Medical sciences (Basel, Switzerland) · 2025
Virtual Biomarkers and Simplified Metrics in the Modeling of Breast Cancer Neoadjuvant Therapy: A Proof-of-Concept Case Study Based on Diagnostic Imaging.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Marino Graziella, De Bonis Maria Valeria, Mecca Marisabel, Sichetti Marzia, Cammarota Aldo, Botte Manuela, Dinardo Giuseppina, Lancellotti Maria Imma, Villonio Antonio, Prudente Antonella, Thodas Alexios, Zifarone Emanuela, Sanseverino Francesca, Modano Pasqualina, Schettini Francesco, Rocca Andrea, Generali Daniele, Ruocco Gianpaolo
Аннотация
BACKGROUND: Neoadjuvant chemotherapy (NAC) is a standard preoperative intervention for early-stage breast cancer (BC). Dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a critical tool for evaluating treatment response and pathological complete response (pCR) following NAC. Computational modeling offers a robust framework to simulate tumor growth dynamics and therapy response, leveraging patient-specific data to enhance predictive accuracy. Despite this potential, integrating imaging data with computational models for personalized treatment prediction remains underexplored. This case study presents a proof-of-concept prognostic tool that bridges oncology, radiology, and computational modeling by simulating BC behavior and predicting individualized NAC outcomes.
METHODS: CE-MRI scans, clinical assessments, and blood samples from three retrospective NAC patients were analyzed. Tumor growth was modeled using a system of partial differential equations (PDEs) within a reaction-diffusion mass transfer framework, incorporating patient-specific CE-MRI data. Tumor volumes measured pre- and post-treatment were compared with model predictions. A 20% error margin was applied to assess computational accuracy.
RESULTS: All cases were classified as true positive (TP), demonstrating the model's capacity to predict tumor volume changes within the defined threshold, achieving 100% precision and sensitivity. Absolute differences between predicted and observed tumor volumes ranged from 0.07 to 0.33 cm3. Virtual biomarkers were employed to quantify novel metrics: the biological conversion coefficient ranged from 4 × 10-7 to 6 × 10-6 s-1, while the pharmacodynamic efficiency coefficient ranged from 1 × 10-7 to 4 × 10-4 s-1, reflecting intrinsic tumor biology and treatment effects, respectively.
CONCLUSIONS: This approach demonstrates the feasibility of integrating CE-MRI and computational modeling to generate patient-specific treatment predictions. Preliminary model training on retrospective cohorts with matched BC subtypes and therapy regimens enabled accurate prediction of NAC outcomes. Future work will focus on model refinement, cohort expansion, and enhanced statistical validation to support broader clinical translation.
METHODS: CE-MRI scans, clinical assessments, and blood samples from three retrospective NAC patients were analyzed. Tumor growth was modeled using a system of partial differential equations (PDEs) within a reaction-diffusion mass transfer framework, incorporating patient-specific CE-MRI data. Tumor volumes measured pre- and post-treatment were compared with model predictions. A 20% error margin was applied to assess computational accuracy.
RESULTS: All cases were classified as true positive (TP), demonstrating the model's capacity to predict tumor volume changes within the defined threshold, achieving 100% precision and sensitivity. Absolute differences between predicted and observed tumor volumes ranged from 0.07 to 0.33 cm3. Virtual biomarkers were employed to quantify novel metrics: the biological conversion coefficient ranged from 4 × 10-7 to 6 × 10-6 s-1, while the pharmacodynamic efficiency coefficient ranged from 1 × 10-7 to 4 × 10-4 s-1, reflecting intrinsic tumor biology and treatment effects, respectively.
CONCLUSIONS: This approach demonstrates the feasibility of integrating CE-MRI and computational modeling to generate patient-specific treatment predictions. Preliminary model training on retrospective cohorts with matched BC subtypes and therapy regimens enabled accurate prediction of NAC outcomes. Future work will focus on model refinement, cohort expansion, and enhanced statistical validation to support broader clinical translation.