Association of Haemoglobin Level with Morbidity and Mortality of Patients with Locally Advanced Oesophageal Carcinoma Undergoing Radiotherapy — A Secondary Analysis of Three Consecutive Clinical Phase III Trials

Abstract

Aims To investigate the strength of association between anaemia and overall survival, locoregional control, and late radiation complications in patients with locally advanced oesophageal carcinoma undergoing radiotherapy with or without chemotherapy and hyperthermia. Materials and methods Between March 1996 and December 2002, 303 patients with locally advanced squamous cell carcinoma of oesophagus enrolled in three consecutive prospective phase III trials conducted in our department were included in this study. These patients received one of the following four irradiation schedules: late course accelerated hyperfractionated (LCAF) radiotherapy alone, LCAF combined with concurrent chemotherapy, LCAF combined with hyperthermia, and continuous accelerated hyperfractionated (CAHF) radiotherapy according to each protocol. According to the haemoglobin levels measured before radiotherapy, patients were stratified to normal haemoglobin group (≥12.0 g/dl for men, or ≥11.0 g/dl for women) or anaemic group (<12.0 g/dl for men, or <11.0 g/dl for women). Overall survival, locoregional control rate and late irradiation toxicity were estimated by Kaplan–Meier method. Results Of 303 eligible patients, 243 patients (80.2%) had normal haemoglobin level and 60 patients (19.8%) were anaemic. The 5-year overall survival was 39% in patients with normal haemoglobin level, whereas, 22%, with anaemia patients ( P = 0.001). The 5-year locoregional control rate at 5 years was 68% in patients with normal haemoglobin, versus 62%, with anaemia patients ( P = 0.050). The 5-year rate of radiation toxicity of grade 3 or greater was 29% in patients with normal haemoglobin level, but it was 8%, with anaemic patients ( P = 0.033). From multivariate analyses, T stage, location of tumour and haemoglobin level were found to be independent predictors for survival. T stage, gender and haemoglobin level were independent predictors for locoregional control. It was also detected that age and haemoglobin level played as independent predictors for development of radiation toxicity. Conclusions For patients with locally advanced oesophageal carcinoma undergone irradiation, anaemia associated a statistically significant reduction in survival and locoregional control rates, but also decreased radiation toxicity rates. Therefore, haemoglobin level should be considered as a stratification variable in prospective clinical trials.