# R2Seg: Training-Free OOD Medical Tumor Segmentation via Anatomical Reasoning and Statistical Rejection

arXiv: https://arxiv.org/abs/2511.12691 · HTML: https://mlsanity.com/paper/2511.12691/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 24 of its 45 references that are in the map.
- First posted on arXiv 16 Nov 2025.

## Builds on (most cited first, 24 of 24)

- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [Chain-of-Thought Prompting Elicits Reasoning in Large Language Models](https://mlsanity.com/paper/2201.11903/) (2022)
- [ReAct: Synergizing Reasoning and Acting in Language Models](https://mlsanity.com/paper/2210.03629/) (2022)
- [Segment Anything](https://mlsanity.com/paper/2304.02643/) (2023)
- [Self-Consistency Improves Chain of Thought Reasoning in Language Models](https://mlsanity.com/paper/2203.11171/) (2022)
- [Tree of Thoughts: Deliberate Problem Solving with Large Language Models](https://mlsanity.com/paper/2305.10601/) (2023)
- [V-Net: Fully Convolutional Neural Networks for Volumetric Medical Image Segmentation](https://mlsanity.com/paper/1606.04797/) (2016)
- [3D U-Net: Learning Dense Volumetric Segmentation from Sparse Annotation](https://mlsanity.com/paper/1606.06650/) (2016)
- [Attention U-Net: Learning Where to Look for the Pancreas](https://mlsanity.com/paper/1804.03999/) (2018)
- [Least-to-Most Prompting Enables Complex Reasoning in Large Language Models](https://mlsanity.com/paper/2205.10625/) (2022)
- [LLaVA-Med: Training a Large Language-and-Vision Assistant for Biomedicine in One Day](https://mlsanity.com/paper/2306.00890/) (2023)
- [Swin-Unet: Unet-like Pure Transformer for Medical Image Segmentation](https://mlsanity.com/paper/2105.05537/) (2021)
- [The Medical Segmentation Decathlon](https://mlsanity.com/paper/2106.05735/) (2021)
- [TotalSegmentator: robust segmentation of 104 anatomical structures in CT images](https://mlsanity.com/paper/2208.05868/) (2022)
- [Continual Test-Time Domain Adaptation](https://mlsanity.com/paper/2203.13591/) (2022)
- [Efficient Test-Time Model Adaptation without Forgetting](https://mlsanity.com/paper/2204.02610/) (2022)
- [A Comprehensive Survey on Test-Time Adaptation under Distribution Shifts](https://mlsanity.com/paper/2303.15361/) (2023)
- [The state of the art in kidney and kidney tumor segmentation in contrast-enhanced CT imaging: Results of the KiTS19 Challenge](https://mlsanity.com/paper/1912.01054/) (2019)
- [BiomedParse: a biomedical foundation model for image parsing of everything everywhere all at once](https://mlsanity.com/paper/2405.12971/) (2024)
- [Test-Time Adaptable Neural Networks for Robust Medical Image Segmentation](https://mlsanity.com/paper/2004.04668/) (2020)
- [A large-scale multicenter breast cancer DCE-MRI benchmark dataset with expert segmentations](https://mlsanity.com/paper/2406.13844/) (2024)
- [SegAgent: Exploring Pixel Understanding Capabilities in MLLMs by Imitating Human Annotator Trajectories](https://mlsanity.com/paper/2503.08625/) (2025)
- [A Simple Image Segmentation Framework via In-Context Examples](https://mlsanity.com/paper/2410.04842/) (2024)
- [Large-scale Long-tailed Disease Diagnosis on Radiology Images](https://mlsanity.com/paper/2312.16151/) (2023)

## Built on by (most cited first, 1 of 1)

- [Beyond Classification: Structured Supervision Aligns Visual Evidence with Medical Semantics](https://mlsanity.com/paper/2609.05937/) (2026)

## Abstract (arXiv)

Foundation models for medical image segmentation struggle under out-of-distribution (OOD) shifts, often producing fragmented false positives on OOD tumors. We introduce R2Seg, a training-free framework for robust OOD tumor segmentation that operates via a two-stage Reason-and-Reject process. First, the Reason step employs an LLM-guided anatomical reasoning planner to localize organ anchors and generate multi-scale ROIs. Second, the Reject step applies two-sample statistical testing to candidates generated by a frozen foundation model (BiomedParse) within these ROIs. This statistical rejection filter retains only candidates significantly different from normal tissue, effectively suppressing false positives. Our framework requires no parameter updates, making it compatible with zero-update test-time augmentation and avoiding catastrophic forgetting. On multi-center and multi-modal tumor segmentation benchmarks, R2Seg substantially improves Dice, specificity, and sensitivity over strong baselines and the original foundation models. Code are available at https://github.com/Eurekashen/R2Seg.