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PURPOSE: Anemia is considered a major factor that counteracts the efficacy of radiotherapy, presumably because of reduced oxygen availability that leads to tumor hypoxia. Nevertheless, anemia is not the only factor defining oxygen availability, because a poor and/or immature vascular network may prevent blood flow and tumor oxygenation. Furthermore, the ability of tumors to upregulate hypoxia-regulated molecular pathways may affect radiosensitivity by mechanisms independent of the traditional concept of "oxygen effect." METHODS AND MATERIALS: In this study, we investigated whether the preoperative blood hemoglobin levels affect the activation status of hypoxia/angiogenic pathways (hypoxia inducible factors [HIF1 alpha and HIF2 alpha], carbonic anhydrase 9, differentiated embryo-chondrocyte protein, vascular endothelial growth factor, and microvessel density), in squamous cell head-and-neck cancer. RESULTS: Hypoxia/angiogenesis pathways were equally activated in tumors, independent of the patient's hemoglobin levels. The expression of HIF alphas was associated with microvessel density (p = 0.01). CONCLUSION: In the present study, we failed to show that a patient's anemia is a main contributor to the activation of hypoxia-regulated molecular pathways in squamous cell head-and-neck cancer. Impaired intratumoral blood flow or tumor-related gene/protein pathologic features may account for this finding. Targeting the hypoxia-regulated molecular cascade emerged as a complementary radiosensitization strategy for a large group of patients with hypoxic tumors, who are unlikely to benefit from conventional approaches aiming to improve intratumoral oxygen delivery through anemia correction.

Original publication




Journal article


Int J Radiat Oncol Biol Phys

Publication Date





67 - 71


Anemia, Basic Helix-Loop-Helix Transcription Factors, Carbonic Anhydrases, Carcinoma, Squamous Cell, Cell Hypoxia, DNA-Binding Proteins, Head and Neck Neoplasms, Hemoglobins, Humans, Hydrogen-Ion Concentration, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Neoplasm Proteins, Neovascularization, Pathologic, Nuclear Proteins, Proteins, Transcription Factors, Vascular Endothelial Growth Factor A