Objective: We will examine the clinical efficacy and safety of photodynamic therapy and its combination with chemotherapy, targeted therapy, and immunotherapy in patients with advanced gastric cancer. Related factors that may have an impact on the efficacy will also be examined, and initially explore the possible mechanism of photodynamic therapy in the immune system of these patients.
Methods: Between November 2019 and November 2022 at the Lanzhou University Second Hospital, 90 patients with gastric cancer who had been diagnosed with pathology and imaging were gathered, and photodynamic therapy was applied to the tumor lesions after injecting the photosensitizer. Different drugs were given to patients according to their conditions after photodynamic therapy. Efficacy was assessed separately for different times: instant period efficacy of PDT (within 1 week after PDT); short-term efficacy of PDT (within 2 months after PDT); and efficacy of combination therapy (after combination therapy). Four groups of patients were created, with 14 patients treated with PDT alone, 18 patients in the group of PDT combined with chemotherapy, 15 patients in the group of PDT combined with targeting and immunotherapy, and 43 patients in the group of PDT combined with chemotherapy, target therapy and immunotherapy. We used endoscopy to monitor the lesions at various times after treatment and detected the tumor markers every three weeks. Meanwhile, we performed the abdominal CT every six weeks and recorded the adverse reactions after PDT and combined therapy, as well as the changes in systemic organ function indexes and haematological toxicity were detected. We used flow cytometry to detect the number of peripheral blood immune cells before and after PDT, and HE staining and immunohistochemical staining were used to test immune cells in the gastric cancer biopsy tissue both before and after PDT. According to Recist1.1 criteria, we evaluated the therapeutic effect of combination therapy, data from patients' long-term follow-up was examined for survival, The relevant influencing factors related to the efficacy of PDT and the risk factors affecting patient prognosis were analyzed.
Results: (1) Instant period efficacy of PDT: 48h after PDT, local lesion necrosis of varying degrees occurred in all patients, with a 94.4% significant necrosis (MON+SN) rate. 1w after PDT, the significant necrosis rate was 100.0%. The obstruction of 22 patients (56.4%) was completely relieved at 1w after PDT, and 13 patients (33.3%) had obvious relief of obstruction symptoms. CEA and CA72-4 show a declining trend 1 w after PDT, with CA72-4 declining significantly.
(2) Short-term efficacy of PDT: Endoscopic evaluation 2 months after PDT revealed that 55 cases (61.1%) achieved SR and 10 cases (11.1%) achieved CR, with an overall efficiency (CR+SR+MR) of 100.0% and a significant efficiency (SR+CR) of 72.2%, among which the significant efficiency of Borrmann type III patients reached 83.0%, which was significantly higher than that of Borrmann type II (55.6%) and Borrmann type IV (61.8%).
(3) Efficacy of combination therapy: It was discovered that CR3 cases (8.57%), PR 16 cases (45.71%), SD 11 cases (31.43%), PD 5 cases (14.29%), ORR 54.29%, and DCR 85.71%, among which male ORR and DCR were significantly better than female after evaluating the efficacy of 35 patients with PDT combined treatment evaluated by recist1.1 criterion. 3D printing images showed that the lesions and surrounding lymph nodes are significantly reduced after combined treatment. The level of CEA and CA72-4 considerably decreased after combination treatment. The median survival time for all patients was 10 months, with a mean survival time of 11.3 months and the cumulative survival rates at 3, 6, 12, and 24 months were 79.9%, 63.5%, 36.1%, and 14.7%, respectively.
(4) Related factors: The short-term efficacy of PDT may be strongly impacted by Borrmann type (P=0.045) and these factors, like preoperative KPS score (P=0.012), clinical stage (P=0.005), Borrmann type (P=0.002), tumor site (P=0.012), tumor size (P= 0.017), whether there was combined targeting and immunotherapy (P=0.002), and whether there was combined surgery (P=0.008), can significantly affect the survival and prognosis of patients.
(5) Safety evaluation: Recent adverse reactions of PDT mainly included fever (38.9%), abdominal pain (44.4%) and nausea (36.7%), all of which were grade 1-2. In addition, 3 patients had mild skin allergic reactions, and haematological toxic reactions were grade 1. No serious adverse events such as perforation of the digestive tract, fistula, or bleeding occurred, and all adverse reactions were relieved spontaneously within 1 week. Following a combination of treatments, nausea (60.5%), vomiting (23.7%), fatigue (44.7%), hypertension (14.5%) and hand-foot syndrome (7.9%) are the main adverse reactions, and no symptoms of grade 3 or above occurred. 28 patients (36.2%) experienced grade 1-3 myelosuppressive responses. Most patients had grade 1-2 hepatic and renal dysfunction,19 patients had thyroid or heart dysfunction, and 27 patients (35.5%) had mild to severe blood albumin drop.
(6) Immune function: Peripheral blood samples from stage III patients had considerably less CD3+, CD3+CD4+, CD3+CD8+, CD4+CD45RA+, CD4+CD45RO+ and CD4+CD25+CD127-% cells after PDT 48h than samples from patients before PDT. Conversely, Stage IV patients had considerably more CD3+, CD3+CD4+, CD3+CD8+, and CD4+CD45RA+ cells in their peripheral blood after PDT 48h than they had before PDT. A comparison of HE stains images of pathological tissues before and after PDT showed that many inflammatory cells gathered from peripheral to tumor tissues after PDT, and the number of CD3+T cells, CD4+T cells, CD8+T cells and macrophages increased significantly after PDT, while the change of B cells and NK cells was not significant.
Conclusion: By regulating the expression of peripheral inflammatory cells and tumor local immune cells, PDT can enhance peripheral immune function and improve the tumor’s local immunological microenvironment. Patients with advanced gastric cancer can dramatically extend their survival by combining PDT with other therapy regimens.