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Evaluating patient-specific neoadjuvant regimens for breast cancer via a mathematical model constrained by quantitative magnetic resonance imaging data.

ABSTRACT: The ability to accurately predict response and then rigorously optimize a therapeutic regimen on a patient-specific basis, would transform oncology. Toward this end, we have developed an experimental-mathematical framework that integrates quantitative magnetic resonance imaging (MRI) data into a biophysical model to predict patient-specific treatment response of locally advanced breast cancer to neoadjuvant therapy. Diffusion-weighted and dynamic contrast-enhanced MRI data is collected prior to therapy, after 1 cycle of therapy, and at the completion of the first therapeutic regimen. The model is initialized and calibrated with the first 2 patient-specific MRI data sets to predict response at the third, which is then compared to patient outcomes (N?=?18). The model's predictions for total cellularity, total volume, and the longest axis at the completion of the regimen are significant within expected measurement precision (P< 0.05) and strongly correlated with measured response (P < 0.01). Further, we use the model to investigate, in silico, a range of (practical) alternative treatment plans to achieve the greatest possible tumor control for each individual in a subgroup of patients (N?=?13). The model identifies alternative dosing strategies predicted to achieve greater tumor control compared to the standard of care for 12 of 13 patients (P < 0.01). In summary, a predictive, mechanism-based mathematical model has demonstrated the ability to identify alternative treatment regimens that are forecasted to outperform the therapeutic regimens the patients clinically. This has important implications for clinical trial design with the opportunity to alter oncology care in the future.

SUBMITTER: Jarrett AM

PROVIDER: S-EPMC7677708 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Evaluating patient-specific neoadjuvant regimens for breast cancer via a mathematical model constrained by quantitative magnetic resonance imaging data.

Jarrett Angela M AM Hormuth David A DA Wu Chengyue C Kazerouni Anum S AS Ekrut David A DA Virostko John J Sorace Anna G AG DiCarlo Julie C JC Kowalski Jeanne J Patt Debra D Goodgame Boone B Avery Sarah S Yankeelov Thomas E TE

Neoplasia (New York, N.Y.) 20201114 12

The ability to accurately predict response and then rigorously optimize a therapeutic regimen on a patient-specific basis, would transform oncology. Toward this end, we have developed an experimental-mathematical framework that integrates quantitative magnetic resonance imaging (MRI) data into a biophysical model to predict patient-specific treatment response of locally advanced breast cancer to neoadjuvant therapy. Diffusion-weighted and dynamic contrast-enhanced MRI data is collected prior to ...[more]

PMID: 33197744

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Project description:Background: Multiparametric magnetic resonance imaging (mpMRI) has emerged as a non-invasive modality to diagnose and monitor prostate cancer. Quantitative metrics on the regions of abnormality have shown to be useful descriptors to discriminate clinically significant cancers. In this study, we evaluate the reproducibility of quantitative imaging features using repeated mpMRI on the same patients. Methods: We retrospectively obtained the deidentified records of patients, who underwent two mpMRI scans within 2 weeks of the first baseline scan. The patient records were obtained as deidentified data (including imaging), obtained through the TCIA (The Cancer Imaging Archive) repository and analyzed in our institution with an institutional review board-approved Health Insurance Portability and Accountability Act-compliant retrospective study protocol. Indicated biopsied regions were used as a marker for our study radiologists to delineate the regions of interest. We extracted 307 quantitative features in each mpMRI modality [T2-weighted MR sequence image (T2w) and apparent diffusion coefficient (ADC) with b values of 0 and 1,400 mm/s2] across the two sequential scans. Concordance correlation coefficients (CCCs) were computed on the features extracted from sequential scans. Redundant features were removed by computing the coefficient of determination (R 2) among them and replaced with a feature that had the highest dynamic range within intercorrelated groups. Results: We have assessed the reproducibility of quantitative imaging features among sequential scans and found that habitat region characterization improves repeatability in ADC maps. There were 19 T2w features and two ADC features in radiologist drawn regions (native raw image), compared to 18 T2w and 15 ADC features in habitat regions (sphere), which were reproducible (CCC ?0.65) and non-redundant (R 2 ? 0.99). We also found that z-transformation of the images prior to feature extraction reduced the number of reproducible features with no detrimental effect. Conclusion: We have shown that there are quantitative imaging features that are reproducible across sequential prostate mpMRI acquisition at a preset level of filters. We also found that a habitat approach improves feature repeatability in ADC. A validated set of reproducible image features in mpMRI will allow us to develop clinically useful disease risk stratification, enabling the possibility of using imaging as a surrogate to invasive biopsies.

Dataset Information

Evaluating patient-specific neoadjuvant regimens for breast cancer via a mathematical model constrained by quantitative magnetic resonance imaging data.

Publications

Evaluating patient-specific neoadjuvant regimens for breast cancer via a mathematical model constrained by quantitative magnetic resonance imaging data.

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