Elming Pernille B, Sørensen Brita S, Oei Arlene L, Franken Nicolaas A P, Crezee Johannes, Overgaard Jens, Horsman Michael R
Department of Experimental Clinical Oncology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
Department of Radiation Oncology, Academic University Medical Centers, University of Amsterdam, 1105AZ Amsterdam, The Netherlands.
Cancers (Basel). 2019 Jan 9;11(1):60. doi: 10.3390/cancers11010060.
Regions of low oxygenation (hypoxia) are a characteristic feature of solid tumors, and cells existing in these regions are a major factor influencing radiation resistance as well as playing a significant role in malignant progression. Consequently, numerous pre-clinical and clinical attempts have been made to try and overcome this hypoxia. These approaches involve improving oxygen availability, radio-sensitizing or killing the hypoxic cells, or utilizing high LET (linear energy transfer) radiation leading to a lower OER (oxygen enhancement ratio). Interestingly, hyperthermia (heat treatments of 39⁻45 °C) induces many of these effects. Specifically, it increases blood flow thereby improving tissue oxygenation, radio-sensitizes via DNA repair inhibition, and can kill cells either directly or indirectly by causing vascular damage. Combining hyperthermia with low LET radiation can even result in anti-tumor effects equivalent to those seen with high LET. The various mechanisms depend on the time and sequence between radiation and hyperthermia, the heating temperature, and the time of heating. We will discuss the role these factors play in influencing the interaction between hyperthermia and radiation, and summarize the randomized clinical trials showing a benefit of such a combination as well as suggest the potential future clinical application of this combination.
低氧区域（缺氧）是实体瘤的一个特征性表现，存在于这些区域的细胞是影响放射抗性的主要因素，并且在恶性进展中起重要作用。因此，人们已经进行了大量的临床前和临床尝试来克服这种缺氧情况。这些方法包括提高氧供应、使缺氧细胞放射增敏或杀死缺氧细胞，或利用高传能线密度（LET）辐射以降低氧增强比（OER）。有趣的是，热疗（39⁻45°C的热处理）能引发其中许多效应。具体而言，它可增加血流量从而改善组织氧合，通过抑制DNA修复实现放射增敏，并且可通过造成血管损伤直接或间接杀死细胞。将热疗与低LET辐射相结合甚至可产生与高LET辐射相当的抗肿瘤效果。各种机制取决于辐射与热疗之间的时间和顺序、加热温度以及加热时间。我们将讨论这些因素在影响热疗与辐射相互作用中所起的作用，总结显示这种联合有益的随机临床试验，并提出这种联合在未来的潜在临床应用。
