CD44v9 is expressed in cancer stem cells (CSC) and stabilizes the glutamate‐cystine transporter xCT on the cytoplasmic membrane, thereby decreasing intracellular levels of reactive oxygen species ...(ROS). This mechanism confers ROS resistance to CSC and CD44v9‐expressing cancer cells. The aims of the present study were to assess: (i) expression status of CD44v9 and xCT in hepatocellular carcinoma (HCC) tissues, including those derived from patients treated with hepatic arterial infusion chemoembolization (HAIC) therapy with cisplatin (CDDP); and (ii) whether combination of CDDP with sulfasalazine (SASP), an inhibitor of xCT, was more effective on tumor cells than CDDP alone by inducing ROS‐mediated apoptosis. Twenty non‐pretreated HCC tissues and 7 HCC tissues administered HAIC therapy with CDDP before surgical resection were subjected to immunohistochemistry analysis of CD44v9 and xCT expression. Human HCC cell lines HAK‐1A and HAK‐1B were used in this study; the latter was also used for xenograft experiments in nude mice to assess in vivo efficacy of combination treatment. CD44v9 positivity was significantly higher in HAIC‐treated tissues (5/7) than in non‐pretreated tissues (2/30), suggesting the involvement of CD44v9 in the resistance to HAIC. xCT was significantly expressed in poorly differentiated HCC tissues. Combination treatment effectively killed the CD44v9‐harboring HAK‐1B cells through ROS‐mediated apoptosis and significantly decreased xenografted tumor growth. In conclusion, the xCT inhibitor SASP augmented ROS‐mediated apoptosis in CDDP‐treated HCC cells, in which the CD44v9‐xCT system functioned. As CD44v9 is typically expressed in HAIC‐resistant HCC cells, combination treatment with SASP with CDDP may overcome such drug resistance.
This study is the first to show high expression of CD44v9, a cancer stem cell marker, in chemoresistant hepatocellular carcinoma cells, which were previously exposed to chemotherapeutic agents through hepatic arterial infusion chemoembolization.
We sought to investigate the clinical profile(s) associated with the discontinuation of lenvatinib (LEN) due to severe adverse events (DLSAE) in patients with unresectable hepatocellular carcinoma ...(HCC). This retrospective study enrolled 177 patients with HCC treated with LEN. Independent factors associated with DLSAE were advanced age, albumin-bilirubin (ALBI) grade 2, fatigue grade ≥ 3, and appetite loss ≥ 2. The overall survival (OS) in the group that did not require DLSAE was significantly longer compared to the group that did require DLSAE (median survival time (MST): not reached vs. 12.8 months, p < 0.001). Moreover, advanced age was the most important variable for DLSAE in a decision tree analysis. Hypertension and hand-foot-skin-reaction (HFSR) were also significantly associated with longer survival, and the occurrence of hypertension was the earliest predictor for improved prognosis, while appetite loss and development of grade ≥ 3 fatigue were predictive of a poor prognosis. We concluded that the appearance of hypertension has potential as an early surrogate marker to predict improved prognosis. Moreover, careful management to avoid discontinuation of treatment leads to longer survival in patients receiving LEN.
Aim
Few studies have reported the efficacy and safety of ramucirumab (RAM) after atezolizumab plus bevacizumab (Atezo/Beva) treatment and the overall associated outcomes. Thus, we aimed to evaluate ...the therapeutic effects and safety of RAM post‐treatment with Atezo/Beva.
Methods
This retrospective study enrolled 46 patients with unresectable hepatocellular carcinoma who were treated with RAM. The patients were classified into the RAM administered following Atezo/Beva failure (n = 12) or RAM administered following other drug failure (n = 34) groups. Progression‐free survival (PFS), overall survival (OS), and adverse event (AE) rates were assessed.
Results
There were significant differences in the objective response rates and disease control rates between the RAM administered following Atezo/Beva and RAM administered following others groups (objective response rate 33.3%. vs. 0.0%, p = 0.001; disease control rate 83.3% vs. 32.3, p = 0.001). Although there was no significant difference in the OS rates, the median PFS rates in the RAM administered following Atezo/Beva group was significantly higher than in the RAM administered following others group (PFS 3.9 months. vs. 1.9 months, p = 0.047). The AE rates were comparable between the two groups; ascites was the most common AE (45.6%). Using decision tree analysis, the presence of splenomegaly and body mass index (BMI) < 19.8 were the first and second splitting variables for RAM‐related ascites, respectively.
Conclusions
The therapeutic effect of RAM increased in patients with Atezo/Beva failure. Patients with splenomegaly and low BMI should be monitored for ascites during RAM treatment.
The therapeutic effect was significantly higher in the ramucirumab (RAM) following atezolizumab plus bevacizumab (Atezo/Beva) group than in the RAM following treatment other than Atezo/Beva group. The development of ramucirumab‐related ascites was associated with splenomegaly and low body mass index.
Background
Atezolizumab plus bevacizumab showed superior progression-free and overall survival compared to sorafenib in the IMbrave150 trial. It would therefore be useful to compare the efficacy of ...lenvatinib and that of atezolizumab plus bevacizumab to determine if a benefit of one therapy against the other exists.
Objective
The aim of the present report was to apply a matching-adjusted indirect comparison (MAIC) to individual participant data (IPD) from patients treated with lenvatinib outside of randomized trials, to aggregate results derived from the IMbrave150 trial.
Patients and methods
Data from 455 patients who received lenvatinib as first-line systemic therapy for unresectable HCC represented the present IPD. Data inclusion were adapted to those reported in the IMbrave150 trial.
Results
Overall survival on atezolizumab plus bevacizumab proved to be superior to lenvatinib (log-rank: 0.001) with a hazard ratio of 0.59 (95% confidence interval 0.46–0.75). The number needed to treat ranged between seven in the first 12 months and five at the 15th month.
Conclusions
The present MAIC highlights that the combination of atezolizumab plus bevacizumab is superior to lenvatinib. However, updated data or sub-analyses of the IMbrave150 trial would provide more robust estimates for such a treatment comparison.
Background: Atezolizumab plus bevacizumab was approved for patients with hepatocellular carcinoma (HCC). Although clinical trials have revealed its efficacy, the outcomes in the real-world clinical ...practice are unclear. We retrospectively evaluated the efficacy and safety of atezolizumab plus bevacizumab for HCC. Materials and Methods: This is a multicenter study conducted between November 2020 and March 2021. Among the 61 patients, 51 were assessed for progression-free survival (PFS), therapeutic response, and adverse events (AEs). Results: The median PFS was 5.4 months. The objective response rate (ORR) was 35.3%. The disease control rate (DCR) was 86.3%. The incidence rates of AEs at any grade and grade >3 were 98.0% and 29.4%, respectively. The most frequent AE at any grade and grade >3 was hepatic disorder. In patients with a previous history of molecular targeted agent (MTA) or the degree of albumin-bilirubin (ALBI) grade, there were no significant differences in the PFS, ORR, DCR, and incidence rates of AEs. Conclusion: The study demonstrated that atezolizumab plus bevacizumab was effective and safe for patients with HCC even in the real-world setting including patients with a previous MTA history or other than ALBI grade 1.
We aimed to evaluate the impact of alternating lenvatinib (LEN) and trans-arterial therapy (AT) in patients with intermediate-stage hepatocellular carcinoma (HCC) after propensity score matching ...(PSM). This retrospective study enrolled 113 patients with intermediate-stage HCC treated LEN. Patients were classified into the AT (
= 41) or non-AT group (
= 72) according to the post LEN treatment. Overall survival (OS) was calculated using the Kaplan-Meier method and analyzed using a log-rank test after PSM. Factors associated with AT were evaluated using a decision tree analysis. After PSM, there were no significant differences in age, sex, etiology, or albumin-bilirubin (ALBI) score/grade between groups. The survival rate of the AT group was significantly higher than that of the non-AT group (median survival time; not reached vs. 16.3 months,
= 0.01). Independent factors associated with OS were AT and ALBI grade 1 in the Cox regression analysis. In the decision tree analysis, age and ALBI were the first and second splitting variables for AT. In this study, we show that AT may improve prognosis in patients with intermediate-stage HCC. Moreover, alternating LEN and trans-arterial therapy may be recommended for patients below 70 years of age with ALBI grade 1.
Background and Aim
Sarcopenia is a prognostic factor in hepatocellular carcinoma (HCC) patients. HCC patients who underwent transcatheter arterial chemoembolization (TACE) are at a risk of muscle ...atrophy. We aimed to investigate the effects of in‐hospital exercise on muscle mass and factors associated with muscle hypertrophy in HCC patients who underwent TACE.
Methods
We enrolled 209 HCC patients who underwent TACE. Patients were classified into either an exercise (n = 102) or control (n = 107) group. In the exercise group, patients were treated with in‐hospital exercise (median 2.5 metabolic equivalents/20–40 min/day). The effects of exercise on muscle mass were evaluated by changes in skeletal muscle index (ΔSMI) between before and after TACE. Factors associated with an increase in SMI were analyzed by logistic regression and decision‐tree analyses.
Results
There was no significant difference in serum albumin and bilirubin levels between the two groups. ΔSMI was significantly higher in the exercise group than in the control group (0.28 cm2/m2 vs −1.11 cm2/m2, P = 0.0029). In the logistic regression analysis, exercise was an independent factor for an increase in SMI (hazard ratio 2.13; 95% confidence interval 1.215–3.846; P = 0.0085). Moreover, the decision‐tree analysis showed that exercise was the initial divergence variable for an increase in SMI (the ratio of increased SMI: 53% in the exercise group vs 36% in the control group).
Conclusions
In‐hospital exercises increased muscle mass in HCC patients who underwent TACE. In addition, exercise was an independent factor for muscle hypertrophy. Thus, in‐hospital exercise may prevent sarcopenia in HCC patients who underwent TACE.
Aims
The prognosis of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE) is still poor. We aimed to evaluate the impact of TACE combined with ...radiofrequency ablation (TACE+RFA) on the prognosis of HCC patients using decision‐tree analysis after propensity score matching.
Methods
This was a retrospective study. We enrolled 420 patients with HCC treated with TACE alone (n = 311) or TACE+RFA (n = 109) between 1998 and 2016 (median age, 72 years; male / female, 272/148; Barcelona Clinic Liver Cancer (BCLC) stage A / B, 215/205). The prognosis of patients who underwent TACE+RFA was compared to patients who underwent TACE alone after propensity score matching. Decision‐tree analysis was used to investigate the profile for prognosis of the patients.
Results
After propensity score matching, there was no significant difference in age, sex, BCLC stage, or albumin–bilirubin (ALBI) score between both groups. The survival rate of the TACE+RFA group was significantly higher than the TACE alone group (median survival time MST 57.9 months vs. 33.1 months, P < 0.001). In a stratification analysis according to BCLC stage, the overall survival rate of the TACE+RFA group was significantly higher than the TACE alone group in BCLC stage A and B (MST 57.9 and 50.7 months vs. 39.8 and 24.5 months P = 0.007 and 0.001, respectively). Decision‐tree analysis showed that TACE+RFA was the third distinguishable factor for survival in patients with α‐fetoprotein level >7 ng/mL and ALBI <−2.08.
Conclusion
Decision‐tree analysis after propensity score matching showed that TACE+RFA could prolong the survival of HCC patients compared to TACE alone.
PDF
