Excerpt
Hypoxia, a characteristic feature of locally advanced solid tumours, has emerged as a key factor in tumour development because it can promote tumour progression and failure of radiotherapy (RT) due to the increased radioresistance of hypoxic cells compared with normally oxygenated cells. As pointed out by Vaupel and Mayer [
1] from the Institute of Physiology and Pathophysiology, University of Mainz, Germany, hypoxia has two faces, like Janus, in tumour biology because (a) it is associated with restrained proliferation, differentiation, necrosis or apoptosis, and (b) it can also lead to the development of an aggressive phenotype. Hypoxia has been suggested as an adverse prognostic factor for patient outcome independent of factors such as tumour stage and nodal status. Studies of tumour hypoxia involving the direct assessment of the oxygenation status have suggested worse disease-free survival for patients with hypoxic cervical cancers or soft tissue sarcomas. In head-and-neck cancers (HNC), the studies suggest that hypoxia is prognostic for survival and local control. Vaupel and Mayer point out also that technical limitations of the direct O
2-sensing technique have prompted the use of surrogate markers for tumour hypoxia, e.g. hypoxia-related endogenous proteins such as hypoxia inducible factor 1 (HIF-1), carbonic anhydrase isozyme IX (CA-IX) and the glucose transporter-1 (GLUT-1), or exogenous bioreductive drugs. In many—though not all—studies, endogenous markers showed prognostic significance for patient outcome. The prognostic relevance of exogenous markers, however, appears to be limited. Alternatively, non-invasive assessment of hypoxia can be achieved with imaging techniques, including positron emission tomography (PET), single-photon emission computed tomography and MRI. As clinical experience with these methods regarding patient prognosis is limited, in the year 2006, the Cancer Imaging Program of the National Cancer Institute convened a workshop to review the status of hypoxia imaging, to assess what is known about the biology of hypoxia as it relates to cancer and cancer therapy and to define clinical scenarios in which in vivo hypoxia imaging could prove valuable [
2]. The discussion resulted in a series of considerations and statements: Hypoxia, or low oxygenation, has emerged as an important factor in tumour biology and response to cancer treatment. It has been correlated with angiogenesis, tumour aggressiveness, local recurrence and metastasis, and it appears to be a prognostic factor for several cancers, including those of the cervix, head and neck, prostate, pancreas and brain. The relationship between tumour oxygenation and response to radiation therapy has been well established, but hypoxia also affects and is affected by some chemotherapeutic agents. Although hypoxia is an important aspect of tumour physiology and response to treatment, the lack of simple and efficient methods to measure and image oxygenation hampers further understanding and limits prognostic usefulness. There is no gold standard for measuring hypoxia; Eppendorf measurement of pO
2 has been used, but this method is invasive. Recent studies have focused on HIF-1 and CA-IX and on developing non-invasive imaging techniques. The workshop yielded recommendations on using hypoxia measurement to identify patients who would respond best to radiation therapy, which would improve treatment planning, but it was also concluded that hypoxia measurement might also prove useful in drug development and in increasing our understanding of tumour biology. …
