Whole-Brain Radiation Therapy With or Without Hippocampal Avoidance in Limited Stage or Extensive Stage Small Cell Lung Cancer

PRIMARY OBJECTIVES: I. Determine whether the 12-month intracranial relapse rate following hippocampal avoidance (HA)-prophylactic cranial irradiation (PCI) is non-inferior compared to the rate following PCI for patients with small cell lung cancer (SCLC). (Randomized Phase II Component \[Non-Inferiority\]) II. Determine whether HA-PCI reduces the likelihood of 6-month deterioration from baseline in Hopkins Verbal Learning Test (HVLT)-Revised (R) delayed recall compared to PCI for patients with SCLC. (Phase III Component \[Efficacy\]) SECONDARY OBJECTIVES: I. Compare time to cognitive failure, as measured by a battery of tests (HVLT-R, Controlled Oral Word Association (COWA) test, and Trail Making Test (TMT) parts A and B), after PCI versus HA-PCI in SCLC. II. Compare time to cognitive failure as separately measured by each test (HVLT-R for Total Recall and Delayed Recognition, COWA test, and TMT parts A and B), after PCI versus HA-PCI for SCLC. III. Compare patient-reported cognitive functioning and other quality of life domains (assessed by the European Organization for Research and Treatment of Cancer \[EORTC\] Quality of Life Questionnaire (QLQ)-Core \[C\]30 and BN20) between PCI versus HA-PCI for patients with SCLC. IV. Compare overall survival after PCI versus HA-PCI for patients with SCLC. V. Compare 12-month intracranial relapse rate (at completion of phase III) and time to intracranial relapse after PCI versus HA-PCI for patients with SCLC. VI. Evaluate adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. VII. Correlate changes in health-related quality of life (HRQOL) domains with changes in cognitive testing outcomes following PCI versus HA-PCI for patients with SCLC. VIII. Assess cost-effectiveness of HA-PCI (intensity modulated radiation therapy \[IMRT\]) and PCI (3-dimensional conformal radiation therapy \[3DCRT\]) using the EuroQual (EQ)-5-Dimensions (5D)-5L. IX. Correlate miRNA signatures with cognitive failure in SCLC patients who received PCI and HA-PCI. X. Evaluate Apolipoprotein E (APOE) genotyping as potential predictor of neurocognitive decline, hippocampal atrophy after brain irradiation and/or differential benefit from hippocampal avoidance. XI. Evaluate baseline MR imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HA-PCI as compared to PCI. TERTIARY OBJECTIVES: I. Collect serum, whole blood, and urine for future translational research analyses. II. Evaluate baseline magnetic resonance (MR) imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HA-PCI as compared to PCI. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo PCI using 3DCRT daily for 2 weeks. ARM II: Patients undergo PCI with HA using IMRT daily for 2 weeks. After completion of study treatment, patients are followed every 3 months for 1 year, then every 6 months until 3 years and then annually until death.