Abstract 621P
Background
Early detection of primary liver cancer (PLC) in patients with liver cirrhosis (LC) or chronic hepatitis virus infection (CHVI) improves survival. The urgent need is convenient and affordable tools with high sensitivity to facilitate timely diagnosis.
Methods
Tissue and plasma samples from 159 healthy individuals and 89 PLC, LC, or CHVI patients were sequenced by a targeted methylation panel (∼70,000 CpGs) to identify candidate methylated DNA markers (MDMs). In phase I, the performance of each selected MDMs was validated in 175 plasma samples (PLC, n=101; LC/CHVI, n=74) by CO-methylation aMplification rEal-Time PCR (COMET) assay. A logistic model was then trained and validated in phase II with 310 plasma samples (hepatocellular carcinoma [HCC], n=212; combined hepatocellular-cholangiocarcinoma [cHCC-CC], n=12; CHVI, n=106; training vs. validation, 2:1).
Results
The 11 selected MDMs with top performance consistently showed significant differences in tissue samples between PLC and LC/CHVI, as well as in plasma samples between PLC and LC/CHVI (P<0.05). In phase I, 8 of the above 11 MDMs with an area under the curve (AUC) over 0.80 to differentiate PLC and LC/CHVI were selected for further investigation. In phase II, the MDM-based model achieved sensitivity of 87.2% (95% confidence interval [CI], 80.8%–92.4%) and 88.0% (78.4%–94.4%), at respective specificity of 97.1% (90.1%–99.7%) and 100% (90.3%–100%) in the training and validation sets. In the validation set, sensitivity in patients with BCLC stage 0, diameter<3 cm, AFP-negative and PIVKA-II-negative was 90.0% (55.5%–99.7%), 88.9% (65.3%–98.6%), 80.6% (64.0%–91.8%), and 81.3% (54.4%–96.0%), respectively. Additionally, our model detected 19 of 24 (79.3%, 57.8%–92.9%) intrahepatic cholangiocarcinoma. Combining AFP and PIVKA-II, the model achieved higher sensitivity of 93.3% (85.1%–97.8%) and specificity of 100.0% (90.3%–100%).
Conclusions
COMET featuring low cost and high accuracy exhibits preferable potential for PLC detection in patients with LC or CHVI. Further validation in a prospective cohort is warranted.
Clinical trial identification
NCT05996666, release date 08/10/2023.
Editorial acknowledgement
Legal entity responsible for the study
Tian Yang.
Funding
National Natural Science Foundation of China (No: 81972726 and 82273074), Dawn Project Foundation of Shanghai (No: 21SG36), Shanghai Health Academic Leader Program (No. 2022XD001).
Disclosure
X. Zhu, L. Zhang, Q. You, J. Xu, Y. Xu, H. Lu, B. Li, G. Wang, S. Cai: Financial Interests, Personal, Full or part-time Employment: Burning Rock Biotech. All other authors have declared no conflicts of interest.
Resources from the same session
87TiP - Phase I expansion study of the tissue factor (TF)–targeting antibody-drug conjugate (ADC) XB002 as a single-agent and combination therapy in patients with advanced solid tumors (JEWEL-101)
Presenter: Mustafa Syed
Session: Poster Display
Resources:
Abstract
88TiP - A phase Ib study of HMBD-001, a monoclonal antibody targeting HER3, with or without chemotherapy in patients with genetic aberrations in HER3 signaling
Presenter: Nick Pavlakis
Session: Poster Display
Resources:
Abstract
93P - Efficacy and safety of fruquintinib (F) + best supportive care (BSC) vs placebo (P) + BSC in refractory metastatic colorectal cancer (mCRC): Asian vs non-Asian outcomes in FRESCO-2
Presenter: Daisuke Kotani
Session: Poster Display
Resources:
Abstract
94P - Sidedness-dependent prognostic impact of gene alterations in metastatic colorectal cancer in the nationwide cancer genome screening project in Japan (SCRUM-Japan GI-SCREEN)
Presenter: Takeshi Kajiwara
Session: Poster Display
Resources:
Abstract
95P - Interim results of a prospective randomized controlled study to compare the clinical outcomes of total neoadjuvant therapy vs long course chemoradiotherapy in locally advanced carcinoma rectum
Presenter: Sandip Barik
Session: Poster Display
Resources:
Abstract
96P - Tyrosine kinase inhibitor (TKI) plus PD-1 blockade in TKI-responsive MSS/pMMR metastatic colorectal adenocarcinoma (mCRC): Updated results of TRAP study
Presenter: Jingdong Zhang
Session: Poster Display
Resources:
Abstract
97P - Asian subgroup analysis of the phase III LEAP-017 trial of lenvatinib plus pembrolizumab vs standard-of-care in previously treated metastatic colorectal cancer (mCRC)
Presenter: Rui-Hua Xu
Session: Poster Display
Resources:
Abstract
98P - Real clinical impact of postoperative surgical complications after colon cancer surgery
Presenter: Toru Aoyama
Session: Poster Display
Resources:
Abstract
99P - Extended lymphadenectomy may not be necessary for MSI-H colon cancer patients after immunotherapy
Presenter: Rongxin Zhang
Session: Poster Display
Resources:
Abstract
100P - Identification of phenomic data in the pathogenesis of colorectal cancer: A UK biobank data analysis
Presenter: Shirin Hui Tan
Session: Poster Display
Resources:
Abstract