{"doi":"10.3389/fonc.2023.1253629","title":"ctDNA-based detection of molecular residual disease in stage I-III non-small cell lung cancer patients treated with definitive radiotherapy","abstract":"Background: Sensitive 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. Methods: A 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. Results: Pre-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). Conclusion: Personalized, 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.","journal":"Frontiers in Oncology","year":2023,"id":337630,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":325302,"name":"Narek Shaverdian","orcid":"0000-0002-0294-8749","position":1,"is_corresponding":false},{"id":867932,"name":"Jordan Eichholz","orcid":null,"position":2,"is_corresponding":false},{"id":1069474,"name":"L.B. Kratochvil","orcid":"0000-0002-7715-6500","position":3,"is_corresponding":false},{"id":962071,"name":"Megan McCune","orcid":null,"position":4,"is_corresponding":false},{"id":108485,"name":"Yonina R. Murciano‐Goroff","orcid":"0000-0001-9027-2891","position":5,"is_corresponding":false},{"id":428194,"name":"Justin Jee","orcid":"0000-0001-9783-0139","position":6,"is_corresponding":false},{"id":237144,"name":"Juliana Eng","orcid":"0000-0002-7630-3054","position":7,"is_corresponding":false},{"id":227921,"name":"Jamie E. Chaft","orcid":"0000-0002-5838-9982","position":8,"is_corresponding":false},{"id":1281,"name":"Mark G. Kris","orcid":"0000-0002-7317-5341","position":9,"is_corresponding":false},{"id":677970,"name":"Ekaterina Kalashnikova","orcid":"0000-0003-1078-0656","position":10,"is_corresponding":false},{"id":1070059,"name":"Jordan Feeney","orcid":null,"position":11,"is_corresponding":false},{"id":516431,"name":"Carly Bess Scalise","orcid":"0000-0002-7612-7791","position":12,"is_corresponding":false},{"id":1069475,"name":"Sumedha Sudhaman","orcid":"0000-0001-9266-7096","position":13,"is_corresponding":false},{"id":1069476,"name":"Charuta C. 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Gelblum","orcid":"0000-0001-7211-6246","position":23,"is_corresponding":false},{"id":1070060,"name":"Kaylie Johnson","orcid":null,"position":24,"is_corresponding":false},{"id":1555,"name":"Charles M. Rudin","orcid":"0000-0001-5204-3465","position":25,"is_corresponding":false},{"id":325306,"name":"Daniel R. Gomez","orcid":"0000-0002-1839-9510","position":26,"is_corresponding":false},{"id":90747,"name":"Pedram Razavi","orcid":"0000-0003-4236-0576","position":27,"is_corresponding":false},{"id":14428,"name":"Jorge S. Reis‐Filho","orcid":"0000-0003-2969-3173","position":28,"is_corresponding":false},{"id":235759,"name":"James M. Isbell","orcid":"0000-0002-7305-876X","position":29,"is_corresponding":false},{"id":227116,"name":"Bob T. Li","orcid":"0000-0001-6661-8733","position":30,"is_corresponding":false},{"id":241186,"name":"Andreas Rimner","orcid":"0000-0002-1214-3856","position":31,"is_corresponding":false},{"id":562899,"name":"Emily S. Lebow","orcid":"0000-0002-6614-0212","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:10:31.133446Z","pmid":"37795442","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}