Capp-seq circulating tumor dna analysis identifies lung cancer progression earlier than CT imaging de

ALBA M GÜERCI

Ciudad de Buenos Aires

Congreso; II BEST of ASTRO en Argentina; 2017

Sociedad Argentina de Terapia Radiante Oncológica SATRO.

Abstract 92AUTORES Y FILIACIONA. A. Chaudhuri1, A. F. Lovejoy1, J. J. Chabon2, A. Newman2, H. Stehr2, C. Say2, S. Aggarwal3, J. N. Carter2, R. B. West2, J. W. Neal1, H. A. Wakelee2, B. W. Loo Jr2, A. Alizadeh2, and M. Diehn2; 1Stanford Cancer Institute, Stanford, CA, 2Stanford University School of Medicine, Stanford, CA, 3Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CAPurpose/Objective(s): Response Evaluation Criteria in Solid Tumors (RECIST) is the primary method used to evaluate response to cancer therapeutics in clinical trials but can be challenging to perform after radiotherapy. Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) is a novel blood-based assay that uses next-generating sequencing to quantitate circulating tumor DNA (ctDNA). We performed a prospective study to compare response evaluation by CAPP-Seq and RECIST after definitive radiotherapy for lung cancer. Materials/Methods: We prospectively enrolled 30 patients treated with definitive radiotherapy for non-metastatic primary lung cancer at our institution between June 2010 and December 2014. Our cohort included 21 (70%) patients with stage III, 5 (16.7%) patients with stage II and 4 (13.3%) patients with stage IB disease. All patients received pre-treatment evaluation by thoracic CT and PET/CT scans and ctDNA quantitation by CAPP-Seq. Twenty-one (70%) patients were treated with chemo-radiation and 9 (30%) were treated with hypofractionated radiotherapy. Following treatment, patients underwent disease surveillance by CT scans and CAPP-Seq every 3-6 months. CT scans were evaluated using RECIST criteria by an experienced radiologist and radiation oncologist. CAPP-Seq was performed at each time point as previously described (Newman et al, Nature Medicine, 2014). Results: Median follow-up time was 20.8 months. Median overall survival was 23.1 months. Sixteen (53.3%) patients progressed based on RECIST criteria, while the remaining 14 (46.7%) patients demonstrated complete response, partial response or stable disease. CAPP-Seq detected ctDNA at or before the time of RECIST progression in all patients who progressed with a lead-time of 113.6 +/- 27.8 days (mean +/- SEM) and did not detect ctDNA at last follow-up in non-progressing patients. In the majority of patients who progressed (11 of 16; 68.8%), ctDNA was detected prior to RECIST progression with a lead-time of 165.2 +/- 28.9 days (mean +/- SEM). The ctDNA concentration at time of progression was 76.6 +/- 50.7 haploid genome equivalents/mL (mean +/- SEM). Two-year overall survival for patients with ctDNA progression was 21.1% versus 90.9% for non-progressors (p=0.0003, HR=6.7, 95% CI=2.4-18.7). Conclusion: Our data suggest that CAPP-Seq-based ctDNA assessment is an accurate and sensitive method for evaluating response to thoracic radiotherapy. On average, detection of ctDNA anticipated imaging-detected disease progression by over 3.5 months, potentially facilitating clinical studies of early therapeutic interventions when disease burden is minimal.