Radiomics-Based Prediction of Treatment Response to TRuC-T Cell Therapy in Patients with Mesothelioma: A Pilot Study.

Simple Summary: T cell receptor fusion constructs (TRuC-Ts) represent a promising next-generation T cell therapy for solid tumors. To enhance their development, improved patient selection is essential. A pilot study was conducted to evaluate the feasibility and performance of a predictive model for treatment responses in mesothelioma patients, leveraging radiomics and machine learning. Radiomics and delta-radiomics (Δradiomics) features from CT scans were analyzed for reproducibility and informativeness, identifying key features for training a random forest classifier. The model achieved an accuracy of 0.75–0.9 in predicting pleural tumor responses, supporting the design of future studies involving 250–400 tumors. This study demonstrated the reproducibility and effectiveness of radiomics/Δradiomics in relation to tumor localization, emphasizing the need for multiple tumor models to create an integrated patient model. These findings provide a foundation for combining tumor-specific models into a unified approach, improving patient selection for TRuC-T therapy in mesothelioma patients. Background/Objectives: T cell receptor fusion constructs (TRuCs), a next generation engineered T cell therapy, hold great promise. To accelerate the clinical development of these therapies, improving patient selection is a crucial pathway forward. Methods: We retrospectively analyzed 23 mesothelioma patients (85 target tumors) treated in a phase 1/2 single arm clinical trial (NCT03907852). Five imaging sites were involved, the settings for the evaluations were Blinded Independent Central Reviews (BICRs) with double reads. The reproducibility of 3416 radiomics and delta-radiomics (Δradiomics) was assessed. The univariate analysis evaluated correlations at the target tumor level with (1) tumor diameter response; (2) tumor volume response, according to the Quantitative Imaging Biomarker Alliance; and (3) the mean standard uptake value (SUV) response, as defined by the positron emission tomography response criteria in solid tumors (PERCISTs). A random forest model predicted the response of the target pleural tumors. Results: Tumor anatomical distribution was 55.3%, 17.6%, 14.1%, and 10.6% in the pleura, lymph nodes, peritoneum, and soft tissues, respectively. Radiomics/Δradiomics reproducibility differed across tumor localizations. Radiomics were more reproducible than Δradiomics. In the univariate analysis, none of the radiomics/Δradiomics correlated with any response criteria. With an accuracy ranging from 0.75 to 0.9, three radiomics/Δradiomics were able to predict the response of target pleural tumors. Pivotal studies will require a sample size of 250 to 400 tumors. Conclusions: The prediction of responding target pleural tumors can be achieved using a machine learning-based radiomics/Δradiomics analysis. Tumor-specific reproducibility and the average values indicated that using tumor models to create an effective patient model would require combining several target tumor models. [ABSTRACT FROM AUTHOR]