Abstract LB-233: Analysis of personalised circulating tumour DNA to monitor recurrence and metastasis in multiple cancer types

Abstract

Abstract Purpose: The evaluation of circulating tumour DNA (ctDNA) is a promising tool to monitor tumour progression and guide personalised treatments. We evaluated ctDNA in plasma samples from 521 Chinese patients with more than 12 tumour types and explored ctDNA’s ability to predict tumour status, especially recurrence and metastasis. Methods: We established a personalised ctDNA panel sequencing, which targeted trunk clonal somatic mutations of each patient calculated by CSMT-tools (monitors tumour load tools based on paired whole exon and cell-free DNA next generation sequencing data, PCT/CN2016/106284) and drug-resistant mutations. The ctDNA content fraction of all somatic mutations was then evaluated. Furthermore, 209 patients were followed up for ctDNA detection and routine examination. Results: Whole exome sequencing was performed on 1121 patients, and 97% of patients were successfully designed personalised ctDNA assays using CSMT-tools. Currently, 521 Chinese patients mainly with colorectal, liver, lung, gastric cancer, glioma or cholangiocarcinoma received at least one ctDNA detection. 66.79%, 50.86%, 42.99%, and 25.72% of these patients had detectable ctDNA with ctDNA content fractions above 0.25%, 0.5%, 1%, and 5%, respectively. At ctDNA content fraction above 0.25%, the detection rate of ctDNA in major cancer types, excluding liver, pancreatic cancer and glioma, was higher than 70%. In glioma, the rate of ctDNA detection in blood was much lower than in cerebrospinal fluid (24.29% vs 80%). Moreover, dynamic changes of ctDNA were significantly correlated with clinical outcomes for patients, with a consistency rate of 89.51%. The consistency rate of most major cancer types was above 90%, but that of glioma (71.43%) and pancreatic cancer (60%) were lower. ctDNA content fraction increased in all patients with recurrence and metastasis, from 2.72 to 59.8 fold. We also detected a drug-resistance process in a lung cancer patient with EGFR_p.E746_A750del. EGFR_p.T790M was first detected after the patient was administered gefitinib for more than a year, 3 months earlier than radiologic progression. Conclusions: Our personalised ctDNA analysis can effectively detect ctDNA. Hence, it can predict tumour progression and guide precise treatment. Citation Format: Guan Wang, Jinwang Wei, Angela Wu, Chun Dai, Wending Sun, Xin Cai, Qiang Xu. Analysis of personalised circulating tumour DNA to monitor recurrence and metastasis in multiple cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-233.