Lee Nancy Y, Mechalakos James G, Nehmeh Sadek, Lin Zhixiong, Squire Olivia D, Cai Shangde, Chan Kelvin, Zanzonico Pasquale B, Greco Carlo, Ling Clifton C, Humm John L, Schöder Heiko
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA.
Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):2-13. doi: 10.1016/j.ijrobp.2007.06.039. Epub 2007 Sep 14.
Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV(h)) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV(h) increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ((18)F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients.
(18)F-FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and (18)F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated (18)F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate (18)F-FMISO PET/CT-guided IMRT plans.
The heterogeneous distribution of (18)F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing (18)F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV(h) and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV(h) for 2 patients and were successful in 1, with normal tissue sparing.
It was feasible to dose escalate the GTV(h) to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients.
缺氧使肿瘤细胞具有放射抗性，限制了放射治疗（RT）的局部区域控制。调强放疗（IMRT）能够靶向大体肿瘤体积（GTV），并有可能在保护正常组织的同时，向缺氧亚体积（GTV(h)）输送更高剂量。蒙特卡洛模型显示，增加GTV(h)的剂量可提高肿瘤控制概率。本研究探讨了氟-18标记的氟米索硝唑正电子发射断层扫描/计算机断层扫描（(18)F-FMISO PET/CT）引导下的IMRT在一组头颈癌（HNC）患者中最大程度提高对放射抗性缺氧区域剂量的可行性。
静脉注射(18)F-FMISO进行PET成像。采用相同的固定方法对CT模拟、氟脱氧葡萄糖PET/CT和(18)F-FMISO PET/CT扫描进行配准。肿瘤边界通过临床检查和可用的影像学检查（包括氟脱氧葡萄糖PET/CT）确定。在氟脱氧葡萄糖PET/CT GTV内(18)F-FMISO摄取增加的区域作为IMRT加量的靶点。勾勒出其他靶点和/或正常结构，或将其转移到治疗计划中，以生成(18)F-FMISO PET/CT引导的IMRT计划。
GTV内(18)F-FMISO的异质性分布表明肿瘤内存在不同程度的缺氧。针对10例HNC患者进行(18)F-FMISO PET/CT引导的IMRT计划，GTV(h)达到84 Gy，GTV达到70 Gy，且未超过正常组织耐受量。我们还尝试对2例患者的GTV(h)给予105 Gy的剂量，其中1例成功，且正常组织得到了保护。
在不超过正常组织耐受量的情况下，将10例患者的GTV(h)剂量提升至84 Gy，1例患者提升至105 Gy是可行的。这些信息为后续以进一步改善HNC患者局部区域控制为目标的缺氧引导IMRT试验提供了重要数据。
