Exploring Strategies for Personalized Radiation Therapy: Part III Identifying genetic determinants for Radiation Response with Meta Learning

Radiation response in cancer is shaped by complex, patient specific biology, yet current treatment strategies often rely on uniform dose prescriptions without accounting for tumor heterogeneity. In this study, we introduce a meta learning framework for one-shot prediction of radiosensitivity measured by SF2 using cell line level gene expression data. Unlike the widely used Radiosensitivity Index RSI a rank-based linear model trained on a fixed 10-gene signature, our proposed meta-learned model allows the importance of each gene to vary by sample through fine tuning. This flexibility addresses key limitations of static models like RSI, which assume uniform gene contributions across tumor types and discard expression magnitude and gene gene interactions. Our results show that meta learning offers robust generalization to unseen samples and performs well in tumor subgroups with high radiosensitivity variability, such as adenocarcinoma and large cell carcinoma. By learning transferable structure across tasks while preserving sample specific adaptability, our approach enables rapid adaptation to individual samples, improving predictive accuracy across diverse tumor subtypes while uncovering context dependent patterns of gene influence that may inform personalized therapy.

Understanding the PULSAR Effect in Combined Radiotherapy and Immunotherapy through Attention Mechanisms with a Transformer Model

PULSAR (personalized, ultra-fractionated stereotactic adaptive radiotherapy) is the adaptation of stereotactic ablative radiotherapy towards personalized cancer management. For the first time, we applied a transformer-based attention mechanism to investigate the underlying interactions between combined PULSAR and PD-L1 blockade immunotherapy based on a murine cancer model (Lewis Lung Carcinoma, LLC). The proposed approach is able to predict the trend of tumor volume change semi-quantitatively, and excels in identifying the potential causal relationships through both self-attention and cross-attention scores.

Performance Deterioration of Deep Learning Models after Clinical Deployment: A Case Study with Auto-segmentation for Definitive Prostate Cancer Radiotherapy

In the past decade, deep learning (DL)-based artificial intelligence (AI) has witnessed unprecedented success and has led to much excitement in medicine. However, many successful models have not been implemented in the clinic predominantly due to concerns regarding the lack of interpretability and generalizability in both spatial and temporal domains. In this work, we used a DL-based auto segmentation model for intact prostate patients to observe any temporal performance changes and then correlate them to possible explanatory variables. We retrospectively simulated the clinical implementation of our DL model to investigate temporal performance trends. Our cohort included 912 patients with prostate cancer treated with definitive radiotherapy from January 2006 to August 2021 at the University of Texas Southwestern Medical Center (UTSW). We trained a U-Net-based DL auto segmentation model on the data collected before 2012 and tested it on data collected from 2012 to 2021 to simulate the clinical deployment of the trained model starting in 2012. We visualize the trends using a simple moving average curve and used ANOVA and t-test to investigate the impact of various clinical factors. The prostate and rectum contour quality decreased rapidly after 2016-2017. Stereotactic body radiotherapy (SBRT) and hydrogel spacer use were significantly associated with prostate contour quality (p=5.6e-12 and 0.002, respectively). SBRT and physicians' styles are significantly associated with the rectum contour quality (p=0.0005 and 0.02, respectively). Only the presence of contrast within the bladder significantly affected the bladder contour quality (p=1.6e-7). We showed that DL model performance decreased over time in concordance with changes in clinical practice patterns and changes in clinical personnel.