WCLC 2025 - Posters & ePosters-P1.07.36 A Three-Gene Signature Predicting Local Recurrence in Stage I-III NSCLC Patients Treated With Radiation Therapy

P1.07.36 A Three-Gene Signature Predicting Local Recurrence in Stage I-III NSCLC Patients Treated With Radiation Therapy

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This study investigates molecular biomarkers predictive of local recurrence in stage I-III non-small cell lung cancer (NSCLC) patients treated with either surgery or radiation therapy (RT). Analyzing data from 1,993 NSCLC patients in the Flatiron-Foundation Medicine Clinico-Genomic Database, the authors assessed associations between gene mutations and outcomes after definitive treatment.<br /><br />Key findings include that mutations in ATM, BRCA1, and RB1 correlate with improved outcomes specifically in RT-treated patients, but not those undergoing surgery, implying these mutations confer radiosensitivity. Conversely, mutations in NFE2L2, TP53, PIK3CA, and KEAP1 were linked to higher local recurrence risk following RT, suggesting they contribute to radioresistance. These mutation-outcome relationships were not observed in surgery patients.<br /><br />The clinical implications propose that radiosensitizing mutations might enable effective RT with lower radiation doses, potentially reducing toxicity, whereas radioresistance-associated mutations could warrant higher radiation doses, closer monitoring, or preference for surgery. This molecular stratification approach can improve personalized treatment decisions in NSCLC management beyond conventional criteria like surgical candidacy and patient preference.<br /><br />Demographic data showed a balanced distribution of age, sex, race, histology, and clinical stage among surgery and RT groups. Most RT patients had stage III NSCLC, while a majority of surgery patients had earlier-stage disease. Various neoadjuvant therapies were used across cohorts.<br /><br />The study highlights the emergent role of genomic biomarkers in predicting NSCLC treatment response and local recurrence risk. The authors advocate for further research to validate these findings, identify additional gene signatures, and explore targeted therapies that may enhance radiosensitization, ultimately refining precision radiotherapy strategies in NSCLC care.

Asset Subtitle

Victor Lee

Meta Tag

Speaker Victor Lee

Topic Early-Stage Non-small Cell Lung Cancer

Keywords

non-small cell lung cancer

NSCLC

local recurrence

molecular biomarkers

radiation therapy

surgery

gene mutations

radiosensitivity

radioresistance

precision radiotherapy