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Guideline Summary
Guideline Title
The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline.
Bibliographic Source(s)
Ammirati M, Cobbs CS, Linskey ME, Paleologos NA, Ryken TC, Burri SH, Asher AL, Loeffler JS, Robinson PD, Andrews DW, Gaspar LE, Kondziolka D, McDermott M, Mehta MP, Mikkelsen T, Olson JJ, Patchell RA, Kalkanis SN. The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010 Jan;96(1):85-96. [34 references] PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

Scope

Disease/Condition(s)

Recurrent or progressive brain metastases

Guideline Category
Management
Treatment
Clinical Specialty
Neurological Surgery
Neurology
Oncology
Pathology
Radiation Oncology
Intended Users
Physicians
Guideline Objective(s)
  • To provide the latest up-to-date evidence-based recommendations for the management of patients with brain metastases centering on questions related to commonly encountered clinical scenarios
  • To systematically review the existing data relevant to the treatment of patients who develop recurrent/progressive brain metastases after initial therapy and to provide recommendations based on this evidence
Target Population

Adults with recurrent/progressive brain metastases who have previously been treated with whole brain radiation therapy (WBRT), surgical resection and/or radiosurgery

Note: Recurrent/progressive brain metastases are defined as metastases that recur/progress anywhere in the brain (original and/or non-original sites) after initial therapy.

Interventions and Practices Considered
  1. Whole brain radiation therapy (WBRT)
  2. Surgical resection
  3. Chemotherapy
  4. Stereotactic radiosurgery (SRS)
Major Outcomes Considered
  • Median survival
  • Recurrence/progression after retreatment
  • Median time to recurrence/progression after retreatment

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

The following electronic databases were searched from 1990 to September 2008: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Registry, and Cochrane Database of Abstracts of Reviews of Effects. The search strategy used a combination of subheadings and text words. The specific search terms used for MEDLINE are provided in Appendix A of the methodology companion (see the "Availability of Companion Documents" field); this search strategy was modified accordingly for appropriate terms for each database searched. Reference lists of included studies were also screened for potentially relevant studies.

An additional electronic database search was conducted to identify randomized trials published from 1970 forward that evaluated different dose/fractionation schedules of whole-brain radiation for the treatment of brain metastases. This was done to capture seminal studies in this area known to have been undertaken in this earlier time frame. The initial electronic search commenced at 1990 given the lack of any known comparative data for radiation, surgical resection and radiosurgery prior to this date, although additional searches were conducted as far back as 1970 as outlined above.

Conference proceedings from the 2006–2008 meetings of the American Association of Neurological Surgeons (AANS), the Congress of Neurological Surgeons (CNS), Society for Neuro-Oncology (SNO), American Society for Radiation Oncology (ASTRO), American Society for Clinical Oncology (ASCO) and the AANS/CNS joint section on tumors satellite symposiums were searched for abstracts eligible for inclusion in the emerging and investigational therapies guideline question.

These citations were screened in duplicate using an online systematic review management system designed by TrialStat. Two independent reviewers evaluated titles and abstracts using a priori eligibility criteria in standardized forms. Cases of disagreement were resolved by a third reviewer. The same process was applied to full text screening of potentially relevant studies. Articles that met the eligibility criteria for one or more of the questions were grouped according to the questions they addressed. Reasons for exclusion were documented.

Eligibility Criteria

(a) What evidence is available regarding the use of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), surgical resection or chemotherapy for the treatment of recurrent and/or progressive brain metastases?

  • Published in English with a publication date of 1990 forward.
  • Patients with recurrent and/or progressive brain metastases.
  • Fully-published primary studies (all study designs for primary data collection included; e.g., randomized controlled trial [RCT], non-randomized trials, cohort studies, control studies or case series).
  • Any study evaluating the use of WBRT, SRS, surgical excision, or chemotherapy alone or in combination.
  • Number of study participants with recurrent and/or progressive brain metastases >5 per study arm for comparative studies and >5 overall for noncomparative studies.
  • For studies evaluating interventions exclusively in patients with recurrent and/or progressive brain metastases, baseline characteristics of study participants are provided by treatment group for comparative designs and overall for non-comparative studies. For studies with mixed populations (i.e., includes participants with conditions other than recurrent and/or progressive brain metastases), baseline characteristics are provided for the sub-group of participants with recurrent and/or progressive brain metastases, and stratified by treatment group for comparative studies.

(b) If WBRT is used, what impact does tumor histopathology have on treatment outcomes?

  • Published in English with a publication date of 1990 forward.
  • Patients with recurrent and/or progressive brain metastases.
  • Fully-published peer-reviewed primary studies (all study designs for primary data collection included; e.g., RCT, non-randomized trials, cohort studies, case–control studies or case series).
  • Any study evaluating the outcome(s) of WBRT by tumor histopathology (or primary tumor type).
  • Number of study participants with recurrent and/or progressive brain metastases >5 per study arm for comparative studies and >5 overall for noncomparative studies.
  • For studies evaluating the outcome(s) of WBRT by histopathology (or primary tumor type) exclusively in patients with recurrent and/or progressive brain metastases, baseline characteristics are presented and stratified by histologic/primary tumor group. For studies with mixed populations (i.e., includes participants with conditions other than recurrent and/or progressive brain metastases), baseline characteristics are presented and stratified by histologic/primary tumor group for the sub-group of participants with recurrent and/or progressive brain metastases.
Number of Source Documents

In total, 30 studies met the eligibility criteria for this question.

Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence

Evidence Classification

Class I: Evidence provided by one or more well-designed randomized controlled clinical trials, including overview (meta-analyses) of such trials

Class II: Evidence provided by well-designed observational studies with concurrent controls (e.g., case control and cohort studies)

Class III: Evidence provided by expert opinion, case series, case reports and studies with historical controls

Methods Used to Analyze the Evidence
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence

Studies which met the eligibility criteria were data extracted by one reviewer and the extracted information was checked by a second reviewer. The PEDro scale was used to evaluate the methodological quality (internal validity) of randomized trials. The quality of comparative studies using non-randomized designs was evaluated using eight items selected and modified from existing scales (see Appendix B in the methodology companion [see the "Availability of Companion Documents" field]).

Evidence and summary tables, reporting the extracted study information and quality assessment, were generated for all of the included studies.

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

The McMaster University Evidence-based Practice Center (EPC), which is an academic research unit partially funded by an EPC grant from the Agency for Healthcare Research and Quality (AHRQ), with specialized expertise in evidence-based medicine and the development of systematic reviews, was contracted to performed the systematic review in consultation with the guideline panel assembled for the initiative. The McMaster EPC also served as facilitators during the guideline development, consensus and writing processes.

The Joint Tumor Section of the American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS) recruited representatives from surgical neuro-oncology (including microsurgical, stereotactic radiosurgery and experimental therapies), radiation oncology (fractionated radiotherapy, stereotactic radiosurgery and brachytherapy) and medical neuro-oncology (chemotherapy and experimental therapies) to form a multi-disciplinary panel of 17 clinical experts who developed the evidence-based practice guidelines from the systematic review results. These 17 experts across several disciplines were all nominated and selected by the Executive Committee of the AANS/CNS Tumor Section based on their clinical expertise and recognized contributions to the field of neuro-oncology in general and brain metastases in particular. The Tumor Section Executive Committee then selected a chairperson for this endeavor to organize and lead the effort, serving also to encourage and manage debate on the various topics involved.

Scope of the Systematic Review and Clinical Practice Guidelines

The specific questions regarding the treatment of brain metastases addressed by the systematic review and the resulting practice guidelines were determined collaboratively by the clinical guideline panel and methodologists at the McMaster EPC. In total, eight questions were agreed upon and these correspond to the eight practice guideline papers in this series. Four of the questions specifically focus on the treatment of patients with newly diagnosed brain metastases (Table 1 in the methodology companion [see the "Availability of Companion Documents" field]), one question addresses the treatment of recurrent/progressive metastatic brain disease (Table 2) and the remaining three questions are relevant to all patients with brain metastases (Table 3). Some of the questions had several parts.

Guideline Panel Consensus and Practice Guideline Approval Process

Small writing groups composed of four to eight members of the clinical guideline panel were assigned to each of the eight questions, and each question had at least one member from each subspecialty as part of the initial writing team. Each group was provided with the included studies and the evidence/summary tables for their specific question, as well as an exhaustive statistical analysis, from the McMaster EPC team. Using this information, the small writing groups were responsible for drafting the clinical practice guideline for their respective questions. The draft guidelines were then circulated to the entire clinical guideline panel for feedback, discussion, and ultimately approval.

Rating Scheme for the Strength of the Recommendations

Levels of Recommendation

Level 1: Generally accepted principles for patient management, which reflect a high degree of clinical certainty (usually this requires Class I evidence which directly addresses the clinical questions or overwhelming Class II evidence when circumstances preclude randomized clinical trials)

Level 2: Recommendations for patient management which reflect clinical certainty (usually this requires Class II evidence or a strong consensus of Class III evidence)

Level 3: Other strategies for patient management for which the clinical utility is uncertain (inconclusive or conflicting evidence or opinion)

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

In accordance with the initial goal of a 1-year time horizon, the completed evidence-based clinical practice guidelines on the management of brain metastases were presented to the Joint Guidelines Committee (JGC) of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons (AANS/CNS) for approval approximately 12 months after starting the evidence review process. As part of their approval process, the JGC could provide input on the content of the clinical practice guidelines. Once approved by the AANS/CNS, the guidelines were also presented to the executive leadership of the Society for Neuro-Oncology (SNO), the American Society for Radiation Oncology (ASTRO), in addition to the AANS/CNS Joint Tumor Section, to offer multidisciplinary review and endorsement with plans for online publication and dissemination in all of the various organized societies concerned with the treatment of brain metastases.

Recommendations

Major Recommendations

The rating schemes used for the strength of the evidence (Class I-III) and the levels of recommendations (1-3) are defined at the end of the "Major Recommendations" field.

What Evidence Is Available Regarding the Use of Whole Brain Radiation Therapy (WBRT), Stereotactic Radiosurgery (SRS), Surgical Resection or Chemotherapy for the Treatment of Recurrent/Progressive Brain Metastases?

Target Population

This recommendation applies to adults with recurrent/progressive brain metastases who have previously been treated with WBRT, surgical resection and/or radiosurgery. Recurrent/progressive brain metastases are defined as metastases that recur/progress anywhere in the brain (original and/or non-original sites) after initial therapy.

Recommendation

Level 3 Since there is insufficient evidence to make definitive treatment recommendations in patients with recurrent/progressive brain metastases, treatment should be individualized based on a patient's functional status, extent of disease, volume/number of metastases, recurrence or progression at original versus non-original site, previous treatment and type of primary cancer, and enrollment in clinical trials is encouraged. In this context, the following can be recommended depending on a patient's specific condition: no further treatment (supportive care), reirradiation (either WBRT and/or SRS), surgical excision or, to a lesser extent, chemotherapy.

If WBRT Is Used in the Setting of Recurrent/Progressive Brain Metastases, What Impact Does Tumor Histopathology Have on Treatment Outcomes?

No studies were identified that met the eligibility criteria for this question.

Definitions:

Evidence Classification

Class I: Evidence provided by one or more well-designed randomized controlled clinical trials, including overview (meta-analyses) of such trials

Class II: Evidence provided by well-designed observational studies with concurrent controls (e.g., case control and cohort studies)

Class III: Evidence provided by expert opinion, case series, case reports and studies with historical controls

Levels of Recommendation

Level 1: Generally accepted principles for patient management, which reflect a high degree of clinical certainty (usually this requires Class I evidence which directly addresses the clinical questions or overwhelming Class II evidence when circumstances preclude randomized clinical trials)

Level 2: Recommendations for patient management which reflect clinical certainty (usually this requires Class II evidence or a strong consensus of Class III evidence)

Level 3: Other strategies for patient management for which the clinical utility is uncertain (inconclusive or conflicting evidence or opinion)

Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

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

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Appropriate use of retreatment in the management of recurrent/progressive brain metastases

Potential Harms
  • Complications of surgery
  • One patient experienced symptoms of dementia attributed to radiation therapy in each of the two series reporting information on longer term adverse effects.

Qualifying Statements

Qualifying Statements

The information in these guidelines reflects the current state of knowledge at the time of completion. The presentations are designed to provide an accurate review of the subject matter covered. These guidelines are disseminated with the understanding that the recommendations by the authors and consultants who have collaborated in their development are not meant to replace the individualized care and treatment advice from a patient's physician(s). If medical advice or assistance is required, the services of a competent physician should be sought. The proposals contained in these guidelines may not be suitable for use in all circumstances. The choice to implement any particular recommendation contained in these guidelines must be made by a managing physician in light of the situation in each particular patient and on the basis of existing resources.

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
Getting Better
Living with Illness
IOM Domain
Effectiveness

Identifying Information and Availability

Bibliographic Source(s)
Ammirati M, Cobbs CS, Linskey ME, Paleologos NA, Ryken TC, Burri SH, Asher AL, Loeffler JS, Robinson PD, Andrews DW, Gaspar LE, Kondziolka D, McDermott M, Mehta MP, Mikkelsen T, Olson JJ, Patchell RA, Kalkanis SN. The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010 Jan;96(1):85-96. [34 references] PubMed External Web Site Policy
Adaptation

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

Date Released
2010 Jan
Guideline Developer(s)
American Association of Neurological Surgeons - Medical Specialty Society
Congress of Neurological Surgeons - Professional Association
Source(s) of Funding

American Association of Neurological Surgeons (AANS) Board, the Congress of Neurological Surgeons (CNS) Executive Committee, and the AANS/CNS Joint Tumor Section Executive Committee

Guideline Committee

Management of Brain Metastases Guideline Panel

Composition of Group That Authored the Guideline

Authors: M. Ammirati, Department of Neurosurgery, Ohio State University Medical Center, Columbus, OH, USA; C. S. Cobbs, Department of Neurosciences, California Pacific Medical Center, San Francisco, CA, USA; M. E. Linskey, Department of Neurosurgery, University of California-Irvine Medical Center, Orange, CA, USA; N. A. Paleologos, Department of Neurology, Northshore University Health System, Evanston, IL, USA; T. C. Ryken, Department of Neurosurgery, Iowa Spine and Brain Institute, Iowa City, IA, USA; S. H. Burri, Department of Radiation Oncology, Carolinas Medical Center, Charlotte, NC, USA; A. L. Asher, Department of Neurosurgery, Carolina Neurosurgery and Spine Associates, Charlotte, NC, USA; J. S. Loeffler, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA; P. D. Robinson, McMaster University Evidence-Based Practice Center, Hamilton, ON, Canada; D. W. Andrews, Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA, USA; L. E. Gaspar, Department of Radiation Oncology, University of Colorado-Denver, Denver, CO, USA; D. Kondziolka, Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; M. McDermott, Department of Neurosurgery, University of California San Francisco, San Francisco, CA, USA; M. P. Mehta, Department of Human Oncology, University of Wisconsin School of Public Health and Medicine, Madison, WI, USA; T. Mikkelsen, Department of Neurology, Henry Ford Health System, Detroit, MI, USA; J. J. Olson, Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA; R. A. Patchell, Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA; S. N. Kalkanis, Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA

Financial Disclosures/Conflicts of Interest

All panel members provided full disclosure of conflicts of interest, if any, prior to establishing the recommendations contained within these guidelines.

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies: Available from the Journal of Neuro-Oncology Web site External Web Site Policy.

Availability of Companion Documents

The following are available:

  • Evidence-based clinical practice parameter guidelines for the treatment of patients with metastatic brain tumors: introduction. J Neurooncol 2010;96:7–10. Electronic copies: Available from the Journal of Neuro-Oncology Web site External Web Site Policy.
  • Methodology used to develop the AANS/CNS management of brain metastases evidence-based clinical practice parameter guidelines. J Neurooncol 2010;96:11–16. Electronic copies: Available from the Journal of Neuro-Oncology Web site External Web Site Policy.
Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on September 15, 2011. The information was verified by the guideline developer on November 5, 2011.

Copyright Statement

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

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