Abstract
BackgroundPancreatic cancer has highly aggressive features, such as local recurrence that leads to significantly high morbidity and mortality and recurrence after successful tumour resection. Intraoperative radiation therapy (IORT), which delivers targeted radiation to a tumour bed, is known to reduce local recurrence by directly killing tumour cells and modifying the tumour microenvironment.MethodsAmong 30 patients diagnosed with pancreatic cancer, 17 patients received IORT immediately after surgical resection. We investigated changes in the immune response induced by IORT by analysing the peritoneal fluid (PF) and blood of patients with and without IORT treatment after pancreatic cancer surgery. Further, we treated three pancreatic cell lines with PF to observe proliferation and activity changes.ResultsLevels of cytokines involved in the PI3K/SMAD pathway were increased in the PF of IORT-treated patients. Moreover, IORT-treated PF inhibited the growth, migration, and invasiveness of pancreatic cancer cells. Changes in lymphocyte populations in the blood of IORT-treated patients indicated an increased immune response.ConclusionsBased on the characterisation and quantification of immune cells in the blood and cytokine levels in the PF, we conclude that IORT induced an anti-tumour effect by activating the immune response, which may prevent pancreatic cancer recurrence.Clinical trial registrationNCT03273374.
Highlights
Pancreatic cancer has highly aggressive features, such as local recurrence that leads to significantly high morbidity and mortality and recurrence after successful tumour resection
Peritoneal fluid from Intraoperative radiation therapy (IORT)-treated patients displayed cytokine composition changes We investigated cytokine changes induced by IORT in the peritoneal fluid (PF) of 30 patients with pancreatic cancer (Fig. 1A)
Our results revealed that the relative signal intensity of 19 cytokines were higher in the IORT PF group than in the no IORT group, whereas levels of 17 cytokines were decreased (Fig. 1B, Supplementary Table S3)
Summary
Pancreatic cancer has highly aggressive features, such as local recurrence that leads to significantly high morbidity and mortality and recurrence after successful tumour resection. Lee et al BMC Cancer (2021) 21:1097 outcomes in pancreatic cancer patients [5,6,7]. These treatments are limited to patients with unresectable or borderline resectable pancreatic cancer, and their clinical use as adjuvant to conventional treatments has not yet been established. Intraoperative radiation therapy (IORT) using a portable instrument delivers a single fraction of high-dose radiation during surgery [8, 9] that effectively focuses intense radiation to a desired site and simultaneously reduces toxicity to normal tissues [4, 10]
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