α-fetoprotein (AFP) response has been proven a key tumor marker for hepatocellular carcinoma (HCC), but its definition remains controversial. This study aims to characterize AFP trajectories after transarterial chemoembolization (TACE) and examine its impact on clinical outcomes. This longitudinal, multicenter, retrospective, cohort study examined data from the electronic medical record system of four hospitals in China between January 1, 2007 to December 31, 2016. A latent class growth mixed model was applied to distinguish potential AFP dynamic changing trajectories. The multivariable Cox models were used to calculate adjusted hazard ratios (aHRs) and 95% CIs for overall survival. Inverse-probability-of-treatment weighted analyses were performed to eliminate unmeasured confounders through marginal structural models. A total of 881 patients, who had intermediate-stage HCC with AFP repeatedly measured 3 to 10 times, were included in the study. Three distinct trajectories were identified using the latent class growth mixture model: high-rising (25.7%; n = 226), low-stable (58.7%; n = 517), and sharp-falling (AFP serological response, 15.6%; n = 138). Compared with the low-stable class, the aHRs for death were 5.13 (3.71, 7.10) and 0.52 (0.33, 0.81) for the high-rising and sharp-falling class, adjusted by gender, baseline major tumor size, intrahepatic lesions number, and logAFP(smooth). Furthermore, high-rising class had a significantly higher HR in the subgroup of female patients (10.60, 95%CI: 6.29, 17.86), age<55 (6.78, 95%CI: 4.79, 9.59) and Child-Pugh class B (23.01, 95%CI:8.07, 65.63) (P = 0.014, 0.046 and 0.033 for interaction, respectively). Trajectories of AFP had the highest relative importance of each parameter to survival, including largest tumor size, intrahepatic lesions number, Child-Pugh class, and baseline AFP. AFP trajectories were associated with overall survival for intermediate-stage HCC after TACE. The Natural Science Foundation of Fujian Province (Nos. 2018J01352, 2016J01576 and 2016J01586); the Science and Technology Innovation Joint Foundation of Fujian Province (Nos. 2017Y9125).

Background: Previous studies have shown that the alpha-fetoprotein (AFP) response has been a key tumour marker in hepatocellular carcinoma (HCC), but its definition remains controversial. Recently, a new study has explored and defined the AFP serological response and used it to explain the subclass of intermediate-stage hepatocellular carcinoma (IM-HCC) with “sharp-falling” AFP change after transarterial chemoembolization (TACE). It may be a new and simple tool for assessing the prognosis of patients. This study aims to explore a simplified AFP trajectory and its impact on overall survival (OS) and disease-free survival (DFS) for IM-HCC after hepatectomy. Patients and Methods: Between January 2007 and May 2012, data from the Sun Yat-sen University Cancer Center was examined in this longitudinal, retrospective cohort study. A generalized additive model was applied to distinguish potential AFP dynamic trajectories. The Kaplan-Meier method was applied to analyze OS and DFS, and multivariate Cox models were used to calculate adjusted hazard ratios (aHRs) and 95% CIs for overall survival. Results: 144 patients who had IM-HCC with at least three AFP repeat measurements were included in the study. Three similar trajectories are displayed using the generalized additive model: low-stable (35.4%; n = 51), high-rising (36.1%; n = 52), and sharp-falling (28.5%; n = 41). Compared with the low-stable class, the aHRs for death were 2.84 (1.50, 5.41) and 0.59 (0.25, 1.40) for the high-rising and sharp-falling classes, adjusted by age and log AFP. Simplified AFP trajectory had higher relative importance than sex, intrahepatic tumor number, Child-Pugh class, and baseline AFP. Conclusion: The simplified AFP trajectory is a promising biomarker for IM-HCC patients undergoing hepatectomy. In the future, it should be verified by a larger population containing various stages of HCC.

Background: There are few effective prediction models for intermediate-stage hepatocellular carcinoma (IM-HCC) patients treated with transarterial chemoembolization (TACE) to predict overall survival (OS) is available. The learning survival neural network (DeepSurv) was developed to showed a better performance than cox proportional hazards model in prediction of OS. This study aimed to develop a deep learning-based prediction model to predict individual OS.

Background: Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage Hepatocellular carcinoma (HCC) patients. However, predicting the survival of HCC patients receiving TACE remains challenging. Methods: In this retrospective study, we analyzed a total of 1805 HCC patients who received TACE. The patients were randomly divided into a training set (n = 1264) and a validation set (n = 541). We examined various prognostic factors within the training set and developed a simple ALFP (ALBI grade, AFP, and Prothrombin time) score, which was subsequently validated using the independent validation set. Results: Our multivariate analysis revealed that baseline ALBI grade 2 or 3, AFP ≥ 100 ng/mL, and PT > 13.1 s were independent unfavorable prognostic factors for HCC patients receiving TACE (p < 0.05). Based on these findings, we constructed the ALFP score, which assigns 1 point each for ALBI grade 2 or 3, AFP ≥ 100 ng/mL, and PT > 13.1 s. The score has a range of 0 to 3, and higher scores are associated with poorer outcomes. The median overall survival (OS) varied significantly among different ALFP score groups, both in the training set and the validation set (p < 0.001). We further examined the ALFP score in subgroups based on tumor diameter and the number of intrahepatic lesions. In each subgroup, higher ALFP scores were consistently associated with lower OS (p < 0.05). Conclusion: Our study confirms the prognostic value of the ALFP score in predicting the survival of HCC patients undergoing TACE. The score incorporates easily obtainable baseline parameters and provides a simple and practical tool for risk stratification and treatment decision-making in HCC patients.

Background: Transarterial chemoembolization (TACE) is the standard first-line therapy for intermediate-stage hepatocellular carcinoma (HCC). However, no latent-classing indices, concerning repeat conventional TACE or switching to another treatment, have been incorporated into the guidelines.