Intra- and intertumor heterogeneity in blood perfusion of human cervical cancer before treatment and after radiotherapy

Abstract

Knowledge of the intratumor heterogeneity in blood perfusion may lead to increased understanding of tumor response to treatment. In the present work, absolute perfusion values, in units of ml/g.min, were determined in 20 tumor subregions of patients with cervical cancer before treatment (n = 12) and after 2 weeks of radiotherapy (n = 8), by using a method based on contrast-enhanced magnetic resonance imaging. The aims were to evaluate the intratumor heterogeneity in perfusion in relation to the intertumor heterogeneity and to search for changes in the heterogeneities during the early phase of therapy. The intra- and intertumor heterogeneity in perfusion were estimated from components of one-way analyses of variance. The mean perfusion differed significantly among the patients before treatment, ranging from 0.044 to 0.12 ml/g x min. Large differences in perfusion were also observed within individual tumors. The heterogeneity was largest in the best perfused tumors, perfusion values ranging, e.g., from 0.055 to 0.29 ml/g x min were observed. The intratumor heterogeneity was similar to the intertumor heterogeneity. The mean perfusion generally increased or tended to increase during radiotherapy, ranging from 0.064 ml/g x min to 0.13 ml/g x min after 2 weeks of treatment. There was a tendency of increased intratumor heterogeneity in perfusion after therapy, consistent with the higher mean value; a difference in perfusion of more than a factor of 10 was seen within some tumors. These results suggest that cervix tumors contain a significant amount of poorly perfused subregions with high treatment resistance. Moreover, the perfusion and perfusion heterogeneity may increase during the early phase of radiotherapy and influence tumor response.