Abstract
Purpose Irreversible electroporation (IRE) has been demonstrated to be a safe and effective method for locally advanced pancreatic cancer (LAPC). The aim of this study was to evaluate the immunomodulatory effect after IRE and to evaluate the prognostic value of variations of the immune parameters in LAPC patients after IRE. Methods Peripheral blood samples of 34 patients were obtained preoperatively and on the third day (D3) and seventh day (D7) after IRE, respectively. The phenotypes of lymphocytes were analyzed by flow cytometry, and dynamic changes of serum levels of cytokines, complement, and immunoglobulin were assayed by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve and concordance index (C-index) were used to compare the survival predictive ability. ResultsThere was a transitory decrease followed by a steady increase for CD4+ T cell, CD8+ T cell, NK cell, IL-2, C3, C4, and IgG while a reverse trend was detected for Treg cell, IL-6, and IL10 after IRE. The alteration of CD8+ T cell between D3 and D7 was identified as a prognostic factor for both overall survival (OS) and progression-free survival (PFS). The values of ROC curve (AUC) and C-indexes of the alteration of CD8+ T cell for OS and PFS were 0.816 and 0.773 and 0.816 and 0.639, respectively, which were larger than those of other immune or inflammation-based indexes. Conclusions This study presented the first evidence of IRE-based immunomodulatory in patients with LAPC. The alteration of CD8+ T cell between D3 and D7 showed relatively good performance and could be used as an effective tool for prognostic evaluation for LAPC patients after IRE.
Highlights
Pancreatic adenocarcinoma is a lethal disease with extremely poor prognosis, which represented the seventh and sixth leading causes of cancer-related death in the world and in China, respectively
Most patients had lower values of inflammatory indexes, such as platelet-to-lymphocyte ratio (PLR), prognostic index (PI), and modified Glasgow Prognostic Score (mGPS), while patients with higher values of neutrophil-to-lymphocyte ratio (NLR) occupied the majority of all patients
In the step of the present study, we evaluated the prognostic factors for overall survival (OS) and progression-free survival (PFS) and showed that elevation of CD8+ T cell was associated with favourable OS and PFS in locally advanced pancreatic cancer (LAPC) patients after Irreversible electroporation (IRE)
Summary
Pancreatic adenocarcinoma is a lethal disease with extremely poor prognosis, which represented the seventh and sixth leading causes of cancer-related death in the world and in China, respectively. 40% of new cases are diagnosed with locally advanced pancreatic cancer (LAPC), which is characterized by the involvement of major vascular structures, such as celiac trunk, superior mesenteric artery, leading to unresectable but nonmetastatic diseases [4]. The high rates of adverse events due to the toxicity of chemotherapy limited the use and promotion of treatment, such as the combination chemotherapy of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), even though it was shown to display some progression in improving the survival of patients with LAPC [7,8,9]. Local therapies were shown to improve the prognosis of LAPC patients with varying degrees of success [10]
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