Brain metastasis (BM) is a major cause of suffering and health costs in cancer patients. Whole-brain radiation therapy (WBRT) offers tumor shrinking and palliation in many cases, but it has been speculated that these benefits may be outweighed by adverse effects on neurocognitive function (NCF).

Two hundred eight BM patients from the WBRT arm of phase III trial PCI-P120-9801 evaluating motexafin gadolinium were analyzed. NCF, assessed by tests of memory, executive function, and fine motor coordination, was correlated to magnetic resonance imaging-measured BM volume. NCF and survival were compared in 135 patients assessable at 2 months with tumor shrinkage below (poor responders) and above (good responders) the population median (45%). Mean NCF scores and BM volume at 4 and 15 months were compared.

Good responders experienced a significantly improved survival (unidirectional P = .03). For all tests, the median time to NCF deterioration was longer in good compared with poor responders, with statistical significance seen for Trailmaking B (executive function), and two Pegboard tests (fine motor). In long-term survivors, tumor shrinkage significantly correlated with preservation of executive function and fine motor coordination (r = 0.68 to 0.88). During the early follow-up period, the population mean NCF scores were dominated by patients with progressive disease. A small subset of 15-month survivors had stable or improving scores, and greater mean BM reduction.

WBRT-induced tumor shrinkage correlates with better survival and NCF preservation. NCF is stable or improved in long-term survivors. Tumor progression adversely affects NCF more than WBRT does, thus making enhancement of radiation response a worthwhile aim in this patient population.