Prospective Study of Hippocampal-Sparing Prophylactic Cranial Irradiation in Limited-Stage Small Cell Lung Cancer

Abstract

Toprospectively evaluate cognitive function and intracranial failure patterns after hippocampal-sparing prophylactic cranial irradiation (PCI) for limited-stage small cell lung cancer (SCLC). Adults with limited-stage SCLC, achieving a complete response to chemoradiotherapy and no brain metastases, were eligible. Patients received PCI 25Gy/10 fractions, with a mean hippocampal dose limited to <8Gy and ≥90% of the brain receiving 90% of the prescription. A diverse battery of neuropsychological testing was performed at baseline and 6 and 12months after PCI. Brain MRI scans were performed at baseline and 6, 12, 18, and 24months. The primary endpoint was memory measured by the Hopkins Verbal Learning Test-Revised Delayed Recall at 6months after PCI. The 25-Gy arm of Radiation Therapy Oncology Group protocol 0212 was used as a reference of potential efficacy. Development of intracranial metastases was recorded. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Eight men and 12 women with a median age of 61years enrolled. Two-year overall survival was 88% (95% confidence interval 68%-100%). There was no significant decline in performance between baseline and 6 or 12months for any of the tests. The association between baseline intelligence quotient and change in performance on testing was not significant. Magnetic resonance imaging revealed asymptomatic brain metastases at a cumulative rate of 20%, with no concurrent extracranial progression. Two patients developed a metastasis in the under-dosed region. Neither involved the dentate gyrus, but 1 involved the avoidance region. Both patients concurrently developed additional metastasis in fully treated brain regions. There were 2 neurologic deaths. This prospective study suggests a potential benefit of hippocampal sparing in limiting the neuropsychological sequelae of brain radiation, but with a risk of failures in the spared region. These data strongly support continued enrollment on ongoing cooperative group randomized trials. Clinical Trials registration number: NCT01797159.