Abstract A51: Personalized monitoring of treatment response using Targeted Digital Sequencing of circulating tumor DNA

摘要: Background: Accurate circulating biomarkers for detecting residual disease can help guide therapy decisions, particularly in early-stage cancer patients. However, currently available methods lack the sensitivity required to confidently assess presence of patients with low tumor burden. To address this need, we have developed TARDIS (Targeted Digital Sequencing), a personalized, multiplexed amplicon sequencing method capable tracking as many 100 or more mutations simultaneously. Methods: We obtained biopsies and longitudinal plasma samples from breast cancer, glioblastoma, pancreatic cancer. Each biopsy was analyzed whole-exome sequencing. Founder were selected, accounting copy number alterations (analyzed using sequenza) consensus allele fraction approach that combined pyclone custom in-house methods. Patient-specific primers designed detect these cfDNA. Error suppression achieved combination unique molecular identifiers fragment sizes group reads into read families. Results: In 33 treated neoadjuvant therapy, targeted between 3 116 (mean 30) per patient 1 4 TARDIS. Prior treatment, detected ctDNA 100% Stage I-III (n=32, 95% CI= 89%-100%). tumor-specific baseline samples. After completion before surgery, levels significantly lower pathologic complete response (pathCR, no evidence at surgery) compared (median fractions 0.003% 0.017%, respectively, p=0.0058, AUC=0.83). Conclusions: enables highly sensitive detection nonmetastatic cancers. Analysis holds promise personalizing extent treatment curable disease. Multiple clinical validation studies across types are ongoing define quantitative thresholds changes could improve decision making. Citation Format: Bradon R. McDonald, Tania Contente-Cuomo, Stephen-John Sammut, Michelle D. Stephens, Ahuva Odenheimer-Bergman, Brenda Ernst, Nieves Perdigones, Suet-Feung Chin, Maria Farooq, Rosa Mejia, Patricia A. Cronin, Karen S. Anderson, Heidi E. Kosiorek, Donald W. Northfelt, Ann McCullough, Bhavika K. Patel, Jeffrey N. Weitzel, Thomas P. Slavin, Carlos Caldas, Barbara Pockaj, Muhammed Murtaza. Personalized monitoring Targeted Sequencing DNA [abstract]. In: Proceedings AACR Special Conference on Advances Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A51.