Ultra sound measures chemo response in locally advance bc

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Quantitative Ultrasound Evaluation of Tumour Cell Death Response in Locally Advanced Breast Cancer Patients Receiving Chemotherapy

Clin Cancer Res. 2013 Feb 22;[Epub Ahead of Print] , A Sadeghi-Naini, N Papanicolau, O Falou, et al

Abstract

In a study in 24 patients with locally advanced breast cancer, quantitative conventional-frequency ultrasound was used to measure response to chemotherapy and could identify responders and nonresponders.

TAKE-HOME MESSAGE

In a study in 24 patients with locally advanced breast cancer, quantitative conventional-frequency ultrasound was used to measure response to chemotherapy and could identify responders and nonresponders.

SUMMARY

OncologySTAT Editorial Team

Imaging methods used to assess the response to chemotherapy in patients with locally advanced breast cancer include magnetic resonance imaging (MRI), x-ray mammography, and ultrasound. Traditionally, these methods assess response by measuring changes in the volume of the tumor. However, tumors may respond to treatment without measurable changes in tumor volume. High-frequency ultrasound can detect changes in tissue structure due to apoptotic cell death, but it has limited tissue penetration depth. In contrast, conventional-frequency ultrasound has decreased resolution but greater tissue penetration. This study evaluated the use of conventional-frequency (~7 MHz) ultrasound to monitor the effects of neoadjuvant chemotherapy in patients with locally advanced breast cancer.

Patients underwent ultrasound examination immediately prior to the start of chemotherapy; at 1, 4, and 8 weeks of treatment; and at 1 week prior to modified radical mastectomy, typically 4 to 6 weeks after chemotherapy was completed. Ultrasounds were conducted as a single continuous sweep over the tumor volume to maintain consistency across visits. Individual tumor regions were also scanned at ~1 cm increments. All patients underwent core needle biopsy and MRI prior to therapy, and were evaluated again by MRI following treatment, immediately prior to surgery, to estimate residual tumor size. At each patient visit, physical examination was conducted and tumor size was estimated. Patients were classified as responders if their tumor decreased in size by ≥ 30%, or if the tumor cellularity (overall volume of viable tumor cells) was very low.

A total of 24 patients enrolled; 11 patients had tumors that were estrogen- and/or progesterone-receptor positive, and 9 had tumors that were Her-2-Neu positive (HER2+). Most patients received anthracycline and taxane-based chemotherapy. A total of 16 of 24 patients had a complete pathologic response or substantial reductions in tumor size and decreases in tumor cellularity, and were classified as responders. In addition, 2 patients were classified as responders based on very low residual tumor cellularity even though the reduction in tumor size was < 30%. The remaining 6 patients were nonresponders; they had progressive disease, or their tumor size changed only slightly, or tumor cellularity remained very high.

Several ultrasound measures showed substantial changes in responding patients, with little or no change in nonresponding patients. Ultrasound spectral backscatter power increased within the tumor region in responding patients. Responding patients also showed considerable changes in parametric images, whereas no such change was observed in nonresponding patients. Mid-band fit (MBF) at the first, fourth, and eighth weeks of treatment and preoperatively increased in responding patients (by 3.5, 9.1, 8.6, and 1.2 dBR), but showed less change in nonresponders (0.3, 1.9, 3.3, and –1.2 dBR, respectively). These differences were statistically significant at week 4 (P = .005) and week 8 (P = .046). For the 0-MHz intercept parameter, responders had increases of 4.0, 8.9, 10.8, and 2.4 dBr, at weeks 1, 4, 8, and preoperative, respectively, compared with nonresponders (–1.3, 1.6, 1.4, and 0.6, respectively), with statistically significant differences at weeks 4 (P = .041) and 8 (P = .046). The generalized gamma α parameters also showed a statistically greater increase in responders compared with nonresponders at week 8 (P = .046). Linear discriminant analysis of MBF and 0-MHz intercept had sensitivities (% of nonresponders identified correctly) and specificities (% of responders identified correctly) of 100.0% and 83.3% at week 4 and 100% and 66.7% at week 8. Scatter plots showed significant separation of responders and nonresponders at week 4 (P = .02).

Quantitative conventional-frequency ultrasound may be used to evaluate patient responses to chemotherapy in patients with locally advanced breast cancer.

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