Addition of whole-brain radiation therapy to standard radiosurgery results in worse learning and memory function for patients with brain tumours

Patients with brain tumours are currently treated with stereotactic radiosurgery (SRS), with or without whole-brain radiotherapy (WBRT), but to date it has been unclear whether addition of WBRT outweighed the risks. In an article published in the November edition of The Lancet Oncology, the authors conclude that patients given WBRT are at greater risk of decline in learning and memory function, and recommend that SRS plus close clinical monitoring be the standard initial treatment. The Article is written by Dr Eric L Chang, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA, and colleagues.

In this randomised controlled trial, patients with one to three newly diagnosed brain metastases were randomly assigned to SRS plus WBRT (28 patients) or SRS alone (30) between 2001 and 2007. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in an assessment called the Hopkins Verbal Learning Test—Revised (HVLT-R) total recall at 4 months. After these 58 patients were recruited, the trial was stopped because there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function at 4 months than were patients assigned to receive SRS alone.

Patients randomly assigned to SRS plus WBRT were more likely to show a significant drop in HVLT-R total recall at 4 months than were patients randomly assigned to SRS alone (52% vs 24%, respectively), despite the fact that patients in the SRS alone group showed a higher overall brain tumour recurrence rate than did those patients in the SRS plus WBRT group. This finding persisted at 6-month follow-up. At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from recurrence at 1 year, compared with 27% of patients who received SRS alone. But despite this difference in recurrence, the authors advise against WBRT because it causes more of decline in brain function. When tumours recur, they could be effectively managed with surgery if spotted early through regular monitoring, with much lower decline in brain function than is seen in those patients receiving WBRT upfront.

The authors say: “Applicability of the findings is dependent on the willingness of patients and their physicians to adhere to a schedule of close monitoring, having consistent access to high-quality MRI, having access to a neurosurgical team willing and able to perform salvage resections when indicated, and applying strict physics quality-assurance procedures for SRS.”

They conclude: “This study provides level 1 evidence to support the use of SRS alone in the initial management of patients newly diagnosed with one to three brain metastases. We recommend that initial SRS alone combined with close clinical monitoring should be the preferred treatment strategy for such patients.”