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[18F]-FLT PET to predict early response to neoadjuvant therapy in KRAS wild-type rectal cancer: a pilot study

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Abstract

Object

This pilot study evaluated the utility of 3′-deoxy-3′[18F]-fluorothymidine ([18F]-FLT) positron emission tomography (PET) to predict response to neoadjuvant therapy that included cetuximab in patients with wild-type KRAS rectal cancers.

Methods

Baseline [18F]-FLT PET was collected prior to treatment initiation. Follow-up [18F]-FLT was collected after three weekly infusions of cetuximab, and following a combined regimen of cetuximab, 5-FU, and radiation. Imaging-matched biopsies were collected with each PET study.

Results

Diminished [18F]-FLT PET was observed in 3/4 of patients following cetuximab treatment alone and in all patients following combination therapy. Reduced [18F]-FLT PET following combination therapy predicted disease-free status at surgery. Overall, [18F]-FLT PET agreed with Ki67 immunoreactivity from biopsy samples and surgically resected tissue, and was predictive of treatment-induced rise in p27 levels.

Conclusion

These results suggest that [18F]-FLT PET is a promising imaging biomarker to predict response to neoadjuvant therapy that included EGFR blockade with cetuximab in patients with rectal cancer.

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Acknowledgments

The authors acknowledge funding from the National Institutes of Health (R25 CA136440, R25 CA092043, K25 CA127349, P50 CA128323, P50 CA095103, R01 CA140628, RC1 CA145138, P30 DK058404, P50 CA127003, UL1 TR000445), the Kleberg Foundation, and Bristol Meyers Squib. The authors acknowledge Frank Revetta for assistance with immunohistochemistry.

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Authors and Affiliations

  1. Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical School, 1161 21st Ave. S., AA1105 MCN, Nashville, TN, 37232-2310, USA

    Eliot T. McKinley, Jennifer M. Watchmaker, Ronald C. Walker & H. Charles Manning

  2. Department of Medicine, Vanderbilt University Medical School, Nashville, TN, USA

    Eliot T. McKinley & Robert J. Coffey

  3. Program in Chemical and Physical Biology, Vanderbilt University, Nashville, TN, USA

    Jennifer M. Watchmaker & H. Charles Manning

  4. Vanderbilt Ingram Cancer Center, Vanderbilt University Medical School, Nashville, TN, USA

    A. Bapsi Chakravarthy, Ronald C. Walker, M. Kay Washington & Robert J. Coffey

  5. Department of Radiation Oncology, Vanderbilt University Medical School, Nashville, TN, USA

    A. Bapsi Chakravarthy

  6. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Jeffrey A. Meyerhardt & Jeffrey A. Engelman

  7. Department of Radiology and Radiological Sciences, Vanderbilt University Medical School, Nashville, TN, USA

    Ronald C. Walker & H. Charles Manning

  8. Radiology Service, Tennessee Valley VA Healthcare System, Nashville, TN, USA

    Ronald C. Walker

  9. Department of Pathology, Vanderbilt University Medical School, Nashville, TN, USA

    M. Kay Washington

  10. Department of Neurosurgery, Vanderbilt University Medical School, Nashville, TN, USA

    H. Charles Manning

  11. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA

    H. Charles Manning

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  1. Eliot T. McKinley
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  9. H. Charles Manning
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Corresponding author

Correspondence to H. Charles Manning.

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McKinley, E.T., Watchmaker, J.M., Bapsi Chakravarthy, A. et al. [18F]-FLT PET to predict early response to neoadjuvant therapy in KRAS wild-type rectal cancer: a pilot study. Ann Nucl Med 29, 535–542 (2015). https://doi.org/10.1007/s12149-015-0974-6

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  • DOI: https://doi.org/10.1007/s12149-015-0974-6

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