Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
J Nucl Med. 2013 Aug;54(8):1209-16. doi: 10.2967/jnumed.112.117010. Epub 2013 Jun 26.
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.
本研究旨在评估 3'-去氧-3'-(18)F-氟代胸苷（(18)F-FLT）PET 在转移性结直肠癌（mCRC）患者接受亚叶酸、5-氟尿嘧啶（5-FU）和奥沙利铂（FOLFOX）治疗时，对标准解剖反应和生存结果的早期预测价值。
主要纳入标准包括组织学证实的 mCRC、≥1 个肝外可测量病变和转移性疾病中无既往化疗。化疗包括第 1 天给予亚叶酸，第 1 和 2 天持续输注 5-FU，第 3 天给予奥沙利铂。在化疗的第 2 个和随后的周期中，奥沙利铂与第 1 天的亚叶酸同时给予。在化疗的第 1 个周期中，进行 3 次 (18)F-FLT PET 扫描：化疗前、5-FU 输注后 24 小时（第 2 天）和化疗结束后 48 小时（第 5 天）。测量 (18)F-FLT 的最大标准化摄取值（SUVMAX）。在接受 3 个周期 FOLFOX 治疗后，通过 CT 评估治疗反应。
本研究纳入了 18 例患者。在接受 3 个周期 FOLFOX 治疗后，反应率为 27.8%（5/18）。在第 2 天， responders 和 nonresponders 的 SUVMAX 均升高（P = 0.043），而仅 responders 的 SUVMAX 在第 5 天与基线相比降低（P = 0.043）。受试者工作特征曲线分析表明，使用第 2 天 SUVMAX 增加的阈值≤45.8%，则诊断 responders 的灵敏度为 100%，特异性为 69.2%，相对危险度为 2.250（P = 0.029）。使用第 5 天 SUVMAX 降低的阈值≥10.6%，则诊断 responders 的灵敏度为 100%，特异性为 76.9%，相对危险度为 2.667（P = 0.007）。低（18）F-FLT 闪烁倾向于患者的生存时间长于高闪烁（2 年总生存率，77.8% vs. 44.4%；P = 0.051）。
在 mCRC 患者中，5-FU 输注期间观察到的（18）F-FLT 闪烁与治疗反应不良相关。（18）F-FLT 闪烁的程度可能用于预测接受输注 5-FU 为基础的化疗的患者的结局。
