3′-Deoxy-3′-18F-Fluorothymidine PET for the Early Prediction of Response to Leucovorin, 5-Fluorouracil, and Oxaliplatin Therapy in Patients with Metastatic Colorectal Cancer
Adult
Male
Time Factors
Organoplatinum Compounds
Leucovorin
Middle Aged
Survival Analysis
Dideoxynucleosides
3. Good health
03 medical and health sciences
Treatment Outcome
0302 clinical medicine
Positron-Emission Tomography
Antineoplastic Combined Chemotherapy Protocols
Humans
Female
Fluorouracil
Neoplasm Metastasis
Colorectal Neoplasms
Aged
DOI:
10.2967/jnumed.112.117010
Publication Date:
2013-06-27T03:19:57Z
AUTHORS (12)
ABSTRACT
The aim of this study was to evaluate 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET for early prediction of the standard anatomic response and survival outcomes in patients with metastatic colorectal cancer (mCRC) receiving leucovorin, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX).The main eligibility criteria included histologically confirmed mCRC, ≥ 1 extrahepatic measurable lesions, and no prior chemotherapy in a metastatic setting. Chemotherapy consisted of leucovorin on day 1, followed by the continuous infusion of 5-FU on days 1 and 2, and oxaliplatin on day 3. In the second and subsequent cycles of chemotherapy, oxaliplatin was administered simultaneously with leucovorin on day 1. (18)F-FLT PET scans were obtained 3 times during the first cycle of chemotherapy: before chemotherapy, 24 h after infusion of 5-FU (day 2), and 48 h after completion of chemotherapy (day 5). The maximum standardized uptake value (SUVMAX) of (18)F-FLT was measured. Treatment responses were assessed by CT after 3 cycles of FOLFOX.Eighteen patients were included in the study. The response rate after 3 cycles of FOLFOX was 27.8% (5/18). The SUVMAX was increased in responders (P = 0.043) and nonresponders (P < 0.001) on day 2 and was decreased, compared with baseline values, on day 5 in responders only (P = 0.043). Receiver-operating-characteristic curve analysis indicated that the use of a threshold of an SUVMAX increase on day 2 of ≤ 45.8% resulted in a sensitivity of 100%, specificity of 69.2%, and relative risk of 2.250 (P = 0.029) for the diagnosis of responders. Use of a threshold of an SUVMAX decrease on day 5 of ≥ 10.6% resulted in a sensitivity of 100%, specificity of 76.9%, and relative risk of 2.667 (P = 0.007). Patients with low (18)F-FLT flare tended to have longer survivals than patients with high flare (2-y overall survival rate, 77.8% vs. 44.4%; P = 0.051).The (18)F-FLT flare observed during 5-FU infusion was associated with poor treatment response in patients with mCRC. The degree of (18)F-FLT flare might be used to predict the outcome of patients who receive infusional 5-FU-based chemotherapy.
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