Limited-Stage Small Cell Lung Cancer: Is Prophylactic Cranial Irradiation Necessary?

Abstract

Prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases in patients with limited stage small cell lung cancer (LS-SCLC). However, PCI is associated with significant neurocognitive sequelae. In prior studies assessing the role of PCI in SCLC, patients have not been consistently staged with pretreatment magnetic resonance imaging (MRI). Modern improvements in staging imaging continue to enhance the ability to detect early brain metastases. We sought to determine if PCI was associated with improved overall survival (OS), progression free survival (PFS), and cumulative incidence (CI) of brain metastases in LS-SCLC patients in the modern era of MRI staging. We identified patients with LS-SCLC treated with curative intent between 2006-2018 staged initially with MRI and no progression of disease after initial therapy. Kaplan-Meier estimates of OS and PFS were calculated and multivariate Cox proportional hazards models were generated. The cumulative incidence of brain metastases was estimated using competing risks methodology. In total, 96 patients were identified, 39 (41%) of whom received PCI. Median follow-up was 39 months. The median OS for the cohort was 34.0 months (95% CI 23.9-55.2) and PFS was 18.3 months (95% CI 10.3-29.9). Median OS in those treated with PCI versus those not treated with PCI was 35.8 months (95% CI 31.8-NR) versus 30.5 months (95% CI 16.1-56.1, p=0.09) while median PFS was 24.4 months (95% CI 19.1-NR) versus 10.6 (95% CI 9.2-29.9, p=0.04). At 2 years, the CI of brain metastases was 12% with PCI and 33% without PCI; this increased to 39% and 33% by 4 years (p=0.68). Multivariate analysis revealed age ≥70 (HR 1.97) and partial response/stable disease after initial therapy (PR/SD) versus complete response (CR; HR 4.26) as significant factors influencing OS. Patients with a PR/SD had an increased of HR 4.99 for PFS whereas patients treated with PCI had a reduced HR for PFS. Stratified by disease response, patients with CR did not benefit from PCI (p=0.67), while those with PR/SD had improved PFS (p=0.02). Overall, PCI was associated with improved PFS and reduced cumulative incidence of brain metastases in the MRI era. Patients who achieved a CR to initial therapy did not experience a significant PFS benefit with the addition of PCI. This data is hypothesis generating and may indicate that subsets of LS-SCLC patients may potentially be spared from the significant neurotoxic sequelae of PCI in the era of modern imaging. Further prospective studies are needed.