CONICET | Buscador de Institutos y Recursos Humanos

Circulating Tumor DNA Analysis during Radiation Therapy for Localized Lung Cancer Predicts Treatment Outcome A. A. Chaudhuri1, A. F. Lovejoy1, J. J. Chabon1, A. Newman1, H. Stehr1, D. J. Merriott2, J. N. Carter1, T. D. Azad1, S. Padda1, M. F. Gensheimer1, H. A. Wakelee1, J. W. Neal1, B. W. Loo Jr1, A. A. Alizadeh1, and M. Diehn1; 1Stanford Cancer Institute, Stanford, CA, 2Stanford University School of Medicine, Stanford, CA Purpose/Objective(s): Identifying lung cancer patients with residual disease following curative intent radiotherapy (RT) or surgery is difficult due to normal tissue changes and inability to detect microscopic disease. Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) is an ultra-sensitive blood-based assay that uses next-generating sequencing to quantitate circulating tumor DNA (ctDNA). We performed a prospective study to determine the prognostic value of CAPP-Seq molecular residual disease (MRD) detection during and after treatment of localized lung cancer patients. Materials/Methods: We applied CAPP-Seq to pre- and post-treatment blood samples from 41 patients treated with chemoRT (n=27, 66%), RT (n=11, 27%) or surgery (n=3, 7%) for stage I-III lung cancer. Detection of ctDNA at a single MRD time-point within 4 months of treatment completion was compared with long-term clinical and radiographic outcomes. For a subset of patients treated with chemoRT (n=13), we also performed CAPP-Seq at a mid-treatment time point (average=3 weeks, range 1.4-3.7). Results: Median follow-up was 35 months. There was no correlation between pre-treatment ctDNA levels and clinical outcomes. Among 38 patients with detectable pre-treatment ctDNA, 19 (50%) had detectable post-treatment ctDNA at the MRD time-point. Patients with detectable post-treatment MRD had significantly worse freedom from progression (HR 37.7; P