Exploratory study on the impact of intestinal low-dose radiation on the efficacy and prognosis of immunotherapy in metastatic non-small cell lung cancer.

Abstract

8571 Background: Radiotherapy (RT) can be a palliative measure for metastases of metastatic non-small cell lung cancer (mNSCLC). However, RT to abdominopelvic metastases can cause additional intestinal radiation, that may lead to microbial imbalance. Recent research have 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. Methods: Collect clinical data from patients with mNSCLC who underwent IO combined with abdominopelvic RT for metastases at Shandong Cancer Hospital over the past five years. Use the Varian Eclipse system to outline the contours of the large and small intestines and record the dosimetric parameter. Calculate overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method, compare inter-group differences using the log-rank test, and analyze risk factors associated with OS and PFS through Cox regression analysis. Results: Exploratively, we set 1 Gy and 3 Gy as the thresholds for the mean intestinal radiation dose. A total of 232 patients were included, with 76 patients (32.8%) having small intestine mean radiation dose (SIMRD) < 1 Gy, and 67 patients (28.9%) having SIMRD between 1-3 Gy. 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 between 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 prolonged OS (14.8 months vs. 22.6 months vs. 7.7 months, P < 0.001) and PFS (7.2 months vs. 10.0 months vs. 4.3 months, P < 0.001). Subgroup analysis of first-line and second-line therapy patients yielded similar conclusions. Compared with the < 1 Gy and 1-3 Gy groups, patients with colon mean radiation dose ≥ 3 Gy also exhibit relatively poor OS (14.8 months vs. 12.6 months vs. 10.1 months, P = 0.036) and PFS (7.4 months vs. 7.3 months vs. 4.2 months, P = 0.006). Multivariate Cox regression analysis showed that SIMRD between 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 prospectively enrolled 14 patients with mNSCLC who received first-line IO combined with metastasis RT, with 9 patients undergoing efficacy evaluation. The results revealed that the ORR was highest (66.7%) in the group with SIMRD between 1-3 Gy, and both 2 patients with progression were in the group with SIMRD ≥ 3 Gy. Conclusions: 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 prospectively collecting blood and feces from patients before and after RT, with the prospective cohort being enrolled.