Lee W R, Berkey B, Marcial V, Fu K K, Cooper J S, Vikram B, Coia L R, Rotman M, Ortiz H
Wake Forest University School of Medicine, Winston-Salem, NC 27157-1030, USA.
Int J Radiat Oncol Biol Phys. 1998 Dec 1;42(5):1069-75. doi: 10.1016/s0360-3016(98)00348-4.
The purpose of the present study is to investigate the strength of association between anemia and overall survival, locoregional failure, and late radiation therapy (RT) complications in a large prospective study of patients with advanced head and neck cancer treated with conventional radiotherapy with or without a hypoxic cell sensitizer.
Between March 1988 and September 1991, 521 patients with Stage III or IV squamous cell carcinoma of the head and neck were entered into a randomized trial examining the addition of etanidazole (SR 2508) to conventional radiation therapy (RT) (66-74 Gy in 33-37 fractions, 5 days a week). Patients with hemoglobin (Hgb) levels measured and recorded prior to the second week of RT were included in this secondary analysis. Hemoglobin levels were stratified as normal (> or = 14.5 gm% for men, > or = 13 gm% for women) or anemic (< 14.5 gm% for men, < 13 gm% for women). Locoregional failure rates were calculated using the cumulative incidence approach. Overall survival was estimated according to the Kaplan-Meier method. Late RT toxicity was scored according to the RTOG morbidity scale. Differences in rates of overall survival, locoregional failure, and late complications were tested by the Cox proportional hazard model.
Of 504 eligible patients, 451 had a Hgb level measured and recorded prior to the second week of RT. One hundred sixty-two patients (35.9%) were considered to have a normal Hgb level and 289 patients (64.1%) were considered to be anemic. The estimated survival rate is 35.7% at 5 years in patients with a normal Hgb, versus 21.7% in anemic patients (p = 0.0016). The estimated locoregional failure rate is 51.6% at 5 years in patients with a normal Hgb, versus 67.8% in anemic patients (p = 0.00028). The estimated rate of grade 3 or greater toxicity is 19.8% at 5 years in patients with a normal Hgb, versus 12.7% in anemic patients (p = 0.063). On multivariate analysis, several variables were found to be independent predictors of survival including: T stage, Karnofsky performance status, N stage, age, total radiation dose to the primary, and Hgb level. Independent predictors of locoregional control included T stage, Karnofsky performance status, N stage, radiation dose, and Hgb level. The only variables which predicted for the development of late RT complications were gender (p = 0.0109) and age (p = 0.0167). These findings were consistent regardless of whether Hgb level was considered a dichotomous or continuous variable.
Low Hgb levels are associated with a statistically significant reduction in survival and an increase in locoregional failure in this large prospective study of patients with advanced head and neck cancer. Hgb level should be considered as a stratification variable in subsequent studies of head and neck cancer. Strategies to increase Hgb prior to RT in patients with head and neck cancer may lead to improved survival and loco-regional control.
本研究旨在通过一项大型前瞻性研究，探讨晚期头颈癌患者在接受常规放疗（无论是否联合使用乏氧细胞增敏剂）时，贫血与总生存期、局部区域复发以及放疗晚期并发症之间的关联强度。
1988年3月至1991年9月期间，521例Ⅲ期或Ⅳ期头颈鳞状细胞癌患者进入一项随机试验，该试验旨在研究在常规放疗（66 - 74 Gy，分33 - 37次，每周5天）基础上加用依他硝唑（SR 2508）的效果。本次二次分析纳入了放疗第二周前测量并记录血红蛋白（Hgb）水平的患者。血红蛋白水平分为正常（男性≥14.5 g%，女性≥13 g%）或贫血（男性<14.5 g%，女性<13 g%）。局部区域复发率采用累积发病率法计算。总生存期根据Kaplan - Meier方法估算。放疗晚期毒性按照RTOG发病率量表评分。总生存期、局部区域复发率和晚期并发症发生率的差异通过Cox比例风险模型进行检验。
在504例符合条件的患者中，451例在放疗第二周前测量并记录了Hgb水平。162例患者（35.9%）Hgb水平正常，289例患者（64.1%）为贫血。Hgb水平正常患者的5年估计生存率为35.7%，贫血患者为21.7%（p = 0.0016）。Hgb水平正常患者的5年局部区域复发估计率为51.6%，贫血患者为67.8%（p = 0.00028）。Hgb水平正常患者的5年3级及以上毒性估计率为19.8%，贫血患者为12.7%（p = 0.063）。多因素分析发现，包括T分期、卡氏功能状态评分、N分期、年龄、原发灶总放疗剂量和Hgb水平在内的多个变量是生存的独立预测因素。局部区域控制的独立预测因素包括T分期、卡氏功能状态评分、N分期、放疗剂量和Hgb水平。预测放疗晚期并发症发生的唯一变量是性别（p = 0.0109）和年龄（p = 0.0167）。无论将Hgb水平视为二分变量还是连续变量，这些结果均一致。
在这项大型晚期头颈癌患者前瞻性研究中，低Hgb水平与生存的统计学显著降低及局部区域复发增加相关。在后续头颈癌研究中，Hgb水平应被视为分层变量。提高头颈癌患者放疗前Hgb水平的策略可能会改善生存和局部区域控制。
