Abstract

Simple SummaryB-mode US is a widely available, inexpensive, and non-invasive technique. This method is used in monitoring the neoadjuvant chemotherapy (NAC) in breast cancer (BC). In the presented study we combined the result from B-mode ultrasound examination with quantitative information about the characteristics and structure of the tissue in predicting the response to neoadjuvant chemotherapy in BC patients. We used echogenicity (ΔEcho) as B-mode features and the Kullback-Leibler divergence (ΔKLD) method as a quantitative parameter to provide information on changes in image echogenicity, to determine differences between the distributions of the ultrasound echo amplitude from tumor during NAC. The ΔKLD parameter alone is an accurate predictor of response to treatment after the second course of therapy (cut-off ≥70%, AUC = 0.85). Combining both parameters (ΔKLD and ΔEcho) led to an increase in sensitivity without significant deterioration of other statistical parameters and allowed to accurately predict non-responding tumors.The aim of the study was to improve monitoring the treatment response in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The IRB approved this prospective study. Ultrasound examinations were performed prior to treatment and 7 days after four consecutive NAC cycles. Residual malignant cell (RMC) measurement at surgery was the standard of reference. Alteration in B-mode ultrasound (tumor echogenicity and volume) and the Kullback-Leibler divergence (kld), as a quantitative measure of amplitude difference, were used. Correlations of these parameters with RMC were assessed and Receiver Operating Characteristic curve (ROC) analysis was performed. Thirty-nine patients (mean age 57 y.) with 50 tumors were included. There was a significant correlation between RMC and changes in quantitative parameters (KLD) after the second, third and fourth course of NAC, and alteration in echogenicity after the third and fourth course. Multivariate analysis of the echogenicity and KLD after the third NAC course revealed a sensitivity of 91%, specificity of 92%, PPV = 77%, NPV = 97%, accuracy = 91%, and AUC of 0.92 for non-responding tumors (RMC ≥ 70%). In conclusion, monitoring the echogenicity and KLD parameters made it possible to accurately predict the treatment response from the second course of NAC.

Highlights

  • Breast cancer (BC) is a disease of significant social importance and is the most common malignant neoplasm in women in Poland and worldwide

  • We focused on the characterization of the tumor echogenicity, which is related to its structure and cellularity, as is the ADC in the magnetic resonance imaging (MRI) image [15,16]

  • In the B-mode assessment, we showed that the change in tumor volume following subsequent courses of neoadjuvant chemotherapy (NAC) is not an accurate parameter when analyzed independently; in combination with the change in echogenicity, it improved the area under the ROC curve (AUC)

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Summary

Introduction

Breast cancer (BC) is a disease of significant social importance and is the most common malignant neoplasm in women in Poland and worldwide. In Poland in 2018, 18,869 BC cases were diagnosed in women and 154 in men [1]. Neoadjuvant chemotherapy (NAC), introduced in 1970, was initially used in locally advanced breast cancer (LABC). NAC is increasingly recommended in the early stages of BC, in the following subtypes: triplenegative cancer (TNBC) and with the presence of HER2 + receptors [2]. The goal of preoperative treatment is to achieve pathological complete response (pCR), which is a surrogate for overall survival (OS), event free survival (EFS), and long-term survival in TNBC and HER2 + subtypes [3]

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