Our purpose was to evaluate neurocognitive function (NCF) and clinical outcomes after early hippocampal avoidance (HA) prophylactic cranial irradiation (PCI) in limited disease (LD) small cell lung cancer (SCLC).

In a phase 2 trial, patients with LD SCLC received HA-PCI concomitant with the second cycle of chemotherapy and thoracic radiation therapy. All patients underwent objective NCF testing at baseline, 6 weeks, and 6 and 12 months after HA-PCI. NCF tests included Hopkins Verbal Learning Test Revised, Controlled Oral Word Association, and Trail Making Tests A and B. The primary endpoint was NCF decline at 6 months after HA-PCI. We assumed ≤30% of patients with no NCF decline to be unpromising. Secondary endpoints included brain metastases-free survival (BMFS), overall survival (OS), and safety of the concomitant treatment.

Among the 44 patients enrolled in the trial, 38 had evaluable NCF assessment at 6 months after HA-PCI. The proportion of evaluable patients showing no NCF decline at 6 and 12 months was 34.2% (90% confidence interval [CI], 21.6-48.8) and 48.5% (95% CI, 30.8-66.5), respectively. Median follow-up was 13.2 months (95% CI, 12.6-14.1). At 12 months, BMFS was 84.2% and OS was 87.7% (95% CI, 73.0-94.7). Four patients died of SCLC, 1 of respiratory failure, 1 of hemorrhage, and 1 for unknown reason. The most frequently reported grade ≥3 acute adverse events were anemia (21.4%), febrile neutropenia (19.1%), and fatigue (14.3%).

The proportion of patients showing no NCF decline 6 and 12 months after early HA-PCI does not appear to be better than, but rather similar to, that observed in patients receiving sequential PCI without HA. Early HA-PCI in LD SCLC is feasible, with observation of promising BMFS and OS in this selected population.