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## Complete Summary

#### GUIDELINE TITLE

The role of high dose rate brachytherapy in the palliation of patients
with non-small cell lung cancer: a clinical practice guideline.

#### BIBLIOGRAPHIC SOURCE(S)

Ung Y, Yu E, Falkson C, Haynes A, Evans WK, Lung Disease Site Group. The
role of high dose rate brachytherapy in the palliation of patients with
non-small cell lung cancer: a clinical practice guideline. Toronto (ON):
Cancer Care Ontario (CCO); 2005 Oct 25. Various p. (Evidence-based
series; no. 7-16). \[42 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

The Evidence-based Series report, initially the full original Guideline,
over time will expand to contain new information emerging from their
reviewing and updating activities.

Please visit the [Cancer Care Ontario Web
site](http://www.cancercare.on.ca/pdf/pebc7-16f.pdf) for details on any
new evidence that has emerged and implications to the guidelines.

### COMPLETE SUMMARY CONTENT

 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)

Symptomatic endobronchial disease in non-small cell lung cancer

#### GUIDELINE CATEGORY

Assessment of Therapeutic Effectiveness\
Treatment

#### CLINICAL SPECIALTY

Oncology\
Pulmonary Medicine\
Radiation Oncology

#### INTENDED USERS

Physicians

#### GUIDELINE OBJECTIVE(S)

-   To evaluate if there is a role for high dose rate endobronchial
    brachytherapy (HDREB) in the palliation of respiratory symptoms in
    patients with non-small cell lung cancer

-   To evaluate what the optimal dose of high dose rate endobronchial
    brachytherapy is in this setting

#### TARGET POPULATION

Adult patients with symptomatic endobronchial disease in non-small cell
lung cancer

#### INTERVENTIONS AND PRACTICES CONSIDERED

1.  High dose rate endobronchial brachytherapy (HDREB)

2.  External beam radiation therapy (EBRT)

#### MAJOR OUTCOMES CONSIDERED

-   Response rates

-   Survival rates

-   Toxicity

-   Symptom control

### 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

**Literature Search Strategy**

MEDLINE (1966 through July 2005), EMBASE (1980 through July 2005),
CANCERLIT (1975 through March 2002), and the Cochrane Library (2005,
Issue 4) databases were searched for evidence relevant to this practice
guideline report. \"Carcinoma, non-small-cell lung\" (Medical subject
heading (MeSH)), \"Lung Neoplasms\" (MeSH), and the phrase \"non small
cell lung\" used as a text word were combined with \"brachytherapy\"
(MeSH), \"radiotherapy dosage\" (MeSH) and each of the following phrases
used as text words: \"brachytherapy,\" \"interstitial radiotherapy,\"
\"seed implant,\" \"high dose,\" or \"HDR\". As the expectation was that
the literature would be limited for this topic, the initial search did
not include restrictions on study design. However, subsequent searches
included the search terms for the following study designs and
publication types: practice guidelines, systematic reviews,
meta-analyses, reviews, randomized controlled trials, controlled
clinical trials, clinical trials, comparative studies, follow-up
studies, prospective studies, and retrospective studies.

In addition, conference proceedings of the American Society of Clinical
Oncology (ASCO) (1995-2005) and the American Society for Therapeutic
Radiology and Oncology (ASTRO) (2000-2005) were searched for abstracts
of relevant trials. The Canadian Medical Association Infobase
(<http://mdm.ca/cpgsnew/cpgs/index.asp>) and the Web site of the
National Guideline Clearinghouse
([http://www.guideline.gov](http://www.guideline.gov/index.asp)) were
also searched for existing evidence-based practice guidelines.

Relevant articles and abstracts were selected and reviewed by three
reviewers, and the reference lists from those sources were searched for
additional trials, as were the reference lists from relevant review
articles.

**Inclusion Criteria**

Articles were selected for inclusion in this systematic review of the
evidence if:

1.  They were fully published reports of randomized controlled trials
    (RCTs), non-controlled prospective studies, or large retrospective
    studies involving more than 100 patients.

2.  The treatment was of symptomatic endobronchial disease in primary
    non-small cell lung cancer (NSCLC).

3.  At least one group in the study received high dose rate
    endobronchial brachytherapy (HDREB), either alone or in combination
    with external beam radiation therapy (EBRT), laser therapy, or
    photodynamic therapy (PDT).

4.  The reported outcomes included symptom control, response, survival,
    or toxicity.

**Exclusion Criteria**

Articles were excluded if they were:

1.  Published in a language other than English

2.  Published in abstract form only

3.  Letters, comments, or editorials

4.  Case studies

#### NUMBER OF SOURCE DOCUMENTS

Six randomized controlled trials (RCTs), eighteen noncontrolled
prospective studies, five large retrospective studies, and one guideline
were included in this systematic review.

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

Expert Consensus (Committee)

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

Not applicable

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review with Evidence Tables

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

As only three of the six randomized trials compared similar treatments,
and all three administered different doses of high dose rate
endobronchial brachytherapy (HDREB), the data were not pooled.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

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

The Program in Evidence-based Care (PEBC) reports consist of a
comprehensive systematic review of the clinical evidence on a specific
cancer care topic, an interpretation of and consensus agreement on that
evidence by Disease Site Groups and Guideline Development Groups, the
resulting clinical recommendations and an external review by Ontario
clinicians in the province for whom the topic is relevant.

The application of high dose rate endobronchial brachytherapy (HDREB)
for lung cancer requires an adequately trained and experienced team that
includes radiation oncologists, thoracic surgeons (or physicians with
expertise in bronchoscopy), and medical physicists. While the aim of
this evidence-based series was not to review the many technical aspects
of the delivery of HDREB, the Lung Cancer Disease Site Group (DSG)
recommends that rigorous quality assurance programs be in effect to
ensure safety and to provide consistency in reporting dose prescriptions
to facilitate comparisons of treatment results.

The analysis of the available evidence does not permit the
recommendation of a standard dose or optimal fractionation for HDREB.
However, a survey of the provincial cancer centres in Ontario was
conducted by one of the guideline authors (Ung) to determine common
practice among centres doing HDREB. The consensus recommendation for
palliation is to use a prescribed dose of 1000 cGy at 1cm from the
central axis given in a single fraction. Technical factors that may
influence dose reduction and the fractionation scheme include the extent
of curvature causing overlap and \"hot spots\" of radiation dose, length
of treatment, and previous external beam radiation exposure in the
treatment volume.

The group of patients that may benefit from HDREB may be defined as
those who have:

1.  Endobronchial tumour causing symptoms of dyspnea, hemoptysis,
    post-obstructive pneumonitis, or intractable cough

2.  Minimal extrinsic compression of the bronchi

3.  Visible endoluminal disease but not complete endobronchial
    obstruction

4.  Failed previous external beam radiation therapy (EBRT) or those who
    are not candidates for further external beam radiation

5.  Good performance status (i.e., Eastern Cooperative Oncology Group,
    (ECOG) [\<]{.underline} 2). Patients with poorer performance status
    caused directly by the endobronchial disease may still be suitable
    for HDR brachytherapy.

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

Not applicable

#### 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

Following the review and discussion of the evidence-based series report,
the Lung Cancer Disease Site Group circulated the clinical practice
guideline and systematic review to clinicians in Ontario for review and
feedback.

Practitioner feedback was obtained through a mailed survey of 117
practitioners in Ontario and included 35 medical oncologists, 22
radiation oncologists, 27 surgeons, 32 respirologists, and a
hematologist. The survey consisted of items evaluating the methods,
results, and interpretive summary used to inform the draft
recommendations and whether the draft recommendations should be approved
as a practice guideline. Written comments were invited. The practitioner
feedback survey was mailed out on May 7, 2004 . Follow-up reminders were
sent at two weeks (post card) and four weeks (complete package mailed
again). The Lung Disease Site Group (DSG) reviewed the results of the
survey.

This evidence-based series reflects the integration of the draft
recommendations with feedback obtained from the external review process.
After being approved by the Lung Disease Site Group, the series was
submitted to the Practice Guidelines Coordinating Committee. Of the 15
panel members, eight members returned ballots of the reviewed document.
However, one panel member is a member of the Lung Disease Site Group and
was not eligible to review the document. Six panel members approved the
document and one member approved the document on condition that changes
to one of the recommendations are changed due to the weak evidence
supporting it.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

-   For patients with previously untreated, symptomatic, endobronchial
    non-small cell lung cancer:

    -   External beam radiation therapy (EBRT) alone is more effective
        for palliation than high dose rate endobronchial brachytherapy
        (HDREB) alone.

    -   The evidence does not provide conclusive results to suggest that
        HDREB and EBRT would provide improved symptom relief over EBRT
        alone.

    -   For patients with complete collapse of the lung due to
        endobronchial obstruction, a surgical core out procedure may be
        needed before EBRT or EBRT with HDREB.

    -   For patients previously treated by EBRT who are symptomatic from
        recurrent disease due to endobronchial obstruction, HDREB is
        recommended, providing that endobronchial brachytherapy is
        technically feasible.

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The recommendations are supported by randomized controlled trials
(RCTs), noncontrolled prospective studies, retrospective studies, and
one guideline.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

-   One randomized trial involving 99 previously untreated patients
    obtained better overall palliation with external beam radiation
    therapy (EBRT) alone compared with high dose rate endobronchial
    brachytherapy (HDREB) alone (physician preference ratings for EBRT,
    p=0.09; patient preference ratings for EBRT, p=0.029). The incidence
    of fatal hemoptysis was comparable in both groups (6% to 8%).
    Although survival was not a specified endpoint of that study, median
    survival was found to be longer (9.4 versus 8.2 months), one-year
    survival higher (38% versus 22%), and overall survival significantly
    better (p=0.04) with EBRT alone.

-   One randomized controlled trial evaluated HDREB in combination with
    EBRT to EBRT alone using biologically equivalent doses for both
    arms. Symptom control for cough was better in patients who were
    treated with EBRT alone compared to HRDEB and EBRT, and survival at
    one year was the same in each group. One randomized controlled trial
    evaluated EBRT compared to EBRT with HDREB boost. Local control was
    better with EBRT and HDREB, but symptom control was not evaluated.

-   Two trials obtained comparable median survival (6.2 versus 6.5
    months and 7.0 versus 8.5 months) and incidence of fatal hemoptysis
    (14% versus 19% and 13% versus 15%) for patients treated with EBRT
    alone or EBRT with HDREB. Combined treatment improved atelectasis in
    one trial (57% versus 35% of patients, respectively, p=0.009),
    although individual symptom scale scores were comparable for both
    treatments. The other trial reported a tendency toward improved
    local control with combined therapy (p=0.052).

-   Median survival (7.4 versus 10.3 months) and incidence of fatal
    hemoptysis (0 versus 1 patient) were similar for
    neodymium-yttrium-aluminum-garnet (Nd-YAG) laser therapy alone or
    combined with HDREB. The symptom-free period was significantly
    longer with the combined treatment (8.5 versus 2.8 months, p\<0.05),
    although toxicity and symptom palliation were not reported by
    treatment group.

-   Eighteen prospective, non-controlled studies evaluated HDREB in
    doses ranging from 4 Gray (Gy) at 2cm from the source axis twice
    daily over two days to a single fraction of 20 Gy at 1cm from the
    source axis. Response rates varied between 20% and 79%, median
    survival between three and 28 months, and one-year survival between
    7% and 78%. Hemoptysis improved for most patients, although fatal
    hemoptysis occurred in between 3% and 32% of patients.

-   Five retrospective studies, each involving more than 100 patients,
    reviewed the role of HDREB alone or in combination with EBRT.
    Treatment intent varied from palliation to radical, using single
    dose or fractionated treatments. Symptom improvement ranged from 46%
    to 94%. The risk of fatal hemoptysis ranged from 3.6% to 21%.

#### POTENTIAL HARMS

-   Fatal hemoptysis is a significant risk of high dose rate
    endobronchial brachytherapy (HDREB), with reported rates as high as
    32%, while the majority of studies reported rates between 4% and 18%
    (see Appendix 2 of the original guideline document). The same
    studies reported improvement of hemoptysis in 19% to 100% of
    patients, while most studies reported improvement in at least 69% of
    patients.

-   Other complications of HDREB are radiation bronchitis, bronchial or
    tracheal stenosis, bronchial necrosis or fistula formation,
    pneumothorax, and non-fatal hemorrhage.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   This guideline addresses only the use of high dose rate
    endobronchial brachytherapy (HDREB) for the palliation of
    symptomatic endobronchial disease and not its use as a radical or
    adjuvant treatment.

-   The occurrence of fatal hemoptysis because of HDREB is a significant
    risk with that therapy, and occurrence rates as high as 32% of
    patients have been reported. However, the majority of studies report
    rates between 4% and 18% of patients.

-   Improvement of hemoptysis as a result of HDREB ranges from 19% to
    100% of patients, with most studies reporting rates of 69% and
    higher.

-   HDREB should be provided by a team of experts that includes
    radiation oncologists, thoracic surgeons (or physicians with
    expertise in bronchoscopy), and medical physicists.

-   HDREB is only possible if afterloading catheters can be inserted
    bronchoscopically. Patients with complete endobronchial obstruction
    are not suitable for HDREB.

-   Treatment alternatives to HDREB include external beam radiation
    therapy (EBRT) (if not previously irradiated),
    neodymium-yttrium-aluminum-garnet (Nd-YAG) laser therapy,
    photodynamic therapy (PDT), and surgical core-out procedure.

-   The optimal dose and fractionation for HDREB for the palliation of
    symptoms of airway obstruction has not yet been determined. However,
    commonly used doses include 1000 cGy at 1cm in a single fraction or
    750 cGy at 1cm in one or two fractions.

-   HDREB may be effectively combined with other endobronchial treatment
    modalities such as neodymium-yttrium-aluminum-garnet laser (Nd-YAG)
    therapy.

-   Care has been taken in the preparation of the information contained
    in this document. Nonetheless, any person seeking to apply or
    consult the practice guideline is expected to use independent
    medical judgment in the context of individual clinical circumstances
    or seek out the supervision of a qualified clinician. Cancer Care
    Ontario makes no representation or guarantees of any kind whatsoever
    regarding their content or use or application and disclaims any for
    their application or use in any way.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

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

#### IOM CARE NEED

Living with Illness

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Ung Y, Yu E, Falkson C, Haynes A, Evans WK, Lung Disease Site Group. The
role of high dose rate brachytherapy in the palliation of patients with
non-small cell lung cancer: a clinical practice guideline. Toronto (ON):
Cancer Care Ontario (CCO); 2005 Oct 25. Various p. (Evidence-based
series; no. 7-16). \[42 references\]

#### ADAPTATION

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

#### DATE RELEASED

2005 Oct 25

#### GUIDELINE DEVELOPER(S)

Program in Evidence-based Care - State/Local Government Agency
\[Non-U.S.\]

#### GUIDELINE DEVELOPER COMMENT

The Program in Evidence-based Care (PEBC) is a Province of Ontario
initiative sponsored by Cancer Care Ontario and the Ontario Ministry of
Health and Long-Term Care.

#### SOURCE(S) OF FUNDING

Cancer Care Ontario\
Ontario Ministry of Health and Long-Term Care

#### GUIDELINE COMMITTEE

Provincial Lung Cancer Disease Site Group

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

For a current list of past and present members, please see the [Cancer
Care Ontario Web
site](http://www.cancercare.on.ca/english/toolbox/qualityguidelines/diseasesite/lung-ebs/lung-dsg/).

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

The members of the Lung Disease Site Group (DSG) disclosed potential
conflicts of interest relating to the topic of this evidence-based
series. No potential conflicts were declared.

#### GUIDELINE STATUS

This is the current release of the guideline.

The Evidence-based Series report, initially the full original Guideline,
over time will expand to contain new information emerging from their
reviewing and updating activities.

Please visit the [Cancer Care Ontario Web
site](http://www.cancercare.on.ca/pdf/pebc7-16f.pdf) for details on any
new evidence that has emerged and implications to the guidelines.

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[Cancer Care Ontario Web
site](http://www.cancercare.on.ca/pdf/pebc7-16f.pdf).

#### AVAILABILITY OF COMPANION DOCUMENTS

The following are available:

-   The role of high dose rate brachytherapy in the palliation of
    patients with non-small cell lung cancer: a clinical practice
    guideline. Toronto (ON): Cancer Care Ontario (CCO), 2005 Nov 25.
    Various p. (Practice guideline; no. #7-16: Section 1). Electronic
    copies: Available in Portable Document Format (PDF) from the [Cancer
    Care Ontario Web
    site](http://www.cancercare.on.ca/pdf/pebc7-16s.pdf).

-   Browman GP, Levine MN, Mohide EA, Hayward RSA, Pritchard KI, Gafni
    A, et al. The practice guidelines development cycle: a conceptual
    tool for practice guidelines development and implementation. J Clin
    Oncol 1995;13(2):502-12.

#### PATIENT RESOURCES

None available

#### NGC STATUS

This summary was completed by ECRI on January 24, 2006. The information
was verified by the guideline developer on February 23, 2006.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions. Please refer to the
[Copyright and Disclaimer
Statements](http://www.cancercare.on.ca/ontariocancernews/copyright.html)
posted at the Program in Evidence-Based Care section of the Cancer Care
Ontario Web site.

### DISCLAIMER

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Date Modified: 11/3/2008