3665 - Real-World Safety Analysis of Radiotherapy Combined with Immune Checkpoint Blockades
Presenter(s)
C. S. Liu1,2, T. T. Kuo3, J. F. Chiou1,4, Y. H. Shao3,5, and L. S. Lu1,6; 1Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan, 2PhD Program of Translational Medicine, Taipei, Taiwan, 3Health Data Analytics and Statistics Center, Taipei Medical University, Taipei, Taiwan, 4Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, 5Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, 6Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
Purpose/Objective(s):
Combing radiotherapy (RT) with immune checkpoint blockades (ICB) has shown synergistic effects in both preclinical and clinical studies. However, the toxicity profiles of such a combination remain unclear. We hypothesized combining RT with ICB may lead to additional organ specific toxicities on top of ICB alone. Since RT information is not available in many ICB trials, we tested the hypothesis with real-world data analysis. The study aims to investigate the safety profile of combining RT with ICB compared with ICB alone in different time sequences regardless of cancer types.Materials/Methods: We conducted a retrospective cohort study using the Taipei Medical University Clinical Research Database (TMUCRD) across three affiliated hospitals from January 01, 2008, to December 31, 2022. Baseline demographic data, laboratory examination, and treatment history were collected. A total of 1830 patients received at least 1 dose of ICBs for 11 types of malignancy were identified. We excluded 445 patients due to missing data, a history of autoimmune diseases, or receiving prior RT for non-cancer indications. The primary endpoint was any grade immune related adverse events (irAEs) by using international classification of diseases 10th Edition, laboratory examinations, and medication list records. Cox proportional hazard regression models were used to estimate the risk of toxicity in patients receiving combination treatments compared to those with ICB alone. A p-value of <0.05 was considered statistically significant.
Results:
A total of 703 patients received combination treatment and 682 patients received ICB alone between 2010 and 2022 were enrolled. After propensity score matching considering age and sex, 296 patients were allocated into each group. The most common types of cancer are lung cancer (32.4%) in combination treatment group and hepatobiliary and pancreatic cancer (27.0%) in the ICB alone group. Toxicity profiles are comparable between two treatment groups in 10 out of 12 CTCAE categories. However, cholangitis (18.58% vs 7.77%, HR: 2.42 (95% CI: 1.49-3.94), p = 0.0001) and pneumonitis (14.77% vs. 7.59%, HR: 2.02 (95% CI: 1.15-3.58), p=0.01) are more common in the combination treatment group. The time sequence analysis showed that the risk of cholangitis increased with concurrent RT with ICB (Adjust HR: 2.39 (95% CI: 1.25-4.56)). Meanwhile the risk of pneumonitis increased with RT followed by ICB (Adjust HR: 4.47 (95% CI: 1.36-16.24)).Conclusion:
Combining RT with ICB may increase the risk of cholangitis and pneumonitis compared to ICB alone. Furthermore, the time sequence between RT and ICB may modulate the occurrence of irAEs. The current study is limited by the retrospective nature and by the lack of detailed RT target definition in the database. Prospective trials are awaited to confirm these findings.