Re-thinking the Role of Thoracic Radiotherapy in the First-Line Treatment for Extensive-Stage Small Cell Lung Cancer.

Abstract

Opinion statement: Extensive-stage small cell lung cancer (ES-SCLC) remains a challenging disease with a poor prognosis, despite recent advances in immunotherapy. The integration of thoracic radiotherapy (TRT) with chemoimmunotherapy has emerged as a promising strategy to improve treatment outcomes. However, the optimal role and timing of TRT in the first-line treatment of ES-SCLC in the immunotherapy era are still under investigation. Traditional approaches to TRT, based on high-dose regimens, have shown limited efficacy in overcoming the immunosuppressive tumor microenvironment (TME) characteristic of SCLC. The advent of low-dose radiotherapy (LDRT) offers a novel perspective by modulating the TME to enhance antitumor immunity. This review aims to re-evaluate the role of TRT, particularly LDRT, in the context of evolving immunotherapy strategies for ES-SCLC. By examining recent clinical trials and preclinical studies, we discuss the potential mechanisms through which LDRT can reshape the TME, promote immune activation, and improve the efficacy of immunotherapy. Additionally, we highlight the ongoing clinical trials that are essential for validating these approaches and determining the optimal treatment paradigms.