Methylated ctDNA Quantification: Noninvasive Approach to Monitoring Hepatocellular Carcinoma Burden.

BACKGROUND: Noninvasive, precision monitoring of hepatocellular carcinoma (HCC) treatment efficacy would greatly facilitate personalized therapy and improve patient outcomes. We hypothesize that quantifying methylated circulating tumor DNA (ctDNA) can be used to effectively monitor HCC burden without the need for biopsy. STUDY DESIGN: Blood samples were collected from 25 patients, 21 with HCC and 4 with benign liver masses, at various timepoints throughout the course of treatment at a high-volume academic medical center. Quantification of methylated ctDNA molecules assessed CpG sites on more than 550 preselected cancer-specific amplicons. The tumor methylation score (TMS) was calculated by measuring the difference between the amount of methylation in the plasma and buffy coat with a normal cutoff value of 120 or less. RESULTS: Among 10 patients with surgical HCC (5 surgical resections and 5 liver transplants), TMS revealed a statistically significant, rapid postoperative decline in 9. One patient who had a persistently elevated TMS on postoperative day 1 was subsequently found to have had metastatic disease. Patients in the negative control cohort all had normal-range pre- and postoperative TMS. Preoperative TMS correlated moderately with tumor burden on pathology (Spearman r = 0.54) of surgical specimens. From 11 subjects undergoing systemic therapy or Y90 radioembolization, analysis of 16 time periods demonstrated that the change in TMS (ΔTMS) was better associated with tumor progression than the change in Δalpha-fetoprotein (area under the curve 0.800 and 0.783, respectively). A composite score combining ΔTMS and Δalpha-fetoprotein further improved performance for detecting tumor progression with an area under the curve of 0.892. CONCLUSIONS: These findings indicate that ctDNA methylation scores can effectively evaluate changes in tumor burden without the need for tumor biopsy.

Current Trends in Surgical Management of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Surgical management, including hepatic resection, liver transplantation, and ablation, offers the greatest potential for a curative approach. This review aims to discuss recent advancements in HCC surgery and identify unresolved issues in the field. Treatment selection relies on the BCLC staging system, with surgical therapies primarily recommended for early-stage disease. Recent studies have shown that patients previously considered unresectable, such as those with portal vein tumor thrombus and uncomplicated portal hypertension, may benefit from hepatic resection. Minimally invasive surgery and improved visualization techniques are also explored, alongside new techniques for optimizing future liver remnant, ex vivo resection, and advancements in hemorrhage control. Liver transplantation criteria, particularly the long-standing Milan criteria, are critically examined. Alternative criteria proposed and tested in specific regions are presented. In the context of organ shortage, bridging therapy plays a critical role in preventing tumor progression and maintaining patients eligible for transplantation. Lastly, we explore emerging ablation modalities, comparing them with the current standard, radiofrequency ablation. In conclusion, this comprehensive review provides insights into recent trends and future prospects in the surgical management of HCC, highlighting areas that require further investigation.