Prognostic Impact of [18F]Fluorothymidine and [18F]Fluoro-D-Glucose Baseline Uptakes in Patients with Lung Cancer Treated First-Line with Erlotinib

3′-deoxy-3′-[18F]fluoro-L-thymidine (FLT) and 2′-deoxy-2′-[18F]fluoro-D-glucose (FDG) are used to visualize proliferative and metabolic activity of tumors. In this study we aimed at evaluating the prognostic value of FLT and FDG uptake measured by positron emission tomography (PET) in patients with metastatic non-small cell lung cancer (NSCLC) prior to systemic therapy with erlotinib. FLT and FDG maximum standardized uptake (SUVmax) values per patient were analyzed in 40 chemotherapy naive patients with advanced NSCLC (stage IV) before treatment with erlotinib. Prior therapy median SUVmax was 6.6 for FDG and 3.0 for FLT, respectively. In univariate analysis, patients with an FDG SUVmax <6.6 had a significantly better overall survival (16.3 months [95% confidence interval [CI] 7.1–25.4 months]) compared to patients with an FDG SUVmax ≥6.6 (3.1 months [95% CI 0.6–5.5 months]) (p<0.001, log rank). Similarly, low FLT uptake (SUVmax <3.0) was associated with significantly longer survival (10.3 months (0–23.3 months, 95% CI) compared to high FLT uptake (3.4 months (0–8.1 months, 95% CI) (p = 0.027). The independent prognostic value of baseline FDG uptake was demonstrated in multivariate analysis (p = 0.05, Cox regression). These data suggest that baseline SUVmax values for both FDG and FLT PET might be further developed as markers for prognostic stratification of patients in advanced NSCLC treated with tyrosine kinase inhibitors (TKI) directed against the epidermal growth factor receptor (EGFR).
Trial RegistrationClinicaltrials.gov, Identifier: NCT00568841

3′-脱氧-3′-[¹⁸F]氟-L-胸腺嘧啶（3′-deoxy-3′-[¹⁸F]fluoro-L-thymidine，FLT）与2′-脱氧-2′-[¹⁸F]氟-D-葡萄糖（2′-deoxy-2′-[¹⁸F]fluoro-D-glucose，FDG）是两类常用于可视化肿瘤增殖与代谢活性的显像剂。本研究旨在评估：在接受厄洛替尼系统治疗前，通过正电子发射断层显像（positron emission tomography, PET）检测的FLT与FDG摄取水平，对转移性非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的预后价值。本研究纳入40例化疗初治的Ⅳ期晚期非小细胞肺癌患者，在其接受厄洛替尼治疗前，对每位患者的FLT与FDG最大标准化摄取值（maximum standardized uptake, SUVmax）开展分析。受试者的基线FDG SUVmax中位数为6.6，FLT SUVmax中位数为3.0。单变量分析结果显示，FDG SUVmax＜6.6的患者总生存期显著优于FDG SUVmax≥6.6的患者：前者为16.3个月[95%置信区间（confidence interval, CI）7.1~25.4个月]，后者为3.1个月[95%CI 0.6~5.5个月]，log-rank检验p＜0.001。类似地，FLT低摄取（SUVmax＜3.0）的患者生存期显著更长，为10.3个月（95%CI 0~23.3个月）；而FLT高摄取患者的生存期仅为3.4个月（95%CI 0~8.1个月，p=0.027）。多变量分析（考克斯回归，Cox regression）结果证实，基线FDG摄取水平具有独立预后价值（p=0.05）。上述研究结果提示，针对接受表皮生长因子受体（epidermal growth factor receptor, EGFR）靶向酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKI）治疗的晚期非小细胞肺癌患者，FDG与FLT PET的基线SUVmax值有望进一步开发为预后分层标志物。本研究已在Clinicaltrials.gov完成注册，标识符为NCT00568841。