged, CT, MRI, or other appropriate imaging 
of the tumor site(s). In general, CT will be the preferred imaging modality unless 
the lesion is not visible on this modality.  PSA will be adequate for follow up in 
prostate participants unless otherwise indicated.
o
Scoring of local control at each treated site will be based on RECIST criteria 
(limited to local disease status).  Each site will be scored separately.
3.5
SURGICAL GUIDELINES
In some cases, participants may require placement of brachytherapy catheters at the time of 
surgical resection. This will be coordinated by the referring oncologist or surgeon. Surgical 
therapy is not included on this protocol

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3.6
RADIATION THERAPY GUIDELINES
This protocol involves radiation therapy given as HDR brachytherapy. In some cases, 
participants may also need to receive external beam radiation therapy. Generally, participants are 
expected to receive their standard external beam radiation therapy care by their referring 
oncologist.  Occasionally, however, participants may not have timely or appropriate access to 
care at home, and in these rare cases, the external beam component may be provided at the NCI 
ROB clinic.  
3.7
COST AND COMPENSATION 
3.7.1
Costs
NIH does not bill health insurance companies or participants for any research or related clinical 
care that participants receive at the NIH Clinical Center.  If some tests and procedures performed 
outside the NIH Clinical Center, participants may have to pay for these costs if they are not 
covered by insurance company.  Medicines that are not part of the study treatment will not be 
provided or paid for by the NIH Clinical Center.    
3.7.2
Compensation
Participants will not be compensated on this study.
3.7.3
Reimbursement 
The NCI will cover the costs of some expenses associated with protocol participation.  Some of 
these costs may be paid directly by the NIH and some may be reimbursed to the 
participant/guardian as appropriate.  The amount and form of these payments are determined by 
the NCI Travel and Lodging Reimbursement Policy.   
3.8
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA
3.8.1
Criteria for removal from protocol therapy
Prior to removal from study, effort must be made to have all subjects complete a safety visit 
approximately 30 days following the last dose of study therapy.
Protocol therapy is complete when the participant has completed the brachytherapy component 
of treatment. This will vary depending on the site of disease treated, see Appendix A.
3.8.2
Off Study Criteria
3.8.2.1
Administrative
Participants who are removed from the study for non-medical or administrative reasons prior to 
the completion of the active course of treatment may be replaced.  A participant may be taken off 
study for the following non- medical or administrative reasons:

Participant refusal of further treatments (reasons must be noted in the participant’s 
records). 

We are no longer able to maintain contact with the participant and/ or their oncologist. 

It is deemed in the best interest of the participant by the PI.

Serious protocol deviation as determined by the PI.

Participant loses capacity to provide consent.

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3.8.2.2
Toxicity
Any participant who develops a grade 4 toxicity considered primarily due to the study treatment. 
However, the toxicity will be followed to assess the duration and resolution.
3.8.2.3
Tumor Progression 
Any participant with clinical or radiographic evidence of progressive disease during the active 
course of treatment will be removed from the study if it is deemed by the PI that additional 
therapy would not be in the best interest of the participant.
3.8.2.4
Concurrent Illness
The development of a concurrent serious medical condition that might preclude or contraindicate 
the further administration of radiation therapy.
3.8.2.5
Completion

The completion of HDR and 12 months follow up 

The participant is unable to complete the radiation treatment process for any reason or is 
non-compliant with the treatment &/ or follow- up requirements

Follow-up is no longer deemed necessary at ROB, and participant has other adequate 
medical care in the community.
3.8.2.6
Death
4
CONCOMITANT MEDICATIONS/MEASURES
4.1
SUPPORTIVE CARE
Most participants are expected to receive their standard supportive care by their referring 
oncologists.  Occasionally, however, participants may not have timely or appropriate access to 
supportive care at home, and in these rare cases, supportive care will be provided at the NIH 
Clinical Center.  Examples of such care include, but are not limited to, the management of acute 
radiation effects/complications, steroid medication, conscious sedation, analgesics, anti-emetics, 
and intravenous hydration.
4.2
CONCURRENT THERAPIES
No investigational drugs or therapies will be administered by NCI ROB personnel in this 
protocol.  However, the participant may be receiving other appropriate cancer therapy based on 
standard practice. This will be coordinated by the referring oncologist.
5
DATA COLLECTION AND EVALUATION
5.1
 DATA COLLECTION
The PI will be responsible for overseeing entry of data into an in-house password protected 
electronic system (C3D) and ensuring data accuracy, consistency and timeliness. The principal 
investigator, associate investigators/research nurses and/or a contracted data manager will assist 
with the data management efforts.  All data obtained during the conduct of the protocol will be 
kept in secure network drives or in approved alternative sites that comply with NIH security 
standards. Primary and final analyzed data will have identifiers so that research data can be 
attributed to an individual human subject participant.

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
Clinical data and acquired images will be recorded in a NCI CCR database (C3D).

Clinical data collection will include: demographic information, pathologic diagnosis, 
clinical stage, history including prior and concurrent therapies, location and measurement 
of lesions, CT reports, lab reports, vital signs, dose of radiation delivered, and toxicity 
assessment.

The results of any procedures and/or tests will be included in the participants’ hospital 
chart and/or research records as appropriate.  Data from these records may be used in 
research and scientific publications.

Data collected may be used anonymously, for publications not originally specified, 
concerning the disease processes and long term effects of treatment.  The data may also 
be used as the basis for new protocols.
All AEs, including clinically significant abnormal findings on laboratory evaluations, regardless 
of severity, will be followed until return to baseline or stabilization. Document AEs from the first 
study intervention through 30 days after the intervention was last administered. Beyond the 30 
days after the last intervention, only adverse events which are serious and related to the study 
intervention need to be recorded. 
An abnormal laboratory value will be considered an AE if the laboratory abnormality is 
characterized by any of the following:

Results in discontinuation from the study

Is associated with clinical signs or symptoms 

Requires treatment or any other therapeutic intervention

Is associated with death or another serious adverse event, including hospitalization. 

Is judged by the Investigator to be of significant clinical impact

If any abnormal laboratory result is considered clinically significant, the investigator will 
provide details about the action taken with respect to the participant’s outcome.
End of study procedures: Data will be stored according to HHS, FDA regulations and NIH 
Intramural Records Retention Schedule regulations as applicable. 
Loss or destruction of data: Should we become aware that a major breach in our plan to protect 
subject confidentiality and trial data has occurred, this will be reported expeditiously per 
requirements in section 6.2.1.  
5.2
RESPONSE CRITERIA
Tumor Response for Solid Tumors: In diseases where targets can be imaged, response will be 
measured using the RECIST criteria only for local sites as this is not a trial of a systemic therapy.  
Response will be scored for each target lesion. Every effort should be made to objectively record 
changes in the participant’s disease process after the HDR procedure.  Measurable criteria should 
always take precedence over subjective criteria.  
5.2.1
Evaluation of target lesions  
In diseases where targets can be imaged, the target lesion is defined as the sites which are 
targeted with HDR as part of this protocol.  The response will be measured with margins defined 

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as the longest diameter measurement on the appropriately specified radiographic imaging.  The 
imaging modality will be that which provided the maximal measurement pretreatment.  This 
imaging modality will be used at each follow-up to determine local control.  If there is evidence 
of clinical progression, the imaging study will be repeated to assess for progression.

Complete Response (CR):  Complete disappearance of the target lesion.  

Partial Response (PR):  at least a 30% decrease in the sum of the longest diameter (LD) of 
the target lesion taking into account the baseline sum LD

Stable/No Response: Does not qualify for CR, PR, or progression.  

Progression: Interval increase in the maximal dimension of the target lesion.

Local Control: will be defined as CR, PR, or stable disease of the treated site (s). Local 
progression on any imaging modality (bone scan, MRI, CT, or PET) obtained during the 
normal course of therapy and follow-up will be considered locally progressive disease.  
5.3
TOXICITY CRITERIA
The study will use the RTOG/EORTC Radiation Morbidity Scoring Scheme to score late effects 
of radiation treatment. The RTOG scoring criteria can be obtained from the RTOG website: 

Acute:   
https://www.rtog.org/ResearchAssociates/AdverseEventReporting/AcuteRadiationMorbi
dityScoringCriteria.aspx, and 

Late: 
https://www.rtog.org/ResearchAssociates/AdverseEventReporting/RTOGEORTCLateRa
diationMorbidityScoringSchema.aspx
6
NIH  REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING PLAN
6.1
DEFINITIONS
Please refer to definitions provided in Policy 801: Reporting Research Events found here.
6.2
OHSRP OFFICE OF COMPLIANCE AND TRAINING / IRB REPORTING
6.2.1
Expedited Reporting 
Please refer to the reporting requirements in Policy 801: Reporting Research Events and Policy 
802 Non-Compliance Human Subjects Research found here.
6.2.2
IRB Requirements for PI Reporting at Continuing Review
Please refer to the reporting requirements in Policy 801: Reporting Research Events found here. 
6.3
NCI CLINICAL DIRECTOR REPORTING 
Problems expeditiously reported to the OHSRP in iRIS will also be reported to the NCI Clinical 
Director.  A separate submission is not necessary as reports in iRIS will be available to the Clinical 
Director.
In addition to those reports, all deaths that occur within 30 days after receiving a research 
intervention should be reported via email to the Clinical Director unless they are due to progressive 
disease.  

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To report these deaths, please send an email describing the circumstances of the death to Dr. Dahut 
at NCICCRQA@mail.nih.gov within one business day of learning of the death.
6.4
NIH REQUIRED DATA AND SAFETY MONITORING PLAN
6.4.1
Principal Investigator/Research Team
The clinical research team will meet on a regular basis weekly, when participants are being 
actively treated on the trial to discuss each participant. Decisions about enrollment and dose 
escalation if applicable will be made based on the toxicity data from prior participants.
All data will be collected in a timely manner and reviewed by the principal investigator or a lead 
associate investigator. Events meeting requirements for expedited reporting as described in 
section 6.2.1 will be submitted within the appropriate timelines.  
The principal investigator will review adverse event and response data on each participant to 
ensure safety and data accuracy. The principal investigator will personally conduct or supervise 
the investigation and provide appropriate delegation of responsibilities to other members of the 
research staff. 
7
STATISTICAL CONSIDERATIONS
The study is designed to determine, in a preliminary fashion, whether the quality of high dose 
rate brachytherapy implants performed in the radiation oncology branch reaches an acceptable 
level. The quality will be examined separately in four body sites. Specifically, we will stratify by 
gynecologic (endometrial and cervical), pulmonary, breast, and prostate cancer. In each strata, 
we will examine the quality of high dose rate brachytherapy with a two-stage optimal design 
(21). An implant will be considered acceptable if 90% of the GTV receives 90% of the dose 
prescribed and 80% of the CTV receives 85% of the prescribed dose.  An implant will be 
unacceptable if the above dose limitations are not met. 
The two-stage design is based on the following assumptions: (i) the procedure will be considered 
of poor overall quality (unacceptable) if less than 65% of participants have acceptable implants 
based on the above criteria (Po=0.65)., (ii) the procedure will be considered of good quality 
(acceptable) if over 90% of participants have acceptable implants based on the above criteria 
(P1=0.90), (iii) within each stratum, the probability of concluding that an unacceptable procedure 
is acceptable is less than 4 % (alpha=0.04), and (iv) within each stratum, the probability of 
concluding that an acceptable procedure is unacceptable is less than 10% (beta=0.10). Based on 
these operating characteristics, the following two-stage design is optimal.  Separately for each of 
the four strata, the first stage will accrue 9 participants. If 7 or more of the 9 implants have an 
acceptable implant, then the study will accrue an additional 19 participants. In any stratum, 
accrual will stop in the first stage if 6 or fewer of 9 participants have an acceptable implant.  
Assuming that we accrue to the second stage, high dose brachytherapy for a particular tumor 
type (stratum) will be considered to be acceptably preformed at the clinical center if 23 or more 
of 28 participants have an acceptable implant.
The error rates stated above are for each of the four strata separately. We note that, with this 
design, there is less than an 12% chance that one or more strata will falsely conclude that the 
procedure is acceptable if the procedure is unacceptable in all 4 strata (Po=0.65). 

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Evaluating local control and late toxicity rates following brachytherapy are also objectives of this 
study. Other studies at NCI and at other institutions have found acceptable toxicity rates (16, 22, 
23, 24).  We will tabulate local control and late toxicity rates by stratum and combined over all 
four strata.   
The maximum accrual will be 28 participants to each of the 4 strata (maximum accrual of 112 
participants). We anticipate that accrual will be completed in 5 years.
8
HUMAN SUBJECTS PROTECTIONS
8.1
RATIONALE FOR SUBJECT SELECTION
Participants will be invited to enroll onto this trial if they are an adult and meet the eligibility 
criteria outlined in section 2.1.  No gender, racial or ethnic groups will be excluded from 
participation in this trial.  Adults who are cognitively impaired prior to study entry will not be 
eligible for study entry because they cannot give informed consent.
8.2
PARTICIPATION OF CHILDREN
Children are not eligible for this protocol therapy due to the very different biology and clinical 
behavior of childhood malignancies. Normal tissue response and toxicity is significantly 
different as well given that many normal tissues are still growing and developing. In addition, the 
oncologic practice in childhood malignancies is to avoid high-dose brachytherapy procedures. 
8.3
EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS
All procedures/tests in this protocol are used routinely in standard care settings with minimal 
associated risks and/or discomforts. Participants on this study will be receiving treatment for their 
malignancy per standard of care. There are no direct medical benefits expected from taking part in 
this study. We hope the information learned from this study will benefit participants in the future. 
The risks and benefits of each procedure/test, as well as the implications of the procedure/test 
results will be discussed thoroughly with the participant prior to the intervention. Specific risks 
and potential complications of each procedure will be outlined in a consent form. When the 
procedure/test poses any risk to the participant, an additional consent will be obtained. 
8.3.1
Radiation risk
Likely medical risks include fatigue, low blood counts and skin reactions at the radiation site. Rare 
medical risks associated with brachytherapy include infection, bleeding, and perforation of the 
treated organ or surrounding organs and development of new cancer.
Participants’ tumors may be exposed to up to 15 Gy of radiation from High Dose Rate 
Brachytherapy. Participants will also receive a much smaller amount of radiation from scans 
used to plan treatment and measure progress. The total scans include up to 4 CT scans.
8.3.2
Imaging risk
Participants may feel discomfort from lying still during imaging. Some participants may also 
experience claustrophobia.
8.3.3
Contrast risk
 Participants may experience an allergic reaction to contrast used during imaging. For 
participants that undergo an MRI with gadolinium, there is a risk for nephrogenic systemic 

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fibrosis for participants with kidney disease. Some participants may also have gadolinium 
retention. Participants with abnormal kidney function will not have an MRI with gadolinium. 
8.3.4
Blood draw risk
Blood draws may cause pain, redness, bruising or infection at the site of the needle stick.  Rarely 
some participants faint.  
8.3.5
Anesthesia risk
8.3.6
The risks associated with anesthesia are nausea, vomiting, headache and back pain. Other 
less likely but serious risks include blood pressure problems, arrhythmias, respiration 
changes, allergic reactions, paralysis, heart attack, stroke, or death.  High dose rate 
brachytherapy implants
Risks associated with implants are pain and discomfort.
8.4
INFORMED CONSENT PROCESS AND DOCUMENTATION
The informed consent document will be provided to the participant for review prior to 
consenting.  A designated study investigator will carefully explain the procedures and tests 
involved in this study, and the associated risks, discomforts and benefits. In order to minimize 
potential coercion, as much time as is needed to review the document will be given, including an 
opportunity to discuss it with friends, family members and/or other advisors, and to ask questions 
of any designated study investigator. A signed informed consent document will be obtained prior 
to entry onto the study.
The initial consent process as well as re-consent, when required, may take place in person or 
remotely (e.g., via telephone or other NIH approved remote platforms) per discretion of the 
designated study investigator and with the agreement of the participant.  Whether in person or 
remote, the privacy of the subject will be maintained. Consenting investigators will be located in 
a private area (e.g., clinic consult room). When consent is conducted remotely, the participant 
will be informed of the private nature of the discussion and will be encouraged to relocate to a 
more private setting if needed.  
8.5
PARTICIPANT ADVOCATE
The participant’s rights representative is available to participants on this protocol at (301) 496-
2626 in Building 10, Room 1C132, NIH. Participants may ask any questions about the study and 
may withdraw their consent at any time without compromising their medical care.
9
REGULATORY AND OPERATIONAL CONSIDERATIONS 
9.1
STUDY DISCONTINUATION AND CLOSURE
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
investigator, and regulatory authorities.  If the study is prematurely terminated or suspended, the 
Principal Investigator (PI) will promptly inform study participants, the Institutional Review Board 
(IRB), and will provide the reason(s) for the termination or suspension.  Study participants will be 
contacted, as applicable, and be informed of changes to study visit schedule.

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 Circumstances that may warrant termination or suspension include, but are not limited to:

Determination of unexpected, significant, or unacceptable risk to participants

Insufficient compliance to protocol requirements

Data that are not sufficiently complete and/or evaluable

Determination that the primary endpoint has been met
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the IRB. 
9.2
QUALITY ASSURANCE AND QUALITY CONTROL
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion.  An individualized quality management plan 
will be developed to describe a site’s quality management.
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution.
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical 
trial is conducted and data are generated and biological specimens are collected, documented 
(recorded), and reported in compliance with the protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory requirements (e.g., 
Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)). 
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities.
9.3
CONFLICT OF INTEREST POLICY
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical.  Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and 
managed. Furthermore, persons who have a perceived conflict of interest will be required to have 
such conflicts managed in a way that is appropriate to their participation in the design and conduct 
of this trial.  The study leadership in conjunction with the National Cancer Institute has established 
policies and procedures for all study group members to disclose all conflicts of interest and will 
establish a mechanism for the management of all reported dualities of interest.
9.4
CONFIDENTIALITY AND PRIVACY
Participant confidentiality and privacy is strictly held in trust by the participating investigators and 
their staff. This confidentiality is extended to cover testing of biological samples and genetic tests 
in addition to the clinical information relating to participants. Therefore, the study protocol, 
documentation, data, and all other information generated will be held in strict confidence. 
All research activities will be conducted in as private a setting as possible.
The study monitor, representatives of the Institutional Review Board (IRB), and/or regulatory 
agencies may inspect all documents and records required to be maintained by the investigator, 

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including but not limited to, medical records (office, clinic, or hospital) and pharmacy records for 
the participants in this study. The clinical study site will permit access to such records.
The study participant’s contact information will be securely stored at the/each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a secure 
location for as long a period as dictated by the reviewing IRB and Institutional policies.
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be stored at the NCI CCR. This will not include the participant’s contact or identifying 
information. Rather, individual participants and their research data will be identified by a unique 
study identification number. The study data entry and study management systems used by the 
clinical site(s) and by NCI CCR research staff will be secured and password protected. At the end 
of the study, all study databases will be archived at the NIH.
To further protect the privacy of study participants, a Certificate of Confidentiality has been issued 
by the National Institutes of Health (NIH).  This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any civil, 
criminal, administrative, legislative, or other proceeding, whether at the federal, state, or local 
level. By protecting researchers and institutions from being compelled to disclose information that 
would identify research participants, Certificates of Confidentiality help achieve the research 
objectives and promote participation in studies by helping assure confidentiality and privacy to 
participants.
  
10 COMMERCIAL DEVICE INFORMATION 
10.1 RADIATION
There will be no IDE obtained for the use of any of the commercial agents used in this study. 
This study meets the criteria under category #1 for exemption for an IDE as this investigation 
involves the use of an already cleared medical device in which the device is used or investigated 
in accordance with the indications in the cleared labeling.
10.2 SOURCE 
The radiation device is a commercial device that will be located in the NIH Clinical Center. 
10.3 TOXICITY 
Refer to section 8.3. 
10.4 ADMINISTRATION PROCEDURES
Refer to section 3.2.

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13) Kuban D, Tucker S, Dong L, et al. Long-term results of the M.D.Anderson randomized 
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Zaider M, Ghilezan M, Hsu IC; American Brachytherapy Society. American 
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MJ. Clinical outcomes of high-dose-rate brachytherapy and external beam radiotherapy 
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GM. High-dose-rate brachytherapy as a monotherapy for favorable-risk prostate cancer: a 
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12 APPENDICES
12.1 APPENDIX A: SUGGESTED DOSES FOR BRACHYTHERAPY ADMINISTRATION PER ABS 
GUIDELINES
A. Cervical Cancer
1. Technique
Three to six HDR treatments will be delivered, based on host factors (inability to tolerate 
treatment, changes in physical findings, poor anatomy for implant) as well as the discretion of 
the treating radiation oncologists. Packing, followed by brachytherapy applicators, will then be 
removed, and the participants recovered in the PACU, where supportive care may include 
analgesia, antibiotics, and douches with hydrogen peroxide and water etc., may be delivered.  
HDR brachytherapy is an outpatient procedure, though very rarely, participants may be admitted 
overnight for observation.  
 Implants may be delivered either during or following the EBRT, with the goal of keeping the 
total duration of treatment to fewer than 8 weeks when possible because of the effect of 
prolonged treatment duration and decreased survival  (4) 
Per ABS guidelines, for early cervical cancer, the following guidelines will be adhered to:
Per ABS guidelines, for advanced cervical cancer, the following guidelines will be adhered to:
(5)
2. Implant Dosimetry And Treatment Planning And Dosage Recommendations 
Optimization of dosimetry is performed that creates the optimal disease coverage. Packing can 
be used to stabilize the geometry. The target is to treat Point A to 80-85 Gy for early stage 
disease and 85-90 Gy for advanced disease.  The dose constraints are to limit the bladder dose to 
the LDR equivalent of 80 Gy and the rectal dose below 75 Gy.

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B. Endometrial Cancer
1. Technique
Participants eligible for the protocol shall have definitive adjuvant radiotherapy or be treated 
because they are deemed to have inoperable disease or are poor surgical candidates.  In some 
cases this regimen may be changed to fit the individual needs and requirements of each 
participant and the number of external beam and brachytherapy treatments may be slightly 
different.  These slight differences will be discussed with the participants prior to the beginning 
of therapy and if necessary during therapy as well.  The radiation therapy for this study is 
considered the “standard of care” of the treatment of endometrial cancer. 
Technical aspects that should be considered for endometrial participants in brachytherapy: a 
rectal tube should be placed, the largest vaginal cylinder possible should be used and 2/3 of the 
vaginal cuff should be targeted.
2.Implant Dosimetry And Treatment Planning And Dosage Recommendations 
Suggested doses of HDR alone to be used for adjuvant treatment of postop are as follows:
Suggested doses of EBRT and HDR to be used for adjuvant treatment of postop endometrial cancer 
are as follows:
The ABS recommends that the proximal 3–5 cm of the vagina be treated; however if a 
characteristic of the participant presentation dictates that more or less of the vagina should be 
treated, then this detail is left to the discretion of the investigator. For serous and clear cell 
histologies, treatment of the entire vaginal canal should be considered. The dose distribution 
should be optimized to deliver the prescribed dose either at the vaginal surface or at 0.5-cm depth.  
The physician should be mindful that when then vaginal recurrence is at the distal vaginal cuff, 
the entire vagina and the inguinal nodes should be considered for treatment.
In those cases in which HDR only for treatment of inoperable primary endometrial cancer 

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In those participants cases in which external beam + HDR is needed for treatment of inoperable 
primary endometrial cancer, the following schedule should be adhered to: 
In participants with vaginal cuff recurrences, the following doses can be considered:
ICRU reference points should be localized and calculated, respecting normal tissue tolerance as 
noted above.
The dose should be limited as follows: the upper vaginal mucosa should receive no more than 
150 Gy, the lower vaginal mucosa should receive between 80-90 Gy and the rectal point dose 
should be less than 70 Gy, the bladder point should be less than 75 Gy. (12)
C. Lung Carcinoma
1. Technique
A flexible nylon catheter will be introduced through the bronchoscope into the lumen and is 
positioned at least 2 cm beyond the visible tumor.  The prescription point should prescribe the 
radiation dose at 10mm from the center of the catheter.  A margin of at least 1-2 cm beyond the 
disease is recommended. 
2. Implant Dosimetry And Treatment Planning And Dosage Recommendations
The ABS recommends for those participants who are undergoing palliative brachytherapy only, 
3 weekly fractions of 7.5 Gy each, 2 fractions of 10 Gy each or 4 fractions of 6 Gy each.
For participants with curative intent, the recommendations are as follows: as a boost to external 
beam radiation therapy, 3 fractions of 5 Gy each or 2 fractions of 7.5 Gy each.  If it is used alone 
in participants who have not received radiotherapy, 5 fractions of 5 Gy each or 3 fractions of 7.5 
Gy each prescribed to 1 cm can be considered.
The plan will be optimized and treatment delivered. (8)

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D. Breast 
1. Technique
Planning target volume is the lumpectomy site with 1-2 cm margin as clinically indicated. The 
CTV = PTV and the prescription dose must encompass the target volume and the dose will be 
prescribed to 1 cm from the applicator surface.
2. Implant Dosimetry And Treatment Planning And Dosage Recommendations
A minimum of 7mm between the skin and balloon should be maintained. During the planning 
process, normal tissue doses will be respected and a three-dimensional calculation with DVH-
based analysis should be created.  Breast dose parameters should include V100, V150, and V200.  
Skin dose parameters should include Dmax. (6)
• Target coverage: ≥ 90% of the dose delivered to ≥ 90% of the target volume
• V150: balloon catheter < 50 cm3
• V200: balloon catheter < 10 cm3
• DHI ≥ 0.75 where DHI = (1 – V150/V100)
• Maximum skin isodose: balloon catheter < 145%
• Primary treatment 34 Gy in 10 fractions over 5 treatment days
If treatment is being delivered as the primary treatment then it should be given as 34 Gy in 10 
fractions over 5 days. Treatment should be administered either before or after chemotherapy (if 
persistent cavity or surgical clips placed).  If chemotherapy will be administered, then the 
recommendation is to wait >2weeks after completion of APBI before initiating (6)
E. Prostate 
1. Technique and dosage recommendations
Definitive boost therapy:  For definitive boost therapy, a single HDR brachytherapy implant 
(1500 cGy/implant) will be delivered within 21 days of a course of external beam radiotherapy 
(4600 cGy, 2Gy/day or 4500 cGy, 1.8 Gy/day). Alternative fractionation schedules include 9.5 
Gy- 11.5 Gy x 2 fractions, 5.5-7.5 Gy x 3, and 4.0-6.0 Gy x 4 fractions.   These regimens are 
those described in the ABS and NCCN guidelines.  
Definitive monotherapy:  The regimen chosen will be based on participant and tumor factors.  
For definitive monotherapy, doses of 12-13.5 Gy x 2 fractions, 9.5 Gy x 4, 10.5 Gy x 3 are 
described by the NCCN and ABS as appropriate monotherapy doses and will be options for 
treatment on this protocol.
Salvage:  For salvage, participants will receive 8 Gy x 4 fractions without external beam 
irradiation.  
Simulation:  Participants will undergo CT simulation for the external beam portion of treatment 
as per routine in the supine position. For EBRT the planning target volume (PTV) will be 
defined as the clinical target volume (CTV) plus a margin defined by the treating physician. The 
external beam component will be delivered in one phase.  Treatment planning goals are to try to 
achieve an isodose distribution where the PTV is covered by at least the 90% isodose line, and 
the 100% isodose line encompasses the CTV. Doses will be prescribed to the 100% isodose line. 

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2. Implant Dosimetry And Treatment Planning 
Clinical Target Volume: The clinical target volume will include at a minimum the prostate 
gland.  The seminal vesicles or areas of extracapsular disease may be included at the discretion 
of the treating physician.   For salvage, the volume will include suspected areas of recurrence.  
Real time planning and optimization based on ultrasound images obtained during the procedure 
will be performed.
The following volumes will be contoured: urethra, bladder, rectal wall, and PTV. The PTV will 
consist of the prostate gland + extraprostatic tumor +/- seminal vesicles. A separate expanded 
planning PTV will be used for optimization, but not for dose reporting.  The dose goal for the 
PTV will include a V100 >95%, a V125 <55%, and a V150 <25%. The constraints will vary by 
the fractionation chosen.  For example, for the 15 Gy boost, the goals will include urethra 
V118<10% and V125<1cc; Rectal V75 < 1cc, V80 < 0.5 cc.  
Dose-volume histograms (DVHs) will be generated for the PTV, rectum, and urethra. The 
following isodose lines will be displayed on the treatment plan: 75% 100% 125%, 150%, and 
200%. Additional isodose lines may be visualized if clinically necessary.
Dose prescription will be tailored according to the dosimetric parameters achieved in the 
optimized treatment plan (10, 11).

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12.2 APPENDIX B: PERFORMANCE STATUS CRITERIA
ECOG Performance Status Scale
Karnofsky Performance Scale
Grade
Descriptions
Percent
Description
100
Normal, no complaints, no 
evidence of disease.
0
Normal activity.  Fully active, 
able to carry on all pre-disease 
performance without restriction.
90
Able to carry on normal activity; 
minor signs or symptoms of 
disease.
80
Normal activity with effort; 
some signs or symptoms of 
disease.
1
Symptoms, but ambulatory.  
Restricted in physically strenuous 
activity, but ambulatory and able 
to carry out work of a light or 
sedentary nature (e.g., light 
housework, office work).
70
Cares for self, unable to carry on 
normal activity or to do active 
work.
60
Requires occasional assistance, 
but is able to care for most of 
his/her needs.
2
In bed <50% of the time.  
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities.  Up and 
about more than 50% of waking 
hours.
50
Requires considerable assistance 
and frequent medical care.
40
Disabled, requires special care 
and assistance.
3
In bed >50% of the time.  
Capable of only limited self-care, 
confined to bed or chair more 
than 50% of waking hours.
30
Severely disabled, 
hospitalization indicated.  Death 
not imminent.
20
Very sick, hospitalization 
indicated. Death not imminent.
4
100% bedridden.  Completely 
disabled.  Cannot carry on any 
self-care.  Totally confined to bed 
or chair.
10
Moribund, fatal processes 
progressing rapidly.
5
Dead.
0
Dead.