Hippos don’t lie.

Top Line: Whole brain radiation (WBRT) is effective at preventing progression of brain metastases, but some question the net benefit if patients still experience neurocognitive decline from the treatment itself.

The Study: In NRG CC001, over 500 patients with brain mets > 0.5 cm from the hippocampi were randomized to standard WBRT or hippocampal avoidance WBRT (HA-WBRT) with a primary endpoint of cognitive decline. All patients received memantine, a medication that blocks the NMDA receptor whose excessive stimulation in dementia is thought to contribute to neurodegeneration. To quantify the primary endpoint, 4 cognitive tests were used and repeated 2, 4, 6, and 12 months after radiation. Time to cognitive failure was defined as a significant decrease in any one of the cognitive tests. Between 2 and 4 months, over half of patients in each arm had cognitive decline. For individual cognitive tests, there was no difference at 2 months (n=298), but then HA-WBRT gained an advantage in executive function at 4 months (n=211) and in learning and memory at 6 months (n=159). Patients who received HA-WBRT reported less trouble remembering things and less speech difficulty at 6 months. As anticipated, there was no difference in intracranial progression or survival. Finally, median survival was 6-7 months so these denominators at various time points dropped pretty quickly.

TBL: The authors (and editors) are so bold as to conclude a hippocampal avoidance technique should now be the standard for care for patients with good performance status receiving whole brain radiation—we’ll see what the payers think. | Brown, J Clin Oncol 2020