2025 Hot Topic in Basic & Translational Science: Small Cell Lung Cancer - ePosters-EP01.09: Subtyping Small Cell Lung Cancer Reveals Inflammatory Subtypes with Improved Radiosensitivity and Chemoradiotherapy Outcomes

EP01.09: Subtyping Small Cell Lung Cancer Reveals Inflammatory Subtypes with Improved Radiosensitivity and Chemoradiotherapy Outcomes

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This document details a study focusing on molecular subtyping of Small Cell Lung Cancer (SCLC) to determine variations in radiosensitivity and treatment outcomes. In this study, 81 samples from 77 patients were analyzed, with the participants having a median age of 66 years, predominantly stage III disease, and a median time to progression (TTP) and overall survival (OS) of 15.5 and 33.9 months, respectively.<br /><br />Through computational analysis (cNMF and differential expression), four molecular subtypes of SCLC were identified: ASCL1-driven (A), NEUROD1-driven (N), inflamed neuroendocrine (I-NE), and inflamed non-neuroendocrine (I-nNE). The inflamed subtypes (I-NE and I-nNE) had higher immune cell composition and demonstrated improved outcomes in response to treatment, showing higher radiosensitivity and longer TTP and survival times. Specifically, SCLC-I-NE had a lower radiosensitivity index (RSI) indicating increased radiosensitivity and better treatment-related outcomes. Conversely, the non-inflamed subtype, SCLC-N, exhibited higher radioresistance with poorer TTP and OS.<br /><br />The study compared two radiotherapy regimens (high-dose and standard dose) for limited-stage SCLC to evaluate the impact of molecular subtypes on radiosensitivity and clinical outcomes. Results show significant correlations between subtype characteristics, RSI, and treatment outcomes, emphasizing the potential benefit of utilizing molecular subtyping in predicting and enhancing personalized treatment strategies for SCLC patients. The inflamed subtypes, with their improved radiosensitivity and potential for better chemoradiotherapy outcomes, highlight the importance of considering immune profiles in therapeutic planning.<br /><br />Authors of the study are associated with the Department of Clinical and Molecular Medicine at the Norwegian University of Science and Technology and the Department of Oncology at St. Olavs hospital, Trondheim University Hospital, Norway. The references cited provide further context for the radiosensitivity index and immune heterogeneity studies in SCLC.

Asset Subtitle

Rafael Oliveira

Keywords

Small Cell Lung Cancer

molecular subtyping

radiosensitivity

treatment outcomes

immune profiles

ASCL1-driven

NEUROD1-driven

inflamed neuroendocrine

radioresistance

personalized treatment