12142 Background: The increasing use of immunotherapy in advanced non-small cell lung cancer (NSCLC) presents a significant challenge in managing adverse events, particularly checkpoint inhibitor-associated pneumonitis (CIP). This potentially life-threatening complication often necessitates discontinuation of immunotherapy, even in patients experiencing tumor response. Presently, there are no reliable models to predict the onset of CIP. This research utilizes CT radiomics to create an innovative approach for anticipating the risk of CIP in patients with NSCLC. Methods: This IRB-approved, retrospective study analyzed data from 159 stage III-IV NSCLC patients undergoing immunotherapy. We categorized patients into pneumonitis (further subdivided into immunotherapy-induced, radiation-induced, and others) and non-pneumonitis groups. Using LIFEx software, we extracted 3D-radiomic features from both tumors and surrounding 1cm thick peritumoral regions. To address scanner-associated variations, a linear mixed-effect radiomics harmonization model was applied. A Random Forest algorithm was then used to develop a classification model predicting CIP occurrence based on the pre-treatment CT radiomic and clinical data. The dataset was split into training (70%) and test (30%) sets. The accuracy of predictions was evaluated using confusion matrix statistics and bootstrapping with 1,000 iterations for median and 95% confidence interval (CI). The performance metrics included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC curve (AUC). Results: 159 patients were analyzed, of which only 19 had checkpoint inhibitor-related pneumonitis. Among which, 17 (54.8%) patients had grade 1 pneumonitis, 12 (38.7%) patients had grade 2 pneumonitis, 2 (6.5%) patients had grade 3 pneumonitis, and none had grade 4 or grade 5 pneumonitis. The model achieved a sensitivity of 0.98 (0.97, 0.99), a specificity of 0.08 (0.05, 0.14), a PPV of 0.91 (0.90, 0.91), and an NPV of 0.33 ± 0.23 for predicting CIP. The AUC of 0.59 (0.56, 0.66) indicates that the model may predict checkpoint inhibitor-associated pneumonitis with an accuracy of 59%. Conclusions: The study provides insights into the potential of radiomic analysis coupled with AI algorithms and the use of harmonization model in predicting CIP among NSCLC patients treated with immunotherapy. However, larger studies are needed to validate our findings and the utility of harmonization models in predicting CIP.
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