2379 - Exploratory Study on the Impact of Intestinal Low-Dose Radiation on the Efficacy and Prognosis of Immunotherapy in Metastatic Non-Small Cell Lung Cancer
Presenter(s)
B. Huang1, K. Wang1,2, J. Zhao1, M. Li1, X. Wang1,2, J. Zhu1, J. Yu3, G. Cai1, and X. Meng1,4; 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 2School of Clinical Medicine, Shandong Second Medical University, Weifang, China, 3Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 4School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
Purpose/Objective(s): Radiotherapy (RT) can serve as a palliative treatment for metastases of metastatic non-small cell lung cancer (mNSCLC). However, RT to abdominopelvic metastases can result in additional intestinal radiation, which may lead to microbial imbalance. Recent research has revealed the influence of intestinal microbiota on immunotherapy (IO). Thus, this study aims to explore the impact of intestinal radiation doses on the efficacy and prognosis of IO for mNSCLC.
Materials/Methods: Collect clinical data from patients with mNSCLC who underwent IO combined with abdominopelvic RT for metastases at one institution over the past five years. Use the treatment planning system to outline the contours of the large and small intestines and record dosimetric parameters. Calculate overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method, compare differences between groups using the log-rank test, and analyze risk factors for OS and PFS using Cox regression analysis.
Results: Exploratively, we set 1 Gy and 3 Gy as thresholds for the mean intestinal radiation dose. A total of 232 patients were included, of whom 76 patients (32.8%) and 67 patients (28.9%) had small intestine mean radiation dose (SIMRD) of < 1 Gy and 1-3 Gy, respectively. 153 patients (65.9%) received first-line IO, while 79 patients (34.1%) received second-line IO. Compared with the < 1 Gy and = 3 Gy groups, patients with SIMRD of 1-3 Gy not only had the highest objective response rate (ORR) after 3 months (21.1% vs. 43.3% vs. 7.9%) but also significantly improved OS (median: 14.8 months vs. 22.6 months vs. 7.7 months, P < 0.001) and PFS (median: 7.2 months vs. 10.0 months vs. 4.3 months, P < 0.001). Subgroup analysis of patients receiving first-line and second-line therapy yielded similar conclusions. Compared with the < 1 Gy and 1–3 Gy groups, patients with colon mean radiation dose of = 3 Gy also exhibited relatively poor OS (median: 14.8 months vs. 13.5 months vs. 10.1 months, P = 0.015) and PFS (median: 7.4 months vs. 7.3 months vs. 4.2 months, P = 0.006). Multivariate Cox regression analysis showed that SIMRD of 1-3 Gy was an independent predictive factor for OS (HR = 0.41, P < 0.001) and PFS (HR = 0.56, P < 0.001). We are also prospectively enrolling patients with mNSCLC who received first-line IO combined with RT for metastatic lesions from the chest to the pelvis, with efficacy evaluations conducted in 13 patients prior to submission. The results revealed that the ORR was highest (50%) in the SIMRD of 1-3 Gy group, with no patients experiencing disease progression, while 2 out of 3 patients with progression were in the SIMRD of = 3 Gy group.
Conclusion: In patients with mNSCLC receiving IO combined with metastasis RT, low SIMRD may significantly enhance the long-term prognosis of IO, potentially relying on the interaction between host immunity and gut microbiota. To validate this hypothesis, we are collecting blood and feces prospectively from patients before and after RT, with the prospective cohort currently being enrolled.