Your browser doesn't support javascript.
loading
Peripheral Circulating Tumor DNA Detection Predicts Poor Outcomes After Liver Resection for Metastatic Colorectal Cancer.
Narayan, Raja R; Goldman, Debra A; Gonen, Mithat; Reichel, Jonathan; Huberman, Kety H; Raj, Sandeep; Viale, Agnes; Kemeny, Nancy E; Allen, Peter J; Balachandran, Vinod P; D'Angelica, Michael I; DeMatteo, Ronald P; Drebin, Jeffrey A; Jarnagin, William R; Kingham, T Peter.
Afiliação
  • Narayan RR; Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Goldman DA; Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Gonen M; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Reichel J; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Huberman KH; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Raj S; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Viale A; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Kemeny NE; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Allen PJ; Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Balachandran VP; Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • D'Angelica MI; Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • DeMatteo RP; Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Drebin JA; Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Jarnagin WR; Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Kingham TP; Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ann Surg Oncol ; 26(6): 1824-1832, 2019 Jun.
Article em En | MEDLINE | ID: mdl-30706231
BACKGROUND: Liver resection can be curative for well-selected metastatic colorectal cancer (CRC) patients. Circulating tumor DNA (ctDNA) has shown promise as a biomarker for tumor dynamics and recurrence following CRC resection. This prospective pilot study investigated the use of ctDNA to predict disease outcome in resected CRC patients. METHODS: Between November 2014 and November 2015, 60 patients with CRC were identified and prospectively enrolled. During liver resection, blood was drawn from peripheral (PERIPH), portal (PV), and hepatic (HV) veins, and 3-4 weeks postoperatively from a peripheral vein (POSTOP). Kappa statistics were used to compare mutated (mt) genes in tissue and ctDNA. Disease-specific and disease-free survival (DSS and DFS) were assessed from surgery with Kaplan-Meier and Cox methods. RESULTS: For the 59 eligible patients, the most commonly mutated genes were TP53 (mtTP53: 47.5%) and APC (mtAPC: 50.8%). Substantial to almost-perfect agreement was seen between ctDNA from PERIPH and PV (mtTP53: 89.8%, κ = 0.73, 95% confidence interval [CI] 0.53-0.93; mtAPC: 94.9%, κ = 0.83, 95% CI 0.64-1.00), as well as HV (mtTP53: 91.5%, κ = 0.78, 95% CI 0.60-0.96; mtAPC: 91.5%, κ = 0.73, 95% CI 0.51-0.95). Tumor mutations and PERIPH ctDNA had fair-to-moderate agreement (mtTP53: 72.9%, κ = 0.44, 95% CI 0.23-0.66; mtAPC: 61.0%, κ = 0.23, 95% CI 0.04-0.42). Detection of PERIPH mtTP53 was associated with worse 2-year DSS (mt+ 79% vs. mt- 90%, P = 0.024). CONCLUSIONS: Peripheral blood reflects the perihepatic ctDNA signature. Disagreement between tissue and ctDNA mutations may reflect the true natural history of tumor genes or an assay limitation. Peripheral ctDNA detection before liver resection is associated with worse DSS.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Biomarcadores Tumorais / DNA Tumoral Circulante / Hepatectomia / Neoplasias Hepáticas Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Surg Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Biomarcadores Tumorais / DNA Tumoral Circulante / Hepatectomia / Neoplasias Hepáticas Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Surg Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos