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.

Abstract

PURPOSE:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

• Authors: 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 Hong
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 46 Issue 8 Pg. 1713-1722 (Jul 2019) ISSN: 1619-7089 [Electronic] Germany
• PMID: 31041456 (Publication Type: Comparative Study, Evaluation Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Dideoxynucleosides
• Phenylurea Compounds
• Pyridines
• Radiopharmaceuticals
• Fluorodeoxyglucose F18
• regorafenib
• alovudine

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Clinical Trials as Topic
• Colorectal Neoplasms (diagnostic imaging, drug therapy, pathology)
• Dideoxynucleosides (adverse effects, standards)
• Female
• Fluorodeoxyglucose F18 (adverse effects, standards)
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Phenylurea Compounds (therapeutic use)
• Positron Emission Tomography Computed Tomography (methods, standards)
• Predictive Value of Tests
• Pyridines (therapeutic use)
• Radiopharmaceuticals (adverse effects)