Extending the Horizon of Early Diagnosis: Lung Cancer Prediction with Vision Transformers

Lung cancer remains a leading cause of cancer-related mortality worldwide, and early diagnosis is critical for improving survival. However, early-stage malignancies can be subtle on chest X-rays, creating challenges for radiologists. This study evaluates Vision Transformers (ViTs) for predicting lung cancer one to two years before clinical diagnosis. We analyzed 259,361 chest X-rays from 91,020 imaging studies at the Jamaica Plains VA Hospital in Boston, MA. The dataset showed extreme class imbalance, approximately 1:150 cancer to non-cancer, which was addressed using hybrid under- and over-sampling and class-weighted loss optimization. Three ViT configurations were evaluated: a model trained from scratch, an ImageNet-pretrained model, and a Corona-pretrained model fine-tuned on the lung cancer dataset. Transfer learning improved performance, with pretrained models exceeding the scratch baseline by 6-10 percentage points in AUC and about 10-12 percent in balanced accuracy. ImageNet-pretrained models showed the most stable overall performance, while Corona-pretrained models achieved higher sensitivity in some settings but greater variability. Moderate resampling ratios, including 1:1 undersampling and 1.5:2 oversampling, provided favorable trade-offs between sensitivity, precision, and computational efficiency, reducing runtime by up to 70 percent without major performance loss. These findings demonstrate the potential of ViTs for early lung cancer risk prediction from routine chest X-rays. Although performance remains below clinical deployment thresholds, the results support further development of ViT-based triage systems to flag high-risk patients for earlier evaluation.

LUNG-KGMM: Knowledge-Guided Multimodal Learning for Lung Cancer Incidence Prediction

Early identification of lung cancer risk is critical for timely intervention, yet existing prediction models are limited by their reliance on single data modalities and their inability to leverage structured clinical knowledge. We propose LUNG-KGMM, a knowledge-guided multimodal framework that integrates longitudinal electronic health records, radiology reports, chest radiograph representations, and guideline-derived knowledge for 1-to-6-year incident lung cancer prediction. To address modality heterogeneity and potential data leakage, we develop a leakage-sanitized report processing pipeline and a horizon-masked cumulative training objective that handles incomplete follow-up. We further introduce a knowledge-graph representation of clinical guidance that encodes report-triggered finding-attribute-action relations as an auditable knowledge stream. We build a multimodal development cohort from the publicly available MIMIC databases and construct a real-world validation cohort from the Xiamen Medical Big Data Platform. Extensive experiments on the MIMIC cohort demonstrate that LUNG-KGMM achieves superior performance over state-of-the-art methods, and validation on the Xiamen cohort further characterizes its cross-cohort portability and the need for local adaptation. The MIMIC development cohort is publicly accessible; the Xiamen cohort is governed by local data privacy regulations.