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

  • Jeong Eun Kim
  • Sun Young Chae
  • Jwa Hoon Kim
  • Hwa Jung Kim
  • Tae Won Kim
  • Kyu-pyo Kim
  • Sun Young Kim
  • Jae-Lyun Lee
  • Seung Jun Oh
  • Jae Seung Kim
  • Jin-Sook Ryu
  • Dae Hyuk Moon
  • Yong Sang HongEmail author
Original Article



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.


18F-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.

Ethical approval

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

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

Supplementary material

259_2019_4330_Fig4_ESM.png (69 kb)
Online Resource 1

Kaplan-Meier curves showing the PFS and OS in patients with metastatic colorectal cancer receiving Regorafenib. (a) The median PFS was 3.6 months (95% CI, 3.34–3.80), and (b) the median OS was 8.5 months (95% CI, 6.95–10.10) (PNG 69 kb)

259_2019_4330_MOESM1_ESM.tif (743 kb)
High resolution image (TIF 742 kb)
259_2019_4330_Fig5_ESM.png (76 kb)
Online Resource 2

Kaplan-Meier curves showing the PFS and OS according to the change of 18F-FLT uptake in patients with colorectal cancer with only extrahepatic metastasis receiving Regorafenib (n = 37). (a) The median PFS was 5.9 months (95% CI, 3.30–8.57) for responders on 18F-FLT PET/CT (patients with a decrease of SUVmax ≥10.6% on day 21 of Regorafenib) and 3.4 months (95% CI, 2.94–3.94) for non-responders (P < 0.001). (b) The median OS was 14.0 months (95% CI, 6.34–21.66) for the responders on 18F-FLT PET/CT and 8.0 months (95% CI, 0.00–16.70) for the non-responders (P = 0.150) (PNG 75 kb)

259_2019_4330_MOESM2_ESM.tif (703 kb)
High resolution image (TIF 702 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jeong Eun Kim
    • 1
  • Sun Young Chae
    • 2
  • Jwa Hoon Kim
    • 1
  • Hwa Jung Kim
    • 3
  • Tae Won Kim
    • 1
  • Kyu-pyo Kim
    • 1
  • Sun Young Kim
    • 1
  • Jae-Lyun Lee
    • 1
  • Seung Jun Oh
    • 2
  • Jae Seung Kim
    • 2
  • Jin-Sook Ryu
    • 2
  • Dae Hyuk Moon
    • 2
  • Yong Sang Hong
    • 1
    Email author
  1. 1.Department of Oncology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
  2. 2.Department of Nuclear Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
  3. 3.Department of Preventive Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea

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