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Updated: Jul 17, 2026
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An Orthotopic Resectional Mouse Model of Pancreatic Cancer
Published on: September 24, 2020
Spatial Configuration of Pancreatic Cancer Is Associated with Disease Recurrence after Neoadjuvant Therapy and
Luis H Cisneros1, Merih D Toruner2, Zafar Siddiqui3
1Mayo Clinic Rochester, MN United States.
Summary
The spatial arrangement of pancreatic cancer cells and stroma after neoadjuvant therapy predicts recurrence risk. Tumor-stroma topology offers prognostic insights beyond traditional measures for pancreatic ductal adenocarcinoma (PDAC).
Area of Science:
- Oncology
- Computational Pathology
- Cancer Biology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) often recurs post-neoadjuvant therapy (NT) and resection.
- Minor pathologic response in PDAC patients leads to heterogeneous recurrence risks.
- Current prognostication may not fully capture risk based on residual tumor burden alone.
Purpose of the Study:
- To investigate if the spatial organization of residual PDAC after NT encodes clinically relevant prognostic information.
- To determine if spatial features of the tumor microenvironment correlate with disease-free survival (DFS).
- To identify novel spatial biomarkers for predicting recurrence risk in PDAC.
Main Methods:
- Retrospective analysis of 203 PDAC patients with minor pathologic response post-NT.
- AI-enabled segmentation of H&E whole-slide images into cancer and stroma.
- Quantification of spatial composition (density) and configuration (intermixing, compactness).
- Multivariable modeling to assess associations between spatial features and DFS, adjusted for clinicopathologic factors.
Main Results:
- Fragmented, interface-rich tumor-stroma ecology with high edge density and reduced aggregation correlated with shorter DFS.
- Two spatial risk models (cancer shape index/stromal variability and stromal patch area/edge density) were independently prognostic.
- Spatial models stratified outcomes where pathologic response and residual cancer area did not.
- High-risk spatial configurations were linked to reduced intratumoral tumor-infiltrating lymphocytes (TILs), suggesting an immune-excluded phenotype.
Conclusions:
- Residual cancer-stroma topology from H&E slides provides independent prognostic signals in PDAC post-NT.
- Spatial risk quantification correlates with tumor-infiltrating immune cells, offering insights into immune exclusion.
- Findings support prospective validation and development of spatially informed adjuvant therapies for PDAC.
