Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, University of Rouen, Rouen, France
Department of Radiation Oncology and Medical Physics, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, Rouen, France.
J Nucl Med. 2017 Jul;58(7):1045-1053. doi: 10.2967/jnumed.116.188367. Epub 2017 Mar 2.
See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant F-misonidazole (F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In F-FMISO-positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral α = 0.05, power 1-β = 0.95). Seventy-nine patients were preincluded, 54 were included, and 34 were F-FMISO-positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%-71%) using RECIST 1.1 (17/34 responders in the F-FMISO-positive group). DFS and overall survival at 1 y were 0.86 (95% CI, 0.77-0.96) and 0.63 (95% CI, 0.49-0.74), respectively. DFS was longer in the F-FMISO-negative patients ( = 0.004). The radiotherapy dose was not associated with DFS when adjusting for the F-FMISO status. One toxic death (66 Gy) and 1 case of grade 4 pneumonitis (>66 Gy) were reported. Our approach results in a response rate of 40% or more, with acceptable toxicity. F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features that could not be reversed by radiotherapy doses up to 86 Gy.
请查看本文第 1043 页的特邀观点。这项多中心 II 期研究调查了在非小细胞肺癌（NSCLC）患者中，肿瘤区域 F-单硝酸异山梨酯（F-FMISO）摄取量显著增加时，增加选择性放疗剂量的情况。符合条件的患者患有局部晚期 NSCLC，且无同时放化疗的禁忌症。PET/CT 上的 F-FMISO 摄取由训练有素的专家进行评估。如果没有摄取，则给予 66 Gy。在 F-FMISO 阳性患者中，将缺氧区域的轮廓转移给放射肿瘤学家。在满足脊髓和肺部剂量限制约束的同时，使放疗剂量尽可能高是必要的。主要终点是 3 个月时的肿瘤反应（完全缓解加部分缓解）。次要终点是毒性、无疾病生存期（DFS）和 1 年总生存期。目标样本量设定为显示 40%或更高的反应率（双侧 α = 0.05，功率 1-β = 0.95）。79 名患者预先纳入，54 名患者纳入，34 名患者为 F-FMISO 阳性，其中 24 名患者接受了高达 86 Gy 的递增剂量。使用 RECIST 1.1，3 个月时的反应率为 54 例中的 31 例（57%；95%置信区间[CI]，43%-71%）（F-FMISO 阳性组中 17/34 例有反应者）。1 年时的 DFS 和总生存期分别为 0.86（95%CI，0.77-0.96）和 0.63（95%CI，0.49-0.74）。F-FMISO 阴性患者的 DFS 更长（= 0.004）。当调整 F-FMISO 状态时，放疗剂量与 DFS 无关。报告了 1 例（66 Gy）毒性死亡和 1 例（>66 Gy）4 级肺炎。我们的方法可产生 40%或更高的反应率，且毒性可接受。在 NSCLC 患者中，F-FMISO 摄取与预后不良的特征密切相关，而高达 86 Gy 的放疗剂量无法逆转这些特征。
