Debate: adjuvant whole brain radiotherapy or not? More data is the wiser choice.

Abstract

Every year 170,000 patients are diagnosed with brain metastases (BMs) in the United States. Traditionally, adjuvant whole brain radiotherapy (AWBRT) has been offered following local therapy with neurosurgery (NSx) and/or stereotactic radiosurgery (SRS) to BMs. The aim is to increase intracranial control, thereby decreasing symptoms from intracranial progression and a neurological death. There is a rapidly evolving change in the radiation treatment of BMs happening around the world. AWBRT is now being passed over in favour of repeat scanning at regular intervals and more local therapies as more BMs appear radiologically, BMs that may never become symptomatic. This change has happened after the American Society for Radiation Oncology (ASTRO) in Item 5 of its “Choosing Wisely 2014” list recommended: “Don't routinely add adjuvant whole brain radiation therapy to SRS for limited brain metastases”. The guidelines are supposed to be based on the highest evidence to hand at the time. This article debates that the randomised controlled trials (RCTs) published prior to this recommendation consistently showed AWBRT significantly increases intracranial control, and avoids a neurological death, what it is meant to do. It also points out that, despite the enormity of the problem, only 774 patients in total had been randomised over more than three decades. These trials were heterogeneous in many respects. This data can, at best, be regarded as preliminary. In particular, there are no single histology AWBRT trials yet completed. A phase two trial investigating hippocampal avoiding AWBRT (HAWBRT) showed significantly less NCF decline compared to historical controls. We now need more randomised data to confirm the benefit of adjuvant HAWBRT. However, the ASTRO Guideline has particularly impacted accrual to trials investigating this, especially the international ANZMTG 01.07 WBRTMel trial. This is an RCT investigating AWBRT following local treatment in patients with one to three BMs from melanoma. WBRTMel has accrued 196 of a required 220 to date but accrual has slowed. HAWBRT may now never be tested in a randomised setting. Encouraging more data in AWBRT is the wiser choice.