The influence of tumor blood flow and microenvironmental factors on the efficacy of radiation, drugs and localized hyperthermia.

It is generally accepted that tumor blood flow, microcirculation, oxygen and nutrient supply, tissue pH distribution, and the bioenergetic status-factors which are usually closely linked and which define the so-called metabolic microenvironment--can markedly influence the therapeutic response of malignant tumors to conventional irradiation, chemotherapy, other nonsurgical treatment modalities, and the cell proliferation activity within tumors. Currently available information on the parameters defining the metabolic micromilieu in human tumors is presented in this review. According to these data, significant variations in these relevant factors are likely to occur between different locations within a tumor, and between tumors of the same grade and clinical stage. The extent and mechanisms by which the microenvironmental factors influence cellular response to standard irradiation, chemotherapeutic drugs, immunotherapy and localized hyperthermia are described and "physiological" barriers to treatment are outlined.