Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability

Hepatocellular carcinoma (HCC) has limited systemic treatment options and a poor prognosis. The immune checkpoint inhibitor pembrolizumab was recently approved for the treatment of solid tumors with microsatellite instability (MSI). However, its clinical utility for the management of HCC remains to be clarified. Here, we present a case of unresectable HCC with MSI that showed an impressive response to pembrolizumab treatment. A 64-year-old man with chronic HCV infection was diagnosed with a large HCC. His severe liver dysfunction and poor performance status prevented any treatment option other than sorafenib. However, sorafenib failed after a few days due to the rapid progression of the tumor. Based on the finding of MSI in a biopsy specimen, immunotherapy using pembrolizumab was initiated. A dramatic improvement in his general condition and a reduction in tumor size were observed after the initiation of pembrolizumab treatment. Among a cohort of 50 consecutive patients with advanced HCC who were refractory to standard systemic therapy, MSI was found only in the present case. Immune checkpoint blockade therapy induced prominent anti-tumor effects in HCC with MSI. Screening for defects in DNA mismatch repair function may be warranted in HCC patients despite the low frequency of MSI

Assessment of Outcome of Hepatic Arterial Infusion Chemotherapy in Patients with Advanced Hepatocellular Carcinoma by the Combination of RECIST and Tumor Markers

To assess the outcome of stable disease (SD) patients with advanced hepatocellular carcinoma (HCC) by tumor markers after the first course of hepatic arterial infusion chemotherapy (HAIC). The study subjects were 156 HCC patients treated with HAIC and classified as Child Pugh A, with no extrahepatic metastasis, and no history of sorafenib treatment. In the study and validation cohorts, the AFP and DCP ratios of patients who were considered SD to the first course of HAIC were analyzed by AUROC for a prediction of response to the second course of HAIC. The imaging response to the first course of HAIC was classified as partial response (PR), SD and progressive disease (PD) in 29 (18.8%), 80 (51.9%), and 44 (28.6%) patients respectively. For SD patients, the α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) ratios of patients who were considered SD to the first course of HAIC were analyzed by the receiver operating characteristic curve for prediction of response to the second course of HAIC in the study cohorts. The area under the curve of AFP ratio was 0.743. The area under the curve of DCP ratio was 0.695. The cut-off values of AFP and DCP ratios were 1.3 and 1.0, respectively. In the validation cohort, the accuracy of the prediction of response in this validation cohort (71.4%) showed no significant difference compared to that in the study cohort (72.4%) (p = 1.0). The results suggested that patients with a high tumor marker ratio could be switched to alternative therapeutic regimens despite the SD response to HAIC

Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma: Seven cases

The combination of intra-arterial low-dose cisplatin and 5-fluorouracil (5-FU) is effective against advanced hepatocellular carcinoma (HCC). Systemic gemcitabine chemotherapy seems effective in many cancers. We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU (GEMFP). Seven patients with non-resectable advanced HCC were treated with GEMFP. One course of chemotherapy consisted of daily intra-arterial cisplatin (20 mg/body weight/hour on d 1, 10 mg/body weight per 0.5 h on d 2-5 and 8-12), followed by 5-FU (250 mg/body weight per 5 h on d 1-5 and 8-12) via an injection port. Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8. The objective response was 57%. The response to GEMFP was as follows: complete response (no patients), partial response (four patients), stable disease (three patients), and progressive disease (no patients). The median survival period was 8 mo (range, 5-55). With regard to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 adverse reactions, seven (100%), seven, six (86%) and one (14%) patients developed leukopenia, neutropenia, thrombocytopenia and anemia, respectively. GEMFP may potentially be effective for non-resectable advanced HCC, but it has severe hematologic toxicity

Transarterial Infusion Chemotherapy Using Cisplatin-Lipiodol Suspension With or Without Embolization for Unresectable Hepatocellular Carcinoma

We evaluate the long-term prognosis and prognostic factors in patients treated with transarterial infusion chemotherapy using cisplatin-lipiodol (CDDP/LPD) suspension with or without embolization for unresectable hepatocellular carcinoma (HCC). Study subjects were 107 patients with HCC treated with repeated transarterial infusion chemotherapy alone using CDDP/LPD (adjusted as CDDP 10mg/LPD 1ml). The median number of transarterial infusion procedures was two (range, one to nine), the mean dose of CDDP per transarterial infusion chemotherapy session was 30 mg (range, 5.0–67.5 mg), and the median total dose of transarterial infusion chemotherapy per patient was 60 mg (range, 10–390 mg). Survival rates were 86-0x1.fc400000008p+0t 1 year, 40 0x1.c617665206557p+855t 3 years, 20 0x1.5687420657461p-505t 5 years, and 16 0x1.5742d676e6f6cp+807t 7 years. For patients with >90% PD accumulation after the first transarterial infusion chemotherapy, rates were 98 0x1.e676f7270206dp+759t 1 year, 60 0x1.46e6120736973p-505t 3 years, and 22 0x1.36f6e676f727p+840t 5 years. Multivariate analysis identified >90% PD accumulation after the first transarterial infusion chemotherapy (p = 0.001), absence of portal vein tumor thrombosis (PVTT; p < 0.001), and Child-Pugh class A (p = 0.012) as independent determinants of survival. Anaphylactic shock was observed in two patients, at the fifth transarterial infusion chemotherapy session in one and the ninth in the other. In conclusion, transarterial infusion chemotherapy with CDDP/LPD appears to be a useful treatment option for patients with unresectable HCC without PVTT and in Child-Pugh class A. LPD accumulation after the first transarterial infusion chemotherapy is an important prognostic factor. Careful consideration should be given to the possibility of anaphylactic shock upon repeat infusion with CDDP/LPD

Migration to the pulmonary artery of nine metallic coils placed in the internal iliac vein for treatment of giant rectal varices

Transcatheter venous embolization with metallic coils is a safe and reliable method for the treatment of pelvic congestion syndrome and pelvic varicocele. While rare, coil migration to the pulmonary arteries is potentially fatal. We report the migration to the pulmonary artery of a cluster of nine metallic microcoils placed in the internal iliac vein to obliterate giant rectal varices. Our patient suffered no severe sequelae. To avoid coil migration to the pulmonary arteries, the coils chosen for placement must take into consideration the characteristics of the target vessels, particularly of larger veins

Impact of skeletal muscle volume on patients with BCLC stage‐B hepatocellular carcinoma undergoing sorafenib therapy

Abstract Aim Skeletal muscle volume has been reported to be an important factor that determines overall survival (OS) and post‐progression survival (PPS) in patients with hepatocellular carcinoma (HCC). However, the impact of skeletal muscle volume on HCC with Barcelona Clinic Liver Cancer (BCLC) stage B (BCLC‐B) remains unclear. We conducted sub‐analyses of a previous study on BCLC‐B and compared our findings with data on HCC with BCLC stage C (BCLC‐C). Methods We retrospectively enrolled 356 patients with HCC (BCLC‐B, n = 78; and BCLC‐C, n = 278) undergoing sorafenib therapy. Prognostic factors were analyzed using various parameters, including skeletal muscle volume. Muscle volume (MV) depletion was designated as less than the median value of the skeletal muscle index for each gender (cutoff value: 45.0 cm2/m2 for male and 38.0 cm2/m2 for female participants). Results Both OS and PPS showed no significant differences in patients with non‐MV depletion and those with MV depletion in the BCLC‐B group (Median OS [MST] 19.3 vs. 13.5 months [p = 0.348]; median PPS 9.7 vs. 10.8 months [p = 0.578]). In the BCLC‐C group, patients with non‐MV depletion had a significantly longer OS and PPS compared to patients with MV depletion (MST 12.4 vs. 9.0 months [p = 0.001] and median PPS 7.9 vs. 5.4 months [p = 0.002]). Multivariate analysis revealed that MV depletion was an independent prognostic factor of OS and PPS in the BCLC‐C group but not in the BCLC‐B group. Conclusions Skeletal muscle volume showed little impact on the clinical outcomes of patients with BCLC‐B undergoing sorafenib therapy

Efficacy of radiofrequency ablation for initial recurrent hepatocellular carcinoma after curative treatment: Comparison with primary cases

a b s t r a c t Objective: To determine the efficacy of radiofrequency ablation (RFA) for initial recurrence of small hepatocellular carcinoma (HCC; ≤3 nodules, each nodule ≤3 cm in diameter) after curative treatment and identify prognostic factors affecting therapeutic outcome, we compared clinical and outcome factors between patients with primary HCC and those with initial recurrent HCC who underwent RFA. Methods: In this retrospective cohort study, 211 HCC patients who underwent RFA were enrolled and comprised two groups: primary group (n = 139) and initial recurrent group (n = 72). We compared local tumor progression, overall survival (OS), disease-free survival (DFS), and RFA safety between the groups. Results: Median follow-up was 53 months. Local tumor progression rate was 5.8% in the primary group and 4.2% in the recurrent group. OS rates at 5 years and 10 years were 63.2% and 25.5% in the primary group and 54.5% and 33.4% in the recurrent group, respectively. Corresponding DFS rates were 30.7% and 14.6% and 19.2% and 11.0%. DFS was significantly shorter in the recurrent group (hazard ratio [HR] = 1.81; 95% confidence interval [CI], 1.27-2.57; P = 0.001). In the recurrent group, time from primary HCC development to recurrence was a determinant of OS (≤2 years; HR = 3.42; 95% CI, 1.52-7.72; P = 0.003). Conclusion: Although local tumor control and OS were similar between the groups, the recurrent group had shorter DFS than the primary group. Time from primary HCC development to recurrence was a prognostic factor for recurrence of HCC

A First Case of Hepatic Angiosarcoma Treated with Recombinant Interleukin-2

A 60 year-old woman was admitted to our hospital because of management of multiple liver tumors. According to image findings and liver biopsy, she was diagnosed as having epithelioid hemangioendothelioma of the liver accompanied by metastases in the spleen, lungs and bones. Based on the spread of the liver tumors and the extensive systemic metastases, she was considered inoperable. Instead, she received hepatic arterial infusion therapy using recombinant interleukin-2. However, she died due to liver failure about two months after admission. Autopsy revealed that the liver tumor was angiosarcoma. It is difficult to differentiate angiosarcoma from epithelioid hemangioendothelioma based on the image findings and pathological findings of percutaneous liver biopsy. Many cases are diagnosed as angiosarcoma at autopsy. There is no established effective treatment for hepatic angiosarcoma, because the tumor stage at the time of diagnosis is often progressive. To date, immunotherapy with recombinant interleukin-2 has been reported to be effective clinically for cutaneous angiosarcoma, such as of the scalp and facial skin. To our knowledge, there have been no reported cases of hepatic angiosarcoma treated with recombinant interleukin-2. Our case is important should recombinant interleukin-2 be considered effective for hepatic angiosarcoma in the future