Amidst the serene morning mist gracing the wutong trees and frost enhancing the ripeness of oranges, the 2024 Annual Meeting of the European Society for Medical Oncology (ESMO) unfolds in Barcelona, Spain, spanning from September 13 to 17. This prestigious event featured groundbreaking research conducted by a collaborative team, including Academician Fan Jia, Professors Jian Zhou and Xinrong Yang from Zhongshan Hospital affiliated with Fudan University, in partnership with Kunyuan Biotechnology. Their findings were selected for a poster presentation, shedding light on the pivotal role of circulating tumor DNA (ctDNA) methylation and mutations in gauging minimal residual disease (MRD) and recurrence after radical liver cancer surgery. This research introduces novel strategies for the postoperative management of early-stage liver cancer patients, promising enhanced survival outcomes with further technological advancements and clinical validations.The study design encompasses recruiting around 200 patients with hepatocellular carcinoma (HCC) who have undergone radical surgery, with a two-year follow-up. Samples of cancer tissue, adjacent tissue, and blood are collected at baseline, one month post-surgery, and subsequently every three months. These samples undergo the GutSeer test, an innovative screening method initially developed for non-invasive early detection and diagnosis of five gastrointestinal cancers, including liver cancer. GutSeer integrates methylation and fragmentomics signals, achieving impressive sensitivity and specificity rates, particularly for liver cancer.
Leveraging GutSeer, the team developed the TORNADO method (Tumor-informed personalized evaluation of MRD). This approach assesses mutations and methylation in regions covered by GutSeer, identifying MRD through personalized tumor-specific mutations and methylation haplotypes.
So far, 73 patients with early-stage HCC who underwent radical resection have been enrolled, with a median follow-up of 11.8 months. Among them, 19 experienced recurrence. The GutSeer early detection model revealed a significant decline in positivity rates from preoperative to postoperative samples. Notably, patients deemed MRD-positive by the TORNADO model one month post-surgery (POM1) faced a substantially higher recurrence risk compared to MRD-negative patients (P<0.0001).
Further analyses confirmed that MRD status predicted by TORNADO at POM1 was strongly associated with recurrence (P<0.001). Moreover, the TORNADO method not only detected recurrence signals earlier but also surpassed conventional markers like AFP and DCP at various follow-up intervals. Combining TORNADO results at POM1 with tumor staging and preoperative levels of total cholesterol (TCHO), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) significantly enhanced the precision of postoperative prognosis predictions.
In conclusion, the preliminary results underscore the crucial role of ctDNA methylation and mutations in assessing MRD status and recurrence in early-stage HCC patients after radical resection. The Tumor-informed MRD detection method outperforms traditional markers, paving the way for improved postoperative monitoring and patient outcomes.
