CAST: Time-Varying Treatment Effects with Application to Chemotherapy and Radiotherapy on Head and Neck Squamous Cell Carcinoma

Causal machine learning (CML) enables individualized estimation of treatment effects, offering critical advantages over traditional correlation-based methods. However, existing approaches for medical survival data with censoring such as causal survival forests estimate effects at fixed time points, limiting their ability to capture dynamic changes over time. We introduce Causal Analysis for Survival Trajectories (CAST), a novel framework that models treatment effects as continuous functions of time following treatment. By combining parametric and non-parametric methods, CAST overcomes the limitations of discrete time-point analysis to estimate continuous effect trajectories. Using the RADCURE dataset [1] of 2,651 patients with head and neck squamous cell carcinoma (HNSCC) as a clinically relevant example, CAST models how chemotherapy and radiotherapy effects evolve over time at the population and individual levels. By capturing the temporal dynamics of treatment response, CAST reveals how treatment effects rise, peak, and decline over the follow-up period, helping clinicians determine when and for whom treatment benefits are maximized. This framework advances the application of CML to personalized care in HNSCC and other life-threatening medical conditions. Source code/data available at: https://github.com/CAST-FW/HNSCC

A Machine Learning Challenge for Prognostic Modelling in Head and Neck Cancer Using Multi-modal Data

Accurate prognosis for an individual patient is a key component of precision oncology. Recent advances in machine learning have enabled the development of models using a wider range of data, including imaging. Radiomics aims to extract quantitative predictive and prognostic biomarkers from routine medical imaging, but evidence for computed tomography radiomics for prognosis remains inconclusive. We have conducted an institutional machine learning challenge to develop an accurate model for overall survival prediction in head and neck cancer using clinical data etxracted from electronic medical records and pre-treatment radiological images, as well as to evaluate the true added benefit of radiomics for head and neck cancer prognosis. Using a large, retrospective dataset of 2,552 patients and a rigorous evaluation framework, we compared 12 different submissions using imaging and clinical data, separately or in combination. The winning approach used non-linear, multitask learning on clinical data and tumour volume, achieving high prognostic accuracy for 2-year and lifetime survival prediction and outperforming models relying on clinical data only, engineered radiomics and deep learning. Combining all submissions in an ensemble model resulted in improved accuracy, with the highest gain from a image-based deep learning model. Our results show the potential of machine learning and simple, informative prognostic factors in combination with large datasets as a tool to guide personalized cancer care.