2126 - Predictive Value and Dynamic Changes of Peripheral Blood Immune-Related Cytokines after Short-Course Radiotherapy Combined with Multimodal Systemic Treatment for Rectal Cancer
Presenter(s)
J. Lei1, J. Shuai2, Q. Xiao1, Y. Tang3, and J. Jin4; 1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China, 2State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (PUMC), Beijing, China, 3State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 4National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Shenzhen, China
Purpose/Objective(s): Short-course radiotherapy (SCRT) followed by chemotherapy is a standard treatment option for locally advanced rectal cancer (LARC). We used the blood samples from a clinical trial which compared SCRT+CAPOX with or without PD-1 inhibitor to investigate the evolution of peripheral blood cytokines.
Materials/Methods: STELLAR II is a phase II/III bridging, prospective, multicenter clinical study. It enrolled patients with stage II/III, pathologically confirmed rectal adenocarcinoma, with the lower tumor border =10cm from the anal verge. Patients were randomly divided into a study group and a control group. Both groups received pelvic SCRT (25Gy/5Gy/5fx). Two weeks after the completion of SCRT, the control group received 4 cycles of CAPOX chemotherapy, while the experimental group received CAPOX plus Sintilimab. Peripheral blood samples were collected before SCRT, after SCRT, and preoperatively. The ProcartaPlex multiplex immunoassay platform was used to quantitatively detect 33 cytokines relevant to the tumor-immunity cycle. The study aimed to: Compare the changing trends in the expression levels of the aforementioned cytokines before and after treatment within each group;between patients who achieved clinical remission (cCR + pCR) and those who did not; between patients who experienced Grade 3 or higher adverse effects (AE) and those who did not.
Results: Blood samples were collected from a total of 37 patients, including 21 in the control group and 16 in the experimental group. Among these, 29 patients underwent surgery, 6 patients chose watch-and-wait strategy, 1 experienced disease progression, and 1 was lost to follow-up. (1) A total of 31 patients had paired samples from pre-radiotherapy and post-radiotherapy. Cytokines with significantly increased expression levels after radiotherapy were: CD80, CXCL16, CXCL10, CXCL9, IL-10, IL-12p70. Cytokines with significantly decreased expression levels were: IL-13, IL-15. (2) 7 patients had paired samples from pre-systemic treatment and post-systemic treatment, but no cytokines with significantly different expression levels were identified. (3) During the neoadjuvant treatment phase, 9 patients experienced Grade 3 AEs. The post-radiotherapy expression level of CXCL10 was predictive of Grade 3 AEs (AUC 0.77 (95% CI, 0.60-0.94)). (4) 15 patients achieved pCR/cCR. Their baseline expression levels of CXCL10 (6.86 pg/mL vs. 10.76 pg/mL, p=0.017) and CXCL9 (0.96 pg/mL vs. 1.67 pg/mL, p=0.048) were significantly lower than those in patients who did not achieve complete response.
Conclusion: The expression levels of immune-related cytokines changed significantly after SCRT. Among them, the expression levels of CXCL10 and CXCL9 were associated with clinical response, while the expression level of CXCL10 was associated with Grade 3 AE. Further analysis of changes in immune response in corresponding tissue biopsies is required.