Computational reactive-diffusive modeling for stratification and prognosis determination of patients with breast cancer receiving Olaparib.

Autor: Schettini F; Medical Oncology Department, Hospital Clinic of Barcelona, C. Villaroel 170, 08036, Barcelona, Spain. schettini@recerca.clinic.cat.; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. schettini@recerca.clinic.cat.; Faculty of Medicine, University of Barcelona, Barcelona, Spain. schettini@recerca.clinic.cat., De Bonis MV; Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Piacenza, Italy., Strina C; Department of Medicine, Surgery and Health Sciences, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy., Milani M; Department of Medicine, Surgery and Health Sciences, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy., Ziglioli N; Department of Medicine, Surgery and Health Sciences, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy., Aguggini S; Department of Medicine, Surgery and Health Sciences, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy., Ciliberto I; Department of Medicine, Surgery and Health Sciences, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy., Azzini C; Department of Medicine, Surgery and Health Sciences, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy., Barbieri G; Department of Medicine, Surgery and Health Sciences, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy., Cervoni V; Department of Medicine, Surgery and Health Sciences, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy., Cappelletti MR; Department of Medicine, Surgery and Health Sciences, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy., Ferrero G; UO Anatomia Patologica ASST di Cremona, Cremona, Italy., Ungari M; UO Anatomia Patologica ASST di Cremona, Cremona, Italy., Locci M; Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy., Paris I; Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy., Scambia G; Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.; Università Cattolica del Sacro Cuore, Rome, Italy., Ruocco G; Modeling and Prototyping Laboratory, College of Engineering, University of Basilicata, Potenza, Italy., Generali D; Department of Medicine, Surgery and Health Sciences, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy. dgenerali@units.it.; Multidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, Cremona, Italy. dgenerali@units.it.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Jul 24; Vol. 13 (1), pp. 11951. Date of Electronic Publication: 2023 Jul 24.
DOI: 10.1038/s41598-023-38760-z
Abstrakt: Mathematical models based on partial differential equations (PDEs) can be exploited to handle clinical data with space/time dimensions, e.g. tumor growth challenged by neoadjuvant therapy. A model based on simplified assessment of tumor malignancy and pharmacodynamics efficiency was exercised to discover new metrics of patient prognosis in the OLTRE trial. We tested in a 17-patients cohort affected by early-stage triple negative breast cancer (TNBC) treated with 3 weeks of olaparib, the capability of a PDEs-based reactive-diffusive model of tumor growth to efficiently predict the response to olaparib in terms of SUV max detected at 18 FDG-PET/CT scan, by using specific terms to characterize tumor diffusion and proliferation. Computations were performed with COMSOL Multiphysics. Driving parameters governing the mathematical model were selected with Pearson's correlations. Discrepancies between actual and computed SUV max values were assessed with Student's t test and Wilcoxon rank sum test. The correlation between post-olaparib true and computed SUV max was assessed with Pearson's r and Spearman's rho. After defining the proper mathematical assumptions, the nominal drug efficiency (ε PD ) and tumor malignancy (r c ) were computationally evaluated. The former parameter reflected the activity of olaparib on the tumor, while the latter represented the growth rate of metabolic activity as detected by SUV max . ε PD was found to be directly dependent on basal tumor-infiltrating lymphocytes (TILs) and Ki67% and was detectable through proper linear regression functions according to TILs values, while r c was represented by the baseline Ki67-to-TILs ratio. Predicted post-olaparib SUV* max did not significantly differ from original post-olaparib SUV max in the overall, gBRCA-mutant and gBRCA-wild-type subpopulations (p > 0.05 in all cases), showing strong positive correlation (r = 0.9 and rho = 0.9, p < 0.0001 both). A model of simplified tumor dynamics was exercised to effectively produce an upfront prediction of efficacy of 3-week neoadjuvant olaparib in terms of SUV max . Prospective evaluation in independent cohorts and correlation of these outcomes with more recognized efficacy endpoints is now warranted for model confirmation and tailoring of escalated/de-escalated therapeutic strategies for early-TNBC patients.
(© 2023. The Author(s).)
Databáze: MEDLINE
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