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A Novel Artificial Intelligence-based Parameterization Approach of the Stromal Landscape in Merkel Cell Carcinoma: a Multi-Institutional Study
Journal article   Peer reviewed

A Novel Artificial Intelligence-based Parameterization Approach of the Stromal Landscape in Merkel Cell Carcinoma: a Multi-Institutional Study

Chau M. Bui, Minh-Khang Le, Masataka Kawai, Huy Gia Vuong, Kristin J. Rybski, Kathleen Mannava, Tetsuo Kondo, Takashi Okamoto, Leah Laageide, Brian Swick, …
Laboratory investigation, Vol.104(9), 102123
09/2024
DOI: 10.1016/j.labinv.2024.102123
PMID: 39147033

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Abstract

Tumor-Stroma Ratio (TSR) has been recognized as a valuable prognostic indicator in various solid tumors. This study aimed to examine the clinicopathological relevance of TSR in Merkel cell carcinoma (MCC) using artificial intelligence (AI)-based parameterization of the stromal landscape and validate TSR scores generated by our AI model versus human-assessed. 112 MCC cases with Whole Slide Images (WSIs) were collected from four different institutions. WSIs were first partitioned into 128x128-pixel “mini-patches” then classified by a novel framework, termed Pre-TumOr And STroma (Pre-TOAST) and TOAST, whose output equaled the probability of the mini-patch representing tumor cells rather than stroma. Hierarchical random samplings of 50 mini-patches per region were performed throughout 50 regions per slide. TSR and Tumor-Stromal Landscape (TSL) parameters were estimated by the maximum-likelihood algorithm. Receiver Operating Characteristic (ROC) curves showed the areas under the curve (AUCs) of Pre-TOAST in discriminating classed of interest (COI) including tumor cells, collagenous stroma, and lymphocytes from non-classes of interest (non-COI) including hemorrhage, space, and necrosis were 1.00. AUCs of TOAST in differentiating tumor cells from related stroma were 0.93. MCC stroma was categorized into TSR-high (TSR≥50%) and TSR-low (TSR<50%) using both AI- and human pathology-based methods. AI-based TSR-high subgroup exhibited notably shorter Metastasis-Free Survival (MFS) with a statistical significance of p=0.029. Interestingly, pathologist-determined TSR subgroups lacked statistical significance in Recurrence-Free Survival (RFS), MFS, and Overall Survival (OS) (p>0.05). Density-based spatial clustering of applications with noise (DBSCAN) analysis identified two distinct Tumor-Stroma Landscape (TSL) clusters: TSL1 and TSL2. TSL2 showed significantly shorter RFS (p=0.045) and markedly reduced MFS (p<0.001) compared to TSL1. TSL classification appears to offer better prognostic discrimination than traditional TSR evaluation in MCC. TSL can be reliably calculated using an AI-based classification framework and predict various prognostic features of MCC.
UV TOAST OS CRS ROC MLE AI DL HRS DBSCAN MCPyV TSL MCC ROI TME AUC TSR HITL WISs MFS COI RFS

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