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Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling.
Chaudhuri, Aadel A; Chabon, Jacob J; Lovejoy, Alexander F; Newman, Aaron M; Stehr, Henning; Azad, Tej D; Khodadoust, Michael S; Esfahani, Mohammad Shahrokh; Liu, Chih Long; Zhou, Li; Scherer, Florian; Kurtz, David M; Say, Carmen; Carter, Justin N; Merriott, David J; Dudley, Jonathan C; Binkley, Michael S; Modlin, Leslie; Padda, Sukhmani K; Gensheimer, Michael F; West, Robert B; Shrager, Joseph B; Neal, Joel W; Wakelee, Heather A; Loo, Billy W; Alizadeh, Ash A; Diehn, Maximilian.
Afiliación
  • Chaudhuri AA; Department of Radiation Oncology, Stanford University, Stanford, California.
  • Chabon JJ; Stanford Cancer Institute, Stanford University, Stanford, California.
  • Lovejoy AF; Stanford Cancer Institute, Stanford University, Stanford, California.
  • Newman AM; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California.
  • Stehr H; Department of Radiation Oncology, Stanford University, Stanford, California.
  • Azad TD; Stanford Cancer Institute, Stanford University, Stanford, California.
  • Khodadoust MS; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California.
  • Esfahani MS; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California.
  • Liu CL; Stanford Cancer Institute, Stanford University, Stanford, California.
  • Zhou L; Stanford Cancer Institute, Stanford University, Stanford, California.
  • Scherer F; Stanford Cancer Institute, Stanford University, Stanford, California.
  • Kurtz DM; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California.
  • Say C; Stanford Cancer Institute, Stanford University, Stanford, California.
  • Carter JN; Stanford Cancer Institute, Stanford University, Stanford, California.
  • Merriott DJ; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California.
  • Dudley JC; Stanford Cancer Institute, Stanford University, Stanford, California.
  • Binkley MS; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California.
  • Modlin L; Stanford Cancer Institute, Stanford University, Stanford, California.
  • Padda SK; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California.
  • Gensheimer MF; Stanford Cancer Institute, Stanford University, Stanford, California.
  • West RB; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California.
  • Shrager JB; Department of Bioengineering, Stanford University, Stanford, California.
  • Neal JW; Department of Radiation Oncology, Stanford University, Stanford, California.
  • Wakelee HA; Department of Radiation Oncology, Stanford University, Stanford, California.
  • Loo BW; Department of Radiation Oncology, Stanford University, Stanford, California.
  • Alizadeh AA; Stanford Cancer Institute, Stanford University, Stanford, California.
  • Diehn M; Department of Pathology, Stanford University, Stanford, California.
Cancer Discov ; 7(12): 1394-1403, 2017 12.
Article en En | MEDLINE | ID: mdl-28899864
ABSTRACT
Identifying molecular residual disease (MRD) after treatment of localized lung cancer could facilitate early intervention and personalization of adjuvant therapies. Here, we apply cancer personalized profiling by deep sequencing (CAPP-seq) circulating tumor DNA (ctDNA) analysis to 255 samples from 40 patients treated with curative intent for stage I-III lung cancer and 54 healthy adults. In 94% of evaluable patients experiencing recurrence, ctDNA was detectable in the first posttreatment blood sample, indicating reliable identification of MRD. Posttreatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months, and 53% of patients harbored ctDNA mutation profiles associated with favorable responses to tyrosine kinase inhibitors or immune checkpoint blockade. Collectively, these results indicate that ctDNA MRD in patients with lung cancer can be accurately detected using CAPP-seq and may allow personalized adjuvant treatment while disease burden is lowest.

Significance:

This study shows that ctDNA analysis can robustly identify posttreatment MRD in patients with localized lung cancer, identifying residual/recurrent disease earlier than standard-of-care radiologic imaging, and thus could facilitate personalized adjuvant treatment at early time points when disease burden is lowest. Cancer Discov; 7(12); 1394-403. ©2017 AACR.See related commentary by Comino-Mendez and Turner, p. 1368This article is highlighted in the In This Issue feature, p. 1355.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasia Residual / ADN Tumoral Circulante / Neoplasias Pulmonares Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Female / Humans / Male Idioma: En Revista: Cancer Discov Año: 2017 Tipo del documento: Article
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasia Residual / ADN Tumoral Circulante / Neoplasias Pulmonares Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Female / Humans / Male Idioma: En Revista: Cancer Discov Año: 2017 Tipo del documento: Article