Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling

Aadel A. Chaudhuri, Jacob J. Chabon, Alexander F. Lovejoy, Aaron M. Newman, Henning Stehr, Tej D. Azad, Michael S. Khodadoust, Mohammad Shahrokh Esfahani, Chih Long Liu, Li Zhou, Florian Scherer, David M. Kurtz, Carmen Say, Justin N. Carter, David J. Merriott, Jonathan C. Dudley, Michael S. Binkley, Leslie Modlin, Sukhmani K. Padda, Michael F. GensheimerRobert B. West, Joseph B. Shrager, Joel W. Neal, Heather A. Wakelee, Billy W. Loo, Ash A. Alizadeh, Maximilian Diehn

Research output: Contribution to journalArticlepeer-review

412 Scopus citations

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.

Original languageEnglish
Pages (from-to)1394-1403
Number of pages10
JournalCancer discovery
Volume7
Issue number12
DOIs
StatePublished - Dec 2017

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