Department of Pulmonary Diseases, VU University Medical Center, and Department of Biostatistics, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
J Nucl Med. 2011 Jan;52(1):48-55. doi: 10.2967/jnumed.110.078261. Epub 2010 Dec 13.
With antiangiogenic agents, tumor shrinkage may be absent, despite survival benefit. The present study assessed the predictive value of molecular imaging for the identification of survival benefit during antiangiogenic treatment with bevacizumab and erlotinib in patients with advanced non-small cell lung cancer.
Patients were evaluated using an imaging protocol including CT, 18F-FDG PET, H2(15)O PET, and dynamic contrast-enhanced MRI to derive measurements on tumor size, glucose metabolism, perfusion, and microvascular permeability. The percentage change in imaging parameters after 3 wk of treatment as compared with baseline was calculated and correlated with progression-free survival (PFS).
Forty-four patients were included, and 40 underwent CT and 18F-FDG PET at both time points. Complete datasets, containing all imaging modalities, were available for 14 patients. Bevacizumab and erlotinib treatment resulted in decreased metabolism, perfusion, and tumor size. A decrease in standardized uptake value or tumor perfusion of more than 20% at week 3 was associated with longer PFS (9.7 vs. 2.8 mo, P=0.01, and 12.5 vs. 2.9 mo, P=0.009, respectively). Whole-tumor Ktrans (the endothelial transfer constant) was not associated with PFS, but patients with an increase of more than 15% in the SD of tumor Ktrans values-that is, an increase in regions with low or high Ktrans values-after 3 wk had shorter PFS (2.3 vs. 7.0 mo, P=0.008). A partial response, according to the response evaluation criteria in solid tumors (RECIST), at week 3 was also associated with prolonged PFS (4.6 vs. 2.9 mo, P=0.017). However, 40% of patients with a partial response as their best RECIST response still had stable disease at week 3. In these cases tumor perfusion was already decreased and Ktrans heterogeneity showed no increase, indicating that the latter parameters seem to be more discriminative than RECIST at the 3-wk time point.
PET and dynamic contrast-enhanced MRI were able to identify patients who benefit from bevacizumab and erlotinib treatment. Molecular imaging seems to allow earlier response evaluation than CT.
评估分子成像对贝伐单抗和厄洛替尼治疗晚期非小细胞肺癌患者生存获益的预测价值。
采用影像学方案（包括 CT、18F-FDG PET、H2(15)O PET 和动态对比增强 MRI）对患者进行评估，以获得肿瘤大小、葡萄糖代谢、灌注和微血管通透性的测量值。计算治疗 3 周后与基线相比的影像学参数变化百分比，并与无进展生存期（PFS）相关。
共纳入 44 例患者，其中 40 例在两个时间点进行了 CT 和 18F-FDG PET 检查。14 例患者有完整的包含所有成像方式的数据集。贝伐单抗和厄洛替尼治疗导致代谢、灌注和肿瘤体积减少。治疗 3 周时标准化摄取值或肿瘤灌注下降超过 20%与更长的 PFS 相关（9.7 对 2.8 个月，P=0.01，12.5 对 2.9 个月，P=0.009）。全肿瘤 Ktrans（内皮传递常数）与 PFS 无关，但治疗 3 周后肿瘤 Ktrans 值标准差增加超过 15%（即低或高 Ktrans 值区域增加）的患者 PFS 更短（2.3 对 7.0 个月，P=0.008）。3 周时根据实体瘤反应评价标准（RECIST）的部分缓解与 PFS 延长相关（4.6 对 2.9 个月，P=0.017）。然而，40%的部分缓解患者在第 3 周仍有稳定的疾病。在这些病例中，肿瘤灌注已经下降，Ktrans 异质性没有增加，这表明后者的参数在第 3 周时比 RECIST 更具鉴别力。
PET 和动态对比增强 MRI 能够识别从贝伐单抗和厄洛替尼治疗中获益的患者。分子成像似乎比 CT 更早地评估反应。
