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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

ME Linskey, DW Andrews, AL Asher, SH Burri, D Kondziolka, PD Robinson, M Ammirati, CS Cobbs, LE Gaspar, JS Loeffler, M McDermott, MP Mehta, T Mikkelsen, JJ Olson, NA Paleologos, RA Patchell, TC Ryken, and SN Kalkanis.

Review published: 2010.

CRD summary

Single dose stereotactic radiosurgery with or without whole brain radiotherapy improved survival compared to whole brain radiotherapy alone in patients with brain metastases and the combination therapy was more effective for local tumour control and maintaining functional status. Survival was equivalent for other treatment comparisons. Limitations with the included studies suggest the authors’ conclusions should be interpreted with some caution.

Authors' objectives

To compare the effectiveness of stereotactic radiosurgery with other treatments in the management of patients with newly-diagnosed metastatic brain tumours.

Searching

MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL) and DARE were searched for publications in English between 1990 and September 2008. Search terms were available from a previous publication (see Other Publications of Related Interest). Reference lists of included studies were searched manually.

Study selection

Randomised controlled trials (RCTs), non-randomised trials, cohort studies and case-control studies that assessed treatment of patients with newly diagnosed brain metastases were eligible for inclusion in the review. Eligible studies could compare one or more of the treatments: whole brain radiation therapy alone versus stereotactic radiosurgery plus whole brain radiation therapy; stereotactic radiosurgery alone versus whole brain radiation therapy plus stereotactic radiosurgery; stereotactic radiosurgery alone versus whole brain radiation therapy alone; stereotactic radiosurgery with or without whole brain radiotherapy or local radiotherapy versus resection with or without whole brain radiotherapy or local radiotherapy; stereotactic radiosurgery with or without resection versus whole brain radiotherapy with or without resection; or single versus multi-dose stereotactic radiosurgery plus whole brain radiation therapy. Eligible studies were required to include five or more patients with newly diagnosed brain metastases for at least two study arms. Studies of mixed populations were eligible if baseline information on patients with newly diagnosed brain metastases were reported separately.

Included studies were of patients with between one and six brain metastases that measured between ≤2.5 cm and ≤4.5 cm. Where reported, types of primary cancer included breast, epithelial ovarian, renal cell, lung or non-small cell lung cancer. Where reported, studies included patients with various levels of Karnofsky performance status (KPS): some studies included patients with KPS more than 50, 60 or more, less than 70 or 70 or more; and other studies stated that patients were matched for KPS score at baseline. The main outcomes of interest were survival rate and time to recurrence/progression, local tumour control and maintenance of functional status.

Two reviewers independently screened studies for inclusion. Disagreements were resolved by a third reviewer.

Assessment of study quality

Randomised controlled trials (RCTs) were assessed for quality using the PEDro scale. Non-randomised studies were assessed according to eight criteria modified from existing scales.

The authors did not state how many reviewers performed the validity assessment.

Data extraction

One reviewer extracted outcome data and significance levels from individual studies; this was checked by a second reviewer.

Methods of synthesis

Data were presented as a narrative synthesis by treatment comparison.

Results of the review

Thirty-one studies (32 publications) (n=>5,338, range 15 to 1,702 patients) were included in the review. Validity scores were not reported in the review, but data were presented in terms of levels of evidence.

Whole brain radiotherapy alone versus whole brain radiotherapy plus stereotactic radiosurgery: Two RCTs, one prospective cohort study and two retrospective cohort studies (one with historical controls) showed that single-dose stereotactic radiosurgery plus whole brain radiotherapy resulted in statistically significantly greater local tumour control compared with whole brain radiotherapy alone in patients with one to four brain tumours and a KPS of 70 or more. One RCT showed statistically significantly greater survival in patients who received stereotactic radiosurgery plus whole brain radiotherapy versus whole brain radiotherapy alone in patients with single brain metastases and with a KPS of 70 or more. The three remaining studies supported the survival benefit but in patients with KPS less than 70.

Stereotactic radiosurgery alone vs whole brain radiotherapy plus stereotactic radiosurgery: One RCT, one prospective cohort study and eight of 10 retrospective cohort studies showed similar survival rates in patients who received stereotactic radiosurgery and those who received stereotactic radiosurgery plus whole brain radiotherapy. The evidence on risk of local and distant recurrence was contradictory.

Surgical resection plus whole brain radiotherapy versus stereotactic radiosurgery plus whole brain radiotherapy: Three of four retrospective cohort studies showed no statistically significant differences in survival rates between the treatment groups.

Stereotactic radiosurgery alone versus whole brain radiotherapy alone: One prospective cohort study, one retrospective cohort study and two retrospective cohort studies with concomitant controls showed a statistically significant survival benefit in patients who received single-dose stereotactic radiosurgery compared to whole brain radiotherapy alone in patients with single or multiple (up to three) brain tumours.

Stereotactic radiosurgery alone versus resection plus whole brain radiotherapy: One RCT and three of four retrospective cohort studies showed no statistically significant difference in median survival for patients with single brain metastases.

Other comparisons were reported in the review, but the evidence was limited.

Authors' conclusions

Single dose stereotactic radiosurgery plus whole brain radiotherapy improved survival compared with whole brain radiotherapy alone in patients with single or multiple brain metastases and was more effective in terms of local tumour control and maintaining functional status in patients with between one and four metastatic brain tumours and KPS of 70 or more. Survival was equivalent in patients who received stereotactic radiosurgery plus whole brain radiotherapy versus those who received stereotactic radiosurgery alone. Similarly, survival rates were equivalent for surgical resection plus whole brain radiotherapy versus stereotactic radiosurgery plus whole brain radiotherapy. Single-dose stereotactic radiosurgery compared to whole brain radiotherapy alone resulted in greater survival in patients with one to three brain tumours.

CRD commentary

The review question was clear and was supported by appropriate criteria for participants, interventions, comparators and study design. Outcomes of interest were not explicitly stated. A number of relevant sources were searched for articles and these included a search for ongoing trials. The search was restricted to English-language articles, so language bias may have been introduced. Although the authors stated that they assessed study quality with previously published criteria, details of these criteria and results of the quality assessment were not reported. The authors highlighted some issues with the included studies (such as patient crossover, early closure of the study and insufficient statistical power). The authors reported that study selection and data extraction were undertaken in duplicate to minimise reviewer error and bias, but did not report the process for quality assessment. Given the differences among patients in terms of performance status and tumour size and number, and the limited data provided on patient characteristics and lack of details on intervention regimens, a narrative synthesis was appropriate.

The authors’ recommendations appeared to reflect the evidence presented, but given limitations with the included studies (for example, some comparisons were based on small study numbers or used less robust study designs) they should be interpreted with some caution.

Implications of the review for practice and research

Practice: The authors stated that regular careful surveillance was required in patients who received stereotactic radiosurgery alone to enable early identification of local and distant recurrences and initiation of salvage therapy as soon as possible.

Research: The authors stated a number of recommendations for research, which included well-powered studies to investigate single-dose stereotactic radiosurgery plus whole brain radiotherapy in patients with two or more metastatic brain tumours of less than 3cm for median survival and patients with KPS below 70. Research was required to compare single-dose resection or stereotactic radiosurgery with or without whole brain radiotherapy versus resection plus whole brain radiotherapy. Further research was needed to find the optimal dose for stereotactic radiosurgery to treat patients with metastatic brain tumours.

Funding

Not stated.

Bibliographic details

Linskey ME, Andrews DW, Asher AL, Burri SH, Kondziolka D, Robinson PD, Ammirati M, Cobbs CS, Gaspar LE, Loeffler JS, McDermott M, Mehta MP, Mikkelsen T, Olson JJ, Paleologos NA, Patchell RA, Ryken TC, Kalkanis SN. The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. Journal of Neuro-Oncology 2010; 96(1): 45-68. [PMC free article: PMC2808519] [PubMed: 19960227]

Other publications of related interest

Robinson PD, Kalkanis SN, Linskey ME, Santaguida PL. Methodology used to develop the AANS/CNS management of brain metastases evidence-based clinical practice parameter guidelines. J Neurooncol 2010; 96:11–16 doi:10.1007/s11060-009-0059-2.

Indexing Status

Subject indexing assigned by NLM

MeSH

Brain Neoplasms /radiotherapy /secondary /surgery; Cranial Irradiation /methods; Evidence-Based Medicine; Humans; Practice Guidelines as Topic /standards; Radiosurgery /methods; Radiotherapy, Adjuvant /methods

AccessionNumber

12010001787

Database entry date

27/10/2010

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 19960227

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