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.
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Abbreviations
- PC:
-
Pancreatic cancer
- NK:
-
Natural killer
- PFS:
-
Progression-free survival
- OS:
-
Overall survival
- RR:
-
Response rate
- DCR:
-
Disease control rate
- MHC:
-
Major histocompatibility complex
- KIRs:
-
Killer cell immunoglobulin-like receptors
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Acknowledgements
We would like to thank the native English speaking scientists of Elixigen Company for editing our manuscript.
Funding
This work was supported by the Science and Technology Program of Tianhe District, Guangzhou, China (Grant Number 201504KW008).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of Guangzhou Fuda Cancer Hospital ethics committee and with the 1964 Declaration of Helsinki.
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Lin, M., Liang, S., Wang, X. et al. Percutaneous irreversible electroporation combined with allogeneic natural killer cell immunotherapy for patients with unresectable (stage III/IV) pancreatic cancer: a promising treatment. J Cancer Res Clin Oncol 143, 2607–2618 (2017). https://doi.org/10.1007/s00432-017-2513-4
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DOI: https://doi.org/10.1007/s00432-017-2513-4