Influence of the hypoxic subvolume on the survival of patients with head and neck cancer

Purpose: Tumor hypoxia is regarded as an important factor influencing radiation response, disease-free, and overall survival of patients with squamous cell carcinoma of the head and neck (SCCHN). This study was performed to reevaluate the prognostic significance of the "classical oxygenation parameters" hypoxic fraction (percentage of pO(2) values < 5 mmHg or < 2.5 mmHg, respectively) and median pO(2), and to determine the influence of a new radiobiological factor. This factor was termed the "hypoxic subvolume" (HSV) and was defined as percentage of pO(2)-values below 5 mmHg multiplied by the total tumor volume. The rationale of this parameter was to quantify approximately the amount of hypoxic tissue which should be correlated to the number of hypoxic cells in the tumor. It is obvious that a tumor of 100 cm(3) with a hypoxic fraction of 20% (HSV = 20 cm(3)) contains more hypoxic cells than a tumor of 100 cm(3) with a hypoxic fraction of 50% (HSV = 0.5 cm(3)). Methods and Materials: Pretreatment pO(2) was assessed in 59 patients with SCCHN with the Eppendorf histograph, and pretreatment volume was determined by ultrasonography (lymphnode metastases) and computer tomography (primaries). All patients were referred to our departments for radiotherapy (n = 27, median dose 70 Gy) or radiochemotherapy(n = 32; 5-FU, mitomycin C, median dose 70 Gy), respectively. All parameters were evaluated using the Kaplan-Meier analysis, and significance was assumed at a p-value of < 0.05 (log-rank test, Cox-Mantel). A multivariate analysis was performed to control for confounding factors. The median follow-up was 233 days. At the time of the evaluation, 34 of the 59 patients were dead. Results: In univariate analyses, the hypoxic fraction (pO(2) < 5 mmHg, pO(2) < 2.5 mmHg [p < 0.05]), the hemoglobin concentration (p < 0.05), and the hypoxic subvolume (p < 0.01) were of prognostic significance for overall survival. In multivariate analysis, the hemoglobin concentration and the hypoxic subvolume (p = 0.01) were significant prognosticators. We found no significant correlation between tumor volume or median pO(2) and overall survival. No clear correlation was found between tumor volume and hypoxic fraction. Conclusion: These data suggest that the total amount of hypoxic tissue, as determined by the hypoxic subvolume, influences the prognosis of patients suffering from SCCHN, In addition, our data confirm the statements of previous studies that low pretherapy pO(2)-values indicate a worse prognosis. (C) 1999 Elsevier Science Inc.