Quantitative mathematical objective evaluation of contrast-enhanced spectral mammogram in the assessment of response to neoadjuvant chemotherapy and prediction of residual disease in breast cancer
Authors: Moustafa Amr Farouk Ibrahim , Kamal Rasha Mohammed , Gomaa Mohammed Mohammed Mohammed , Mostafa Shaimaa , Mubarak Roaa , El-Adawy Mohamed 
Published: October 2019

Abstract

Background
The aim of the study is to initiate a new quantitative mathematical objective tool for evaluation of response to neoadjuvant chemotherapy (NAC) and prediction of residual disease in breast cancer using contrast-enhanced spectral mammography (CESM). Forty-two breast cancer patients scheduled for receiving NAC were included. All patients underwent two CESM examinations: pre and post NAC. To assess the response to neoadjuvant chemotherapy, we used a mathematical image analysis software that can calculate the difference in the intensity of enhancement between the pre and post neoadjuvant contrast images (MATLAB and Simulink) (Release 2013b). The proposed technique used the pre and post neoadjuvant contrast images as inputs. The technique consists of three main steps: (1) preprocessing, (2) extracting the region of interest (ROI), and (3) assessment of the response to chemotherapy by measuring the percentage of change in the intensity of enhancement of malignant lesions in the pre and post neoadjuvant CESM studies using a quantitative mathematical technique. This technique depends on the analysis of number of pixels included within the ROI. We compared this technique with the currently used method of evaluation: RECIST 1.1 (response evaluation criteria in solid tumors 1.1) and using another combined response evaluation approach using both RECIST 1.1 in addition to a subjective visual evaluation. Results were then correlated with the postoperative pathology evaluation using Miller–Payne grades. For statistical evaluation, patients were classified into responders and non-responders in all evaluation methods.

Results
According to the Miller–Payne criteria, 39/42 (92.9%) of the participants were responders (Miller–Payne grades III, IV, and IV) and 3/42 (7.1%) were non-responders (Miller–Payne grades I and II). Using the proposed technique, 39/39 (100%) were responders in comparison to 38/39 patients (97.4%) using the combined criteria and 34/39 (87.2%) using the RECIST 1.1 evaluation. The calculated correlation coefficient of the proposed quantitative objective mathematical technique, RECIST 1.1 criteria, and the combined method was 0.89, 0.59, and 0.69 respectively. With classification of patients into responder and non-responders, the objective mathematical evaluation showed higher sensitivity, positive and negative predictive values, and overall accuracy (100%, 97.5%, 100%, and 85.7% respectively) compared to RECIST 1.1 evaluation (87.2%, 97.1%, 28.6%, and 54.8% respectively) and the combined response method (97.4%, 97.4%, 66.7%, and 85.7% respectively).

Conclusion
Quantitative mathematical objective evaluation using CESM images allows objective quantitative and accurate evaluation of the response of breast cancer to chemotherapy and is recommended as an alternative to the subjective techniques as a part of the pre-operative workup.