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 radiotherapy 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 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 (≥ 14.5 gm% for men, ≥ 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.

Results: 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.

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 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.