@article{7e9a7de8ea0844bda4693e86aead2459,
title = "Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling",
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.",
author = "Chaudhuri, {Aadel A.} and Chabon, {Jacob J.} and Lovejoy, {Alexander F.} and Newman, {Aaron M.} and Henning Stehr and Azad, {Tej D.} and Khodadoust, {Michael S.} and Esfahani, {Mohammad Shahrokh} and Liu, {Chih Long} and Li Zhou and Florian Scherer and Kurtz, {David M.} and Carmen Say and Carter, {Justin N.} and Merriott, {David J.} and Dudley, {Jonathan C.} and Binkley, {Michael S.} and Leslie Modlin and Padda, {Sukhmani K.} and Gensheimer, {Michael F.} and West, {Robert B.} and Shrager, {Joseph B.} and Neal, {Joel W.} and Wakelee, {Heather A.} and Loo, {Billy W.} and Alizadeh, {Ash A.} and Maximilian Diehn",
note = "Funding Information: A.F. Lovejoy is principal scientist I at Roche Sequencing Solutions. A.M. Newman has ownership interest in CiberMed, Inc., is a co-inventor on patents related to ctDNA detection and other cancer biomarkers, and is a consultant/advisory board member for Roche and Merck. S.K. Padda is a consultant/advisory board member for G1 Therapeutics, AstraZeneca, and Janssen. M.F. Gensheimer reports receiving a commercial research grant from Varian Medical Systems. J.W. Neal reports receiving commercial research grants from Genen-tech/Roche, Merck, ArQule, Novartis, Boehringer Ingelheim, Nektar, and ARIAD, and is a consultant/advisory board member for Clovis Oncology, Boehringer Ingelheim, ARMO Biosciences, Nektar Therapeutics, ARIAD Pharmaceuticals/Takeda, Eli Lilly & Co., and Physician Resource Management. A.A. Alizadeh has ownership interest in CiberMed, is a co-inventor for patent filings related to cancer biomarkers, and is a consultant/advisory board member for Genentech, Roche, Gilead, and Celgene. M. Diehn reports receiving a commercial research grant from Varian Medical Systems, has ownership interest in CiberMed and in patent filings related to cancer biomarkers including ctDNA, and is a consultant/advisory board member for Roche. No potential conflicts of interest were disclosed by the other authors. Funding Information: This work was supported with grants from the Radiological Society of North America (A.A. Chaudhuri), the National Science Foundation (J.J. Chabon; DGE-114747), the Department of Defense (M. Diehn), the National Cancer Institute (M. Diehn and A.A. Aliza-deh; R01CA188298), the US National Institutes of Health Director{\textquoteright}s New Innovator Award Program (M. Diehn; 1-DP2-CA186569), the Virginia and D.K. Ludwig Fund for Cancer Research (M. Diehn and A.A. Alizadeh), a Stanford Cancer Institute-Developmental Cancer Research Award (M. Diehn and A.A. Alizadeh), and the CRK Faculty Scholar Fund (M. Diehn). Funding sources played no role in the writing of this manuscript or the decision to submit it for publication. Publisher Copyright: {\textcopyright} 2017 American Association for Cancer Research.",
year = "2017",
month = dec,
doi = "10.1158/2159-8290.CD-17-0716",
language = "English",
volume = "7",
pages = "1394--1403",
journal = "Cancer discovery",
issn = "2159-8274",
number = "12",
}