An important discovery on combination of irreversible electroporation and allogeneic natural killer cell immunotherapy for unresectable pancreatic cancer - PubMed (original) (raw)
An important discovery on combination of irreversible electroporation and allogeneic natural killer cell immunotherapy for unresectable pancreatic cancer
Mao Lin et al. Oncotarget. 2017.
Abstract
Purpose: To study the safety and clinical efficacy on combination of irreversible electroporation and allogeneic natural killer cell therapy for treating Stage III/IV pancreatic cancer, evaluating median progression free survival (PFS), and overall survival (OS).
Results: Adverse events of all patients were limited to grades 1 and 2, including local (mainly tussis 13.4%, nausea and emesis 7.1%, pain of puncture point 29.6% and duodenum and gastric retention 4.3%) and systemic (mainly fatigue 22.3%, fever 31.6%, and transient reduction of intraoperative blood pressure 25.1% and white cell count reduction 18.3%) reactions, fever was the 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 7.4 months (3.6-11.2 months): in stage III group, median PFS was higher in IRE-NK group (9.3 months) than in IRE group (8.1 months, P = 0.0465), median OS was higher in IRE-NK (13.2 months) than in IRE (11.4 months, P = 0.0411), and median PFS was higher in who received multiple NK than single NK (9.8 months vs.8.1 months, P = 0.0423, respectively), median OS who received multiple NK was higher than single NK (13.9 months vs.12.3 months, P = 0.0524, 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 (9.8 months) than in IRE (8.7 months, P = 0.0397), the DCR in IRE-NK (66.7%) was higher than in IRE (42.9%, P < 0.05).
Materials and methods: Between July 2016 and May 2017, we enrolled 71 patients who met the enrollment criteria. The patients were divided into stage III (32 patients, 17 patients received only IRE and 15 patients received IRE-NK (Irreversible electroporation- natural killer): 8 patients underwent a course of NK and 7 patients underwent ≥ 3 courses) and stage IV (39 patients, 22 patients received only IRE and 17 patients received IRE-NK: 9 patients underwent a course of NK and 8 patients underwent ≥ 3 courses). The safety and short-term effects were evaluated firstly, then the median PFS, median OS, response rate (RR) and disease control rate (DCR) were assessed.
Conclusions: Combination of irreversible electroporation and 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.
Keywords: allogeneic natural killer cell; clinical efficacy; irreversible electroporation; pancreatic cancer.
Conflict of interest statement
CONFLICTS OF INTEREST We declared that we have no conflicts of interest.
Figures
Figure 1. Error bar chart shows amylase values before and after IRE
Compared with pre-IRE, there was no significant increase in amylase levels at 1 day after IRE and 7 day after IRE (P > 0.05).
Figure 2. Change of CA 19–9
There was no difference between IRE and IRE-NK group at day 1, and 7 post-treatment (P > 0.05), but at 1 month post-treatment, CA19–9 expression was lower in the IRE-NK than in the IRE (P < 0.05).
Figure 3. CT scans taken before, during and after IRE-NK therapy
Patient 1: (A–C) (Female patient, 70 years old, T4N1M0, stage III): A. Pre-IRE CT showed a compressed duodenum and encased common bile duct and pancreatic duct due to the tumor, which was 3.1 × 2.2 cm (red arrow) in dimension; B. during IRE, two electrodes were inserted and the distance between them was 2.0 cm, as shown in this CT image; C. three month post-IRE-NK, CT showed no enhancement in the occupying lesion, with mild shrinkage of the area. Patient 2: (D–F) (Male patient, 59 years old, T4N1M1, stage IV): D. A contrast-enhanced CT scan taken before IRE showed a 5.7 × 4.2 cm contrast-enhanced lesion (red arrow) in the neck and body of the pancreas; (E) Two IRE electrodes were inserted into the tumor; F. CT scan taken two months after IRE-NK showed a 5.7 × 4.0 cm lesion with a large area of necrosis in the neck and body of the pancreas. Patient 3: (G-I) (male patient, 51 years old, T4NxM0, stage III): G. pancreatic head carcinoma, tumor size was about 4.1 × 3.5 cm (red arrow) and performed IRE ablation; H. 2 months after IRE, the tumor was reduced to 3.3 × 2.4 cm; I. 3 months after IRE, the tumor was reduced to 2.4 × 1.8 cm.
Figure 4. Correlation of median PFS and OS with type of treatment
(A) Comparison of median PFS between 17 patients who underwent IRE and 15 patients who underwent IRE-NK in stage III group; (B) Comparison of median OS between 17 patients who underwent IRE and 15 patients who underwent IRE-NK in stage III group; (C) Comparison of median PFS between 22 patients who underwent IRE and 17 patients who underwent IRE-NK in stage IV group; (D) Comparison of median OS between 22 patients who underwent IRE and 17 patients who underwent IRE-NK in stage IV group.
Figure 5. Correlation between median PFS and OS with courses of NK
(A) Comparison of median PFS between 8 patients who underwent single NK and 7 patients who underwent multiple NK in stage III group; (B) Comparison of median OS between 8 patients who underwent single NK and 7 patients who underwent multiple NK in stage III group; (C) Comparison of median PFS between 9 patients who underwent single NK and 8 patients who underwent multiple NK in stage IV group; (D) Comparison of median OS between 9 patients who underwent single NK and 8 patients who underwent multiple NK in stage IV group.
Figure 6
(A) Consort diagram. The patients were divided into stage III (32 patients, 17 patients received only IRE and 15 patients received IRE-NK: 8 patients underwent a course of NK and 7 patients underwent ≥ 3 courses) and stage IV (39 patients, 22 patients received only IRE and 17 patients received IRE-NK: 9 patients underwent a course of NK and 8 patients underwent ≥ 3 courses); (B) Procedure of IRE-NK therapy. All enrolled patient's kinsfolk were informed and peripheral blood collected for NK at 7days before IRE, IRE carried out at day 9, and at day 12, NK cell completed culture and infused intravenously at d 13~15.
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