Mao Lin1,2, Shuzhen Liang1, Xiaohua Wang1, Yinqing Liang1, Mingjie Zhang3, Jibing Chen4,5, Lizhi Niu6,7,8, Kecheng Xu1,2. 1. Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School, Guangzhou, China. 2. Fuda Cancer Institute, Guangzhou, China. 3. Hank Bioengineering Co., Ltd, Shenzhen, China. 4. Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School, Guangzhou, China. linmaogz@163.com. 5. Fuda Cancer Institute, Guangzhou, China. linmaogz@163.com. 6. Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School, Guangzhou, China. 18922210657@163.com. 7. Fuda Cancer Institute, Guangzhou, China. 18922210657@163.com. 8. Department of Oncology, Fuda Cancer Hospital, Jinan University School, Guangzhou, China. 18922210657@163.com.
Abstract
PURPOSE: This study was attempted to investigate the safety and clinical efficacy of percutaneous irreversible electroporation combined with allogeneic natural killer cell therapy for treating stage III/IV pancreatic cancer, evaluate median progression-free survival (PFS), and overall survival (OS). METHODS: Between March 2016 and February 2017, we enrolled 67 patients who met the enrollment criteria. According to the latest NCCN Guidelines, the patients were divided into stage III (35 patients, 16 patients received only irreversible electroporation (IRE) and 19 patients received IRE-NK: 8 patients underwent one course NK and 11 patients underwent ≥3 courses) and stage IV (32 patients, 14 patients received only IRE and 18 patients received IRE-NK: 8 patients underwent one course NK and 10 patients underwent ≥3 courses). The safety and short-term effects were evaluated first, then the median PFS, median OS, response rate (RR) and disease control rate (DCR) were assessed. RESULTS: Adverse events of all patients were limited to grades A and B, included local (mainly cough 12.7%, nausea and emesis 6.8%, pain of puncture point 25.3% and duodenum and gastric retention 5.9%) and systemic (mainly fatigue 21.5, fever 33.5%, and blood pressure intraoperative transient reduction 27.4% and white cell count reduction 22.6%) reactions, fever was most frequent. The serum amylase level at 24 h and 7 d after IRE was not significantly changed compared to those before IRE (P > 0.05). CA19-9 value was lower in IRE-NK group than in IRE at 1 month after treatment (P < 0.05). After a median follow-up of 7.9 months (3.8-12.1 months): in stage III group, median PFS was higher in IRE-NK group (9.1 months) than in IRE group (7.9 months, P = 0.0432), median OS was higher in IRE-NK (13.6 months) than in IRE (12.2 months; P = 0.0327), and median PFS was higher in who received multiple NK than single NK (9.9 vs. 8.2 months; P = 0.0387, respectively), median OS who received multiple NK was higher than single NK (13.7 vs. 12.1 months; P = 0.0451, respectively), the RR in IRE-NK (63.2%) was higher than in IRE (50.0%; P < 0.05); in stage IV group, median OS was higher in IRE-NK (10.2 months) than in IRE (9.1 months; P = 0.0367), the DCR in IRE-NK (66.7%) was higher than in IRE (42.9%; P < 0.05). CONCLUSION: Percutaneous irreversible electroporation combined with allogeneic natural killer cell immunotherapy significantly increased median PFS and median OS in stage III pancreatic cancer and extended the median OS of stage IV pancreatic cancer. Multiple allogeneic natural killer cells infusion was associated with better prognosis to stage III pancreatic cancer.
PURPOSE: This study was attempted to investigate the safety and clinical efficacy of percutaneous irreversible electroporation combined with allogeneic natural killer cell therapy for treating stage III/IV pancreatic cancer, evaluate median progression-free survival (PFS), and overall survival (OS). METHODS: Between March 2016 and February 2017, we enrolled 67 patients who met the enrollment criteria. According to the latest NCCN Guidelines, the patients were divided into stage III (35 patients, 16 patients received only irreversible electroporation (IRE) and 19 patients received IRE-NK: 8 patients underwent one course NK and 11 patients underwent ≥3 courses) and stage IV (32 patients, 14 patients received only IRE and 18 patients received IRE-NK: 8 patients underwent one course NK and 10 patients underwent ≥3 courses). The safety and short-term effects were evaluated first, then the median PFS, median OS, response rate (RR) and disease control rate (DCR) were assessed. RESULTS: Adverse events of all patients were limited to grades A and B, included local (mainly cough 12.7%, nausea and emesis 6.8%, pain of puncture point 25.3% and duodenum and gastric retention 5.9%) and systemic (mainly fatigue 21.5, fever 33.5%, and blood pressure intraoperative transient reduction 27.4% and white cell count reduction 22.6%) reactions, fever was most frequent. The serum amylase level at 24 h and 7 d after IRE was not significantly changed compared to those before IRE (P > 0.05). CA19-9 value was lower in IRE-NK group than in IRE at 1 month after treatment (P < 0.05). After a median follow-up of 7.9 months (3.8-12.1 months): in stage III group, median PFS was higher in IRE-NK group (9.1 months) than in IRE group (7.9 months, P = 0.0432), median OS was higher in IRE-NK (13.6 months) than in IRE (12.2 months; P = 0.0327), and median PFS was higher in who received multiple NK than single NK (9.9 vs. 8.2 months; P = 0.0387, respectively), median OS who received multiple NK was higher than single NK (13.7 vs. 12.1 months; P = 0.0451, respectively), the RR in IRE-NK (63.2%) was higher than in IRE (50.0%; P < 0.05); in stage IV group, median OS was higher in IRE-NK (10.2 months) than in IRE (9.1 months; P = 0.0367), the DCR in IRE-NK (66.7%) was higher than in IRE (42.9%; P < 0.05). CONCLUSION: Percutaneous irreversible electroporation combined with allogeneic natural killer cell immunotherapy significantly increased median PFS and median OS in stage III pancreatic cancer and extended the median OS of stage IV pancreatic cancer. Multiple allogeneic natural killer cells infusion was associated with better prognosis to stage III pancreatic cancer.
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