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Cancer ; 130(10): 1758-1765, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38422026

RESUMO

BACKGROUND: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay. METHODS: This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single-nucleotide variants in plasma samples. RESULTS: The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001). CONCLUSIONS: ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasia Residual , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasia Residual/genética , Neoplasia Residual/diagnóstico , Detecção Precoce de Câncer/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Adulto , Idoso de 80 Anos ou mais , Reação em Cadeia da Polimerase Multiplex/métodos
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