3′-Deoxy-3’-18F-Fluorothymidine and 18F-Fluorodeoxyglucose positron emission tomography for the early prediction of response to Regorafenib in patients with metastatic colorectal cancer refractory to all standard therapies
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The purpose of this study was to evaluate the value of 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for early prediction of standard anatomic response and survival outcomes in patients with metastatic colorectal cancer (mCRC) receiving Regorafenib.
Sixty-eight patients with mCRC refractory to standard cytotoxic chemotherapy were enrolled and received Regorafenib (160 mg/day on days 1–21, following a 7-day break). Standard anatomical response was evaluated every 8 weeks. Both scans were performed before and on day 21 of Regorafenib.
Of the 61 patients included in per-protocol analysis, complete response was not observed, but partial response was observed in 8.2% (n = 5), stable disease in 67.2% (n = 41), and progressive disease in 24.6% (n = 15). The objective response rate was 8.2% and disease control rate 75.4%. Five responders (8.2%) and 13 non-responders (21.3%) met the CT and 18F-FLT PET/CT criteria (maximum standardized uptake value decrease ≥ 10.6% for responders). Forty-three (70.5%) exhibited discordant responses on CT and 18F-FLT PET/CT (McNemar test, P < 0.001). At a median follow-up of 8.9 months, median progression-free survival (PFS) and median overall survival (OS) were 3.6 months (95% confidence interval [CI], 3.34–3.80 months) and 8.5 months (95% CI, 6.95–10.10 months), respectively. Comparison of PFS and OS according to 18F-FLT PET/CT response revealed slightly longer PFS (P = 0.015) in responders, but the correlation with OS was not significant. The PET Response Criteria in Solid Tumours (PERCIST) of 18F-FDG PET/CT revealed differences in PFS and OS between partial metabolic response (PMR) and non-PMR (P = 0.048 and P = 0.014, respectively), and between progressive metabolic disease (PMD) and non-PMD (P = 0.189 and P = 0.007, respectively).
Survival outcome was significantly associated with PERCIST using 18F-FDG PET/CT but the change of 18F-FLT uptake was only slightly associated with PFS. 18F-FDG PET/CT can be used as imaging biomarker to predict clinical outcomes early in patients with mCRC receiving Regorafenib.
Keywords18F-fluorothymidine 18F-fluorodeoxyglucose Positron emission tomography Regorafenib Metastatic colorectal cancer
This study was supported by a grant (2014-9079) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea, and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C2383). Regorafenib was kindly provided by Bayer.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Asan Medical Center and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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