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Hypoxia in Melanoma: Using Optical Spectroscopy and EF5 to Assess Tumor Oxygenation Before and During Regional Chemotherapy for Melanoma

  • Regional Cancer Therapies
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

There is increasing evidence that tumor hypoxia plays a significant role in the chemoresistance of melanoma, but to our knowledge, real-time tumor oxygenation during isolated limb infusion (ILI) has not been studied. We sought to demonstrate the feasibility of measuring real-time alterations in tissue oxygenation.

Methods

Consecutive patients with histologically confirmed in-transit melanoma were enrolled onto a prospective single-arm pilot study and administered the hypoxia marker drug EF5. All patients were treated with ILI. Optical spectroscopy readings were obtained at three locations: two discrete target lesions and one normal skin control. Measurements were taken at 11 predefined time points during ILI.

Results

A total of six patients were enrolled onto this pilot study. Intratumor and normal skin optical spectroscopy readings were found to have discrete inflection points throughout the duration of therapy, corresponding with established time points. Baseline hypoxia as measured by both optical spectroscopy and EF5 immunofluorescence was variable, but on the basis of optical spectra, tumors appeared to become more hypoxic compared to normal skin after tourniquet application. The optical hypoxia signature was variable between patients while hemoglobin absorption increased.

Conclusions

To our knowledge, this is the first use of real-time optical spectroscopy to evaluate oxygenation and perfusion within melanoma lesions during regional chemotherapy. We report our development of this new noninvasive means of assessing tumor vascular function, which has the potential to be a powerful tool for noninvasive examination of the melanoma tumor microenvironment.

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Acknowledgment

This work was supported by NIH R01-CA40355, NIH 5T32CA093245-10, and the Melanoma Research Alliance.

Disclosure

GMP and Duke University have financial interest in Zenalux Biomedical Inc., which is commercializing optical spectroscopy technologies.

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Authors and Affiliations

  1. Department of Surgery, Duke University Medical Center, Durham, NC, USA

    Paul J. Speicher MD, Georgia M. Beasley MD, MHS, Michael E. Lidsky MD, Paul J. Mosca MD, PhD & Douglas S. Tyler MD

  2. Duke University School of Medicine, Durham, NC, USA

    Betty Jiang BS

  3. Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA

    Gregory M. Palmer PhD, Peter M. Scarbrough PhD & Mark W. Dewhirst DVM, PhD

  4. Division of Surgical Oncology, Duke University Medical Center, Durham, NC, USA

    Paul J. Mosca MD, PhD & Douglas S. Tyler MD

Authors
  1. Paul J. Speicher MD
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  2. Georgia M. Beasley MD, MHS
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  3. Betty Jiang BS
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  4. Michael E. Lidsky MD
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  5. Gregory M. Palmer PhD
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  7. Paul J. Mosca MD, PhD
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  8. Mark W. Dewhirst DVM, PhD
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  9. Douglas S. Tyler MD
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Corresponding author

Correspondence to Paul J. Speicher MD.

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Speicher, P.J., Beasley, G.M., Jiang, B. et al. Hypoxia in Melanoma: Using Optical Spectroscopy and EF5 to Assess Tumor Oxygenation Before and During Regional Chemotherapy for Melanoma. Ann Surg Oncol 21, 1435–1440 (2014). https://doi.org/10.1245/s10434-013-3222-0

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  • DOI: https://doi.org/10.1245/s10434-013-3222-0

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