Prognostic implications of hemoglobin levels before and after surgery as well as before and after radiochemotherapy for head and neck tumors.

Abstract

Several studies have shown that tumor cells may develop resistance to radiotherapy, proliferating under hypoxic conditions. Following surgery, patients may develop low hemoglobin levels, which may cause low oxygen conditions. This retrospective analysis was undertaken to determine the impact of low hemoglobin levels in patients with head and neck tumors treated with combined-modality therapy (surgery and postoperative radiochemotherapy). We studied 120 patients with mostly advanced head and neck tumors (88% stage III/IV) who had undergone macroscopically complete resections of their primary tumors and lymph node metastases. At 20-277 days after surgery (median: 51.3 days), these patients received postoperative chemoradiotherapy (56.7 Gy of radiation over 28-49 days and cisplatin 6 mg/m(2) body surface area on radiation treatment days with a cumulative dose of 96 mg/m(2)). Normal hemoglobin levels were considered to be 12 g/dl for females and 13 g/dl for males. Decreased hemoglobin levels before or after surgery and before or after chemoradiotherapy were correlated with the prognosis. Preoperatively, 99 of 114 patients (87%) had normal levels of hemoglobin compared with only 20 of 107 patients (19%) postoperatively. At the onset of radiochemotherapy, the hemoglobin levels of 82 of 116 patients (71%) were within the normal range. After radiochemotherapy, however, 62 of 114 patients (54%) had normal hemoglobin levels. Univariate analysis (Kaplan-Meier method and log-rank test) showed that patients with decreased pre- or postoperative hemoglobin levels had significantly worse locoregional control ( P=0.032 and P=0.0001, respectively) and lower overall survival ( P=0.0013 and P=0.0002, respectively) than patients with normal hemoglobin levels. The 3-year locoregional control rates in patients with preoperative hemoglobin levels that were normal, were reduced by 1-2 g/dl or were reduced by more than 3 g/dl, respectively, were 78%, 55% and 50%. Correlated with normal and diminished postoperative hemoglobin levels, the 3-year locoregional control rates were 90%, 84% and 50%, respectively. There was no correlation between prognosis and hemoglobin level at the onset or after radiochemotherapy. On multivariate analysis, only the postoperative hemoglobin level remained a prognostic factor for locoregional control ( P=0.0241) and overall survival ( P=0.0080). We conclude that low postoperative hemoglobin levels resulting from blood loss may influence the efficacy of postoperative radiochemotherapy in patients with head and neck cancer. Early intervention to raise the postoperative hemoglobin level may result in better tumor control and overall survival after combined-modality therapy.