Tumor oxygenation: a new predictive parameter in locally advanced cancer of the uterine cervix

Abstract

Experimental evidence suggests that hypoxia may increase the malignant potential and reduce the sensitivity toward nonsurgical treatment modalities in solid rodent tumors. However, the importance of tumor hypoxia in human malignancies is still uncertain. We have developed a clinically applicable standardized procedure for the determination of intratumoral pO2 in advanced cervical cancers by use of a computerized polarographic needle electrode histograph. To evaluate the significance of tumor oxygenation as a new oncologic parameter we initiated an open prospective clinical trial at the University of Mainz Medical Center in June 1989. Until October 1992 50 patients with advanced cervical cancers entered the study. Tumor oxygenation measured in these 50 patients was independent from various patient and tumor characteristics, including hemoglobin concentration, FIGO stage, and tumor size. Thirty-three patients receiving standard radiotherapy with or without chemotherapy (RT +/- CT) were analyzed for treatment outcome. Intratumoral pO2 histography revealed median pO2 < or = 10 mm Hg (low pO2 tumors) in 15 of the 33 patients; in 19 tumors pO2 fractions < or = 5 mm Hg (low pO2 fractions) were found. After a median follow-up of 24 months (range 6 to 40 months) Kaplan-Meier life table analysis showed significantly shorter survival and recurrence-free survival for patients with low pO2 tumors treated with RT +/- CT. According to the Cox proportional hazards model the low pO2 fraction was the most powerful single predictor of survival and recurrence-free survival. The results of this study are consistent with the view that radiobiologically hypoxic tumors are less radiocurable but mechanisms of treatment failure other than the effect of hypoxia on the radiation response cannot be excluded. Intratumoral pO2 histography in advanced cervical cancers enables pretherapeutic selection of low pO2 tumors as candidates for modified treatment approaches.