ctDNA-based detection of molecular residual disease in stage I-III non-small cell lung cancer patients treated with definitive radiotherapy

Autor: Emily S. Lebow, Narek Shaverdian, Jordan E. Eichholz, Leah B. Kratochvil, Megan McCune, Yonina R. Murciano-Goroff, Justin Jee, Juliana Eng, Jamie E. Chaft, Mark G. Kris, Ekaterina Kalashnikova, Jordan Feeney, Carly Bess Scalise, Sumedha Sudhaman, Charuta C. Palsuledesai, Meenakshi Malhotra, Michael Krainock, Himanshu Sethi, Alexey Aleshin, Minetta C. Liu, Annemarie F. Shepherd, Abraham J. Wu, Charles B. Simone, Daphna Y. Gelblum, Kaylie A. Johnson, Charles M. Rudin, Daniel R. Gomez, Pedram Razavi, Jorge S. Reis-Filho, James M. Isbell, Bob T. Li, Andreas Rimner
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Oncology, Vol 13 (2023)
Druh dokumentu: article
ISSN: 2234-943X
DOI: 10.3389/fonc.2023.1253629
Popis: BackgroundSensitive and reliable biomarkers for early detection of recurrence are needed to improve post-definitive radiation risk stratification, disease management, and outcomes for patients with unresectable early-stage or locally advanced non-small cell lung cancer (NSCLC) who are treated with definitive radiation therapy (RT). This prospective, multistate single-center, cohort study investigated the association of circulating tumor DNA (ctDNA) status with recurrence in patients with unresectable stage I-III NSCLC who underwent definitive RT.MethodsA total of 70 serial plasma samples from 17 NSCLC patients were collected before, during, and after treatment. A personalized, tumor-informed ctDNA assay was used to track a set of up to 16 somatic, single nucleotide variants in the associated patient’s plasma samples.ResultsPre-treatment ctDNA detection rate was 82% (14/17) and varied based on histology and stage. ctDNA was detected in 35% (6/17) of patients at the first post-RT timepoint (median of 1.66 months following the completion of RT), all of whom subsequently developed clinical progression. At this first post-RT time point, patients with ctDNA-positivity had significantly worse progression-free survival (PFS) [hazard ratio (HR): 24.2, p=0.004], and ctDNA-positivity was the only significant prognostic factor associated with PFS (HR: 13.4, p=0.02) in a multivariate analysis. All patients who developed clinical recurrence had detectable ctDNA with an average lead time over radiographic progression of 5.4 months, and post-RT ctDNA positivity was significantly associated with poor PFS (p
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