Association Between Prophylactic Cranial Irradiation and Improved Overall Survival in Small Cell Lung Cancer

Abstract

While prior evidence had suggested that prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) may improve overall survival, a more recent trial did not demonstrate a survival benefit in patients with extensive-stage (ES)-SCLC. In light of conflicting evidence, the role of PCI in both limited-stage (LS) and ES-SCLC remains controversial. We therefore examine the use and outcomes of PCI in a large, curated, and contemporary cohort of patients with SCLC. We performed a retrospective cohort analysis of patients with LS-SCLC and ES-SCLC diagnosed between January 1, 2013 to September 30, 2019 from the nationwide Flatiron Health electronic health record-derived de-identified database. Receipt of radiation and PCI were chart-confirmed. Kaplan-Meier estimate, log-rank test, and multivariable Cox proportional hazards modeling (with forward selection of demographics, smoking history, practice type, cancer stage, and performance status variables with p<0.1 on univariate model) were used for time-to-event analysis. We performed sequential landmark analysis to account for immortal time bias. The landmark was chosen by increasing the required minimum length of survival for inclusion until the proportional hazards assumption was no longer violated. A total of 6,489 patients with SCLC were included in our cohort. Patients had a median age of 67 (IQR 60-74), 3,106 (47.9%) were male, 4,837 (74.5%) were white, 6,378 (98.3%) had a smoking history, and 6,066 (93.5%) were treated in a community setting. There were 2,091 (32.2%) limited-stage and 4,038 (62.2%) extensive-stage patients. Overall documented PCI use decreased from 24.2% of patients diagnosed in 2013 to 16.0% of patients diagnosed in 2018 (p<0.001). For limited-stage patients, documented PCI use decreased from 46.2% in 2013 to 35.2% in 2018 (p = 0.005), and for extensive-stage patients decreased from 13.9% in 2013 to 7.0% in 2018 (p<0.001). On multivariable analysis using a landmark of 256 days, documented PCI use was significantly associated with improved overall survival (HR 0.68, 95% CI 0.60-0.77, p<0.001; log-rank p<0.001). After restricting analysis to only extensive-stage patients, using the same landmark, documented use of PCI was still significantly associated with improved overall survival (HR 0.79, 95% CI 0.70-0.90, p<0.001; log-rank p<0.001). PCI is associated with improved overall survival for both LS-SCLC and ES-SCLC patients in the real-world setting, though further research is needed to determine how much of this effect is due to patient selection. Despite conflicting clinical trial results being demonstrated in the extensive-stage setting, documented PCI use has decreased significantly among both limited-stage and extensive-stage patients.