Spatio-temporal modeling of the tumor microenvironment for prediction of patient-specific response to chemotherapy


Tumor heterogeneity, understood as the intrinsic (e.g., mutations, dysregulation, metabolic reprogramming) and extrinsic (e.g., nutrient/drug perfusion, interactions with surrounding tissues and the tumor microenvironment (TME)) to the cells that constitute the tumor, drives the variability of response to neoadjuvant chemotherapy. SimBioSys has developed TumorScope, a platform capable of capturing the chemical and biophysical interactions within the tumor and with the surrounding tissue by integrating these factors into a virtual tumor model.

TumorScope makes individualized predictions of the response of each patient’s tumor to NACT. It utilizes three-dimensional biophysical simulations that model the dynamic tumor microenvironment (TME). The platform allows modelling of nutrient transport and drug behavior through perfusion and predicts when and where different regions of the tumor grow and die, and how that translates to overall response to treatment. TumorScope also incorporates multi-omics data, imaging data, pathology, and patient characteristics to simulate tumor biology of individual patient tumors.

We have validated our approach in breast cancer by comparing TumorScope simulations against actual tumor response to neoadjuvant chemotherapy in over 400 patients. Simulations were initialized using each patient’s pretreatment MRI and pathology data and run from the beginning of therapy to the specified surgical date. The simulated tumor volumetric percent response (calculated as the ratio of change in tumor volume to initial volume) at the time of surgery was then compared with actual tumor volumetric percent response extracted from presurgical MRIs. Moreover, using TumorScope as a decision support system, we predicted patient response to multiple chemotherapies. For patients with event free survival data available we performed a Cox proportional hazard analysis.

Using SimBioSys TumorScope we predicted a pre-surgical tumor volumetric response with a median error of 0.03% and median absolute deviation of 8.2%. For patients with available EFS data, we found a significant difference associated with having a final simulated volume greater than 0.01 cc.

The SimBioSys TumorScope accurately predicts patient specific responses to NACT using only standard-of-care pre-treatment diagnostic data. These predictions can support decision making and enable the selection of less-toxic regimens for patients in which a robust response is predicted, and more aggressive treatments or alternative treatment strategies when response is likely to be poor.

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