Consolidation Radiation Therapy for Extensive Stage Small Cell Lung Cancer: Determining the Optimal Dose Using the National Cancer Data Base

Abstract

Multiple randomized controlled trials have shown a benefit with consolidative thoracic radiation therapy (TRT) for patients with extensive stage small cell lung cancer (ES-SCLC) who have responded to chemotherapy. Various fractionation regimens are used for TRT ranging from 30 Gy in 10 fractions in the CREST trial to 54 Gy delivered twice daily over 36 fractions in a clinical trial by Jeremic et al. In this study, we utilize the National Cancer Database (NCDB) to assess optimal dose for consolidative TRT for ES-SCLC. We searched the NCDB for all patients with ES-SCLC managed with induction chemotherapy followed by TRT from 2004 to 2014. Patients with brain metastases, prior cancer history or treatment with palliative intent were excluded. Patients treated with TRT prior to 60 days or after 180 days from the start of chemotherapy were excluded to omit patients requiring upfront or delayed palliative RT respectively. All retrievable demographic, tumor specific, and treatment factors were recorded. The overall survival (OS) was estimated using the Kaplan-Meier method, according to prescribed dose as well as equivalent dose in 2 Gy fractions (EQD2) with univariate and multivariate Cox models. Factors significant on univariate analysis (UVA) were incorporated into a multivariate survival model. A total of 754 patients with ES-SCLC treated with chemotherapy followed by TRT were identified, with a median follow up of 35.2 months (95% CI 31.1-42.6). Modes of TRT dose were identified and subsequently dose levels were stratified into 30 Gy or less (n=159), 30.01-50 Gy (n=368), and >50 Gy (n=227). To account for various fractionations, dose was also converted into EQD2 utilizing an alpha-beta ratio of 10 Gy approximated to match dose cohorts, stratified into 36 Gy or less (n=159), 36.01-50 Gy (n=368), >50 Gy (n=227). Decreased OS compared pairwise with other groups was significantly associated with dose 30 Gy or less (p<0.001) or an EQD2 36 Gy or less (P<0.001). Median survival for an EQD2 of 36 Gy or less was 10.9 months (95% CI 9.7-11.8), for EQD2 36.01-50 Gy was 14.4 months (95% CI 13.2-15.6), and > 50 Gy was 14.2 months (95% CI 12.6-15.5). UVA was significant for EQD2, insurance status with Medicare and level of education, with no significant difference according to age, race, Charleson-Deyo comorbidity score, type of or distance from treatment facility or income. On multivariate analysis, taking into account age, race, insurance status and education level and EQD2, only EQD2 remained a significant predictor of survival, with a HR of 0.55 (95% CI 0.44-0.67, p<0.001) for an EQD2 of 36.01-50 Gy, and a HR of 0.60 (95% CI 0.48-0.75, p<0.001) for an EQD2 > 50 Gy. This largest modern hospital-based analysis suggests consolidation TRT with doses greater than 30 Gy and an EQD2 > 36 Gy is associated with improved OS in ES-SCLC.