Department of Nuclear Medicine, Georges Pompidou European Hospital, Assistance Publique–Hôpitaux de Paris, Paris Descartes University, Paris, France.
J Nucl Med. 2011 Jul;52(7):1048-55. doi: 10.2967/jnumed.110.084517. Epub 2011 Jun 16.
The aims of this cohort study were to evaluate initial tumor hypoxia in metastatic renal cell carcinoma (mRCC) and its changes after sunitinib treatment, using (18)F-fluoromisonidazole PET/CT, and investigate the possible prognostic value of initial tumor hypoxia or its changes under sunitinib therapy.
Antiangiogenic-naive patients with mRCC were prospectively enrolled in this cohort study. Before initiation of sunitinib, CT defined up to 10 targets that were assessed at 1 and 6 mo according to the response evaluation criteria in solid tumors (RECIST). Pretreatment target uptake of (18)F-fluoromisonidazole was compared with uptake at 1 mo. Targets were considered hypoxic when their maximal standard uptake value was above mean blood value + 2 SDs. Hypoxic volumes were also computed. Relationships between initial hypoxia status, initial degree of hypoxia, its change at 1 mo, and overall or progression-free survival (OS and PFS, respectively) were assessed by survival analysis.
Fifty-three patients were included. Median follow-up was 16.8 mo. (18)F-fluoromisonidazole uptake significantly decreased in initially hypoxic target metastases but did not change in others (-22%, P < 10(-4), vs. +1.5%, P = 0.77; P = 10(-3) between groups). Seventy-five percent of patients with hypoxic metastases were free of progressive disease at 4.8 mo (95% confidence interval, 2.99-11.83), compared with 11.3 mo (95% confidence interval, 3.08-36.9) for other patients (P = 0.02), whereas OS was not significantly different. Changes in tumor hypoxia were not related to PFS or OS.
Sunitinib reduced hypoxia in initially hypoxic RECIST target metastases but did not induce significant hypoxia in nonhypoxic RECIST target metastases. Patients with initially hypoxic targets have shorter PFS than others.
本研究旨在通过使用 18F-氟咪索硝唑正电子发射断层扫描/计算机断层扫描（18F-fluoromisonidazole PET/CT）评估转移性肾细胞癌（mRCC）患者的初始肿瘤乏氧情况及其在舒尼替尼治疗后的变化，并探讨初始肿瘤乏氧及其在舒尼替尼治疗下的变化对预后的可能预测价值。
本研究为前瞻性队列研究，纳入未经抗血管生成治疗的 mRCC 患者。在开始舒尼替尼治疗前，根据实体瘤疗效评价标准（RECIST）评估 1 和 6 个月时的最多 10 个靶病灶。比较（18）F-氟咪索硝唑的预处理靶摄取与 1 个月时的摄取。当最大标准摄取值大于平均血值+2 个标准差时，将靶病灶定义为缺氧。还计算了缺氧体积。通过生存分析评估初始缺氧状态、初始缺氧程度、1 个月时的变化与总生存（OS）和无进展生存（PFS）之间的关系。
共纳入 53 例患者，中位随访时间为 16.8 个月。（18）F-氟咪索硝唑摄取在最初缺氧的转移灶中明显下降，但在其他病灶中无变化（-22%，P<10（-4），vs.+1.5%，P=0.77；两组间差异有统计学意义，P=10（-3））。4.8 个月时，75%的缺氧转移灶患者无疾病进展（95%可信区间为 2.99-11.83），而其他患者为 11.3 个月（95%可信区间为 3.08-36.9）（P=0.02），但 OS 无显著差异。肿瘤乏氧变化与 PFS 或 OS 无关。
舒尼替尼降低了最初缺氧的 RECIST 靶转移灶的乏氧程度，但未诱导非缺氧的 RECIST 靶转移灶的显著乏氧。与其他患者相比，最初存在缺氧靶病灶的患者 PFS 更短。
