Phase III randomized trial of Prophylactic Cranial Irradiation with or without Hippocampus Avoidance in SCLC (NCT01780675).

Abstract Purpose To compare neurocognitive functioning in Small Cell Lung Cancer patients(SCLC) who received prophylactic cranial irradiation(PCI) with or without hippocampus avoidance (HA). Material and Methods In a multicenter randomized phase III trial (NCT01780675) patients with SCLC were randomized to standard PCI (25 Gy /10 fractions) or HA-PCI. Neuropsychological tests were performed at baseline and 4, 8, 12, 18 and 24 months after PCI. The primary endpoint was total recall on the Hopkins Verbal Learning Test- Revised(HVLT-R) at 4 months; a decline of at least 5 points from baseline was considered a failure. Secondary endpoints included other cognitive outcomes, evaluation of the incidence and location of brain metastases and overall survival(OS). Results From April 2013 until March 2018 a total of 168 patients were randomized. The median follow-up time was 26 .6 months. In both treatment arms 70% of patients had limited disease and baseline characteristics were well balanced. Decline on the HVLT-R total recall score at 4 months was not significantly different between the arms: 29% of PCI patients dropped ≥5 points and 28% of HA-PCI patients (p=1.000). Performance on other cognitive tests measuring memory, executive function, attention, motor function and processing speed did not change significantly different over time between the groups. The OS was not significantly different. The cumulative incidence of brain metastases at 2 years was 20% (95% CI: 12% - 29%) for the PCI arm and 16% (95% CI: 7% - 24%) for the HA-PCI arm. Conclusion This randomized phase III trial did not show lower probability of cognitive decline in SCLC patients receiving hippocampus avoidance PCI compared to conventional PCI. No increase in brain metastases at 2 years was observed in the HA- PCI arm.