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Monitoring of neoadjuvant chemotherapy using multiparametric, 23Na sodium MR, and multimodality (PET/CT/MRI) imaging in locally advanced breast cancer

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Abstract

We prospectively investigated using advanced magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) to identify radiological biomarkers for treatment response in patients receiving preoperative systemic therapy (PST) for locally advanced breast cancer. Patients with a stage II or III breast cancer receiving PST were selected and underwent positron emission tomography (PET), magnetic resonance imaging (MRI), and breast biopsies at baseline and after the first cycle of PST (days 7–8) during the full course of treatment. PET/CT was acquired after injection of 2-deoxy-2-[18F]-fluoro-d-glucose (18FDG, 0.22 mCi/kg) and quantified with standardized uptake value assessment (SUV). Diagnostic breast MRI and sodium (23Na) was acquired at 1.5 T. Total tissue sodium concentration (TSC), response criteria in solid tumors (RECIST), and volumes were quantified. Treatment response was determined by pathological assessment at surgery. Immunohistochemistry values of the proliferative index (Ki-67) were performed on biopsy specimens. Six of nineteen eligible women (43 ± 11 years) who received PST underwent radiological imaging of 18FDG-PET/CT and MRI for at least two cycles of treatment. Five patients had a pathological partial response (pPR) and one had pathological non-response (pNR). TSC decreased 21% in responders with increases in the non-responder (P = 0.03). Greater reduction in SUV was observed in responders (38%) compared to the non-responder (22%; P = 0.03). MRI volumes decreased after cycle 1 by 42% (responders) and 35% (non-responder; P = 0.11). Proliferation index Ki-67 declined in responders in the first cycle (median = 47%, range = 29–20%), but increased (4%) in the non-responder. Significant decreases in TSC, SUV, and Ki-67 were observed in responders with increases in TSC and Ki-67 in non-responders. Our results demonstrate the feasibility of using multi-modality proton, 23Na MRI, and PET/CT metrics as radiological biomarkers for monitoring response to PST in patients with operable breast cancer.

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Acknowledgments

We thank all the patients for participating in these studies. We are grateful for the help of Mary McAllister, MA., Lucie Bower, Dr. Donald Peck, and Dr. Hamid Soltanian-Zadeh, Henry Ford Hospital, Detroit, MI for the Eigentool image analysis software used for image processing. Part of this work was funded in part by the National Institute of Health Grants: R01CA100184, P50CA103175, Breast Specialized Program of Research Excellence P50CA88843, 5P30CA006973, U01CA070095, U01CA140204, Avon:01-2009-031, and Damon Runyon-Lilly Clinical Investigator Award CI-3 from the Damon Runyon Cancer Research Foundation.

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Authors and Affiliations

  1. The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Michael A. Jacobs, Ronald Ouwerkerk, David A. Bluemke & Richard Wahl

  2. Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Michael A. Jacobs, Antonio C. Wolff, Edward Gabrielson, Hind Warzecha, Stacie Jeter, Richard Wahl & Vered Stearns

  3. Department of Radiology and Oncology, The Johns Hopkins University School of Medicine, Traylor Blg, Rm 217, 712 Rutland Ave, Baltimore, MD, 21205, USA

    Michael A. Jacobs

  4. Cardiovascular Imaging, NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases), BLDG 10-CRC, RM 3-5340, MSC 1263, 10 Center Drive, Bethesda, MD, 20892, USA

    Ronald Ouwerkerk

  5. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Edward Gabrielson & Hind Warzecha

  6. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Antonio C. Wolff, Stacie Jeter & Vered Stearns

  7. Radiology and Imaging Sciences, National Institutes of Health Clinical Center, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD, 20892, USA

    David A. Bluemke

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  1. Michael A. Jacobs
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Correspondence to Michael A. Jacobs.

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Jacobs, M.A., Ouwerkerk, R., Wolff, A.C. et al. Monitoring of neoadjuvant chemotherapy using multiparametric, 23Na sodium MR, and multimodality (PET/CT/MRI) imaging in locally advanced breast cancer. Breast Cancer Res Treat 128, 119–126 (2011). https://doi.org/10.1007/s10549-011-1442-1

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