Monitoring breast cancer response to neoadjuvant chemotherapy with ultrasound signal statistics and integrated backscatter

Abstract

BackgroundNeoadjuvant 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.MethodsThe 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.ResultsStatistically 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.ConclusionsQuantitative 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.

A Novel Model Incorporating Tumor Stiffness, Blood Flow Characteristics, and Ki-67 Expression to Predict Responses After Neoadjuvant Chemotherapy in Breast Cancer

“…The results showed that tumor stiffness and BS at t2 had the best performance, which is consistent with the optimal time point reported in previous studies with MRI and PET (34,35). This finding may be attributed to the following reason: NACT initially alters the biomechanical properties and microvascular perfusion in the tumor, whereas morphological changes that can be observed on imaging occur later (33,36). Several studies also showed that tumor size variation is not a sensitive index to distinguish responders from non-responders (37).…”

<p>Evaluation of the Efficacy of Neoadjuvant Chemotherapy for Breast Cancer</p>

“…30 The ultrasonic signal statistics and integrated backscatter can monitor the response to NAC effectively. 31 Ultrasound can measure the axillary lymph node response to NAC accurately also 32 .However, ultrasound is operator-dependent, and breast cancer typically becomes less cellular after NAC, even if no marked decrease in size is observed. 33 Sometimes ultrasound imaging of residual tumor burden is insufficient to predict the actual response to neoadjuvant chemotherapy with adequate accuracy.…”

Multiparametric ultrasound examination for response assessment in breast cancer patients undergoing neoadjuvant therapy

“…The IBC was determined from the backscattering coefficient in the frequency range 5–12 MHz, corresponding to the transducer band. The method was described in detail previously 13 . A reference phantom (1126 B, Dansk Phantom Service) was used in the measurements and the RF data was collected from a 3 × 3 mm window, which was a sufficient size to provide reliable values of scattering parameters.…”

“…Another promising direction for the early evaluation of tumour responses to NAC therapy is the use of quantitative ultrasound (QUS). Some initial studies were able to identify changes on QUS as early as one week after NAC, using parameters such as integrated backscattering coefficient (IBC) and average acoustic concentration 12 , 13 .…”