Julio Garcia-Aguilar

Jorge Tapias Gomez, Despoina Kanata, Aneesh Rangnekar et al.

Increasing evidence supports watch-and-wait (WW) surveillance for patients with rectal cancer who show clinical complete response (cCR) at restaging following total neoadjuvant treatment (TNT). However, objectively accurate methods to early detect local regrowth (LR) from follow-up endoscopy images during WW are essential to manage care and prevent distant metastases. Hence, we developed a Siamese Swin Transformer with Dual Cross-Attention (SSDCA) to combine longitudinal endoscopic images at restaging and follow-up and distinguish cCR from LR. SSDCA leverages pretrained Swin transformers to extract domain agnostic features and enhance robustness to imaging variations. Dual cross attention is implemented to emphasize features from the two scans without requiring any spatial alignment of images to predict response. SSDCA as well as Swin-based baselines were trained using image pairs from 135 patients and evaluated on a held-out set of image pairs from 62 patients. SSDCA produced the best balanced accuracy (81.76\% $\pm$ 0.04), sensitivity (90.07\% $\pm$ 0.08), and specificity (72.86\% $\pm$ 0.05). Robustness analysis showed stable performance irrespective of artifacts including blood, stool, telangiectasia, and poor image quality. UMAP clustering of extracted features showed maximal inter-cluster separation (1.45 $\pm$ 0.18) and minimal intra-cluster dispersion (1.07 $\pm$ 0.19) with SSDCA, confirming discriminative representation learning.

Jorge Tapias Gomez, Despoina Kanata, Aneesh Rangnekar et al.

Clinical trial studies indicate benefit of watch-and-wait (WW) surveillance for patients with rectal cancer showing a complete or near clinical response (CR) directly after treatment (restaging). However, there are no objectively accurate methods to early detect local tumor regrowth (LR) in patients undergoing WW from follow-up exams. Hence, we developed Temporal Rectal Endoscopy Cross-attention (TREX), a longitudinal deep learning approach that combines pairs of images acquired at restaging and follow-up to distinguish CR from LR. TREX uses pretrained Swin Transformers in a siamese setting to extract features from longitudinal images and dual cross-attention to combine the features without spatial co-registration between image pairs. TREX and Swin-based baselines were trained under two settings: (a) detecting LR or CR at the last available follow-up and (b) early detection of LR at 3--6, 6--12, and 12--24 months before clinical confirmation. TREX achieved the highest accuracy in detecting LR with a high sensitivity of 97% $\pm$ 6% and a balanced accuracy of 90% $\pm$ 3%, and outperformed all baselines in early detection at both 3--6 (74% $\pm$ 1%) and 6--12 months (62% $\pm$ 4%) prior to clinical detection. Clinical validation via a surgeon survey showed that TREX matched attending-level overall accuracy (TREX: 86.21% vs.\ Clinicians: 87.84% $\pm$ 1.28%). Finally, we explored TREX's ability to predict treatment response by combining pre-treatment (pre-TNT) and restaging endoscopies, achieving a balanced accuracy of 73% $\pm$ 12%. These results show that longitudinal deep learning analysis of endoscopy may improve surveillance and enable earlier identification of rectal cancer regrowth.

Aneesh Rangnekar, Joao Miranda, Natally Horvat et al.

Pretraining on large-scale datasets has been shown to improve transformer generalizability, even for out-of-domain (OOD) modalities and tasks. However, two common assumptions often fail under OOD transfer: that downstream datasets can be adapted to the fixed input geometry of pretrained models and that pretrained representations transfer effectively across imaging modalities. We show that these assumptions break down through two interacting failure modes in CT-to-MRI transfer: inefficient token usage caused by zero-padding to match pretrained input dimensions and ineffective feature adaptation. These failures led to accuracy degradation despite extensive fine-tuning. We investigated these failure modes using two CT-pretrained hierarchical shifted-window transformer backbones, SMIT and Swin UNETR, pretrained with different objectives and datasets. Mechanistic analysis introduced 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 in MRI tasks. ADI increased with zero-padding, while high feature reuse did not necessarily correspond to improved accuracy. To mitigate these issues, we introduced two interventions: a tumor-aware augmentation strategy to improve tumor appearance heterogeneity coverage and an anisotropic cropping strategy to restore token efficiency. Fine-tuning on identical rectal MRI datasets improved detection rates to 224/247 (90.7%) for SMIT and 219/247 (88.7%) for Swin UNETR, demonstrating improved robustness under CT-to-MRI transfer. This study is among the first to examine when pretrained transformers fail to transfer effectively across imaging modalities and how simple mitigation strategies, motivated by mechanistic analysis of datasets, can reduce transfer limitations while improving robustness and MRI detection.

Jorge Tapias Gomez, Aneesh Rangnekar, Hannah Williams et al.

Endoscopic images are used at various stages of rectal cancer treatment starting from cancer screening, diagnosis, during treatment to assess response and toxicity from treatments such as colitis, and at follow up to detect new tumor or local regrowth (LR). However, subjective assessment is highly variable and can underestimate the degree of response in some patients, subjecting them to unnecessary surgery, or overestimate response that places patients at risk of disease spread. Advances in deep learning has shown the ability to produce consistent and objective response assessment for endoscopic images. However, methods for detecting cancers, regrowth, and monitoring response during the entire course of patient treatment and follow-up are lacking. This is because, automated diagnosis and rectal cancer response assessment requires methods that are robust to inherent imaging illumination variations and confounding conditions (blood, scope, blurring) present in endoscopy images as well as changes to the normal lumen and tumor during treatment. Hence, a hierarchical shifted window (Swin) transformer was trained to distinguish rectal cancer from normal lumen using endoscopy images. Swin as well as two convolutional (ResNet-50, WideResNet-50), and vision transformer (ViT) models were trained and evaluated on follow-up longitudinal images to detect LR on private dataset as well as on out-of-distribution (OOD) public colonoscopy datasets to detect pre/non-cancerous polyps. Color shifts were applied using optimal transport to simulate distribution shifts. Swin and ResNet models were similarly accurate in the in-distribution dataset. Swin was more accurate than other methods (follow-up: 0.84, OOD: 0.83) even when subject to color shifts (follow-up: 0.83, OOD: 0.87), indicating capability to provide robust performance for longitudinal cancer assessment.