Speakers - CIRWC 2024

Abstract

Introduction: Photodynamic therapy (PDT) has been gradually applied to treating gastrointestinal tumors due to its advantages of good targeting, few side effects, and repeatable treatment. However, there are few clinical studies on cholangiocarcinoma and ampullary carcinoma, and the effect on the tumor immune microenvironment is still unclear. Therefore, this paper studies the safety, effectiveness, and combined immune and target therapy of PDT in cholangiocarcinoma and ampullary carcinoma. Clinical efficacy of treatment. And further, explore the possible underlying mechanism affecting the clinical efficacy.

Methods: A total of 22 patients who were diagnosed with cholangiocarcinoma and ampullary carcinoma by imaging or pathology in the Cancer Center of Lanzhou University Second Hospital from December 2019 to November 2023 were included in this retrospective study and received PDT. Patients were divided into two groups using different treatment methods: a PDT combined stent group and 13 patients (P-S, n=13). Nine patients were in the PDT combined stent, Tislelizumab, and Bevacizumab group (P-S-IT, n=9). Evaluation of the short-term clinical curative effect of patient treatment: liver function indicators, tumor markers, and biliary obstruction under spyglass in some patients one week after PDT. Long-term clinical curative effect evaluation: stent unobstructed period, survival period.

Along with the treatment cycle, adverse reactions after PDT and combined therapy were further recorded, and changes in systemic organ function indicators and hematological toxicity were detected. HE staining was used to evaluate tissue necrosis after PDT, and immunohistochemical staining was used to detect the infiltration of immune cells (CD3, CD4, CD8, CD20, CD56, CD68, Inos, CD163, PD-L1, and Foxp3) in tumor tissue before and after PDT. Flow cytometry was used to evaluate the immune status of peripheral blood before and after PDT.

Results: Short-term clinical efficacy: P-S group and P-S-IT group in terms of liver function indicators (ALT, AST, γ-GT, ALP, TBIL, DBIL, IBIL), tumor markers (CA-199, CA125, CEA) and obstruction under spyglass Not statistically significant. Long-term efficacy evaluation: the stent patency rates of the P-S-IT group and P-S group at 2, 4, 6, 8, and 12 months were: 100%, 100%, 56%, 56% and 100%, 69%, 15%, 0%, and the median unblocked period were 331 days and 126 days (P=0.0005). Compared with the median survival period of P-S-IT and P-S- patients, they were 329 days and 204 days (P=0.0011). The main adverse reactions of PDT were abdominal pain (100%), fever (41%), and photosensitivity reaction (4.5%). There were no severe adverse reactions such as perforation, bleeding, and infection. The main adverse effects of combination therapy were rash (9%), nausea and vomiting (66%), hypothyroidism (4.5%), leukopenia (33.3%), and thrombocytopenia (44%), all of which were grade 1-2. Immunological evaluation: (1) HE staining results before and after PDT treatment showed that at 24h, 48h and 72h after PDT. The necrosis was aggravated with the prolongation of time. (2) The results of immunohistochemistry before and after PDT treatment showed that after 48 hours of PDT, CD3, CD4, CD8, CD68, Inos in tumor tissue increased significantly (P<0.05), PD-L1, CD20, CD56 had no significant changes, Foxp3, CD163 It showed a downward trend (P<0.05). (3) The results of peripheral blood immune cell flow cytometry before and after PDT treatment showed that after PDT48h, WBC, NEUT, PD-1 increased (P<0.05), CD3+, CD3+CD4+, CD3+CD8+, CD4+CD45RA+, CD4+CD45RO+, CD8+CD45RA+ showed a downward trend (P<0.05), CD19+, CD8+CD45RO+ had no significant changes.

Conclusion: PDT can improve the clinical efficacy of patients with cholangiocarcinoma and ampullary carcinoma by improving peripheral immune function and regulating the local immune microenvironment of the tumor. Combining immune checkpoint inhibitors and targeted therapy further prolongs the survival of patients and unblocked stents period.