Hippocampal Avoidance During Prophylactic Cranial Irradiation for Patients With Small Cell Lung Cancer: Randomized Phase II/III Trial NRG-CC003

PURPOSE: Hippocampal avoidance (HA) during therapeutic whole-brain radiotherapy reduces the risk of neurocognitive function (NCF) toxicity in patients with brain metastasis. This trial hypothesized that HA during prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) leads to noninferior intracranial relapse (ICR) and reduction in NCF toxicity. METHODS: This randomized phase II/III trial enrolled patients with SCLC, no brain metastases, and response to chemotherapy. The primary end points were 12-month ICR (noninferiority design, randomized phase II) and 6-month Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall (DR) failure (phase III). Secondary end points were failure in any NCF test, health-related quality of life (HRQOL), overall survival (OS), and toxicity. RESULTS: = .88). CONCLUSION: Although the study did not meet its primary end point of DR preservation, HA during PCI reduces the risk of overall neurocognitive toxicity with noninferior ICR risk and similar survival.