Do malignant tumors need oxygen to survive radiotherapy?
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Abstract
The pathological vascular network in malignant tumors is generally irregular and chaotic. Euoxic clonogenic tumor cells (radiosensitive) are gathered around the vessels, which are unevenly distributed within the tumor volume. The results of many clinical studies [mainly on head and neck (H&N) cancers] have convincingly shown that extension of the overall irradiation time (OTT) needs a pronounced increase in the total dose (TD). It was strongly suggested that the results reflect an accelerated clonogens repopulation, which likely neutralizes about 30% of the cell kill effect of each dose fraction, and it potentially increases to even 80% towards the end of conventional irradiation. However so far, this mechanism’s activity seems to be quantitatively exaggerated, since towards the end of irradiation, residual 101–102 cancer cells likely become hypoxic and highly resistant to 2 Gy fractions. Thus, local hypoxia should likely be considered as a dominant process responsible for clinical failure. Accelerated repopulation of only a few cellular survivors does not seem reliable. The efficacy of various chemical radiosensitizers, bioreductive drugs, and immuno-boosts are presented and discussed. Finally, it becomes clear that conventional 2 Gy fractionated radiotherapy should no longer be considered as an effective regimen to achieve local tumor control of locally advanced cancer higher than 50%. Pronounced improvement of the RT might be expected using an initial conventional dose of 50 Gy given in 25 fractions followed by a boost of 4–5 large dose (hypo) fractions of 5–6 Gy or by local brachytherapy.
Keywords: tumor oxygenationcell kill effecthypoxiaradiosensitizersimmuno-boosts
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