Circulating tumor DNA monitoring for recurrence detection and treatment response assessment in 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 ∼80% of post-resection patients recur. Here we sought to analyze the utility of longitudinal testing with ctDNA in patients (pts) with HCC.

Methods: This is a multicenter retrospective study that included 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 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 (Nf34): recurrence monitoring after curative liver Tx; Cohort B (Nf25): recurrence monitoring after curative-intent surgical resection; Cohort C (Nf7): pts with known recurrence monitored for treatment response/disease progression. Longitudinal ctDNA testing was performed by using SignateraTM 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: 00 to 262 days). Among the ctDNA-negative patients (Nf16), only one pt experienced clinical recurrence that was >1 year after the most recent ctDNA testing. 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 chemotherapy.

Conclusion: Longitudinal testing with ctDNA is critical in identifying early recurrence post-curative treatments including transplant or surgical resection. Similarly, monitoring treatment response in the palliative setting can help resolve ambiguous imaging results.