Tumor-informed assessment of circulating tumor DNA and its incorporation into practice for patients with hepatobiliary cancers.

Media type: E-Article

Title: Tumor-informed assessment of circulating tumor DNA and its incorporation into practice for patients with hepatobiliary cancers

Contributor: Kasi, Pashtoon Murtaza; Budde, Griffin; Dayyani, Farshid; Botta, Gregory P.; Diehl, Adam; King, Gentry Teng; Malla, Midhun; Abdelrahim, Maen; Hanna, Diana L.; Schafer, Liudmila N.; Tejani, Mohamedtaki Abdulaziz; Krainock, Michael; Billings, Paul R.; Olshan, Perry; Aushev, Vasily N.; Aleshin, Alexey

imprint: American Society of Clinical Oncology (ASCO), 2021

Language: English

DOI: 10.1200/jco.2021.39.15_suppl.4103

ISSN: 1527-7755; 0732-183X

Keywords: Cancer Research ; Oncology

Origination:

Footnote:

Description: 4103 Background: Hepatocellular carcinoma (HCC) and biliary tract cancers [BTC - including cholangiocarcinoma (CCA) and gall bladder cancers (GBC)] represent a heterogeneous group of diseases. Glycoprotein-based tumor markers like alpha-fetoprotein (AFP) or carbohydrate antigen 19-9 (CA-19-9) though part of standard-of-care (SOC), lack sensitivity, and specificity. A fair proportion of these cancers do not produce these glycoproteins. Circulating tumor DNA (ctDNA) testing can fill this void and be used for the assessment of molecular residual disease (MRD), as well as for surveillance purposes in patients with HCC or BTC. Prospective evaluation of this methodology in clinical practice has been limited to date. Methods: A personalized and tumor-informed multiplex PCR assay (Signatera bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA. Serial time points were collected on a subset of patients to monitor their ctDNA levels in response to treatment. Results: Here we analyzed 200 plasma samples from a total of 90 patients with HCC (n=27) and BTC (n=63), comprising 46 patients with CCA and 17 patients with GBC. Sample-level ctDNA positivity rates, determined using a tumor-informed assay are presented in table. ctDNA detection was significantly associated with the stage of disease (Wilcoxon rank-sum test, p<0.05). Serial time point analysis was performed on a subset of patients (n=56) that had 2-7 time points available and correlations between ctDNA levels and clinical response were noted and will be presented. Conclusions: Our study is the first to set the benchmark for the utility and feasibility of using a tumor-informed assay in this cohort of hepatobiliary cancers. With adjuvant chemotherapy already a SOC for BTC, and immunotherapy being studied for HCC alongside other novel agents for CCA and GBC, assessment of MRD or ctDNA clearance on therapy would be of value as an additional tool in identifying patients at high risk for recurrence/metastasis. The utility of this study would also lie in incorporation in clinical trials to enrich and study those who are at the highest risk of recurrence i.e. ctDNA positive.[Table: see text]

Access State: Open Access

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