J Nucl Med 2011 Oct;52 (10): 1573-9. [IF:7.022]
Molecular imaging with 11C-PD153035 PET/CT predicts survival in non-small cell lung cancer treated with EGFR-TKI: a pilot study
Meng X , Loo BW , Ma L , Murphy JD , Sun X , Yu J .
Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong, China.
山东济南山东省肿瘤医院放射肿瘤科
Abstract：
Outcomes are suboptimal when molecularly targeted therapies are used in patient populations unselected for the molecular target. This pilot study examines the correlation of PET using (11)C-labeled 4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline ((11)C-PD153035), an imaging biomarker of epidermal growth factor receptor (EGFR), with outcomes in patients with non-small cell lung cancer (NSCLC) treated with the EGFR tyrosine kinase inhibitor erlotinib. Patients with advanced chemotherapy-refractory NSCLC were prospectively enrolled on a trial of erlotinib at a dose of 150 mg daily and imaged by (11)C-PD153035 PET/CT at baseline, after 1-2 wk, and after 6 wk from the start of treatment. Overall survival and progression-free survival (OS and PFS, respectively) times were correlated with the (11)C-PD153035 standardized uptake value (SUV) at each of the imaging times. Twenty-one patients were enrolled. Follow-up to progression was complete in all patients and to death in 18 of 21. By Cox regression analysis, baseline maximum SUV correlated strongly with OS and PFS (hazard ratio = 0.40, P = 0.002, and hazard ratio = 0.044, P < 0.001, respectively) independent of histology. Patients with higher maximum SUV (≥median) survived more than twice as long as patients with lower maximum SUV (median OS = 11.4 vs. 4.6 mo, P = 0.002; PFS = 4.4 vs. 1.8 mo, P < 0.001). However, (11)C-PD153035 uptake on follow-up scans was less well correlated with survival. Our preliminary results suggest (11)C-PD153035 PET/CT may be a noninvasive and rapid method for identifying patients with refractory advanced NSCLC of adenocarcinoma or squamous histology likely to respond to the EGFR tyrosine kinase inhibitor but not for monitoring treatment response.
摘要
当分子靶向用于治疗未筛选分子靶点的患者人群时结果未达到标准。本实验考察了正电子发射断层扫描（PET）和EGFR酪氨酸激酶抑制剂厄洛替尼治疗非小细胞肺癌（NSCLC）患者的结果之间的联系。该实验中使用C（11）标志的4-N-(3-溴苯胺)-6,7-二甲氧基喹唑啉（（11）C-PD153035）作为表皮生长因子受体（EGFR）的成像生物标志物。试验中晚期化疗失败的非小细胞肺癌患者，服用厄洛替尼剂量150mg 每天一次。分别在治疗开始、1-2周后，以及6周后用(11)C-PD153035 JINGXING PET-CT成像,总生存率（OS）和无进展生存期(PFS)与每次成像时(11)C-PD153035的标准化摄入值（SUV）有关。试验总共入组21位患者，随访直到21人中18个死亡才结束。考克斯回归分析，基线最大的标准化摄入值与总生存率和无进展生存期有很强的相关性（分别为：风险比=0.40，P=0.002和风险比=0.044，P< 0.001）.摄入值高的患者存活时间是摄入值低的患者的2倍多（平均OS=11.4vs4.6mo，P=0.002；PFS=4.4vs1.8mo，P P< 0.001）。但是，随访发现（11)C-PD153035摄入与存活的相关性不是很好。我们的初步研究结果表明（11)C-PD153035 PET/CT能对EGFR酪氨酸激酶抑制剂治疗做出反应而不是单纯的对治疗进行监测，所以可以作为一种非侵入性的快速识别患者晚期难治性腺癌或鳞癌组织的一种方法。
