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

Eliot T. McKinley; Jennifer M. Watchmaker; A. Bapsi Chakravarthy; Jeffrey A. Meyerhardt; Jeffrey A. Engelman; Ronald C. Walker; M. Kay Washington; Robert J. Coffey; H. Charles Manning

doi:10.1007/s12149-015-0974-6

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

Eliot T. McKinley, Jennifer M. Watchmaker, A. Bapsi Chakravarthy, Jeffrey A. Meyerhardt, Jeffrey A. Engelman, Ronald C. Walker, M. Kay Washington, Robert J. Coffey, H. Charles Manning

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English
Pages (from-to)	535-542
Number of pages	8
Journal	Annals of Nuclear Medicine
Volume	29
Issue number	6
DOIs	https://doi.org/10.1007/s12149-015-0974-6
State	Published - 25 Jul 2015
Externally published	Yes

Keywords

Cetuximab
EGFR
F-FLT
Rectal cancer
Treatment response

Access to Document

10.1007/s12149-015-0974-6

Cite this

McKinley, E. T., Watchmaker, J. M., Bapsi Chakravarthy, A., Meyerhardt, J. A., Engelman, J. A., Walker, R. C., Kay Washington, M., Coffey, R. J., & Charles Manning, H. (2015). [¹⁸F]-FLT PET to predict early response to neoadjuvant therapy in KRAS wild-type rectal cancer: a pilot study. Annals of Nuclear Medicine, 29(6), 535-542. https://doi.org/10.1007/s12149-015-0974-6

@article{faf4c709b3da43149d9c7dbebc99e6d7,

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

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.",

keywords = "Cetuximab, EGFR, F-FLT, Rectal cancer, Treatment response",

author = "McKinley, {Eliot T.} and Watchmaker, {Jennifer M.} and {Bapsi Chakravarthy}, A. and Meyerhardt, {Jeffrey A.} and Engelman, {Jeffrey A.} and Walker, {Ronald C.} and {Kay Washington}, M. and Coffey, {Robert J.} and {Charles Manning}, H.",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2015, The Japanese Society of Nuclear Medicine.",

year = "2015",

month = jul,

day = "25",

doi = "10.1007/s12149-015-0974-6",

language = "English",

volume = "29",

pages = "535--542",

journal = "Annals of Nuclear Medicine",

issn = "0914-7187",

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TY - JOUR

T1 - [18F]-FLT PET to predict early response to neoadjuvant therapy in KRAS wild-type rectal cancer

T2 - a pilot study

AU - McKinley, Eliot T.

AU - Watchmaker, Jennifer M.

AU - Bapsi Chakravarthy, A.

AU - Meyerhardt, Jeffrey A.

AU - Engelman, Jeffrey A.

AU - Walker, Ronald C.

AU - Kay Washington, M.

AU - Coffey, Robert J.

AU - Charles Manning, H.

N1 - Funding Information: 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. Publisher Copyright: © 2015, The Japanese Society of Nuclear Medicine.

PY - 2015/7/25

Y1 - 2015/7/25

N2 - 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.

AB - 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.

KW - Cetuximab

KW - EGFR

KW - F-FLT

KW - Rectal cancer

KW - Treatment response

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U2 - 10.1007/s12149-015-0974-6

DO - 10.1007/s12149-015-0974-6

M3 - Article

C2 - 25899481

AN - SCOPUS:84937971846

SN - 0914-7187

VL - 29

SP - 535

EP - 542

JO - Annals of Nuclear Medicine

JF - Annals of Nuclear Medicine

IS - 6