Date Published: March 14, 2019
Publisher: Public Library of Science
Author(s): Hanna Piotrzkowska-Wróblewska, Katarzyna Dobruch-Sobczak, Ziemowit Klimonda, Piotr Karwat, Katarzyna Roszkowska-Purska, Magdalena Gumowska, Jerzy Litniewski, Giandomenico Roviello.
Neoadjuvant chemotherapy (NAC) is used in patients with breast cancer to reduce tumor focus, metastatic risk, and patient mortality. Monitoring NAC effects is necessary to capture resistant patients and stop or change treatment. The existing methods for evaluating NAC results have some limitations. The aim of this study was to assess the tumor response at an early stage, after the first doses of the NAC, based on the variability of the backscattered ultrasound energy, and backscatter statistics. The backscatter statistics has not previously been used to monitor NAC effects.
The B-mode ultrasound images and raw radio frequency data from breast tumors were obtained using an ultrasound scanner before chemotherapy and 1 week after each NAC cycle. The study included twenty-four malignant breast cancers diagnosed in sixteen patients and qualified for neoadjuvant treatment before surgery. The shape parameter of the homodyned K distribution and integrated backscatter, along with the tumor size in the longest dimension, were determined based on ultrasound data and used as markers for NAC response. Cancer tumors were assigned to responding and non-responding groups, according to histopathological evaluation, which was a reference in assessing the utility of markers. Statistical analysis was performed to rate the ability of markers to predict the final NAC response based on data obtained after subsequent therapeutic doses.
Statistically significant differences (p<0.05) between groups were obtained after 2, 3, 4, and 5 doses of NAC for quantitative ultrasound markers and after 5 doses for the assessment based on maximum tumor dimension. Statistical analysis showed that, after the second and third NAC courses the classification based on integrated backscatter marker was characterized by an AUC of 0.69 and 0.82, respectively. The introduction of the second quantitative marker describing the statistical properties of scattering increased the corresponding AUC values to 0.82 and 0.91. Quantitative ultrasound information can characterize the tumor's pathological response better and at an earlier stage of therapy than the assessment of the reduction of its dimensions. The introduction of statistical parameters of ultrasonic backscatter to monitor the effects of chemotherapy can increase the effectiveness of monitoring and contribute to a better personalization of NAC therapy.
Neoadjuvant chemotherapy (NAC) was initially used in locally advanced breast cancer (LABC) and in the case of inflammatory cancer . Currently, it is also recommended in patients with triple-negative cancer (TNBC), with the presence of HER-2 + receptors (Luminal B HER2-positive and HER-positive non-luminal subtype), and in cases of luminal B HER2-negative tumors with low expression of hormone receptors, with high grade of malignancy (G3) in patients at an early age (≤ 35 years) in the second or third stage of cancer [2–4]. Neoadjuvant chemotherapy reduces the risk of metastases and micrometastases in distant organs. It also reduces the neoplastic focus and decreases the frequency of the recurrences and the mortality of patients.
The results obtained suggest that ENS provides useful information to monitor NAC. Thus, the statistical properties of ultrasonic backscattering were important in monitoring chemotherapy effects on an equal footing with IBSC. Our studies have shown that tumor quantitative parameters when maintained at the same level after NAC courses predict a poor response to the treatment. At the same time, the decrease in ENS and the increase in IBSC are characteristic of a positive tumor response. The presented results suggest that quantitative ultrasound information can characterize the tumor’s pathological response better and at an earlier stage of therapy than the assessment of the reduction of its dimensions based on ultrasound imaging. Statistical analysis proved that, after the second chemotherapy the final result can be effectively predicted based on linear combination of changes in the values of the ENS and IBSC. This significant result, if confirmed in a larger group of cases, suggests that the introduction of ultrasound backscatter statistics parameters to monitor the effects of chemotherapy may increase the effectiveness of monitoring and contribute to a better personalization of the NAC therapy.