Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis.

BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.

Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib.

BACKGROUND: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. PATIENTS AND METHODS: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. RESULTS: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin-bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). CONCLUSION: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.

External radiotherapy for biliary decompression of hilar cholangiocarcinoma.

Obstructive jaundice due to hilar cholangiocarcinoma is difficult to decompress because of the location of the tumor. We used external radiation alone for biliary decompression and reviewed its efficacy in this study. Subjects comprised 14 patients diagnosed as having inoperable hilar cholangiocarcinoma by ultrasonography, percutaneous transhepatic cholangiography, and CT scanning. The total bilirubin level on admission ranged from 0.4 to 34.6 mg/dl (mean: 11.0 mg/dl). These patients were irradiated with a 4MeV linear accelerator using parallel opposing fields measuring from 7 x 7 cm to 8 x 10 cm. The total radiation dose ranged from 50 Gy to 60 Gy and in fractions of 1.8-2.0 Gy per day. No patient underwent further biliary decompression after percutaneous transhepatic cholangiography, and irradiation was performed immediately after diagnosis. Eleven of the 14 patients received the full dose of external radiation. Three patients discontinued radiotherapy because of severe vomiting and nausea, pneumonia, and a hemorrhagic gastric ulcer. In 10 of the 11 patients, the serum total bilirubin level returned to normal (p < 0.005) and no cholangitis occurred. Obstructive jaundice recurred in one patient, and serum total bilirubin returned to normal again after further irradiation. Eight of the 11 patients could be discharged from hospital and returned to society. The survival time of the 11 patients ranged from 3 to 25 months and the 12-month survival rate was 50% (Kaplan-Meier method). This study suggests that external radiation therapy is an effective treatment for biliary decompression in patients with unresectable hilar cholangiocarcinoma.

Streptococcal toxic shock syndrome: report of two cases.

Two Japanese cases of streptococcal toxic shock syndrome (STSS) are reported. The first patient was a 45-year-old male who developed necrotizing fasciitis and myositis of the left thigh, refractory hypotension, hepatic dysfunction and acute renal failure; the patient died despite treatment. Streptococcus pyogenes was isolated from the inflamed fascia. The second patient was a 69-year-old female who had coagulopathy, polymyositis and hepatic function abnormality. Streptococcus pyogenes was isolated from blood culture. She was immediately placed on high-dose ampicillin as well as other supportive measures, and she survived.

[Clinical study of continuous local arterial-infusion chemotherapy for severely advanced hepatocellular carcinoma (HCC) using reservoir].

We attempted continuous local arterial-infusion chemotherapy using reservoir for patients with severely advanced hepatocellular carcinoma (HCC), with no indications for operation, PEIT or TAE because of the advanced clinical stage, Vp-factor, and so on. Twenty-two HCC patients were given continuous arterial-infusion of 5-FU + CDDP and were observed for 36-443 days from June, 1991 to December, 1992. Until the end of 1992, we had 3 partial response (PR) cases and 3 progressive disease (PD) cases, and the other cases showed no change (NC). Except for a case in which therapy was stopped because of renal failure, no patients were disturbed by side effects, and 68.2% of the patients completed all of their therapy as outpatients. Because CDDP can amplify the effect of 5-FU in addition to its own effect as a biochemical modulator, and because continuous infusion can strengthen the effect of 5-FU and reduce the side effects of CDDP, we consider continuous local arterial-infusion of 5-FU and CDDP to be an effective therapy for severely advanced HCC. This treatment does not cure the carcinoma but helps to slow its progress and assure good QOL.