Abstract 181P
Background
HCC accounts for ∼90% of primary hepatic cancers. Despite standard of care resection or liver transplantation (LT), relapse rates are still 40-70% and 8-20%, respectively. Here we evaluated the utility of serial ctDNA testing to predict the risk of relapse/progression in patients (pts) with HCC.
Methods
We retrospectively analyzed 672 plasma samples from 120 pts with HCC. The curative-intent treatments were LT (67/120, 56%), hepatectomy (48/120, 40%), or liver directed/systemic therapy (5/120, 4%) for inoperable pts. Pts were divided into 4 sub-cohorts: Cohort A (N=64): recurrence monitoring after LT; Cohort B (N=47): recurrence monitoring after hepatectomy; Cohort C (N=4): monitoring treatment response in pts with known recurrence; Cohort D (N=5): monitoring treatment response in pts with inoperable disease. A personalized, tumor-informed 16-plex PCR-NGS assay (SignateraTM, Natera, Inc.) was used for ctDNA testing. The MRD window was defined as up to 12 weeks post LT or resection, before starting adjuvant therapy.
Results
The median pts age was 65 (19-83) years; median follow-up was 21.2 (2.5- 60.4) months. The stage distribution included 37 (30.8%)/ 50 (41.6%)/ 19 (15.8%)/ 12 (10.0%)/ 2 (1.6%) with I/II/III/IV/NA respectively. Cohort A: all 36 pts with testing available in the MRD window were ctDNA negative; 97.2% (35/36) remained negative. One pt turned ctDNA positive upon serial testing and had disease-related death 340 days after ctDNA positivity. Longitudinally, among 61 pts with imaging available within 6 months of a ctDNA test, 99.5% (223/224) sample level specificity was observed. In cohort B, ctDNA was detected in 22.5% (7/31) pts within the MRD window, 4 experienced clinical recurrence and 3 had short follow-up. Among 42 of pts with imaging available within 6 months of a ctDNA test, ctDNA positivity was prognostic for recurrence (RFS; HR 12, 95% CI 3.7-38, p<0.0001). Cohorts C and D: on-treatment ctDNA dynamics were concordant with treatment response as measured by imaging.
Conclusions
Serial ctDNA testing is a valuable tool to identify recurrence early post resection and LT. ctDNA is also useful for treatment response monitoring in the recurrence setting and can help resolve ambiguous imaging results.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Brdiges, T. Tin, C. Brewer, V. Aushev, C.C. Palsuledesai, A. Jurdi: Financial Interests, Institutional, Other, Employment and stock/stock option: Natera. M.C. Liu: Financial Interests, Personal and Institutional, Other, Dr. Minetta C. Liu Liu also reports grants (funding to Mayo Clinic) from Eisai, Exact Sciences, Genentech, Genomic Health, GRAIL, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, Tesaro; travel support from AstraZeneca, Genomic Health, and Ionis; and Ad hoc advisory board meetings (all funds to Mayo Clinic): AstraZeneca, Celgene, Roche/Genentech, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, Syndax: Natera. All other authors have declared no conflicts of interest.