Routine laboratory trajectories encode the onset of organ-level complications in cancer

We introduce an in-domain supervised pipeline designed to counter the out-of-distribution performance drop that hampers supervised biomedical NLP models, a problem observed when models trained on pathology reports are moved across cancer registries. Our contribution is a reproducible recipe for training a supervised classifier from routinely collected cancer registry data. It describes how to build the in-domain training set and a production-matched holdout, and to choose operating points that keep the false-negative rate (FNR) very low while keeping reviewer workload manageable. The pipeline standardizes data curation with facility-stratified sampling and separate handling of reports linked to registry cases, and includes a blinded manual audit to estimate positive-case prevalence and label noise. On a 418k-report holdout set, the Kentucky model achieved FNR 0.003 and false-positive rate (FPR) 0.097, improving over the Seattle-trained MOSSAIC OncoID baseline (FNR 0.010, FPR 0.183) and raising F1 from 0.860 to 0.922. In a blinded manual review of 600 reports, estimated positive prevalence declined from 0.500 to 0.398, indicating substantial label noise with errors concentrated in rare primary sites.

Blood-based biomarkers underpin clinical diagnosis and management, yet their interpretation relies largely on fixed population reference intervals that ignore stable, intra-patient variability. As such, population-based interpretation can mask meaningful deviation from an individual's baseline, risking delayed disease detection. To remedy this, there have been increasing efforts to personalize blood biomarker interpretation using individual testing histories. However, these methods may overfit to sparse data, inflating false-positive rates and unnecessary follow-up, and can also unwittingly include unrecognized or subclinical disease. Here, we leverage nearly 2 billion longitudinal laboratory measurements from over 1.6 million individuals across North America, the Middle East, and East Asia, to show that while laboratory values are highly individual, purely personalized intervals routinely overfit, classifying up to 68% of measurements as abnormal, without corresponding associations with adverse clinical outcomes. We then introduce NORMA, a conditional transformer-based framework that generates reference intervals by conditioning on both a patient's history and population-level data about "normal" variation. NORMA-derived intervals achieve higher precision for predicting outcomes, including mortality, acute kidney injury, and chronic disease. These findings caution against over-personalization in laboratory medicine and demonstrate that anchoring individual trajectories to population-level priors outperforms either approach alone. To promote transparency, we publicly release the model, code, and an interactive user interface for accessible, individualized laboratory interpretation.

Modernizing cancer registries with deep learning is opening new opportunities to automate labor-intensive tasks such as the coding of pathology reports. However, progress is constrained by the scarcity of report-level human-annotated training data. Cancer registries generate substantial volumes of expert-assigned labels as a routine product of their operations, but these exist at the patient level and are not linked to the individual pathology reports that informed them, limiting their direct use for training models. We develop an efficient framework for training deep learning classifiers by leveraging these operationally-generated labels without requiring per-report human annotation, demonstrated for tumor group classification at the BC Cancer Registry. We use Attention-Based Multiple Instance Learning (ABMIL) to recover the lost link between patient-level labels and the reports that informed them, leveraging the attention the model places on each report to distil a large, noisily-labeled corpus into a compact, high-quality per-report training dataset. A classifier fine-tuned on a distilled dataset achieved a macro F1 of 0.83, outperforming established baselines across most tumor groups. By turning routine operational labels into high-quality training data without additional annotation or large-scale computing infrastructure, ABMIL offers a practical and accessible route to automating cancer registry workflows.