This is part 1 of what will hopefully be an ongoing series of posts to attempt to remove some of the mystery around radiation therapy. I’m going to begin by explaining the rationale behind treating cancer with radiation and then move on to the behind the scenes details that go into delivering a therapeutic dose of radiation. This is a simplified view of radiation biology, so keep in mind that the true situation is more complex and still not completely understood.
Many types of cells in your body constantly divide in order to replace cells that have died or been sloughed off. However, several mechanisms are in place to keep these cells from growing out of control. Some cells have internal programming that kills them once they have divided a certain number of times. There are also intercellular signals that prevent cells from growing beyond the extent of their proper environment. Cancer cells have lost these controls. They can divide an indefinite number of times and expand throughout the body. Not all cells in a tumor have this ability; the ones that do are called clonogens. A single clonogen can potentially grow into a life threatening tumor.
In order to control a tumor, we must kill all the clonogens within it. The problem is that a high enough dose of radiation to kill every clonogen will also kill normal tissue cells surrounding the tumor. It is virtually impossible to give a curative dose to a tumor without the surrounding tissue also receiving a dose as high or higher. If enough normal tissue cells are killed, the patient may experience severe and possible life threatening effects. There is a saving grace, though. Radiation therapy takes advantage of a major difference between tumor and normal tissue cells, though: tumor cells divide much more rapidly than normal tissue cells. This makes sense as the reason a tumor endangers the patients’ life is its uncontrolled and rapid growth rate.
To understand why the rate of cell division makes such a big difference, we need to know exactly how radiation kills cells. Ionizing radiation creates free radicals that can react with the DNA in cells and damage it by breaking the strands of the double helix. Radiation can also interact with DNA directly and damage it. Regardless of how DNA damage occurs, there are a few possible outcomes. The cell may recognize the DNA damage and kill itself in a process called apoptosis, i.e. programmed cell death. Or, when the next cell division occurs, if the cell’s chromosomes are too damaged then the cell will spontaneously die. However, if there is enough time before the next cell division then the cell may be able to repair its DNA and therefore survive. This is the crucial distinction between normal cells and tumor cells; tumor cells have less time to repair DNA before cell division occurs, and are therefore more likely to be killed by ionizing radiation.
There is yet another wrinkle that complicates the treatment of tumors with radiation. DNA is a double helix and has two strands. If only one strand is broken, the cell is more likely to be able to repair the DNA. If both strands are broken (and both breaks are close to one another), the cell will possibly be unable to heal. Interactions of ionizing radiation are what is called a stochastic, or random, process. Every particle of incident radiation has a certain probability of causing DNA damage. The higher the dose, the more likely it is that a strand of a cell’s DNA will be damaged and the more likely the cell will die.
Now we are presented with a conundrum. We want to give the tumor a high enough dose to kill all of the clonogens, but not such a high dose that normal tissue cells are unable to repair themselves. If all of the dose is given in a single treatment, it is very difficult to meet both of these objectives (unless advanced patient positioning techniques are used). However, we can accomplish both by spreading the total dose out over a number of treatments. This is called fractionation, and it will be the subject of my next post in this series.
References
Hall, E and Giaccia, A (2005) Radiobiology for the Radiologist, Lippincott Williams and Wilkins
Perez, C et.al. (2007) Principles and Practice of Radiation Oncology, Lippincott Williams and Wilkins
