AUTHOR=Longo Vito , Della Corte Carminia Maria , Russo Alessandro , Spinnato Francesca , Ambrosio Francesca , Ronga Riccardo , Marchese Antonella , Del Giudice Teresa , Sergi Concetta , Casaluce Francesca , Gilli Marina , Montrone Michele , Gristina Valerio , Sforza Vincenzo , Reale Maria Lucia , Di Liello Raimondo , Servetto Alberto , Lipari Helga , Longhitano Claudio , Vizzini Laura , Manzo Anna , Cristofano Antonella , Paolelli Loretta , Nardone Annalisa , De Summa Simona , Perrone Antonella , Bisceglia Carmela , Derosa Caterina , Nardone Valerio , Viscardi Giuseppe , Galetta Domenico , Vitiello Fabiana 

TITLE=Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1289434

DOI=10.3389/fimmu.2023.1289434

ISSN=1664-3224

ABSTRACT=Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune response. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune response induced by RT are also presented. Methods: A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy. Results: Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and