Benefit of Conversion Therapy in Patients with Unresectable Hepatocellular Carcinoma: A Propensity Score-Matched Study.

Purpose: This study aimed to investigate the benefit of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC). Patients and Methods: A retrospective cohort study was conducted involving 40 patients initially deemed unresectable HCC (uHCC). They received surgery following successful conversion therapy involving lenvatinib. The patients were matched in a 1:1 ratio to with a control group who underwent direct surgery, based on pre-treatment clinical data. Results: The median recurrence-free survival (RFS) duration for the conversion therapy cohort was notably longer than that of the direct surgery cohort (25 months vs 11 months). Furthermore, the 1- and 2-year RFS rates were significantly higher in the conversion therapy group compared to the direct surgery group (1 year: 70.5% vs 40.1%; 2 years: 49.0% vs 19.1%). The survival curves indicated a statistically significantly longer RFS in the conversion therapy cohort compared to the direct surgery cohort (P = 0.007). While patients achieving good remission based on both RECIST 1.1 and mRECIST criteria showed superior median RFS, no significant disparity was observed in the survival curves. The subgroup analysis revealed significantly improved prognosis among patients in the conversion therapy group who were male, older, had a history of alcohol consumption, were non-smokers, had liver cirrhosis, possessed Child-Pugh A liver function, had a tumor diameter exceeding 5 cm, and had an AFP ≥ 400 ng/mL. Among the cohort of 40 patients, only 8 individuals encountered severe adverse reactions, which were managed through dose reduction. None of the patients experienced multiple severe adverse reactions concurrently. Conclusion: For patients with unresectable hepatocellular carcinoma, conversion therapy offers a significantly better prognosis than direct surgery for uHCC patients.

Sorafenib combined with TACE improves survival in patients with hepatocellular carcinoma with vascular invasion.

Sorafenib is a recommended first-line therapy for advanced hepatocellular carcinoma (HCC). However, when used as monotherapy in patients in advanced stages, the prognosis remains suboptimal. This study aimed to evaluate the impact of transcatheter arterial chemoembolization (TACE) on survival outcomes in patients with advanced HCC treated with sorafenib, as well as to identify which subgroups may benefit most from the addition of TACE. This single-institution retrospective study included 92 patients diagnosed with Barcelona Clinic liver cancer (BCLC) stage C HCC who received sorafenib between August 2011 and December 2016. We assessed the influence of different treatment modalities on prognosis using multivariable regression analysis. Patients were categorized into three subgroups: those with vascular invasion, those with distant metastasis, and those with both risk factors. Baseline comparisons indicated no significant differences in clinical characteristics among the three groups. Survival analysis showed no statistically significant difference in overall survival (OS) between the subgroups. However, in the overall cohort of patients with BCLC stage C, multifactorial Cox regression analysis identified pre-treatment alpha-fetoprotein (AFP) levels (p = 0.020), alkaline phosphatase (ALP) levels (p = 0.034), and the absence of combination TACE therapy (p = 0.008) as independent risk factors affecting OS. Further subgroup Cox analyses revealed that the lack of combination TACE therapy was an independent risk factor for OS in both the vascular invasion group and the group with both risk factors. In conclusion, for patients with advanced HCC receiving sorafenib, the addition of TACE may enhance long-term survival, particularly in those with vascular invasion.

Digital communication activities and EFL learners' willingness to communicate and engagement: Exploring the intermediate language learners' perceptions.

EFL/ESL teachers have used digital communication activities to teach language skills. However, the effect of digital communication activities on EFL learners' Willingness to Communicate (WTC) in classrooms and learner engagement has yet to be well investigated. This study examined the influence of digital communication activities on the engagement and willingness to communicate of intermediate English as a Foreign Language (EFL) learners. It also assessed the potential advantages of integrating digital communication into language learning contexts. A mixed-methods approach involving pretest-posttest comparisons and qualitative interviews was employed. In the quantitative phase, four intact classes of 80 intermediate Chinese EFL learners were recruited and assigned to control and experimental groups. They attempted the scales (WTC and engagement) before and after treatment. However, 20 EFL learners exposed to digital communication activities were interviewed. The research revealed notable enhancements in affective, cognitive, and behavioral engagement among the experimental group. Moreover, a substantial positive effect on EFL learners' willingness to communicate was observed, particularly in speaking, writing, reading, and comprehension activities. Findings have practical implications for EFL teachers and learners to use digital communication activities to enhance the learners' WTC in the classroom and different aspects of engagement.

A Retrospective Study on Predicting Recurrence of Intermediate-Stage Hepatocellular Carcinoma After Radical Therapy.

Purpose: This study aimed to investigate the potential benefits of radical therapy in patients with stage B disease. Patients and Methods: A retrospective analysis was conducted on a cohort of 437 patients diagnosed with stage B hepatocellular carcinoma, who underwent either hepatic resection (HR) or radiofrequency ablation (RFA) at the Cancer Institute and Hospital of Tianjin Medical University from May 2011 to May 2022. Multivariate COX regression analysis was performed to identify the independent prognostic factors related to recurrence-free survival (RFS). The performance of the developed nomogram was evaluated using various statistical measures, including the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: Multivariate analysis revealed that tumor diameter, number of tumors, number of involved liver segments, alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), lactate dehydrogenase (LDH), and systemic immune inflammation index (SII) were independent prognostic factors influencing patients' RFS, and these factors were incorporated into the nomogram. The C-index of the nomogram in the training cohort was 0.721, and the AUC at 2 and 3 years was 0.772 and 0.790, respectively. These values were appreciably higher than commonly used clinic staging systems and other predictive models. The calibration curve and DCA demonstrated good calibration and net benefit. Survival analysis comparing stage B patients who received radical treatment with stage A patients with multiple lesions did not reveal a significant difference in Kaplan-Meier survival curves (P=0.91). Conclusion: The nomogram provided a precise prediction of the recurrence for stage B hepatocellular carcinoma patients undergoing radical treatment. Furthermore, certain stage B patients may benefit from radical treatment.

Characterization and therapeutic perspectives of differentiation-inducing therapy in malignant tumors.

Cancer is a major public health issue globally and is one of the leading causes of death. Although available treatments improve the survival rate of some cases, many advanced tumors are insensitive to these treatments. Cancer cell differentiation reverts the malignant phenotype to its original state and may even induce differentiation into cell types found in other tissues. Leveraging differentiation-inducing therapy in high-grade tumor masses offers a less aggressive strategy to curb tumor progression and heightens chemotherapy sensitivity. Differentiation-inducing therapy has been demonstrated to be effective in a variety of tumor cells. For example, differentiation therapy has become the first choice for acute promyelocytic leukemia, with the cure rate of more than 90%. Although an appealing concept, the mechanism and clinical drugs used in differentiation therapy are still in their nascent stage, warranting further investigation. In this review, we examine the current differentiation-inducing therapeutic approach and discuss the clinical applications as well as the underlying biological basis of differentiation-inducing agents.

Lenvatinib plus sintilimab with or without transarterial chemoembolization for intermediate or advanced stage hepatocellular carcinoma: a propensity score-matching cohort study.

In this retrospective study, we compared the efficacy and safety of lenvatinib plus sintilimab, with or without transarterial chemoembolization (TLS vs. LS), in patients with intermediate or advanced stage hepatocellular carcinoma (HCC). Eligible patients who received combination therapy with TLS or LS at Tianjin Medical University Cancer Institute & Hospital from December 2018 to October 2020 were propensity score matched (PSM) to correct for potential confounding biases between the two groups. The primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS), overall response rate (ORR) and treatment-related adverse events (TRAEs). Cox proportional hazards models were used to identify prognostic factors. The study included 152 patients (LS group, n=54, TLS group, n=98). After PSM, patients in the TLS group had significantly longer PFS (11.1 versus 5.1 months, P=0.033), OS (not reached versus 14.0 months, P=0.0039) and ORR (modified Response Evaluation Criteria in Solid Tumors: 44.0% versus 23.1%; P=0.028) than those in the LS group. In the multivariate Cox regression analysis, the treatment regimen (TLS versus LS) was an independent predictor for both PFS (HR=0.551; 95% CI: 0.334-0.912; P=0.020) and OS (HR=0.349; 95% CI: 0.176-0.692; P=0.003) and CA19-9 level was an independent predictor for OS (HR=1.005; 95% CI: 1.002-1.008; P=0.000). No significant differences in the incidence of grade ≥3 TRAEs were reported between the two treatment groups. In conclusion, triple combination therapy with TLS improved survival with an acceptable safety profile compared with LS in patients with intermediate or advanced stage HCC.

A Retrospective Analysis of Conversion Therapy with Lenvatinib, Sintilimab, and Arterially-Directed Therapy in Patients with Initially Unresectable Hepatocellular Carcinoma.

Purpose: The purpose of this study was to investigate the triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy as a conversion therapy for initially unresectable hepatocellular carcinoma (HCC). Patients and Methods: We retrospectively analyzed data from all HCC patients who underwent lenvatinib plus sintilimab plus arterially-directed therapy at Tianjin Medical University Cancer Hospital between December 2018 and October 2020. Of 98 enrolled patients, 37 patients were classified as potentially resectable. We compared the potentially resectable population (PRP) with the non-potentially resectable population (NPRP). The primary study endpoint was conversion rate, and secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: The baseline characteristics were comparable between populations except for a higher proportion of patients with extrahepatic metastases in the NPRP versus PRP (23/61 [37.7%] vs 3/37 [8.1%], respectively; p=0.003). For PRP, the ORR was 67.6% based on RECIST v1.1 (75.7% based on mRECIST), conversion rate was 40.5% (15/37). Of the 15 patients who underwent surgical resection, three achieved complete pathological remission. The median follow-up for all patients was 28 months (range: 2-47). For NPRP, the ORR was 22.9% based on RECIST v1.1 (31.1% based on mRECIST), The median PFS for PRP was significantly longer than that of NPRP (25 vs 13 months, p = 0.0025). The median OS for PRP was significantly longer than that of NPRP (not reached VS 21 months, p=0.014). Hypertension was the most common grade ≥3 adverse reaction in both PRP and NPRP. No new safety signals were observed for any of the treatments. Conclusion: The triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy can convert potentially unresectable HCC into resectable disease and improve long-term survival.

Predictive Value of Preoperative Serum AFP, CEA, and CA19-9 Levels in Patients with Single Small Hepatocellular Carcinoma: Retrospective Study.

Purpose: This study aimed to explore the relationship between the tumor marker score (TMS) and the postoperative recurrence of single small hepatocellular carcinoma (HCC). Patients and Methods: A total of 409 patients with one resectable HCC with a diameter of 3 cm or less who visited Tianjin Medical University Cancer Institute & Hospital from January 2010 to December 2014 were included in this study. Their alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) levels were classified into low and high groups using X-tile software. Each patients' TMS was calculated as the sum of each tumor marker (low = 0; high = 1). Results: A total of 142 patients were classified as TMS0, 171 as TMS1, and 96 as TMS2. Kaplan-Meier analysis illustrated that TMS could divide the patients into groups with remarkably different prognoses, and the patients with high TMS had worse recurrence-free survival (RFS) than those with low TMS. Multivariate analysis showed that TMS, age, and HBeAg positive were the independent predictors of RFS rate. Subgroup analysis revealed that high TMS was a stable risk factor relative to TMS0. Receiver operating curves showed that the 1-, 3-, and 5-year area under curve (AUC) values of TMS were 0.698, 0.662, and 0.673, respectively. The AUC of TMS was higher than that of other common prognostic models in time-dependent receiver operating curve. Conclusion: TMS was an independent prognostic factor for the postoperative recurrence of a single small HCC and can provide a well-discriminated risk stratification, thus contributing to prognostic prediction and adjuvant therapeutic development.