Mains Jill Rachel, Donskov Frede, Pedersen Erik Morre, Madsen Hans Henrik Torp, Rasmussen Finn
From the Departments of *Radiology, and †Oncology, Aarhus University Hospital, Aarhus, Denmark.
Invest Radiol. 2017 Feb;52(2):103-110. doi: 10.1097/RLI.0000000000000315.
The aim was to explore the potential for using dynamic contrast-enhanced computed tomography as a noninvasive functional imaging biomarker before and during the early treatment of metastatic renal cell carcinoma (mRCC).
Dynamic contrast-enhanced computed tomography scans were performed at baseline and after 5 and 10 weeks' treatment in 69 prospectively included mRCC patients receiving treatment with interferon alpha and interleukin 2 (n = 26); interferon alpha, interleukin 2, and bevacizumab (n = 24); sunitinib (n = 7); pazopanib (n = 5); or temsirolimus (n = 7). Using a prototype software program (Advanced Perfusion and Permeability Application, Philips Healthcare, Best, the Netherlands), blood volume (BV), blood flow (BF), and permeability surface area product (PS) were calculated for each tumor at baseline, week 5, and week 10. These parameters as well as relative changes between baseline and weeks 5 and 10 were tested for associations with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier curves and log-rank tests.
Using the 25th percentile as the cutoff, baseline BV for all patients independent of subsequent treatment was statistically significantly associated with PFS (10.8 vs 5.3 months, P = 0.007) and OS (35.2 vs 13.3 months, P = 0.001), and baseline BF was significantly associated with OS (31.7 vs 14.6 months, P = 0.024) with high values for both parameters being associated with significantly longer PFS and OS. Baseline PS was not associated with PFS or OS.In patients treated with angiogenesis inhibitors (bevacizumab, sunitinib, pazopanib, or temsirolimus), the relative change in BV from baseline to week 5 using 25th percentile as the cutoff was associated with PFS (5.6 vs 24.8 months, P = 0.001) and OS (19.1 months vs not reached, P = 0.008) and from baseline to week 10 with PFS (8.1 vs 16.4 months, P = 0.014) and OS (15.5 months vs not reached, P = 0.002). The relative change in BF from baseline to week 5 using medians as the cutoff was associated with PFS (5.5 vs 14.3 months, P = 0.018) and OS (14.6 vs 31.7 months, P = 0.027). The relative change in BF from baseline to week 10 using 25th percentile as the cutoff was associated with PFS (8.3 vs 46.9 months, P = 0.011) and OS (19.1 vs 53.0 months, P = 0.006). For both parameters, the largest reductions during early treatment were associated with increased PFS and OS.In patients receiving immunotherapy only (interferon alpha and interleukin 2), relative changes in PS between baseline and weeks 5 and 10 were significantly associated with PFS with larger increases associated with longer PFS. In patients receiving angiogenesis inhibitors, the relative changes in PS between baseline and week 10 were significantly associated with PFS and OS with larger reductions associated with favorable outcomes.
In patients with mRCC treated with angiogenesis inhibitors, the largest reductions in BV and BF between baseline and weeks 5 and 10 were associated with favorable outcomes. At baseline, the lowest BV and BF were associated with the poorest outcomes regardless of the subsequent treatment. Early reductions in PS were associated with favorable outcomes for those treated with angiogenesis inhibitors and with poor outcomes for those treated with immunotherapies.
旨在探索在转移性肾细胞癌（mRCC）早期治疗之前及治疗期间，使用动态对比增强计算机断层扫描作为一种非侵入性功能成像生物标志物的潜力。
对69例前瞻性纳入的接受α干扰素和白细胞介素2治疗（n = 26）；α干扰素、白细胞介素2和贝伐单抗治疗（n = 24）；舒尼替尼治疗（n = 7）；帕唑帕尼治疗（n = 5）；或替西罗莫司治疗（n = 7）的mRCC患者，在基线时以及治疗5周和10周后进行动态对比增强计算机断层扫描。使用一个原型软件程序（Advanced Perfusion and Permeability Application，飞利浦医疗保健公司，荷兰贝斯特），在基线、第5周和第10周时为每个肿瘤计算血容量（BV）、血流（BF）和通透表面积乘积（PS）。使用Kaplan-Meier曲线和对数秩检验，对这些参数以及基线与第5周和第10周之间的相对变化进行检验，以确定其与无进展生存期（PFS）和总生存期（OS）的相关性。
以第25百分位数作为临界值，所有患者无论后续治疗如何，基线BV与PFS（10.8个月对5.3个月，P = 0.007）和OS（35.2个月对13.3个月，P = 0.001）在统计学上显著相关，基线BF与OS（31.7个月对14.6个月，P = 0.024）显著相关，两个参数的高值均与显著更长的PFS和OS相关。基线PS与PFS或OS均无关。在接受血管生成抑制剂治疗（贝伐单抗、舒尼替尼、帕唑帕尼或替西罗莫司）的患者中，以第25百分位数作为临界值，从基线到第5周BV的相对变化与PFS（5.6个月对24.8个月，P = 0.001）和OS（19.1个月对未达到，P = 0.008）相关，从基线到第10周与PFS（8.1个月对16.4个月，P = 0.014）和OS（15.5个月对未达到，P = 0.002）相关。以中位数作为临界值，从基线到第5周BF的相对变化与PFS（5.5个月对14.3个月，P = 0.018）和OS（14.6个月对31.7个月，P = 0.027）相关。以第25百分位数作为临界值，从基线到第10周BF的相对变化与PFS（8.3个月对46.9个月，P = 0.011）和OS（19.1个月对53.0个月，P = 0.006）相关。对于这两个参数，早期治疗期间最大的降低与PFS和OS增加相关。在仅接受免疫治疗（α干扰素和白细胞介素2）的患者中，基线与第5周和第10周之间PS的相对变化与PFS显著相关，增加越大与PFS越长相关。在接受血管生成抑制剂治疗的患者中，基线与第10周之间PS的相对变化与PFS和OS显著相关，降低越大与良好结局相关。
在接受血管生成抑制剂治疗的mRCC患者中，基线与第5周和第10周之间BV和BF的最大降低与良好结局相关。在基线时，无论后续治疗如何，最低的BV和BF与最差的结局相关。PS的早期降低对于接受血管生成抑制剂治疗的患者与良好结局相关，而对于接受免疫治疗的患者与不良结局相关。
