RT-Super: Learning Tumor Segmentation from Longitudinal Images and Reports

Multi-cancer segmentation in computed tomography (CT) is fundamentally limited by the scarcity of tumor masks across different organs. We present Merlin Plus, the first large-scale CT dataset with radiologist-created tumor masks across 9 organs. Merlin Plus extends the Merlin dataset by adding 1,153 per-voxel tumor masks and longitudinal metadata. To create these tumor masks, we developed a report-based active-learning framework in which radiology reports identify tumor cases for annotation and support training of a tumor segmentation model. The model generates initial masks, which radiologists review and correct to produce the final masks, reducing annotation burden while maintaining high-quality annotations. Besides tumor masks, the longitudinal metadata in Merlin Plus enables temporal modeling of cancer progression. By directly addressing the major bottleneck of limited multi-cancer segmentation masks, Merlin Plus supports scalable multi-organ cancer detection, segmentation, and longitudinal analysis in CT. Dataset is available at: https://github.com/MrGiovanni/MerlinPlus

Accurate delineation of tumors and surrounding organs-at-risk is essential for radiotherapy, surgery and treatment response assessment, yet remains time-consuming and expertise-intensive. Existing artificial intelligence systems often require manual spatial prompts or task-specific retraining, while generic class labels provide limited semantic grounding for heterogeneous disease targets. Here we present SyRe, a promptable segmentation foundation model based on Synergistic vision-language Reinforcement. SyRe strengthens bidirectional interaction between visual and linguistic representations to improve semantically grounded spatial understanding. To support large-scale training, we introduce the Color Region Description strategy and construct SyReData, comprising 20 million image-mask-description triplets across 9 modalities and 229 segmentation tasks. Training with diversified prompt forms further enables open-ended prompting, invalid-prompt rejection and flexible switching between single- and multi-target analysis. SyRe achieves accurate text-prompted segmentation across diverse clinical scenarios, with particularly strong performance on disease-related targets. Across 28 unseen external datasets, including 20 cancer types and multinational in-house cohorts, SyRe generalizes robustly under real-world distribution shifts. SyRe-generated masks also preserve clinically relevant quantitative information in pathology and yield radiomics features that stratify survival and improve prognostic modeling across five retrospective CT and MRI tumor cohorts. Finally, clinician-in-the-loop refinement enables efficient case-level correction when greater precision is required. These results establish SyRe as a generalizable foundation for scalable quantitative oncology and clinician-guided segmentation refinement.

Although self-supervised pretraining is expected to learn broadly transferable representations, its effectiveness across imaging modalities substantially different from the pretraining domain, and on complex tumor-segmentation tasks, remains understudied. Evaluating CT-pretrained transformers on MRI rectal cancer segmentation, we identified two interacting failure modes in CT-to-MRI transfer: (a) inefficient token usage caused by zero-padding to match pretrained input dimensions, and (b) ineffective feature adaptation. We investigated these vulnerabilities using two primary CT-pretrained hierarchical shifted-window transformer backbones, SMIT and Swin UNETR, together with VoCo as a large-scale-pretrained supporting benchmark; these models differ in pretraining objectives and datasets. Mechanistic analysis leveraged an attention dilution index (ADI), an entropy-based metric quantifying attention diverted toward uninformative padding tokens, and centered kernel alignment (CKA) to measure feature reuse during MRI adaptation. ADI increased with zero-padding, while high feature reuse did not necessarily translate to improved downstream accuracy. To mitigate these issues, we introduced two interventions: a tumor-aware augmentation strategy to expand tumor appearance heterogeneity coverage, and an anisotropic cropping strategy to restore token efficiency. Fine-tuning with these strategies on identical rectal MRI datasets yielded detection rates of 91.1% (225/247) and 88.7% (219/247) for the primary SMIT and Swin UNETR backbones, with the supporting VoCo benchmark reaching 90.3% (223/247), demonstrating significantly improved robustness under CT-to-MRI transfer. This study is among the first to examine when pretrained transformers fail to transfer across imaging modalities and demonstrates how targeted mitigation strategies can systematically overcome cross-modality transfer limitations.