Tumor Mutational Burden as a Predictive Biomarker for HCC Recurrence Post-Resection

Introduction:
A study published in the Annals of Surgery introduces Tumor Mutational Burden (TMB) from circulating tumor DNA (ctDNA) as a superior biomarker for predicting the recurrence of hepatocellular carcinoma (HCC) following curative resection. This method could enhance postoperative surveillance and patient management.

Background:
Current surveillance methods for HCC relapse, primarily using Alpha-fetoprotein (AFP), show limited efficacy. The study investigates the potential of ctDNA-derived TMB, calculated as the number of somatic mutations per megabase of genomic material, as an alternative.

Methodology:
The cohort consisted of 47 patients who underwent curative resection for HCC. Postoperative ctDNA was analyzed using the Guardant360 platform, with follow-ups extending up to 43.2 months. TMB was measured, and its association with recurrence-free survival (RFS) and overall recurrence was assessed.

Results:

• Postoperative identifiable ctDNA was present in 87.2% of patients.
• Detectable TMB correlated with significantly reduced RFS (6.9 vs. 14.7 months; P=0.049).
• A higher recurrence rate was observed in patients with detectable TMB (42.9% vs. 11.5%; P=0.02).
• ROC analysis established a TMB cut-off of 4.8 mutations/megabase for predicting recurrence (P=0.002) and RFS (P=0.025).
• TMB outperformed AFP in predicting recurrence and survival outcomes (AUC 0.752 vs. 0.550).

Conclusions:
The findings suggest that TMB from postoperative ctDNA is a robust predictor of HCC recurrence, offering an improvement over AFP. Implementing ctDNA-based TMB assessment could refine postoperative monitoring protocols and enable earlier intervention, potentially improving patient prognoses. Further large-scale studies are warranted to confirm these results and explore additional applications.

URL:https://doi.org/10.1097/SLA.0000000000006386