Changes in tumor oxygen tension during radiotherapy of uterine cervical cancer: Relationships to changes in vascular density, cell density, and frequency of mitosis and apoptosis

Purpose: Changes in oxygen tension (pO(2)) during the early phase of fracti onated radiotherapy were studied in 22 patients with uterine cervical cance r. The aims were to investigate (a) whether possible changes in pO(2) diffe red among and within tumors and (b) whether the changes could be attributed to changes in vascular density, cell density, and frequency of mitosis and apoptosis. Methods and Materials: The pO(2) was measured polarographically in four reg ions of the tumors before treatment and after 2 weeks of radiotherapy. The vascular density, cell density, and frequency of mitosis and apoptosis were determined from biopsies taken from the tumor regions after each pO(2) mea surement. Results: The changes in pO(2) during therapy differed among the tumors and were correlated to pO(2) before treatment (p < 0.001). The direction of the changes was consistent throughout the tumors; all regions in tumors with i ncreased oxygenation had increased or no change in pO(2) and vice versa. Th e tumors with increased pO(2) (n = 10) had a large decrease in cell density and a significant increase in apoptotic frequency. In contrast, the tumors with decreased pO(2) (n = 10) had a smaller decrease in cell density (p = 0.014) and no significant increase in apoptotic frequency. Vascular density and mitotic frequency showed no change during therapy; however, vascular d amage other than decreased vascular density was observed. Conclusion: These results indicate that the oxygenation of cervix tumors ge nerally changes during the early phase of radiotherapy. The change depends on the balance between the factor leading to an increase and that leading t o a decrease in oxygenation; i.e., decreased cell density and vascular dama ge, respectively. Increased apoptotic frequency may contribute to a large d ecrease in cell density and hence increased oxygenation during therapy. (C) 2000 Elsevier Science Inc.