Multimodal machine learning predictions of treatment response and survival in advanced pancreatic cancer from the COMPASS trial.

4181 Background: Pancreatic cancer is an aggressive malignancy with limited therapeutic options and a poor prognosis. Current approaches to prognostication are limited, especially in advanced disease. We explored whether machine learning integrating multi-modal data could predict outcomes in advanced pancreatic cancer. Methods: We developed and evaluated machine learning models predicting disease control rate and one-year survival from the COMPASS trial (NCT02750657). Data modalities included clinical features, histopathology, radiology, RNAseq, and whole-genome sequencing (WGS). After pre-processing, we applied LASSO and XGBoost to each modality and early and late fusion techniques. Hyperparameter tuning and performance assessment were performed using repeated nested cross-validation. The PurIST RNAseq classifier served as a baseline. Area under the curve (AUC) was the primary metric. Results: The cohort included 260 patients (105 female; median age 64 [IQR 58–70]; 141 treated with FOLFIRINOX, 97 with gemcitabine and nab-paclitaxel). 170 (65%) achieved disease control and 168 (65%) survived at least one year. The performance of the machine learning models is shown in the Table. Predictions from the unimodal models had limited correlation with each other (the maximum pairwise correlation averaged across folds was between clinical and histopathology models, 0.21). The late fusion models up-weighted data modalities with stronger unimodal performance. Conclusions: Multiple individual data modalities can predict outcomes in advanced pancreatic cancer, with PurIST serving as a strong baseline. Despite differing predictions across data modalities, multimodal integration did not improve prognostic performance in this cohort. AUC for the PurIST baseline, the top 2 unimodal models, and the best fusion model for each outcome. Outcome Data Modality AUC (95% confidence interval) Disease control PurIST 0.69 (0.69, 0.70) Radiomics 0.75 (0.72, 0.79) RNAseq 0.71 (0.70, 0.72) Fusion (late) 0.71 (0.69, 0.73) One-year survival PurIST 0.63 (0.62, 0.63) DNA mutations 0.64 (0.61, 0.66) RNAseq 0.57 (0.55, 0.60) Fusion (early) 0.61 (0.56, 0.66)