2026-04-14T04:29:10Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/129872025-05-03T03:20:49Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Canale, Matteo author Angeli, Davide author Tedaldi, Gianluca author Priano, Ilaria author Urbini, Milena author Petracci, Elisabetta author 2025-04-25T05:57:36Z 2025-04-25T05:57:36Z 2025-02-20 Immunotherapy; Small-cell lung cancer; Tumor mutation burden Inmunoterapia; Cáncer de pulmón de células pequeñas; Carga de mutación tumoral Immunoteràpia; Càncer de pulmó de cèl·lules petites; Càrrega de mutació tumoral Objective: Extensive stage Small-Cell Lung Cancer (ES-SCLC) is the most lethal lung cancer, and the addition of immunotherapy conferred a slight survival benefit for patients. Extensive molecular profiling of patients treated with chemotherapy (CT) or chemotherapy plus immunotherapy (CT+IO) would be able to identify molecular factors associated with patients' survival. Material and methods: In this retrospective study, 99 ES-SCLC patients were considered. Of the 79 includible patients, 42 received CT (median age 71 y/o, I-IIIQ: 65-76), and 37 received CT+IO (median age 71 y/o, I-IIIQ 66-75). The FoundationOne CDx assay was performed on patients' tumor tissues. Results: The most mutated genes were TP53 (99%), RB1 (78%), PTEN (23%) and MLL2 (20%), with no significant differences between the treatment groups. As a continuous variable, Tumor Mutation Burden (TMB) had an effect on patients' progression-free survival (PFS) by type of treatment (HR 1.81 (95%, CI: 0.99-3.31) and HR 0.84 (95%, CI: 0.56-1.26) for patients treated with CT and CT+IO, respectively). TMB was also computed and dichotomized using two different cut-offs: considering cut-offs of 10 mut/Mb and >16 mut/Mb, 45 patients (57%) and 68 patients (86.1%) had a low TMB, respectively. A high TMB (cut-off 10 mut/Mb) predicted worse PFS in patients treated with CT (p=0.046); even though not statistically significant, a high TMB (cut-off 16 mut/Mb) predicted a better survival in patients treated with CT+IO. Moreover, at univariate analysis, MLL2 mutations were associated with better prognosis in the overall case series (HRPFS = 0.51, 95% CI: 0.28-0.94), and overall survival (HROS = 0.52, 95% CI: 0.28-0.97). Conclusion: In ES-SCLC, TMB is associated with worse survival in patients treated with CT alone, and with better survival in patients treated with CT+IO, whether considered as a continuous or a dichotomized variable, at different cut-offs. Alterations in epigenetic factors are also associated to better patient prognosis. http://hdl.handle.net/11351/12987 Anomalies cromosòmiques Pulmons - Càncer - Tractament Pulmons - Càncer - Aspectes genètics Quimioteràpia combinada Pulmons - Càncer - Prognosi Marcadors tumorals PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Small Cell Lung Carcinoma Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma pulmonar de células pequeñas Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales Genomic Profiling of Extensive Stage Small-Cell Lung Cancer Patients Identifies Molecular Factors Associated with Survival