Dataset Information

Personalized neoantigen vaccine prevents postoperative recurrence in hepatocellular carcinoma patients with vascular invasion.

ABSTRACT: BACKGROUND:Clinically, prophylactic anti-recurrence treatments for hepatocellular carcinoma (HCC) patients after radical surgery are extremely limited. Neoantigen based vaccine can generate robust anti-tumor immune response in several solid tumors but whether it could induce anti-tumor immune response in HCC and serve as a safe and effective prophylactic strategy for preventing postoperative HCC recurrence still remain largely unclear. METHODS:Personalized neoantigen vaccine was designed and immunized for 10 HCC patients with high risk of postoperative recurrence in a prime-boost schedule. The safety and immune response were assessed through adverse events, tissue sequencing, ELISpot, TCR sequencing. The clinical response was evaluated by recurrence-free survival (RFS) and personalized circulating tumor DNA (ctDNA) sequencing. RESULTS:In the 10 enrolled patients, no obvious adverse events were observed during neoantigen vaccinations. Until the deadline of clinical trial, 8 of 10 patients were confirmed with clinical relapse by imaging, the other 2 patients remained relapse-free. From receiving first neoantigen vaccination, the median RFS of 10 patients were 7.4 months. Among 7 patients received all planned neoantigen vaccinations, 5 of them demonstrated neoantigen-induced T cell responses and have significantly longer RFS after radical surgery than other 5 patients without responsive neoantigens or only with prime vaccination and propensity scores matching control patients (p = 0.035). Moreover, tracking personalized neoantigen mutations in ctDNA could provide real-time evaluation of clinical response in HCC patients during neoantigen vaccination and follow up. CONCLUSION:Personalized neoantigen vaccine is proved as a safe, feasible and effective strategy for HCC anti-recurrence, and its progression could be sensitively monitored by corresponding neoantigen mutations in ctDNA, and thus provided solid information for individualized medicine in HCC. TRIAL REGISTRATION:This study was registered at Chinese Clinical Trial Registry; Registration number: ChiCTR1900020990 .

SUBMITTER: Cai Z

PROVIDER: S-EPMC8667400 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundFew studies have focused on the prognosis of patients with hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage 0‒C in terms of early recurrence and 5-years overall survival (OS). We sought to develop nomograms for predicting 5-year OS and early recurrence after curative resection of HCC, based on a clinicopathological‒radiological model. We also investigated whether different treatment methods influenced the OS of patients with early recurrence.MethodsRetrospective data, including clinical pathology, radiology, and follow-up data, were collected for 494 patients with HCC who underwent hepatectomy. Nomograms estimating OS and early recurrence were constructed using multivariate Cox regression analysis, based on the random survival forest (RSF) model. We evaluated the discrimination and calibration abilities of the nomograms using concordance indices (C-index), calibration curves, and Kaplan‒Meier curves. OS curves of different treatments for patients who had recurrence within 2 years after curative surgery were depicted and compared using the Kaplan-Meier method and the log-rank test.ResultsMultivariate Cox regression revealed that BCLC stage, non-smooth margin, maximum tumor diameter, age, aspartate aminotransferase levels, microvascular invasion, and differentiation were prognostic factors for OS and were incorporated into the nomogram with good predictive performance in the training (C-index: 0.787) and testing cohorts (C-index: 0.711). A nomogram for recurrence-free survival was also developed based on four prognostic factors (BCLC stage, non-smooth margin, maximum tumor diameter, and microvascular invasion) with good predictive performance in the training (C-index: 0.717) and testing cohorts (C-index: 0.701). In comparison to the BCLC staging system, the C-index (training cohort: 0.787 vs. 0.678, 0.717 vs. 0.675; external cohort 2: 0.748 vs. 0.624, 0.729 vs. 0.587 respectively, for OS and RFS; external cohort1:0.716 vs. 0.627 for RFS, all p value<0.05), and model calibration curves all showed improved performance. Patients who underwent surgery after tumor recurrence had a higher reOS than those who underwent comprehensive treatments and supportive care.ConclusionsThe nomogram, based on clinical, pathological, and radiological factors, demonstrated good accuracy in estimating OS and recurrence, which can guide follow-up and treatment of individual patients. Reoperation may be the best option for patients with recurrence in good condition.

Dataset Information

Personalized neoantigen vaccine prevents postoperative recurrence in hepatocellular carcinoma patients with vascular invasion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets