Improved Overall Survival in Patients Receiving Prophylactic Cranial Irradiation for Node-Negative Limited Stage Small Cell Lung Cancer

Abstract

Roughly one in three patients present with limited stage at the time of small cell lung cancer (SCLC) diagnosis, although SCLC has a high propensity to metastasize to distant sites. Combined modality thoracic radiotherapy and/or surgery and chemotherapy have become the standard of care, and incorporation of prophylactic cranial irradiation (PCI) has been shown to improve overall survival (OS) in several studies and meta-analyses. Data are limited on the potential benefit of PCI in patients without evidence of lymph node involvement (N0). We retrospectively investigated the importance of prognostic factors, including receipt of PCI, in patients with limited stage T1-4N0 SCLC who were registered in the National Cancer Database (NCDB). From the NCDB, we identified a total of 3600 patients with limited stage SCLC without lymph node involvement, who were diagnosed from 2010-2015. Kaplan-Meier analyses, log-rank tests, and multivariate Cox proportional hazards models were used to examine the impact of prognostic factors, including receipt of PCI, on OS. Median age at SCLC diagnosis was 70 years and median OS was 20 months. The majority of the patients were white (n = 3,217, 89.4%) and female (n = 2,027, 56.3%). Patients were primarily treated at a Comprehensive Community Cancer Program (n = 1,686, 46.9%) or Academic Center (n = 1,017, 28.3%) and had insurance through the government (n = 2,787, 77.4%). A minority of patients (n = 293, 8.1%) underwent PCI as part of their initial therapy. Most patients had T1 disease (n = 1,771, 49.2%). With multivariate analysis accounting for age at diagnosis, race, sex, facility type, insurance status, performance status, T stage, and receipt of surgery or systemic therapy, patients who underwent PCI had improved OS (HR = 0.62, p<0.001) with median survival of 44 months compared to 18 months for those who did not. Black race (HR = 0.83, p<0.05), male sex (HR = 0.84, p<0.001), T1 disease (HR = 0.79, p<0.001), receipt of surgery (HR = 0.38, p<0.001), receipt of systemic therapy (H = 0.75, p<0.001), treatment at an Academic Center (HR = 0.89, p<0.05) and private insurance (HR = 0.83, P<0.01) were also associated with improved OS. For patients with limited stage SCLC treated in the era of MR imaging and who were coded as having N0 disease at the time of initial staging, PCI is associated with improved OS in our hypothesis-generating study. Limitations in these analyses include inability to account for selection biases and under-reporting receipt of PCI. These results are consistent with previous work that supports the use of PCI in patients with limited stage SCLC and may help to inform future discussions regarding prevention of metastases to the brain.