Cancer vascularization: Implications in radiotherapy?

Purpose: Although hypoxia is considered a major cause of failure of radioth erapy, the mechanisms of tumor hypoxia are unclear, and effective ways for its correction or targeting are missing. Tumoral vasculature is the vehicle for the hemoglobin to reach the tumoral stroma, Although anemia has long b een focused on as an important parameter related to tumor hypoxia, differen ces in vascular density may also affect the intratumoral access of hemoglob in. Methods and Materials: In the present study, we examined the vascular densi ty in 1459 human carcinomas. The distribution of the vascular density withi n tumors was studied in 436 non-small-cell lung carcinomas and 298 breast c arcinomas. Results: The vascular density was found to vary up to 22-fold ev en among tumors of the same histology. Overall, the vascular density was significantly higher in the tumor periphe ry as compared to inner areas, Three different patterns of vascularization were identified in both lung and breast cancer specimens; (I) tumors with l ow or (2) tumors with high vessel density throughout the tissue section, an d (3) tumors with high vessel density in the tumor periphery and low in inn er areas. The death rate following surgery showed a direct association with the vascular density in lung, breast, colon, and endometrial cancer, In in operable gastric cancer patients treated with chemotherapy, and in head and neck cancer patients treated with radical chemoradiotherapy there was a 'U -like' association of the death rate with the vascular density suggesting t hat very low (poor oxygen and drug availability) and very high (intensified angiogenic pathways) vascularization are both linked to poor outcome. Conclusion: The present study stresses the importance of the vascular densi ty as a putative variable that may have affected the results of large clini cal trials that investigated the role of anemia, hyperbaric oxygen, hypoxic sensitizers, or even of combined chemoradiotherapy in the outcome of radia tion treatment. (C) 2000 Elsevier Science Inc.