Hapten-enhanced overall survival time in advanced hepatocellular carcinoma by ultro-minimum incision personalized intratumoral chemoimmunotherapy

PURPOSE: To compare the therapeutic effects of ultra-minimum incision personalized intratumoral chemoimmunotherapy (UMIPIC) with intratumoral chemotherapy (ITCT) in the treatment of advanced hepatocellular carcinomas and to analyze the effect of hapten as an immune booster. MATERIALS AND METHODS: Patients with advanced hepatocellular carcinomas were treated with UMIPIC or ITCT with the same therapeutic procedure; the UMIPIC method had a proprietary regimen including an oxidant, a cytotoxic drug, and hapten, while ITCT delivered the same drug excluding hapten. Of 339 patients in total, 119 of the UMIPIC patients (n=214) had response data and 214 had survival data, and of the ITCT patients (n=125), 61 had response data and 125 had survival data. Tumor response was assessed with a computed tomography scan 6–8 weeks after the initial treatment; the survival rate was evaluated by follow-up visits. Tumor size was classified as small (<5 cm), large (5–10 cm), or very large (>10 cm); tumor sizes with liver function categorized using Child–Pugh class (A and B) were analyzed by correlation with overall survival. RESULTS: The response rates (complete response + partial response + stable disease) were 78.68% and 81.52% in the UMIPIC and ITCT groups, respectively, with no statistically significant difference; however, the median overall survival was 7 months for UMIPIC (test) and 4 months for ITCT (control), respectively (P<0.01). The 6-month and 1-year survival rates for UMIPIC and ITCT were 58.88% vs 32.3% and 30.37% vs 13.6%, respectively (P<0.01). Single and multiple UMIPIC revealed significant improvement in overall survival compared to that of ITCT. Child–Pugh class A patients had a longer duration of survival compared to Child–Pugh class B patients in UMIPIC therapy. CONCLUSION: Hapten had enhanced therapeutic effect with improvement in the survival duration in UMIPIC compared to ITCT. After reexamination, the response rate was not different due to inflammation caused by hapten. Hapten has been found to play an important role in immunotherapy to improve patient survival.