Treatment of Mesothelioma with Radiotherapy

Abstract

Radiation therapy is a therapeutic modality that uses ionizing radiation to treat cancers and some nonmalignant conditions. Ionizing radiation kills cells by damaging DNA (1). Approximately two thirds of the DNA damage caused by ionizing radiation is from indirect action, that is, damage caused by free radicals generated mostly from the ionization of water (1). The remainder of the damage caused by radiation is through direct ionization of DNA. Radiation damage is also highly dependent on the presence of oxygen. The cytotoxicity of radiation is approximately three times greater in the presence of oxygen than that which occurs in an anoxic environment (1). Hypoxia in human tumors has been extensively investigated and may be a physiologic cause for radiation resistance (2–4). The absorbed dose of radiation therapy is prescribed in units called gray (Gy). The clinical use of radiation therapy in the United States is usually fractionated, that is, delivered in small doses daily. In general, for definitive or curative radiation therapy courses, a daily dose of 180 or 200cGy per day is used. A total dose of radiation therapy for a curative course is usually between 5000 and 7000cGy. For palliative courses of radiation therapy, daily doses between 250 and 400cGy are used for a total dose of between 2000 to 3500cGy. The biologic basis for fractionation is that greater tumor cell kill can be achieved with fractionation relative to normal tissue effects by exploiting the 4 Rs: cellular repair, reassortment of tumor cells into sensitive phases of the cell cycle, reoxygenation of tumor cells, and repopulation of normal tissues. The total dose of radiation therapy used clinically is, in general, dependent on the radiation doses that the normal tissues within the radiation field can tolerate (so-called tolerance doses). There are some tumors that are quite radioresponsive, and for these tumors, doses below normal tissue tolerances can be used. However, for most solid tumors, including mesothelioma, the dose of radiation therapy that is prescribed is based on the tolerance of the normal tissues. In the case of mesothelioma, normal tissues that are sensitive to the effects of radiotherapy are