960P - Personalized circulating tumor DNA (ctDNA) monitoring for recurrence detection and treatment response assessment in hepatocellular carcinoma (HCC)

Background

HCC is an aggressive malignancy, accounting for ∼90% of primary hepatic cancers. While surgical resection and liver transplantation (Tx) can be curative, 8-20% of post-Tx and 40-70% of post-resection patients recur. Here we sought to analyze the utility of longitudinal testing with ctDNA in patients (pts) with HCC.

Methods

This multicenter study retrospectively analyzed 227 plasma samples from 66 pts with HCC. The curative-intent surgeries included liver Tx (41/66, 62%) and hepatectomy (23/66, 34%); two pts (3%) who were inoperable received liver directed and systemic targeted therapy. Five of the 41 post-Tx pts received additional resection for oligometastatic recurrence prior to ctDNA testing. The cohort was analyzed based on 3 mutually exclusive sub-cohorts: Cohort A (N=34): recurrence monitoring after curative liver Tx; Cohort B (N=25): recurrence monitoring after curative-intent surgical resection; Cohort C (N=7): pts with known recurrence monitored for treatment response/disease progression. Longitudinal ctDNA testing was performed using the Signatera^TM bespoke mPCR NGS assay.

Results

The cohort distribution included: 28 (42.4%) / 21 (31.8%) / 7 (10.6%) / 9 (13.6%) stage I/II/III/IV pts with a median age of 67 years (range: 21-84); median follow-up of 584 days (range: 79 - 1537). In cohort A, all patients were ctDNA-negative and remained recurrence-free.In cohort B, postsurgical ctDNA was detected in 9 (36%) patients, 6 experienced clinical recurrence and 3 had limited follow-up. The median lead time of ctDNA detection over clinical recurrence was 52 days (range: 0-262). Among the ctDNA-negative patients (N=16), only one pt experienced clinical recurrence; this was >1 year after the last ctDNA test. In cohort C, on-treatment ctDNA dynamics were concordant with treatment response in 4 pts as measured by imaging. The remaining 3 pts were persistently ctDNA-negative on/shortly after systemic therapy.

Conclusions

Longitudinal testing with ctDNA is critical in identifying early recurrence post surgical resection. Similarly, monitoring treatment response in the palliative setting can help resolve ambiguous imaging results.

Clinical trial identification

N/A

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Brdiges: Financial Interests, Institutional, Advisory Board, Full-time employment and stock or option to own stock at Natera, Inc. Name: Antony Tin: Natera, Inc.. T. Tin, C. Brewer, A. Jurdi, M.C. Liu: Financial Interests, Personal and Institutional, Advisory Board: Natera Inc. All other authors have declared no conflicts of interest.