Anemia is associated with decreased survival and increased locoregional failure in patients with locally advanced head and neck carcinoma: A secondary analysis of RTOG 85-27

Purpose: 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 radio therapy with or without a hypoxic cell sensitizer. Methods and Materials: Between March 1988 and September 1991, 521 patients with Stage III or IV squamous cell carcinoma of the head and neck were ente red into a randomized trial examining the addition of etanidazole (SR 2508) to conventional radiation therapy (RT) (66-74 Gy in 33-37 fractions, 5 day s a week). Patients with hemoglobin (Hgb) levels measured and recorded prio r to the second week of RT were included in this secondary analysis. Hemogl obin levels were stratified as normal (greater than or equal to 14.5 gm% fo r men, greater than or equal to 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 accordin g to the Kaplan-Meier method. Late RT toxicity was scored according to the RTOG morbidity scale. Differences in rates of overall survival, locoregiona l failure, and late complications were tested by the Cox proportional hazar d model. Results: Of 504 eligible patients, 451 had a Hgb level measured and recorde d prior to the second week of RT. One hundred sixty-two patients (35.9%) we re considered to have a normal Hgb level and 289 patients (64.1%) were cons idered to be anemic. The estimated survival rate is 35.7% at 5 years in pat ients 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 ra te of grade 3 or greater toxicity is 19.8% at 5 years in patients with a no rmal Hgb, versus 12.7% in anemic patients (p = 0.063). On multivariate anal ysis, several variables were found to be independent predictors of survival including: T stage, Karnofsky performance status, N stage, age, total radi ation dose to the primary, and Hgb level. Independent predictors of locoreg ional control included T stage, Karnofsky performance status, N stage, radi ation dose, and Hgb level. The only variables which predicted for the devel opment of late RT complications were gender (p = 0.0109) and age (p = 0.016 7). These findings were consistent regardless of whether Hgb level was cons idered a dichotomous or continuous variable. Conclusion: 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 leve l should be considered as a stratification variable in subsequent studies o f 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 c ontrol. (C) 1998 Elsevier Science Inc.