Systemic chemo-immunotherapy for advanced-stage hepatocellular carcinoma

AIM: To evaluate the therapeutic efficacy of systemic chemo-immunotherapy for advanced hepatocellular carcinoma (HCC). METHODS: Twenty-six patients with advanced HCC were treated by using systemic chemo-immunotherapy (PIAF regimen), which consisted of dsplatin (20 mg/m2) intravenously daily for 4 consecutive day, doxorubicin (40 mg/m2) intravenously on day 1, 5-fluorouracil (400 mg/m2) intravenously daily for 4 consecutive day, and human recombinant a-interferon-2a (5 Mu/m2) subcutaneous injection daily for 4 consecutive day. The treatment was repeated every 3 wk, with a maximum of six cycles. RESULTS: A total of 90 cycles of PIAF treatment were administered, with a mean number of 3.9 cycles per patient. Eight patients received six cycles of treatment (group A), and the remaining 18 were subjected to two to five cycles (group B). There were 0 complete response, 4 partial responses, 9 static diseases and 13 progressive diseases, with a disease control rate of 50% (13/26). The 1-year survival rate was 24.3%, with a median survival time of 6.0 mo. Group A had a remarkably better survival as compared with group B, the 1- and 2-year survival rates were 62.5% vs 6.1% and 32.3% vs 0%, and a median survival time was 12.5 mo vs5.0 mo (P= 0.001). CONCLUSION: Systemic chemo-immunotherapy using PIAF regimen represented an effective treatment and could improve the survival rate and prolong the survival time in selected patients with advanced HCC.

Efficacy and safety of subsequent radiotherapy in patients with advanced-stage hepatocellular carcinoma treated with immune checkpoint inhibitors

Background:The development of immunotherapy resistance is associated with a poor prognosis in patients diagnosed with hepatocellular carcinoma(HCC)who are undergoing treatment with immune checkpoint inhibitors(ICI).This study aimed to evaluate the efficacy and safety of subsequent radiotherapy(RT)for patients with advanced-stage HCC who had lesion enlargement or new lesions(NLs)during ICI therapy.Methods:This retrospective observational study enrolled 36 patients with advanced-stage HCC who underwent subsequent RT for lesion enlargement or NLs during ICI therapy from two centers.The primary endpoints were progression-free survival(PFS)and overall survival(OS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),1-and 2-year local control(LC)rates,in-field PFS(IFPFS),out-field PFS(OFPFS),and safety.Results:The median follow-up time was 15.3 months.The median PFS was 7.4 months[95%confidence interval(CI):3.1-11.7 months],and the median OS was 18.8 months(95%CI:17.1-20.5 months).ORR and DCR were 38.9%and 72.2%,respectively.In addition,the median IFPFS was 17.8 months(95%CI:11.5-24.2 months),median OFPFS was 7.9 months(95%CI:3.4-12.5 months),and estimated 1-and 2-year LC rates were 67.1%and 31.9%,respectively.The most common treatment-related adverse events(all grades)were diarrhea(33.3%),rash(30.6%),and malaise(27.8%);a total of 14(38.9%)patients developed grade 3-4 AEs.Conclusions:Subsequent RT showed reliable antitumor effects and an acceptable safety profile in patients with advanced-stage HCC who had unsatisfactory response to ICI therapy;therefore,it could serve as an optional salvage strategy.

Interventional treatment for unresectable hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The Barcelona clinic liver cancer classification is the current standard classification system for the clinical management of patients with HCC and suggests that patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization(TACE). Interventional treatments such as TACE, balloon-occluded TACE, drug-eluting bead embolization, radioembolization, and combined therapies including TACE and radiofrequency ablation, continue to evolve, resulting in improved patient prognosis. However, patients with advanced-stage HCC typically receive only chemotherapy with sorafenib, a multi-kinase inhibitor, or palliative and conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidatesfor systemic therapy. However, these patients require therapy that is more effective than sorafenib or conservative treatment. Several researchers try to perform more effective therapies, such as combined therapies(TACE with radiotherapy and sorafenib with TACE), modified TACE for HCC with arterioportal or arteriohepatic vein shunts, TACE based on hepatic hemodynamics, and isolated hepatic perfusion. This review summarizes the published data and data on important ongoing studies concerning interventional treatments for unresectable HCC and discusses the technical improvements in these interventions, particularly for advanced-stage HCC.

Treatment options in patients with metastatic gastric cancer:Current status and future perspectives

Despite advances in the treatment of gastric cancer, it remains the world’s second highest cause of cancer death. As gastric cancer is often diagnosed at an advanced stage, systemic chemotherapy is the mainstay of treatment for these patients. However, no standard palliative chemotherapy regimen has been accepted for patients with metastatic gastric cancer. Palliative chemotherapy including fluoropyrimidine, platin compounds, docetaxel and epirubicin prolongs survival, and improves a high quality of life to a greater extent than best supportive care. The number of clinical investigations associated with targeted agents has recently increased. Agents targeting the epidermal growth factor receptor 1 and human epidermal growth factor receptor 2 (HER2) have been widely tested. Trastuzumab was the first target drug developed, and pivotal phase III trials showed improved survival when trastuzumab was integrated into cisplatin/fluoropyrimidine-based chemotherapy in patients with metastatic gastric cancer. Trastuzumab in combination with chemotherapy was thus approved to be a new standard of care for patients with HER2-positive advanced esophagogastric adenocarcinoma. Thus, the evaluation of HER2 status in all patients with metastatic gastroesophageal adenocarcinoma should be considered. Other agents targeting vascular endothelial growth factor, mammalian target of rapamycin, and other biological pathways have also been investigated in clinical trials, but showed little impact on the survival of patients. In this review, systemic chemotherapy and targeted therapies for metastatic gastric cancer in the first- and second-line setting are summarized in the light of recent advances.