Circulating tumour DNA in patients with hepatocellular carcinoma across tumour stages and treatments

Objective
Circulating tumour DNA (ctDNA) is a promising non-invasive biomarker in cancer. We aim to assess the dynamic of ctDNA in patients with hepatocellular carcinoma (HCC).

Design
We analysed 772 plasmas from 173 patients with HCC collected at the time of diagnosis or treatment (n=502), 24 hours after locoregional treatment (n=154) and during follow-up (n=116). For controls, 56 plasmas from patients with chronic liver disease without HCC were analysed. All samples were analysed for cell free DNA (cfDNA) concentration, and for mutations in TERT promoter, CTNNB1, TP53, PIK3CA and NFE2L2 by sequencing and droplet-based digital PCR. Results were compared with 232 corresponding tumour samples.

Results
In patients with active HCC, 40.2% of the ctDNA was mutated vs 14.6% in patients with inactive HCC and 1.8% in controls (p

Leggi
Ottobre 2024

Effectiveness of peritoneal lavage fluid circulating tumour cells and circulating tumour DNA in the prediction of metachronous peritoneal metastasis of gastric cancer (pT4NxM0/pT1-3N+M0) after radical resection: protocol of a prospective single-centre clinical study

Background
Gastric cancer (GC) is the fourth leading cause of cancer mortality worldwide. Peritoneal metastasis (PM) is a significant cause of death in patients with GC, and presents a major challenge in clinical diagnosis and treatment. Predicting the occurrence of PM in high-risk patients, and diagnosing and treating PM in advance to improve patient survival, remains an unsolved problem in clinical practice. Given the low positive rate of cytology and difficulty in diagnosing occult PM, new molecular markers and detection technologies for early diagnosis require urgent validation. The primary objective of this study is to observe and evaluate the predictive effect of intraoperative peritoneal lavage fluid (PLF) circulating tumour cells (CTC) and circulating tumour DNA (ctDNA) levels in patients with pT4NxM0/pT1-3N+M0 GC on metachronous PM after R0 resection.

Methods and analysis
This prospective single-centre clinical study is conducted at Renji Hospital, Shanghai Jiao Tong University School of Medicine. In this study, 200 cases of patients with pT4NxM0/pT1-3N+M0 gastric adenocarcinoma older than 18 years will be screened. Participants will undergo intraoperative PLF CTC and ctDNA testing and will be followed up for 2 years, with imaging assessments performed every 3–6 months until PM occurrs. The primary outcome is the incidence of PM 1 year after surgery, which will be estimated using Clopper-Pearson method, with 95% CIs calculated and compared between groups. Secondary outcome include the incidence of PM 2 years after surgery, overall survival and disease progression. Data will be analysed using the Kaplan-Meier method and the log-rank test.

Ethics and communication
Informed consent has been obtained from all subjects. This protocol has been approved by the Ethics Committee of Renji Hospital, Shanghai Jiao Tong University School of Medicine (LY2023-142-B). The findings will be disseminated through peer-reviewed manuscripts, reports and presentations.

Trial registration number
ChiCTR2300074910.

Leggi
Ottobre 2024