Frontiers in Oncology (Sep 2023)

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

  • Emily S. Lebow,
  • Emily S. Lebow,
  • Narek Shaverdian,
  • Jordan E. Eichholz,
  • Leah B. Kratochvil,
  • Megan McCune,
  • Yonina R. Murciano-Goroff,
  • Yonina R. Murciano-Goroff,
  • Justin Jee,
  • Justin Jee,
  • Juliana Eng,
  • Juliana Eng,
  • Jamie E. Chaft,
  • Mark G. Kris,
  • 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,
  • Charles M. Rudin,
  • Daniel R. Gomez,
  • Pedram Razavi,
  • Pedram Razavi,
  • Jorge S. Reis-Filho,
  • James M. Isbell,
  • James M. Isbell,
  • Bob T. Li,
  • Bob T. Li,
  • Andreas Rimner

DOI
https://doi.org/10.3389/fonc.2023.1253629
Journal volume & issue
Vol. 13

Abstract

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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<0.0001).ConclusionPersonalized, longitudinal ctDNA monitoring can detect recurrence early in patients with unresectable NSCLC patients undergoing curative radiation and potentially risk-stratify patients who might benefit most from treatment intensification.

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