Learning from Lost Provenance: Multiple Instance Learning for Cancer Registry Tumor Group Classification
Authors: Leonard Ruocco, Jonathan Simkin, Lovedeep Gondara, Gregory Arbour, Raymond Ng
Abstract
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.
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.
Deep learning models for CT scan analysis are often limited by the scarcity of precise pixel-level annotations, which require significant radiologist effort to produce. Training on scan-level labels alone reduces annotation requirements but introduces challenges: low supervision ratios and large input volumes make models prone to overfitting and shortcut learning. In this work, we investigate two complementary methods to address these challenges: multi-instance learning (MIL) and anatomical filtering. MIL divides CT volumes into 2D slice instances, enabling efficient 2D architectures with ImageNet pretraining rather than computationally demanding 3D models. Anatomical filtering uses Compass, our self-supervised body part regression model, to crop scans to pathology-relevant subregions without requiring segmentation masks. We evaluate two MIL frameworks - Attention-based MIL (ABMIL) and FocusMIL - on kidney tumor classification across one internal dataset (TUH) and two external datasets (KiTS23 and TCGA-KiRC). Our best models achieve F1 = 0.83 on the internal test set using only scan-level labels. We further show that anatomical filtering with the Compass model is critical for the out-of-distribution generalization of embedding-based ABMIL, while instance-based FocusMIL demonstrates greater inherent robustness to distribution shift. While evaluated on kidney tumors, we consider this a proof-of-concept for a broader weakly supervised CT classification pipeline applicable to other organs and pathologies.
Accurate assessment of tumor proportion score (TPS) in non-small cell lung cancer (NSCLC) is critical for treatment planning and prognosis. Key challenges include the tedious manual work required to annotate each slide, combined with the limited number of experts certified for this task. Multiple instance learning (MIL) has proven to be an effective approach for predicting TPS scores at the slide level; however, existing methods struggle with non-expressive (zero class) images. Our approach involves two models: (1) an embedding-extraction and multiclass-classification network that captures the histopathological features of individual patches, and (2) a MIL model that aggregates these embeddings to predict zero-inflated beta (ZIBeta) parameters representing the overall TPS probability distribution for the entire slide. Using only slide-level TPS scores as labels, we demonstrate how this end-to-end framework can leverage a novel distribution-based architecture to improve prediction accuracy and explainability. ZIBeta modeling significantly outperforms baseline linear and ridge regression while capturing expected accuracy through distribution concentration.
Krzysztof Pysz, Artur Bartczak, Jarosław Kwiecień +2