Prediction of pathological complete response to neoadjuvant chemotherapy for primary breast cancer comparing interim ultrasound, Shear Wave elastography and MRI

Andrew Evans; Patsy Whelehan; Alastair Thompson; Colin Purdie; Lee Jordan; Jane Macaskill; Shelley Waugh; Frances Fuller-Pace; Katrin Brauer; Sarah Vinnicombe

doi:10.1055/a-0797-4532

Senologie - Zeitschrift für Mammadiagnostik und -therapie, Table of Contents

Senologie - Zeitschrift für Mammadiagnostik und -therapie 2018; 15(04): 229-237
DOI: 10.1055/a-0797-4532

Original Article

Prediction of pathological complete response to neoadjuvant chemotherapy for primary breast cancer comparing interim ultrasound, Shear Wave elastography and MRI

Prädiktion der pathologischen Komplettremission nach neoadjuvanter Chemotherapie bei primärem Mammakarzinom mittels Interim Ultraschall, Shearwave-Elastografie und MRT

Andrew Evans

¹Imaging and Technology, Dundee University, Dundee, United Kingdom of Great Britain and Northern Ireland

,

Patsy Whelehan

²Breast Imaging, Ninewells Hospital, Dundee, United Kingdom of Great Britain and Northern Ireland

,

Alastair Thompson

³Breast Surgery, University of Texas MD Anderson Cancer Center, Houston, United States

,

Colin Purdie

⁴Pathology, Ninewells Hospital, Dundee, United Kingdom of Great Britain and Northern Ireland

,

Lee Jordan

⁴Pathology, Ninewells Hospital, Dundee, United Kingdom of Great Britain and Northern Ireland

,

Jane Macaskill

⁵Breast Surgery, Ninewells Hospital, Dundee, United Kingdom of Great Britain and Northern Ireland

,

Shelley Waugh

⁶Medical Physics, Ninewells Hospital, Dundee, United Kingdom of Great Britain and Northern Ireland

,

Frances Fuller-Pace

⁷Cancer, Dundee University, Dundee, United Kingdom of Great Britain and Northern Ireland

,

Katrin Brauer

²Breast Imaging, Ninewells Hospital, Dundee, United Kingdom of Great Britain and Northern Ireland

,

Sarah Vinnicombe

¹Imaging and Technology, Dundee University, Dundee, United Kingdom of Great Britain and Northern Ireland

› Author Affiliations

Abstract

Background Prediction of pathological complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NACT) may influence planned surgical approaches in the breast and axilla. The aim of this project is to assess the value of interim shear wave elastography (SWE), ultrasound (US) and magnetic resonance imaging (MRI) after 3 cycles in predicting pCR.

Methods 64 patients receiving NACT had baseline and interim US, SWE and MRI examinations. The mean lesion stiffness at SWE, US and MRI diameter was measured at both time points. We compared four parameters with pCR status: a) Interim mean stiffness ≤ or > 50 kPat; b) Percentage stiffness reduction; c) Percentage US diameter reduction and d) Interim MRI response using RECIST criteria. The Chi square test was used to assess significance.

Results Interim stiffness of ≤ or > 50 kPat gave the best prediction of pCR with pCR seen in 10 of 14 (71 %) cancers with an interim stiffness of ≤ 50 kPat, compared to 7 of 50 (14 %) of cancers with an interim stiffness of > 50 kPat, (p < 0.0001) (sensitivity 59 %, specificity 91 %, PPV 71 %, NPV 86 % and diagnostic accuracy 83 %). Percentage reduction in stiffness was the next best parameter (sensitivity 59 %, specificity 85 %, p < 0.0004) followed by reduction in MRI diameter of > 30 % (sensitivity 50 % and specificity 79 %, p = 0.03) and % reduction in US diameter (sensitivity 47 %, specificity 81 %, p = 0.03). Similar results were obtained from ROC analysis.

Conclusion SWE stiffness of breast cancers after 3 cycles of NACT and changes in stiffness from baseline are strongly associated with pCR after 6 cycles.

Zusammenfassung

Hintergrund Die Prädiktion der pathologischen Komplettremission (pCR) bei primärem Mammakarzinom nach neoadjuvanter Chemotherapie (NACT) kann die geplante chirurgische Herangehensweise in Brust und Axilla beeinflussen. Ziel dieser Arbeit ist die Beurteilung des Wertes von Interim Shearwave-Elastografie (SWE), Ultraschall (US) und Magnetresonanztomografie (MRI) nach 3 Zyklen für die Vorhersage einer pCR.

Methoden Bei 64 Patienten mit NACT wurden Anfangs- und Interim-Untersuchungen mittels US, SWE und MRT durchgeführt. Die mittlere Steifigkeit der Läsion mittels SWE-, US- und MRT-Durchmesser wurde zu beiden Zeitpunkten bestimmt. Wir verglichen vier Parameter mit dem pCR-Status: a) Interim mittlere Steifigkeit ≤ oder > 50 kPat, b) prozentuale Reduktion der Steifigkeit, c) prozentuale Reduktion des US-Durchmessers und d) Interim MRT-Antwort mittels RECIST-Kriterien. Der Chi-Square-Test wurde zur Beurteilung der Signifikanz angewandt.

Ergebnisse Die Interim-Steifigkeit von ≤ oder > 50 kPat führte zur besten Prädiktion einer pCR, mit einer pCR bei 10 von 14 (71 %) Karzinomen mit einer Interim-Steifigkeit von ≤ 50 kPa im Vergleich zu 7 von 50 (14 %) Karzinomen mit einer Interim-Steifigkeit von > 50 kPat. (p < 0,0001) (Sensitivität 59 %, Spezifität 91 %, positiver Vorhersagewert 71 %, negativer Vorhersagewert 86 % und diagnostische Treffsicherheit 83 %). Die prozentuale Reduktion der Steifigkeit war der zweitbeste Parameter (Sensitivität 59 %, Spezifität 85 %, p < 0,0004) gefolgt der Reduktion des MRI-Durchmessers um > 30 % (Sensitivität 50 % und Spezifität 79 %, p = 0,03) und einer prozentualen Reduktion des US-Durchmessers (Sensitivität 47 %, Spezifität 81 %, p = 0,03). Ähnliche Ergebnisse wurden mittels ROC-Analyse erzielt.

Schlussfolgerung Die SWE-Steifigkeit von Mammakarzinomen nach 3 NACT-Zyklen und die Veränderungen der Steifigkeit im Bezug zum Anfangswert sind eng mit einer pCR nach 6 Zyklen assoziiert.

Key words

ultrasound - shear wave elastography - breast cancer - neoadjuvant chemotherapy - MR imaging

Full Text

References

References
1 Marinovich ML, Macaskill P, Irwig L. et al. Agreement between MRI and pathologic breast tumor size after neoadjuvant chemotherapy, and comparison with alternative tests: individual patient data meta-analysis. BMC Cancer 2015; 15: 662
2 Shin HJ, Kim HH, Ahn JH. et al. Comparison of mammography, sonography, MRI and clinical examination in patients with locally advanced or inflammatory breast cancer who underwent neoadjuvant chemotherapy. Br J Radiol 2011; 84: 612-620
3 Galbán CJ, Ma B, Malyarenko D. et al. Multi-site clinical evaluation of DW-MRI as a treatment response metric for breast cancer patients undergoing neoadjuvant chemotherapy. PLoS One 2015; 10: e0122151
4 Bufi E, Belli P, Di Matteo M. et al. Effect of breast cancer phenotype on diagnostic performance of MRI in the prediction to response to neoadjuvant treatment. Eur J Radiol 2014; 83: 1631-1638
5 Parikh J, Selmi M, Charles-Edwards G. et al. Changes in primary breast cancer heterogeneity may augment midtreatment MR imaging assessment of response to neoadjuvant chemotherapy. Radiology 2014; 272: 100-112
6 Hylton NM, Blume JD, Bernreuter WK. et al. Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy--results from ACRIN 6657/I-SPY TRIAL. Radiology 2012; 263: 663-672
7 Evans A, Whelehan P, Thomson K. et al. Differentiating benign from malignant solid breast masses: value of shear wave elastography according to lesion stiff-ness combined with gray scale ultrasound according to BI-RADS classification. Br J Cancer 2012; 107: 224-229
8 Berg WA, Cosgrove DO, Dore CJ. et al. Shear-wave elastography improves the specificity of breast US: The BE1 multinational study of 939 masses. Radiology 2012; 262: 435-449
9 Evans A, Rauchhaus P, Whelehan P. et al. Does shear wave ultrasound independently predict axillary lymph node metastasis in women with invasive breast cancer?. Breast cancer research and treatment 2014; 143: 153-157
10 Evans A, Armstrong S, Whelehan P. et al. Can Shear Wave Elastography Predict Response to Neo-adjuvant Chemotherapy in Women with Invasive Breast Cancer?. BJC 2013; 109: 2798-2802
11 Lee SH, Chang JM, Han W. et al. Shear-Wave Elastography for the Detection of Residual Breast Cancer after Neoadjuvant Chemotherapy. Ann Surg Oncol 2015; 22 (Suppl. 03) S376-S384
12 Ma Y, Zhang S, Li J. et al. Comparison of strain and shear-wave ultrasonic elastography in predicting the pathological response to neoadjuvant chemotherapy in breast cancers. Eur Radiol 2016; 27: 2282-2291
13 Jing H, Cheng W, Li ZY. et al. Early Evaluation of Relative Changes in Tumor Stiffness by Shear Wave Elastography Predicts the Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer. J Ultrasound Med 2016; 35: 1619-1627 Epub 2016 Jun 14
14 Evans A, Whelehan P, Thomson K. et al. Quantitative shear wave ultrasound elastography: initial experience in solid breast masses. Breast Cancer Research 2010; 12: R104
15 Gounaris I, Provenzano E, Vallier AL. et al. Accuracy of unidimensional and volumetric ultrasound measurements in predicting good pathological response to neoadjuvant chemotherapy in breast cancer patients. Breast Cancer Research and treatment 2011; 127: 459-469
16 Cosgrove DO, Berg WA, Dore CJ. et al. Shear wave elastography for breast masses is highly reproducible. European Radiology 2012; 22: 1023-1032
17 Paluch-Shimon S, Friedman E, Berger R. et al. Neo-adjuvant doxorubicin and cyclophosphamide followed by paclitaxel in triple-negative breast cancer among BRCA1 mutation carriers and non-carriers. Breast Cancer Res Treat 2016; 157: 157-165
18 Heil J, Kümmel S, Schaefgen B. et al. Diagnosis of pathological complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy techniques. Brit J Cancer 2015 113: 1565-1570
19 Avril S, Muzic Jr RF, Plecha D. et al. 18F-FDG PET/CT for Monitoring of Treatment Response in Breast Cancer. J Nucl Med 2016; 57 (Suppl. 01) 34S-39S
20 Patten DK, Zacharioudakis KE, Chauhan H. et al. Sentinel lymph node biopsy after neo-adjuvant chemotherapy in patients with breast cancer: Are the current false negative rates acceptable?. Breast 2015; 24: 318-320
21 Evans A, Armstrong S, Whelehan P. et al. Can Shear Wave Elastography Predict Response to Neo-adjuvant Chemotherapy in Women with Invasive Breast Cancer?. BJC 2013; 109: 2798-2802