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A Prospective Study of Circulating Tumor DNA to Guide Matched Targeted Therapy in Lung Cancers.
Sabari, Joshua K; Offin, Michael; Stephens, Dennis; Ni, Andy; Lee, Adrian; Pavlakis, Nick; Clarke, Stephen; Diakos, Connie I; Datta, Sutirtha; Tandon, Nidhi; Martinez, Andres; Myers, Mackenzie L; Makhnin, Alex; Leger, Ysleni; Yu, Helena A; Paik, Paul K; Chaft, Jamie E; Kris, Mark G; Jeon, Jeong O; Borsu, Laetitia A; Ladanyi, Marc; Arcila, Maria E; Hernandez, Jennifer; Henderson, Samantha; Shaffer, Tristan; Garg, Kavita; DiPasquo, Dan; Raymond, Christopher K; Lim, Lee P; Li, Mark; Hellmann, Matthew D; Drilon, Alexander; Riely, Gregory J; Rusch, Valerie W; Jones, David R; Rimner, Andreas; Rudin, Charles M; Isbell, James M; Li, Bob T.
Afiliación
  • Sabari JK; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Offin M; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Stephens D; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Ni A; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Lee A; Northern Cancer Institute, University of Sydney, Sydney, Australia.
  • Pavlakis N; Northern Cancer Institute, University of Sydney, Sydney, Australia.
  • Clarke S; Northern Cancer Institute, University of Sydney, Sydney, Australia.
  • Diakos CI; Northern Cancer Institute, University of Sydney, Sydney, Australia.
  • Datta S; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Tandon N; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Martinez A; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Myers ML; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Makhnin A; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Leger Y; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Yu HA; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Paik PK; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Chaft JE; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Kris MG; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Jeon JO; Diagnostic Molecular Pathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Borsu LA; Diagnostic Molecular Pathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Ladanyi M; Diagnostic Molecular Pathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Arcila ME; Diagnostic Molecular Pathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Hernandez J; Resolution Bioscience, Redmond, WA.
  • Henderson S; Resolution Bioscience, Redmond, WA.
  • Shaffer T; Resolution Bioscience, Redmond, WA.
  • Garg K; Resolution Bioscience, Redmond, WA.
  • DiPasquo D; Resolution Bioscience, Redmond, WA.
  • Raymond CK; Resolution Bioscience, Redmond, WA.
  • Lim LP; Resolution Bioscience, Redmond, WA.
  • Li M; Resolution Bioscience, Redmond, WA.
  • Hellmann MD; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Drilon A; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Riely GJ; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Rusch VW; Thoracic Service, Department of Surgery.
  • Jones DR; Thoracic Service, Department of Surgery.
  • Rimner A; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Rudin CM; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • Isbell JM; Thoracic Service, Department of Surgery.
  • Li BT; Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
J Natl Cancer Inst ; 111(6): 575-583, 2019 Jun 01.
Article en En | MEDLINE | ID: mdl-30496436
ABSTRACT

BACKGROUND:

Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is commercially available and increasingly adopted in clinical practice despite a paucity of prospective data to support its use.

METHODS:

Patients with advanced lung cancers who had no known oncogenic driver or developed resistance to current targeted therapy (n = 210) underwent plasma NGS, targeting 21 genes. A subset of patients had concurrent tissue NGS testing using a 468-gene panel (n = 106). Oncogenic driver detection, test turnaround time (TAT), concordance, and treatment response guided by plasma NGS were measured. All statistical tests were two-sided.

RESULTS:

Somatic mutations were detected in 64.3% (135/210) of patients. ctDNA detection was lower in patients who were on systemic therapy at the time of plasma collection compared with those who were not (30/70, 42.9% vs 105/140, 75.0%; OR = 0.26, 95% CI = 0.1 to 0.5, P < .001). The median TAT of plasma NGS was shorter than tissue NGS (9 vs 20 days; P < .001). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 56.6% (60/106, 95% CI = 46.6% to 66.2%). Among patients who tested plasma NGS positive, 89.6% (60/67; 95% CI = 79.7% to 95.7%) were also concordant on tissue NGS and 60.6% (60/99; 95% CI = 50.3% to 70.3%) vice versa. Patients who tested plasma NGS positive for oncogenic drivers had tissue NGS concordance of 96.1% (49/51, 95% CI = 86.5% to 99.5%), and directly led to matched targeted therapy in 21.9% (46/210) with clinical response.

CONCLUSIONS:

Plasma ctDNA NGS detected a variety of oncogenic drivers with a shorter TAT compared with tissue NGS and matched patients to targeted therapy with clinical response. Positive findings on plasma NGS were highly concordant with tissue NGS and can guide immediate therapy; however, a negative finding in plasma requires further testing. Our findings support the potential incorporation of plasma NGS into practice guidelines.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / ADN Tumoral Circulante / Neoplasias Pulmonares Tipo de estudio: Clinical_trials / Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: J Natl Cancer Inst Año: 2019 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / ADN Tumoral Circulante / Neoplasias Pulmonares Tipo de estudio: Clinical_trials / Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: J Natl Cancer Inst Año: 2019 Tipo del documento: Article