Wei Zhao1, Lige Qiu1,2, Huajiang Liu3, Ying Xu4, Meixiao Zhan1, Wei Zhang2, Yongjie Xin1, Xu He1, Xiangyu Yang1, Jing Bai5, Jing Xiao1, Yanfang Guan4,5, Qiyang Li2, Lianpeng Chang5, Xin Yi5, Yong Li1, Xudong Chen2, Ligong Lu1. 1. Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, China. 2. 2 Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China. 3. Department of Intervention Therapy, The First Affiliated Hospital of Hainan Medical University, Haikou, China. 4. Department of Computer Science and Technology, School of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China. 5. Geneplus-Beijing Institute, Beijing, China.
Abstract
BACKGROUND: Imaging and alpha fetoprotein (AFP) measurement are used as surveillance methods during interventional therapy in patients with unresectable liver cancer, but their accuracy has been challenged in patients receiving drug perfusion therapy. Circulating tumor DNA (ctDNA) can reflect tumor load and treatment efficacy. Studies of the prognostic value of ctDNA in unresectable liver cancer are needed. METHODS: Forty-two patients with unresectable liver cancer were prospective enrolled in this study. Pre-treatment, in-treatment plasma samples and available matched tissue samples were collected. Targeted-capture sequencing of 1,021 genes that are frequently mutated in solid tumors. RESULTS: Targeted-capture sequencing of 1,021 genes that are frequently mutated in solid tumors revealed that the most frequently mutated genes in ctDNA were TP53 (52.4%) and TERT (35.7%). The ctDNA abundance was more closely correlated with tumor size than the AFP level and was also related to BCLC stage (P<0.001). Gene mutations profile in ctDNA with progressed disease. PD patients were enriched in TP53 mutation group compared with TP53 wildtype group (P=0.0221). Moreover, interventional therapy was more effective in patients without TP53 mutation (OS: P=0.0589; PFS: 0.0411). The dynamic change of ctDNA showed consistent or more sensitivity than imaging for evaluating treatment response. The tumor mutation burden was highly consistent between tissue and blood samples (P<0.0001). CONCLUSIONS: ctDNA was a reliable biomarker to assist in diagnosis and evaluation of prognosis and treatment efficacy in advanced liver cancer. Considering that biopsy is unnecessary when advanced liver cancer is diagnosed, ctDNA may be an ideal biomarker for evaluating tumor mutation burden prior to immunotherapy. 2020 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: Imaging and alpha fetoprotein (AFP) measurement are used as surveillance methods during interventional therapy in patients with unresectable liver cancer, but their accuracy has been challenged in patients receiving drug perfusion therapy. Circulating tumor DNA (ctDNA) can reflect tumor load and treatment efficacy. Studies of the prognostic value of ctDNA in unresectable liver cancer are needed. METHODS: Forty-two patients with unresectable liver cancer were prospective enrolled in this study. Pre-treatment, in-treatment plasma samples and available matched tissue samples were collected. Targeted-capture sequencing of 1,021 genes that are frequently mutated in solid tumors. RESULTS: Targeted-capture sequencing of 1,021 genes that are frequently mutated in solid tumors revealed that the most frequently mutated genes in ctDNA were TP53 (52.4%) and TERT (35.7%). The ctDNA abundance was more closely correlated with tumor size than the AFP level and was also related to BCLC stage (P<0.001). Gene mutations profile in ctDNA with progressed disease. PD patients were enriched in TP53 mutation group compared with TP53 wildtype group (P=0.0221). Moreover, interventional therapy was more effective in patients without TP53 mutation (OS: P=0.0589; PFS: 0.0411). The dynamic change of ctDNA showed consistent or more sensitivity than imaging for evaluating treatment response. The tumor mutation burden was highly consistent between tissue and blood samples (P<0.0001). CONCLUSIONS: ctDNA was a reliable biomarker to assist in diagnosis and evaluation of prognosis and treatment efficacy in advanced liver cancer. Considering that biopsy is unnecessary when advanced liver cancer is diagnosed, ctDNA may be an ideal biomarker for evaluating tumor mutation burden prior to immunotherapy. 2020 Journal of Gastrointestinal Oncology. All rights reserved.
Authors: C K Y Ng; G G Di Costanzo; N Tosti; V Paradiso; M Coto-Llerena; G Roscigno; V Perrina; C Quintavalle; T Boldanova; S Wieland; G Marino-Marsilia; M Lanzafame; L Quagliata; G Condorelli; M S Matter; R Tortora; M H Heim; L M Terracciano; S Piscuoglio Journal: Ann Oncol Date: 2018-05-01 Impact factor: 32.976
Authors: Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray Journal: Int J Cancer Date: 2014-10-09 Impact factor: 7.396
Authors: Alphonse E Sirica; Gregory J Gores; John D Groopman; Florin M Selaru; Mario Strazzabosco; Xin Wei Wang; Andrew X Zhu Journal: Hepatology Date: 2019-03-25 Impact factor: 17.298