OncoReason: Structuring Clinical Reasoning in LLMs for Robust and Interpretable Survival Prediction
This work addresses the need for accurate and interpretable models in high-stakes clinical decision support for precision oncology, representing a domain-specific advancement.
The paper tackled the problem of predicting cancer treatment outcomes by developing a multi-task learning framework that aligns large language models with clinical reasoning for survival prediction, achieving improvements such as a +6.0 F1 score increase and 12% reduction in MAE with Chain-of-Thought prompting, and state-of-the-art interpretability and predictive performance with Group Relative Policy Optimization.
Predicting cancer treatment outcomes requires models that are both accurate and interpretable, particularly in the presence of heterogeneous clinical data. While large language models (LLMs) have shown strong performance in biomedical NLP, they often lack structured reasoning capabilities critical for high-stakes decision support. We present a unified, multi-task learning framework that aligns autoregressive LLMs with clinical reasoning for outcome prediction on the MSK-CHORD dataset. Our models are trained to jointly perform binary survival classification, continuous survival time regression, and natural language rationale generation. We evaluate three alignment strategies: (1) standard supervised fine-tuning (SFT), (2) SFT with Chain-of-Thought (CoT) prompting to elicit step-by-step reasoning, and (3) Group Relative Policy Optimization (GRPO), a reinforcement learning method that aligns model outputs to expert-derived reasoning trajectories. Experiments with LLaMa3-8B and Med42-8B backbones demonstrate that CoT prompting improves F1 by +6.0 and reduces MAE by 12%, while GRPO achieves state-of-the-art interpretability and predictive performance across BLEU, ROUGE, and BERTScore. We further show that existing biomedical LLMs often fail to produce valid reasoning traces due to architectural constraints. Our findings underscore the importance of reasoning-aware alignment in multi-task clinical modeling and set a new benchmark for interpretable, trustworthy LLMs in precision oncology.