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
Affiliations
- Emily S. Lebow
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Emily S. Lebow
- The University of Pennsylvania, Philadelphia, Pennsylvania
- Narek Shaverdian
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Jordan E. Eichholz
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Leah B. Kratochvil
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Megan McCune
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Yonina R. Murciano-Goroff
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Yonina R. Murciano-Goroff
- Weill Cornell Medicine, Cornell University, New York, NY, United States
- Justin Jee
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Justin Jee
- Weill Cornell Medicine, Cornell University, New York, NY, United States
- Juliana Eng
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Juliana Eng
- Weill Cornell Medicine, Cornell University, New York, NY, United States
- Jamie E. Chaft
- Weill Cornell Medicine, Cornell University, New York, NY, United States
- Mark G. Kris
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Mark G. Kris
- Weill Cornell Medicine, Cornell University, New York, NY, United States
- Ekaterina Kalashnikova
- Natera, Inc., Austin, TX, United States
- Jordan Feeney
- Natera, Inc., Austin, TX, United States
- Carly Bess Scalise
- Natera, Inc., Austin, TX, United States
- Sumedha Sudhaman
- Natera, Inc., Austin, TX, United States
- Charuta C. Palsuledesai
- Natera, Inc., Austin, TX, United States
- Meenakshi Malhotra
- Natera, Inc., Austin, TX, United States
- Michael Krainock
- Natera, Inc., Austin, TX, United States
- Himanshu Sethi
- Natera, Inc., Austin, TX, United States
- Alexey Aleshin
- Natera, Inc., Austin, TX, United States
- Minetta C. Liu
- Natera, Inc., Austin, TX, United States
- Annemarie F. Shepherd
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Abraham J. Wu
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Charles B. Simone
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Daphna Y. Gelblum
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Kaylie A. Johnson
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Charles M. Rudin
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Charles M. Rudin
- Weill Cornell Medicine, Cornell University, New York, NY, United States
- Daniel R. Gomez
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Pedram Razavi
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Pedram Razavi
- Weill Cornell Medicine, Cornell University, New York, NY, United States
- Jorge S. Reis-Filho
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- James M. Isbell
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- James M. Isbell
- Weill Cornell Medicine, Cornell University, New York, NY, United States
- Bob T. Li
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Bob T. Li
- Weill Cornell Medicine, Cornell University, New York, NY, United States
- Andreas Rimner
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
- DOI
- https://doi.org/10.3389/fonc.2023.1253629
- Journal volume & issue
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Vol. 13
Abstract
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.
Keywords
- circulating tumor DNA (ctDNA)
- tumor-informed
- molecular residual disease (MRD)
- non-small cell lung cancer (NSCLC)
- definitive radiation
- prognostic biomarker