Purpose To assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC). Methods Patients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines. Results Baseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P <0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥0.7 vs <0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5–7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment. Conclusion Lenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.

Skin toxicity was associated with favorable outcomes with sorafenib therapy for advanced HCC. Nursing intervention contributed to better adherence, which may improve the efficacy of sorafenib.

Patients with advanced hepatocellular carcinoma (HCC) undergoing molecular targeted therapy often experience non-negligible adverse events (AEs). Paradoxically, certain AEs are reportedly associated with a good prognosis. We aimed to identify factors predictive of treatment duration and overall survival (OS) in patients with HCC undergoing lenvatinib therapy. Forty-six consecutive patients with advanced HCC who received lenvatinib therapy from April 2018 to November 2019 were prospectively followed until November 2019. Treatment efficacy was assessed according to the modified Response Evaluation Criteria in Solid Tumors for 2–3 months after therapy initiation. The disease control rate (DCR) was defined as the percentage of patients with a complete response, partial response, or stable disease. The DCR was 65.2%, with a median survival of 10.2 months. Grade 2/3 hypoalbuminemia resulted in shorter treatment duration. Factors predictive of longer OS were a Child-Pugh score of 5 at baseline and the occurrence of Grade 2/3 hypothyroidism. Conversely, Grade 2/3 hypoalbuminemia was associated with a poorer prognosis. An AE of Grade 2/3 hypothyroidism was associated with a better prognosis in patients receiving lenvatinib treatment for advanced HCC. Continuing anticancer therapy with appropriate thyroid hormone replacement may contribute to longer OS.

BackgroundThis study aimed to identify the health-related quality of life (HRQOL) domains associated with prognosis by assessing longitudinal alterations in HRQOL in patients with advanced hepatocellular carcinoma receiving sorafenib.MethodsWe prospectively assessed HRQOL by administering the SF-36 questionnaire 3-monthly to consecutive patients with advanced hepatocellular carcinoma receiving sorafenib. We evaluated the impact of HRQOL on their overall survival and duration of treatment with sorafenib using Cox's proportional hazards model.ResultsThere were 54 participants: 42 (78 %) were male, the median age was 71 years, 24 (44 %) had hepatitis C virus infection, 33 (61 %) had Child-Pugh scores of 5, and 30 (56 %) had TNM stage IV hepatocellular carcinoma. The median overall survival and treatment duration were 9 and 5 months, respectively, and 40 patients (74 %) died. Thirteen patients receiving sorafenib over a 1-year period maintained all domain scores >40, without a significant decline during the treatment period. In contrast, physical functioning, physical role, and vitality scores declined continuously and significantly in the year before death (in the 40 patients who died). Previous curative treatment and physical functioning scores ≥40 at baseline were significantly associated with longer overall survival by multivariate analysis. Social functioning scores ≥40, absence of vascular invasion, and lower DCP value were significant predictors of longer treatment duration.ConclusionsHRQOL was not significantly impaired in those patients who were able to complete a 1-year course of sorafenib treatment. Baseline physical functioning scores ≥40 and social functioning scores ≥40 were significantly associated with longer overall survival and longer treatment duration, respectively. Thus, HRQOL could be a valuable marker to predict the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2908-7) contains supplementary material, which is available to authorized users.

A 60-year-old man received interferon/ribavirin combination therapy for chronic hepatitis C in 2002 and achieved sustained virological response. In 2008, a hepatocellular carcinoma (HCC) with a diameter of 60 mm appeared and surgical resection was performed. In March 2011, the patient was referred to our hospital because of portal lymph node swelling. Abdominal ultrasonography, dynamic CT and dynamic MRI did not show any tumors in the liver, but revealed portal lymph node swelling (18 × 11 mm). Taking the elevation of serum des-γ-carboxy prothrombin and alpha-fetoprotein levels, including the lectin-bound type, into consideration, we made the diagnosis of HCC metastasis to the portal lymph node. We started sorafenib therapy at a dose of 800 mg/day, but discontinued it after 11 days due to grade 3 hand-foot skin reaction and rash. In spite of treatment termination, portal lymph node swelling disappeared and the serum des-γ-carboxy prothrombin and alpha-fetoprotein levels normalized. We considered that our patient achieved complete response to sorafenib according to the Response Evaluation Criteria in Solid Tumors (RECIST). The patient maintains remission up to June 2012, more than 1 year after the discontinuation of sorafenib therapy. Sorafenib could be a good option for unresectable or recurrent HCC.