Evans Sydney M, Fraker Douglas, Hahn Stephen M, Gleason Kristen, Jenkins W Timothy, Jenkins Kevin, Hwang Wei-Ting, Zhang Paul, Mick Rosemarie, Koch Cameron J
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):922-7. doi: 10.1016/j.ijrobp.2005.05.068.
To study the 2-nitroimidazole agent EF5 as a surrogate for measuring hypoxia in a series of patients with soft tissue sarcomas, and to determine whether hypoxia measured with this technique was associated with patient outcome.
Patients with soft tissue sarcomas of the head and neck, extremity, trunk, or retroperitoneum for whom surgical excision was the initial treatment of choice, were given 21 mg/kg EF5 24-48 hours before surgery. Biopsy specimens were stained for EF5 binding with fluorescence-labeled monoclonal antibodies, and the images were analyzed quantitatively. Endpoints included the relationship between EF5 binding, clinically important prognostic factors, and patient outcome.
Two patients with recurrent and 14 patients with de novo sarcomas were studied. There were seven low-grade, one intermediate-grade, and eight high-grade tumors. No relationship was found between EF5 binding and patient age, sex, hemoglobin level, or tumor size. In de novo tumors, the presence of mitoses and histologic grade were positively correlated with hypoxia. High-grade and -stage de novo tumors had higher levels of EF5 binding compared with low-grade and -stage tumors. Patients with de novo tumors containing moderate to severe hypoxia (> or = 20% EF5 binding), high grade, or > or = 7% mitoses were more likely to develop metastases.
Further studies in a larger cohort of patients are necessary to determine whether hypoxia, as measured by EF5 binding, is an independent prognostic factor for outcome in high-grade sarcomas. Such data should be useful to identify high-risk patients for clinical trials to determine whether early chemotherapy will influence the occurrence of metastasis.
研究2-硝基咪唑类药物EF5作为测量一系列软组织肉瘤患者缺氧情况的替代指标，并确定用该技术测量的缺氧情况是否与患者预后相关。
对头颈部、四肢、躯干或腹膜后软组织肉瘤患者，手术切除为首选初始治疗方法，在手术前24 - 48小时给予21 mg/kg EF5。活检标本用荧光标记单克隆抗体进行EF5结合染色，并对图像进行定量分析。观察终点包括EF5结合、临床重要预后因素与患者预后之间的关系。
研究了2例复发肉瘤患者和14例初发肉瘤患者。有7例低级别、1例中级别和8例高级别肿瘤。未发现EF5结合与患者年龄、性别、血红蛋白水平或肿瘤大小之间存在关联。在初发肿瘤中，有丝分裂的存在和组织学分级与缺氧呈正相关。与低级别和低分期肿瘤相比，高级别和高分期初发肿瘤的EF5结合水平更高。初发肿瘤中存在中度至重度缺氧（EF5结合≥20%）、高级别或有丝分裂≥7%的患者更易发生转移。
需要在更大规模的患者队列中进行进一步研究，以确定通过EF5结合测量的缺氧是否是高级别肉瘤预后的独立预测因素。这些数据对于识别高危患者进行临床试验以确定早期化疗是否会影响转移的发生应该是有用的。
