Answer:
In most situations, high energy photons (x-rays) are used in radiation treatments. These photons are produced in two ways. Either electrons are accelerated in linear accelerators and directed to impinge on metallic targets to produce x-ray photons (4-20 million electron volts), or high-energy photons are obtained from the nuclear decay of CO60. These megavoltage photons are skin sparing compared to the older kilovoltage or orthovoltage (less than 1 million volts) irradiation. Brachytherapy refers to placement of radioactive material directly on or within tumors.
Radiation deprives cells of their ability to replicate via DNA damage which comes about as a result of the ionizing effect of high-energy radiation. The type and extent of DNA damage is variable ranging from nucleoside base changes to double strand breaks. Although the molecular effects of radiation are very rapid, occurring within seconds, the time to cell death is quite variable, typically occurring at the time of the next mitosis. Once the cells are dead, their products must be removed, and this time course can vary as well. So, it is difficult to base clinical decisions on the observed rate of tumor response to irradiation. The same reasoning applied to the histopathologic response.
In vitro studies show a cell survival curve that is best described by a linear quadratic equation. The linear (alpha) component predominates at lower doses per fraction and applies to tumors and acute responding tissues (oral mucosa, skin). The quadratic (beta) component is very much fraction size dependent and applies to late-responding cells such as subcut, CNS and bone). For this reason, late complications such as fibrosis and osteonecrosis are reduced when the fraction size is decreased.
Dosages vary, but for subclinical disease will range from 40 to 60 Gy (4000 to 6000 rads) and for gross disease from 60 to 80 Gy, given in conventional fractionization (2 Gy per fraction, 5 fractions per week) Fractionization schemes can be altered (accelerated or hyperfractionated) to reduce the overall damage to normal tissues. The average tumor contains approx 109 cells per cubic cm. Tumors containing less than 107 cells are not clinically detectable. A “complete response” as a measure of tumor cure is therefore a very primitive assessment of treatment efficacy, and it is not a substitute for long-term observation.
Hypoxic cells are 2.5 to 3.0 times more resistant to the lethal effects of radiation than well-oxygenated cells. Efforts to overcome this problem have included hyperbaric oxygen, compounds that selectively sensitize hypoxic cells and the use of high-linear-energy transfer radiation (neutrons or pymazons) whose biologic effect is not influenced by the lack of oxygen.
Preoperative radiation offers the advantage of an undisturbed vascular bed (less hypoxia), initial treatment of all sites of disease, treatment of smaller volumes (all surgically manipulated tissue must be treated postop), and less risk of tumor seeding. The disadvantages are that tissues will be harder to manipulate secondary to fibrosis, and wound healing problems and infection will be more prevalent.
The advantage of postoperative radiation include a lower risk of healing problems, avoiding inadequate resection secondary to tumor regression and unnecessary radiation in patients with very early or disseminated disease detected at the time of surgery. Attempts should be made to avoid radiation to the wound for at least 6-10 days since during this proliferative phase the wound has a large number of macrophages and fibroblasts that are quite radiosensitive, but before the time of dense fibroplasia and ischemia (and also before the tumor begins to recover and grow again). One rule of thumb is to wait a week for each week during which therapy was administered. In head and neck cancer, a randomized trial has shown no difference in overall efficacy in preop versus postop radiation.