Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine:: A substudy of Trans-Tasman Radiation Oncology Group study 98.02
Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine:: A substudy of Trans-Tasman Radiation Oncology Group study 98.02
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DOI：
10.1200/jco.2005.05.2878
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发表时间：
2006-05-01
影响因子：
45.3
通讯作者：
Peters, LJ
中科院分区：
文献类型：
--
作者：
Rischin, D;Hicks, RJ;Peters, LJ
目的确定III期或IV期头颈部鳞癌患者肿瘤缺氧、治疗方案和局部区域衰竭（LBF）之间的关系，这些患者被随机分配到放疗组（70 Gy， 35次，7周），第1、4和7周加替拉帕胺和顺铂，第2和3周单独加替拉帕胺（TPZ/CIS），或第6和7周顺铂和输注氟尿嘧啶（chemoboost）。患者和方法45名患者被纳入一项更大的随机试验的缺氧成像亚研究。示踪剂给药后2小时进行预处理和中期治疗[F-18]-氟米唑正电子发射断层扫描（FMISO-PET），对原发肿瘤和淋巴结的摄取进行定性评分。结果32例（71%）患者在原发性和淋巴结性疾病中均可检测到缺氧。在接受化疗的患者中，10例无缺氧患者中有1例发生LBF，而13例缺氧患者中有8例发生LBF；低氧患者发生LRF的风险显著高于低氧患者（精确对数秩，P= 0.038；危险比[HR]=7.1）。相比之下，在接受TPZ/CIS方案的患者中，19例低氧肿瘤患者中只有1例发生LRF；化疗加速患者发生LRF的风险显著增高（P= 0.001； HR=15）。同样，仅看原发部位，在低氧原发患者中，TPZ/CIS治疗的8例患者中没有一例局部失败，而化疗的9例患者中有6例局部失败（P=011； HR=0）。结论：在接受非替拉帕嗪放化疗方案的患者中，FMISO-PET成像显示缺氧与LRF的高风险相关。我们的数据提供了第一个临床证据来支持实验观察，即替拉帕嗪通过特异性靶向缺氧肿瘤细胞起作用。
Purpose To determine the association between tumor hypoxia, treatment regimen, and locoregional failure (LBF) in patients with stage III or IV squannous cell carcinoma of the head and neck randomly assigned to radiotherapy (70 Gy in 35 fractions over 7 weeks) plus either tirapazamine and cisplatin in weeks 1, 4, and 7 and tirapazamine alone in weeks 2 and 3 (TPZ/CIS) or cisplatin and infusional fluorouracil during weeks 6 and 7 (chemoboost).Patients and Methods Forty-five patients were enrolled onto a hypoxic imaging substudy of a larger randomized trial. Pretreatment and midtreatment [F-18]-fluoromisonidazole positron emission tomography scans (FMISO-PET) were performed 2 hours after tracer administration, with qualitative scoring of uptake in both primary tumors and nodes.Results Thirty-two patients (71%) had detectable hypoxia in either or both primary and nodal disease. In patients who received chemoboost, one of 10 patients without hypoxia had LBF compared with eight of 13 patients with hypoxia; the risk of LRF was significantly higher in hypoxic patients (exact log-rank, P=.038; hazard ratio [HR]=7.1). By contrast, in patients who received the TPZ/CIS regimen, only one of 19 patients with hypoxic tumors had LRF; risk of LRF was significantly higher in chemoboost patients (P=.001; HR=15). Similarly, looking at the primary site alone, in patients with hypoxic primaries, zero of eight patients treated with TPZ/CIS experienced failure locally compared with six of nine patients treated with chemoboost (P=011; HR=0).Conclusion Hypoxia on FMISO-PET imaging, in patients receiving a nontirapazamine-containing chemoradiotherapy regimen, is associated with a high risk of LRF. Our data provide the first clinical evidence to support the experimental observation that tirapazamine acts by specifically targeting hypoxic tumor cells.