Impact of Early Prophylactic Cranial Irradiation With Hippocampal Avoidance on Neurocognitive Function in Patients With Limited Disease Small Cell Lung Cancer. A Multicenter Phase 2 Trial (SAKK 15/12).

PURPOSE 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). METHODS AND MATERIALS In a phase II trial, patients with LD SCLC received HA-PCI concomitant to the 2nd cycle of chemotherapy and thoracic radiotherapy. All patients underwent objective NCF testing at baseline, 6 weeks, 6 and 12 months after HA-PCI. NCF tests included Hopkins Verbal Learning Test Revised, Controlled Oral Word Association, and Trail Making Tests (TMT) A and B. The primary endpoint was NCF decline at 6 months after HA-PCI. We assumed ≤ 30% of patients with no NCF decline as unpromising. Secondary endpoints included brain metastases free survival (BMFS), overall survival (OS), and safety of the concomitant treatment. RESULTS 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% 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 due to SCLC, 1 due to respiratory failure, 1 due to 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%). CONCLUSIONS The proportion of patients showing no NCF decline 6 and 12 months after early HA-PCI does not appear to be better, 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