Leveraging Large Language Models and Survival Analysis for Early Prediction of Chemotherapy Outcomes

Chemotherapy improves survival for some patients with breast cancer, but doctors cannot reliably predict who. Current guidelines rely on recurrence scores as a proxy for treatment benefit, which may contribute to the overprescription of chemotherapy. Here we present a causal multi-modal AI model that predicts personalized chemosensitivity using routinely collected pathology and clinical information. We developed our model on a multi-national dataset of 9,141 patients (twelve cohorts, nine countries) and evaluated it on another 1,994 patients (five cohorts, three countries). The model generated treatment-specific recurrence probabilities for each patient, with near-perfect calibration and strong prognostic discrimination across both 5- and 10-year follow-up horizons. Moreover, its chemotherapy benefit predictions demonstrated robust predictive performance, and out-performed existing recurrence-score-based tests. Compared to the standard of care, using the model to support personally tailored therapeutic decisions could reduce the number of patients receiving chemotherapy by 30% while achieving the same recurrence-free rate. Tumors predicted to be highly chemosensitive displayed concordant molecular and morphological programs of proliferation, cell cycle progression, and replication stress. The model's predictive capabilities transferred zero-shot to non-breast cancers, indicating our causal multi-modal AI approach may provide a universal strategy to predict treatment outcomes across cancer types.

A significant amount of data held in Oncology Electronic Medical Records (EMRs) is contained in unstructured provider notes -- including but not limited to the chemotherapy (or cancer treatment) outcome, different biomarkers, the tumor's location, sizes, and growth patterns of a patient. The clinical studies show that the majority of oncologists are comfortable providing these valuable insights in their notes in a natural language rather than the relevant structured fields of an EMR. The major contribution of this research is to report an LLM-based framework to process provider notes and extract valuable medical knowledge and phenotype mentioned above, with a focus on the domain of oncology. In this paper, we focus on extracting phenotypes related to breast cancer using our LLM framework, and then compare its performance with earlier works that used knowledge-driven annotation system, paired with the NCIt Ontology Annotator. The results of the study show that an LLM-based information extraction framework can be easily adapted to extract phenotypes with an accuracy that is comparable to the classical ontology-based methods. However, once trained, they could be easily fine-tuned to cater for other cancer types and diseases.

Cancer survival prediction supports treatment planning, risk stratification, and follow-up management. Existing methods use structured clinical variables, whole-slide images, genomic profiles, or multimodal inputs, while patient reports remain underexplored. We study report-centric survival prediction using reports that organize pathological, clinical, and molecular evidence. Large language models (LLMs) can reason over such reports, but case-wise time regression introduces two mismatches. First, a formulation mismatch arises because survival evaluation depends on ordering comparable patients, whereas independent time predictions do not enforce ranking consistency. Second, a supervision mismatch arises because a censored patient's observed time indicates survival beyond that point and cannot serve as an exact regression target, although it still implies orderings relative to patients who died earlier. To address these mismatches, we propose CACSurv, a Concordance-Aligned Comparative framework for report-centric survival prediction. CACSurv reformulates survival modeling as mini-cohort comparative reasoning, where an LLM predicts relative prognostic orderings. We introduce concordance-aligned rewards derived from comparable relations under right censoring, enabling censored outcomes to provide ranking supervision without exact event-time targets. At inference, Monte Carlo Reference Aggregation compares each patient with sampled references and aggregates positions into a cohort-level ranking. We establish TCGA-SurvReport, a benchmark covering six TCGA cancer cohorts. CACSurv achieves the highest C-index on all six cohorts and an average C-index of 0.722, outperforming the strongest published survival model by 6.5 percentage points and the strongest LLM time-regression baseline by 4.2 percentage points. Our code, models, and dataset will be available at https://github.com/xmed-lab/CACSurv.