ASCO15: Compromised cognitive function negates the benefits of adjuvant whole-brain radiation therapy for limited brain metastases

A late-breaking abstract highlighted in the Plenary Session at the 2015 annual meeting of the American Society of Clinical Oncology (ASCO; 29 May–2 June, IL, USA) added to the long-running debate concerning the use of whole-brain radiation therapy (WBRT) for the treatment of brain metastases. The presentation detailed the results of a Phase III trial in which patients with 1–3 brain metastases were assigned to receive radiosurgery or radiosurgery followed by WBRT. Individuals who received WBRT following radiosurgery were more likely to experience cognitive decline and were not associated with a significant increase in survival.

“We used to offer WBRT early on, but we now know that the toxicities of this therapy are worse for the patient than cancer growth or recurrences in the brain,” commented senior study author Jan C Buckner of Mayo Clinic (MN, USA). “We expect that practice will shift to reserve the use of WBRT for salvage treatment and end-stage palliative care.”

Overall, 213 patient were enrolled into the NCCTG N0574 study, all of whom had 1–3 small brain metastases that had been confirmed as <3 cm by contrast MRI. Of those enrolled, patients had a median age of 60 years, with lung cancer representing the most common primary disease (68%).

These individuals were randomized to treatment with either stereotactic radiosurgery alone, or stereotactic radiosurgery followed by WBRT. Cognitive testing was carried out both before and after treatment was received, with baseline characteristics well balanced between the study groups. The primary endpoint of the study was cognitive progression, which was defined as decline >1 SD from baseline in any of the six cognitive tests at 3 months.

At 3-month follow-up, 90% of those patients treated with radiosurgery followed by WBRT displayed cognitive decline, compared with 64% in the radiosurgery group. Specifically, the individuals treated with WBRT had a greater decline in immediate recall (30% vs 8%), delayed recall (51% vs 20%), and verbal communication (19% vs 2%) compared with the radiosurgery alone arm. The study demonstrates that there was no statistically significant increase in overall survival with the addition of WBRT, but intracranial tumor control was increased (66.1% and 50.5% with radiosurgery alone at 6/12 months vs 88.3% and 84.9% with radiosurgery +WBRT [p < 0.001]).

The study authors believe that these results could have broad implications for oncology practice. Buckner continued, remarking that the ongoing results of this trial will likely help determine which therapy should represent the standard of care for these patients.

Providing the ASCO perspective, Brian Michael Alexander of the Dana-Farber Cancer Institute (MA, USA) commented: “This study will help shape treatment decisions for thousands of current and future patients. As doctors, we want the very best for our patients, and sometimes giving less treatment offers the better result. In patients treated with radiosurgery, the benefits of adding whole brain radiation must be weighed against the risks and side effects of treatment, and this study helps us identify the tradeoffs involved.”

Source: ASCO press release; ASCO 2015 LBA4: NCCTG N0574 (Alliance): A phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases.

Want to learn more about radiosurgery and the role of WBRT for the treatment of brain metastases? Watch our exclusive webinar on the topic.