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Perfusion contrast-enhanced ultrasound to predict early lymph-node metastasis in breast cancer

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Japanese Journal of Radiology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate whether quantitative analysis of perfusion contrast-enhanced ultrasound (CE-US) could predict early lymph-node (LN) metastasis in clinically node-negative breast cancer.

Materials and methods

In this prospective study, 64 breast cancer patients were selected for perfusion CE-US imaging. Regions of interest were placed where the strongest and weakest signal increases were found to obtain peak intensities (PIs; PImax and PImin, respectively) for time–intensity curve analyzes. The PI difference and PI ratio were calculated as follows: PI difference = PImax−PImin; PI ratio = PImax/PImin.

Results

Forty-seven cases were histologically diagnosed as negative for LN metastasis and 17 were positive. There was a significant difference in PImin and the PI ratio between the LN-negative and -positive metastasis groups (p = 0.0053 and 0.0082, respectively). Receiver-operating curve analysis revealed that the area under the curve of PImin and the PI ratio were 0.73 and 0.72, respectively. The most effective threshold for the PI ratio was 1.52, and the sensitivity, specificity, positive predictive value, and negative predictive value were 59% (10/17), 87% (41/47), 63% (10/16), and 85% (41/48), respectively.

Conclusions

Parameters from the quantitative analysis of perfusion CE-US imaging showed significant differences between the LN-negative and -positive metastasis groups in clinically node-negative breast cancer.

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Abbreviations

CE-US:

Contrast-enhanced ultrasound

LN:

Lymph node

PIs:

Peak intensities

SLNB:

Sentinel LN biopsy

TIC:

Time–intensity curve

MVD:

Microvessel density

AUC:

Area under the curve

ROI:

Regions of interest

ICC:

Interclass correlation coefficient

ROC:

Receiver-operating characteristic

References

  1. Nemoto T, Vana J, Bedwani RN, Baker HW, McGregor FH, Murphy GP. Management and survival of female breast cancer: results of a national survey by the American College of Surgeons. Cancer. 1980;45(12):2917–24.

    Article  PubMed  CAS  Google Scholar 

  2. Banerjee M, George J, Song EY, et al. Tree-based model for breast cancer prognostication. J Clin Oncol. 2004;22:2567–75.

    Article  PubMed  Google Scholar 

  3. Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer. Oncologist. 2004;9:606–1.

    Article  PubMed  Google Scholar 

  4. Swenson KK. Comparison of side effects between sentinel lymph node and axillary lymph node dissection for breast cancer. Ann Surg Oncol. 2002;9:745–53.

    Article  PubMed  Google Scholar 

  5. Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24:2206–23.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Giuliano AE. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305:569.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Esen G, Gurses B, Yilmaz MH, et al. Gray scale and power Doppler US in the preoperative evaluation of axillary metastases in breast cancer patients with no palpable lymph nodes. Eur Radiol. 2005;15:1215–23.

    Article  PubMed  Google Scholar 

  8. Abe H, Schmidt RA, Kulkarni K, et al. Axillary lymph nodes suspicious for breast cancer metastasis: sampling with us-guided 14-gauge core-needle biopsy—clinical experience in 100 patients 1. Radiology. 2009;250:41–9.

    Article  PubMed  Google Scholar 

  9. Bedi DG, Krishnamurthy R, Krishnamurthy S, et al. Cortical morphologic features of axillary lymph nodes as a predictor of metastasis in breast cancer. in vitro sonographic study. Am J Roentgenol. 2008;191:646–52.

    Article  Google Scholar 

  10. Abe H, Schmidt RA, Sennett CA, et al. US-guided core needle biopsy of axillary lymph nodes in patients with breast cancer: why and how to do it. Radiographics. 2007;27:S91–S99.

    Article  PubMed  Google Scholar 

  11. Scaranelo AM, Eiada R, Jacks LM, et al. Accuracy of unenhanced MR imaging in the detection of axillary lymph node metastasis: study of reproducibility and reliability. Radiology. 2012;262:425–34.

    Article  PubMed  Google Scholar 

  12. Shien T, Akashi-Tanaka S, Yoshida M, et al. Evaluation of axillary status in patients with breast cancer using thin-section CT. Int J Clin Oncol. 2008;13:314–9.

    Article  PubMed  Google Scholar 

  13. Loveless ME, Li X, Huamani J, et al. A method for assessing the microvasculature in a murine tumor model using contrast-enhanced ultrasonography. J Ultrasound Med. 2008;27:1699–709.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Szabó BK, Saracco A, Tánczos E, et al. Correlation of contrast-enhanced ultrasound kinetics with prognostic factors in invasive breast cancer. Eur Radiol. 2013;23:3228–36.

    Article  PubMed  Google Scholar 

  15. Li L, Mori S, Sakamoto M, et al. Mouse model of lymph node metastasis via afferent lymphatic vessels for development of imaging modalities. PLoS One. 2013;8:e55797.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Li L, Mori S, Kodama M, et al. Enhanced sonographic imaging to diagnose lymph node metastasis: importance of blood vessel volume and density. Cancer Res. 2013;73:2082–9.

    Article  PubMed  CAS  Google Scholar 

  17. Rubaltelli L, Beltrame V, Tregnaghi A, et al. Contrast-enhanced ultrasound for characterizing lymph nodes with focal cortical thickening in patients with cutaneous melanoma. Am J Roentgenol. 2011;196:W8–W12.

    Article  Google Scholar 

  18. Rubaltelli L, Corradin S, Dorigo A, et al. Automated quantitative evaluation of lymph node perfusion on contrast-enhanced sonography. Am J Roentgenol. 2007;188:977–83.

    Article  Google Scholar 

  19. Wan CF, Du J, Fang H, et al. Enhancement patterns and parameters of breast cancers at contrast-enhanced US: correlation with prognostic factors. Radiology. 2012;262:450–9.

    Article  PubMed  Google Scholar 

  20. Pitre-Champagnat S, Leguerney I, Bosq J, et al. Dynamic contrast-enhanced ultrasound parametric maps to evaluate intratumoral vascularization. Investig Radiol. 2015;50:212–7.

    Article  Google Scholar 

  21. Du J, Li F-H, Fang H, et al. Correlation of real-time gray scale contrast-enhanced ultrasonography with microvessel density and vascular endothelial growth factor expression for assessment of angiogenesis in breast lesions. J Ultrasound Med. 2008;27:821–3.

    Article  PubMed  Google Scholar 

  22. Mori N, Mugikura S, Takahashi S, et al. Quantitative analysis of contrast-enhanced ultrasound imaging in invasive breast cancer: a novel technique to obtain histopathologic information of microvessel density. Ultrasound Med Biol. 2017;43:607–14.

    Article  PubMed  Google Scholar 

  23. Ecanow JS, Abe H, Newstead GM, et al. Axillary staging of breast cancer: what the radiologist should know. Radiographics. 2013;33:1589–612.

    Article  PubMed  Google Scholar 

  24. Murphy CD, Jones JL, Javid SH, et al. Do sentinel node micrometastases predict recurrence risk in ductal carcinoma in situ and ductal carcinoma in situ with microinvasion? Am J Surg. 2008;196:566–8.

    Article  PubMed  Google Scholar 

  25. American College of Radiology. Breast imaging reporting and data system (BI-RADS). 5th ed. Reston: Reston American College of Radiology; 2013.

    Google Scholar 

  26. Schneider CA, Rasband WS, Eliceiri KW, et al. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671–5.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159.

    Article  PubMed  CAS  Google Scholar 

  28. Ignee A, Jedrejczyk M, Schuessler G, et al. Quantitative contrast enhanced ultrasound of the liver for time intensity curves—reliability and potential sources of errors. Eur J Radiol. 2010;73:153–8.

    Article  PubMed  Google Scholar 

  29. Gadre A, Briner W, O’Leary M. A scanning electron microscope study of the human cervical lymph node. Acta Otolaryngol (Stockh.). 1994;114:87–90.

    Article  CAS  Google Scholar 

  30. Herman PG, Kim C-S, de Sousa MA, et al. Microcirculation of the lymph node with metastases. Am J Pathol. 1976;85:333.

    PubMed  CAS  PubMed Central  Google Scholar 

  31. Ohta T, Nishioka M, Nakata N, et al. Five cases of axillary lymph node metastatic breast cancer on contrast-enhanced sonography. J Ultrasound Med. 2015;34:1131–7.

    Article  PubMed  Google Scholar 

  32. Goldberg BB, Merton DA, Liu J-B, et al. Contrast-enhanced sonographic imaging of lymphatic channels and sentinel lymph nodes. J Ultrasound Med. 2005;24:953–65.

    Article  PubMed  Google Scholar 

  33. Omoto K, Matsunaga H, Take N, et al. Sentinel node detection method using contrast-enhanced ultrasonography with sonazoid in breast cancer: preliminary clinical study. Ultrasound Med Biol. 2009;35:1249–56.

    Article  PubMed  Google Scholar 

  34. Cox K, Taylor-Phillips S, Sharma N, et al. Enhanced pre-operative axillary staging using intradermal microbubbles and contrast-enhanced ultrasound to detect and biopsy sentinel lymph nodes in breast cancer: a potential replacement for axillary surgery. Br J Radiol. 2018;91(1082):20170626.

    PubMed  PubMed Central  Google Scholar 

  35. Zhao J, Zhang J, Zhu Q-L, et al. The value of contrast-enhanced ultrasound for sentinel lymph node identification and characterisation in pre-operative breast cancer patients: a prospective study. Eur Radiol. 2018;28(4):1654–61.

    Article  PubMed  Google Scholar 

  36. Veronesi U, De Cicco C, Galimberti V, et al. A comparative study on the value of FDG-PET and sentinel node biopsy to identify occult axillary metastases. Ann Oncol. 2006;18:473–8.

    Article  PubMed  Google Scholar 

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Acknowledgements

This study was supported by JSPS KAKENHI 26461783 and 15K09913. The authors would like to thank Yumi Fujimoto in Tohoku University Hospital and Shomo Chou in Tohoku University for their kind support. We thank James P. Mahaffey, Ph.D., from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, Seiryo 1-1, Sendai, 980-8574, Japan

    Naoko Mori, Shunji Mugikura, Mikiko Suzuki, Li Li, Shoki Takahashi & Kei Takase

  2. Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Seiryo 1-1, Sendai, 980-8574, Japan

    Minoru Miyashita

  3. Department of Physiological Laboratory Center, Tohoku University Hospital, Seiryo 1-1, Sendai, 980-8574, Japan

    Yumiko Kudo

  4. Department of Orthopedic Surgery, Tohoku University Graduate School of Medicine, Seiryo 1-1, Sendai, 980-8574, Japan

    Yu Mori

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  1. Naoko Mori
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Correspondence to Naoko Mori.

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Conflict of interest

Naoko Mori has nothing to disclose. Shunji Mugikura has nothing to disclose. Minoru Miyashita has nothing to disclose. Yumiko Kudo has nothing to disclose. Mikiko Suzuki has nothing to disclose. Li Li has nothing to disclose. Yu Mori has nothing to disclose. Shoki Takahashi has nothing to disclose. Kei Takase has nothing to disclose.

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Mori, N., Mugikura, S., Miyashita, M. et al. Perfusion contrast-enhanced ultrasound to predict early lymph-node metastasis in breast cancer. Jpn J Radiol 37, 145–153 (2019). https://doi.org/10.1007/s11604-018-0792-6

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  • DOI: https://doi.org/10.1007/s11604-018-0792-6

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