Cancer 202---Radiation therapy

(NB: as is usual with my more "science-y" posts, oversimplification is the rule. --PalMD)

It's been a very long while since I've updated my series on cancer. I keep meaning to, but you know how things go. Lately, though, I've been curious about radiation oncology, the use of ionizing radiation to treat cancers. What set me off was a recent Times article about some pretty crappy practices. Radiation oncology requires a very thorough education in physics and medicine and the field attracts some of the best minds, but no field is immune to unethical behavior (which in this case I feel is more important than the incompetence itself).

Anyway, radiation---it scares the crap out of people. We call magnetic resonance imaging "MRI" instead of the original "NMR" (nuclear magnetic resonance) mostly because the idea of being in a machine with the word "nuclear" on it freaks people out. Of course, radiation is a normal part of living. We are exposed to high energy electro-magnetic radiation daily, both from the Earth and from space. If fact, ionizing radiation from the sun is the primary cause of skin cancer.

Very shortly after ionizing radiation was discovered in the late 19th century, it was applied to the treatment of cancerous tumors, albeit in a very crude way. As knowledge of physics and medicine grew, so did the sophistication of treatments. Early on, of course, it wasn't understood exactly how radiation damaged living tissue. If you aim x-rays at healthy skin for long enough the skin starts to turn red in a way similar to a sun burn. If you want to get that radiation to a tumor somewhere under the skin, then simply aiming an x-ray at the skin above it is going to kill skin long before it kills tumor. Thankfully, people are rather clever. In the early 20th century, doctors tried inserting radium directly into tumors, and tried fractionating treatments of external beam radiation so that each individual dose was not too toxic to the overlying structures. These techniques allowed killing more tumor cells than normal cells.

But let's back up a little here and examine some of the basics.

Ionizing radiation refers to subatomic particles or electromagnetic waves that are energetic enough to strip away electrons from atoms. In medicine, it is usually produced either by a linear accelerator or by the decay of radioactive elements. It affects living tissue in a variety of ways. The key to any cancer therapy is the removal or killing of cancer cells. Surgery removes cancer cells, chemotherapy and radiation kill them.

Radiation effects on tissue

If you think back to high school physics, you'll remember that you can think of light (electromagnetic radiation) as a particle (photon) or a wave. As the high-energy photons of ionizing radiation pass into a human body, they strip away electrons from various molecules (usually water molecules, since we are mostly water) creating charged molecules, or "ions". Though a process called Compton Scatter, these electrons interact with more molecules, creating more ions, until the energy of the original source is "used up". This process, whereby radiation strips electrons from water molecules, creates "free radicals", which interact readily with other molecules. Yes, these are the same free radicals spoken of by folks trying to sell you "anti-oxidants", but this is the real deal. These radicals interact with DNA molecules, often breaking both strands beyond repair, killing the cell.

This process of free-radical production relies on the presence of oxygen. By the time tumors are large enough to be visible, they have often outgrown their blood supply and their centers are relatively short on oxygen (they are "hypoxic"). Therefore, the radiation has less effect deep in the tumor, and if you have residual tumor, you still have cancer. Tumors can be surgically "debulked", that is, removed as much as is possible, leaving residual tumor less hypoxic and more susceptible to radiation.

Of course, all this free-radical-DNA-braking isn't so good for normal cells. One way to deal with this is through "fractionation" of the total radiation dose. Different cells respond differently to radiation, and tumor cells are often more sensitive than normal cells (oversimplification alert!). If you give a smaller dose of radiation, the normal tissues have time to repair themselves in between doses (so do the tumors, but not as effectively). Also, as fractionated doses kill the outer layer of the tumor, the inner bits are exposed to more oxygen, making them more susceptible to further radiation doses.

How to get radiation to the tumor

As mentioned earlier, simply beaming radiation at someone can cause a bit of damage to normal tissues such as skin while failing to sufficiently damage a tumor deep inside the body. The best thing would be for radiation to be delivered to as many tumor cells as possible, and as few normal cells as possible. While external beam radiation is still used extensively and normal tissue spared using fractionation and other techniques, there are some interesting ways of delivering radiation more specifically to a tumor. One such technique is "gamma knife". With careful computer modeling and excellent imaging techniques, hundreds of weaker beams of gamma radiation can be aimed at a tumor at once. These weak beams do little damage to the tissue they pass through, but when they arrive simultaneously at the site of the tumor, the additive damage is significant (edited secondary to physicist correcting me. --PalMD). This technique is especially useful in the brain, where it is important to spare normal brain tissue from the effects of radiation.

Another way to deliver radiation directly to a tumor is to simply put radioactive substances in it. This is the basis of brachytherapy. When external beam radiation is applied, for example, to a prostate cancer, the radiation has a chance to interact with all sorts of normal tissues, such as the rectum. This can lead to severe side-effects, such as bloody diarrhea. It is possible to choose a radioactive isotope that releases radiation over a very short distance in a short period of time, and to implant "seeds" of the isotope in the prostate (or other tissue). This spares the surrounding tissue as the radiation is released into the tumor. Since the half-life of the isotope is short, the seeds rapidly become harmless. Brachytherapy has become an important tool in fighting prostate cancers while minimizing some of the worst side-effects of therapy.

Radiation is a powerful tool in medicine, but like any tool, whether it be a knife or a pill, it must be wielded properly and ethically. The best medicine combines good science, compassion, and ethical behavior to help people. Radiation therapy is one of medicine's most sophisticated techniques, and must be used only by certain experts. It's also really cool.