The Diminishing Role of Whole-Brain Radiation Therapy in the Treatment of Brain Metastases

Abstract

Is there a role for whole-brain radiation therapy in the treatment of brain metastases?-Limited.An estimated 400 000 patients with cancer will develop brain metastases (BrM) this year, and more than half will undergo whole-brain radiation therapy (WBRT). Multiple phase 3 trials have provided level 1 evidence to support the use of single-fraction stereotactic radiosurgery (SRS) alone in patients with 1 to 3 BrM because WBRT has no survival benefit and is associated with impaired cognitive function and quality of life (QOL). There is also emerging evidence to support that SRS may be the appropriate treatment for patients with 4 or more BrM as well. With recent advancement in systemic therapy with central nervous system penetration, the role of WBRT has been further diminished in the management of patients with BrM.

Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial

“…However, debate exists within the oncology community regarding the role of adjuvant WBRT among select populations. (6, 7) Whereas a secondary analysis of the JROSG-99 trial had demonstrated an overall survival benefit to WBRT among lung cancer patients with favorable diagnosis-specific graded prognostic assessment (DS-GPA) scores(8), an exploratory analysis of the EORTC 22952 trial found no such benefit. (9) In consequence of the persistent, conflicting evidence related to the effect of WBRT on survival in patient sub-populations, we sought to evaluate outcomes of non-small cell lung cancer (NSCLC) patients according to the receipt of WBRT and DS-GPA score within the North Central Cancer Treatment Group N0574 (Alliance) trial.…”

Metastatic Brain Disease from Non-small Cell Lung Cancer – Getting Back to the Drawing Board

“…The UK MRC QUARTZ trial (Quality of Life After Treatment (Radiotherapy and Steroids) for Brain Metastases) is the only randomised trial sufficiently powered to fully address the palliative utility of WBRT for patients with brain metastases from NSCLC. The completion and publication of the MRC QUARTZ trial has generated an extensive and healthy discourse in the general, neuro-oncology and lung oncology journals and communities, recognising it as a practice-changing trial [4,5,30,31].…”

“…The combination of whole brain radiotherapy (WBRT) and steroids was previously bench-marked as the standard of care for patients with brain metastases from all primary tumour sites, despite the lack of any randomised controlled data supporting this approach [2,3]. It is increasingly recognised that the use of WBRT can no longer be automatically deemed the first port of call in the palliative setting [4,5]. The main drivers for this change in our radiotherapeutic approach have been the completion and publication of the UK Medical Research Council (MRC) QUARTZ trial [6], plus the increasing body of level I evidence showing that local ablative options (using stereotactic radiosurgery [SRS] or surgical resection) can provide a durable and acceptable quality of survival time for highly selected patients, including those with underlying NSCLC [7e9], coupled with concerns regarding the potential longterm cognitive impact from WBRT [5,10].…”

Prophylactic Cranial Irradiation (PCI) versus Active MRI Surveillance for Small Cell Lung Cancer: The Case for Equipoise

“…[63][64][65][66][67][68] The consistency of these clinical and pathophysiologic findings, in the absence of an OS benefit from WBRT, has changed the landscape of management of BMs across most histologic types in favor of avoiding WBRT when patients can be safely managed with radiosurgery alone. 69,70 Clear parallels exist between PCI and WBRT regarding the risk-benefit considerations for QoL, cognition, and survival. If PCI does not in fact improve OS in the modern era of MRI staging, surveillance, and salvage therapy options-as is suggested by the Japanese trial for ES-SCLC 12 and is now an open question for LS-SCLC-there is meaningful precedent from the WBRT literature for a reappraisal of the role of PCI in contemporary practice.…”

“…If PCI does not in fact improve OS in the modern era of MRI staging, surveillance, and salvage therapy options-as is suggested by the Japanese trial for ES-SCLC 12 and is now an open question for LS-SCLC-there is meaningful precedent from the WBRT literature for a reappraisal of the role of PCI in contemporary practice. 69,70 Radiosurgery and SCLC Looking forward, by avoiding compulsory radiation to the entire brain and identifying more patients with limited BMs, increasing adoption of active surveillance should open the door to further investigation of radiosurgery as a truly first-line therapy in selected patients with SCLC. 71 The historical role of PCI has almost certainly contributed to a more resilient acceptance of WBRT for limited BMs in SCLC despite the transition toward radiosurgery for limited BMs in most other histologic types.…”