Time from Stereotactic Radiotherapy to Immunotherapy Is a Predictor for Outcome in Stage IV Non-Small Cell Lung Cancer

Rodney Wegner,Stephen Abel,Shaakir Hasan,Vivek Verma,Athanasios Colonias,Richard White,Dulabh Monga,Gene Finley

doi:10.29245/2578-3009/2019/2.1171

Abstract

Immunotherapy (IMT) has revolutionized the treatment of stage IV non-small cell lung cancer (NSCLC). However, optimal timing of IMT in relation to stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) is unknown. Utilizing the National Cancer Database, we examined trends in IMT use in metastatic NSCLC patients and the potential survival implications of IMT timing in relation to SBRT/SRS. We queried the NCDB for patients with Stage IV NSCLC diagnosed between 2004-2015. Patients receiving IMT and SBRT/SRS to any site were included. Multivariate logistic regression identified predictors of IMT use. Receiver operator characteristic curve analysis determined an a priori timeframe between SBRT and IMT predictive of optimal overall survival (OS). Univariate and multivariate analyses identified factors predictive of OS. Propensity-adjusted Cox proportional hazard ratios were used to mitigate indication bias. Of 13,862 eligible patients, 371 received IMT. The majority (75%) received chemotherapy. IMT use was associated with improved median OS on univariate analysis (17 vs. 13 months, p<0.0001). Adenocarcinoma histology, chemotherapy use, and recent treatment year were associated with IMT. On multivariate propensity-adjusted Cox regression, predictors for improved OS included: younger age, lower comorbidity score, lower grade, private insurance, IMT use, and female sex. Patients treated ≥ 21 days (a priori threshold) after SBRT/SRS initiation had improved median OS (19 vs. 15 months, p=0.0335). In patients with Stage IV NSCLC, IMT use following SBRT/SRS has increased. OS improved when IMT was given ≥3 weeks after initiating SBRT/SRS; suggesting a potential optimal time-frame between RT and IMT.

Highlights

Lung cancer remains the leading cause of cancer mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the vast majority of cases[1]
Utilizing the National Cancer Database, we examined trends in IMT use in metastatic nonsmall cell lung cancer (NSCLC) patients and the potential survival implications of IMT timing in relation to stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS)
Despite the mounting evidence regarding the facilitative relationship between radiation therapy (RT) and IMT, optimal timing of both modalities remains limited to theoretical discussions rather than having an established evidence base

Summary

Introduction

Lung cancer remains the leading cause of cancer mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the vast majority of cases[1]. Despite advances in diagnostic imaging and population based screening recommendations, many NSCLC patients still present with advanced disease[2]. In patients with stage IV disease, systemic therapy, in the form of chemotherapy, has been the mainstay of treatment. The development of targeted therapy for gene mutations in NSCLC has helped individualize treatment for this patient population[3]. The role for immunotherapy (IMT) in advanced NSCLC continues to expand, and is quickly becoming the standard of care[4, 5]. Radiation therapy (RT) is playing a larger role in the metastatic setting. Limited to palliation, RT has been increasingly utilized in the treatment of oligometastatic disease, as emerging data suggests improved outcomes[6, 7]

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Discussion

Conclusion