Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong, China.
J Nucl Med. 2011 Oct;52(10):1573-9. doi: 10.2967/jnumed.111.092874. Epub 2011 Sep 8.
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.
当分子靶向治疗用于未经分子靶点选择的患者人群时，结果并不理想。这项初步研究检查了使用（11）C 标记的 4-N-（3-溴苯胺基）-6,7-二甲氧基喹唑啉（（11）C-PD153035）进行正电子发射断层扫描（PET）与接受表皮生长因子受体（EGFR）酪氨酸激酶抑制剂厄洛替尼治疗的非小细胞肺癌（NSCLC）患者结局之间的相关性。
前瞻性地招募了晚期化疗耐药性 NSCLC 患者，每天接受 150mg 的厄洛替尼治疗，并在基线、治疗开始后 1-2 周和 6 周时进行（11）C-PD153035 PET/CT 成像。总生存时间（OS）和无进展生存时间（PFS）分别与每个成像时间的（11）C-PD153035 标准化摄取值（SUV）相关。
共纳入 21 例患者。所有患者均完成了进展随访，21 例中有 18 例完成了死亡随访。通过 Cox 回归分析，基线最大 SUV 与 OS 和 PFS 强烈相关（风险比=0.40，P=0.002，风险比=0.044，P<0.001），与组织学无关。最大 SUV 较高（≥中位数）的患者的生存时间是最大 SUV 较低的患者的两倍多（中位 OS=11.4 个月对 4.6 个月，P=0.002；PFS=4.4 个月对 1.8 个月，P<0.001）。然而，随访扫描中的（11）C-PD153035 摄取与生存的相关性较差。
我们的初步结果表明，（11）C-PD153035 PET/CT 可能是一种非侵入性、快速的方法，用于识别对 EGFR 酪氨酸激酶抑制剂有反应但不能用于监测治疗反应的腺癌或鳞状组织学的晚期难治性 NSCLC 患者。
