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Diffuse optical tomography changes correlate with residual cancer burden after neoadjuvant chemotherapy in breast cancer patients

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Abstract

Purpose

Breast cancer (BC) patients who achieve a favorable residual cancer burden (RCB) after neoadjuvant chemotherapy (NACT) have an improved recurrence-free survival. Those who have an unfavorable RCB will have gone through months of ineffective chemotherapy. No ideal method exists to predict a favorable RCB early during NACT. Diffuse optical tomography (DOT) is a novel imaging modality that uses near-infrared light to assess hemoglobin concentrations within breast tumors. We hypothesized that the 2-week percent change in DOT-measured hemoglobin concentrations would associate with RCB.

Methods

We conducted an observational study of 40 women with stage II–IIIC BC who received standard NACT. DOT imaging was performed at baseline and 2 weeks after treatment initiation. We evaluated the associations between the RCB index (continuous measure), class (categorical 0, I, II, III), and response (RCB class 0/I = favorable, RCB class II/III = unfavorable) with changes in DOT-measured hemoglobin concentrations.

Results

The RCB index correlated significantly with the 2-week percent change in oxyhemoglobin [HbO2] (r = 0.5, p = 0.003), deoxyhemoglobin [Hb] (r = 0.37, p = 0.03), and total hemoglobin concentrations [HbT] (r = 0.5, p = 0.003). The RCB class and response significantly associated with the 2-week percent change in [HbO2] (p ≤ 0.01) and [HbT] (p ≤ 0.02). [HbT] 2-week percent change had sensitivity, specificity, positive, and negative predictive values for a favorable RCB response of 86.7, 68.4, 68.4, and 86.7%, respectively.

Conclusion

The 2-week percent change in DOT-measured hemoglobin concentrations was associated with the RCB index, class, and response. DOT may help guide NACT for women with BC.

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Abbreviations

A:

Doxorubicin

BC:

Breast cancer

BMI:

Body mass index

C:

Cyclophosphamide

CT:

Computerized tomography

DOT:

Diffuse optical tomography

[Hb]:

Deoxyhemoglobin concentration

[HbO2]:

Oxyhemoglobin concentration

[HbT]:

Total hemoglobin concentration

HER2:

Human epidermal growth factor receptor 2

HR:

Hormone receptor

MRI:

Magnetic resonance imaging

NACT:

Neoadjuvant chemotherapy

nm:

Nanometer

NPV:

Negative predictive value

pCR:

Pathologic complete response

PET:

Position emission tomography

PPV:

Positive predictive value

RCB:

Residual cancer burden

ROI:

Region of interest

SD:

Standard deviation

T:

Paclitaxel

US:

Ultrasound

WF:

Water fraction

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Funding

This study was funded by Grants from the Komen Foundation for the Cure Post Doctoral Fellowship Research Grant to EAL, National Science Foundation Integrative Graduate Education and Research Traineeship program on Optical Techniques for Actuation, Sensing, and Imaging of Biological Systems at Columbia University to JEG, and the Natural Sciences and Engineering Research Council of Canada (NSERC) to MF. This publication was also supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant No. KL2 TR000081 to KK. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This research was also supported in part by the Witten Family Fund.

Author information

Author notes

    Authors and Affiliations

    1. Division of Hematology/Oncology, Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, 9th Floor, New York, NY, 10032, USA

      Emerson A. Lim

    2. Department of Biomedical Engineering, Columbia University, 500 West 120th Street, 341 Mudd Bldg, New York, NY, 10027, USA

      Jacqueline E. Gunther

    3. Department of Radiology, Columbia University, 650 West 168th Street, Black Building, Rm 1727, New York, NY, 10032, USA

      Hyun K. Kim

    4. Philips Research Americas, 2 Canal Park, 3rd Floor, Cambridge, MA, 02141, USA

      Molly Flexman

    5. Department of Pathology and Cell Biology, Columbia University Medical Center, 630 West 168th Street, VC 14-215, New York, NY, 10032, USA

      Hanina Hibshoosh

    6. Division of Hematology/Oncology, Department of Medicine, Department of Epidemiology, Columbia University Medical Center, 161 Fort Washington Avenue, 10th Floor, New York, NY, 10032, USA

      Katherine Crew, Kevin Kalinsky & Dawn L. Hershman

    7. Department of Surgery, Columbia University Medical Center, 161 Fort Washington Avenue, 10th Floor, New York, NY, 10032, USA

      Bret Taback

    8. Herbert Irving Comprehensive Cancer Center, 161 Fort Washington Avenue, Mezzanine, New York, NY, 10032, USA

      Jessica Campbell

    9. Department of Biomedical Engineering, Columbia University, Engineering Terrace 351, Mail Code 8904, New York, NY, 10027, USA

      Andreas Hielscher

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    1. Emerson A. Lim
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    Corresponding author

    Correspondence to Emerson A. Lim.

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    Conflict of interest

    All authors declare that they have no conflict of interest.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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    :Informed consent was obtained from all individual participants included in the study.

    Additional information

    Emerson A. Lim, Jacqueline E. Gunther, Andreas Hielscher and Dawn L. Hershman have contributed equally to this work.

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    Lim, E.A., Gunther, J.E., Kim, H.K. et al. Diffuse optical tomography changes correlate with residual cancer burden after neoadjuvant chemotherapy in breast cancer patients. Breast Cancer Res Treat 162, 533–540 (2017). https://doi.org/10.1007/s10549-017-4150-7

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