(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.
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I just read the cancer series you linked as well as this post. Very informative! For example, I did not know about the stages of cell growth and why that made surgery + other treatment necessary sometimes.
In the last three years I've met three radioncologists (sp?) -- the first for treatment of my meningioma, the second for treatment of my husband's prostate cancer, and the third who is currently treating my Dad's lung cancer.
What they all have in common is a thorough excitement about their work and a desire to share information. I've never had any other treatment so thoroughly explained. The doc treating my Dad spent over two hours explaining to us how the treatment worked, how and why treatment plans were made and reviewed and showing off his equipment. It was fascinating because he was so knowledgeable and so excited about the subject.
Thanks for writing these posts.
As I understand it, NMR was never "nuclear" in the sense of radiation anyway. It's a powerful magnetic field that keeps the electrons from flip-flopping their spins. As the field is relaxed, some of the electrons start switching spins, and others don't, depending on what kinds of chemical bonds they are participating in (IIRC).
One small quibble: you write that "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 (remembering that EM radiation can be thought of as a wave, and when waves all peak at once, you get an additive peak)."
The wave properties don't really come into play here, because the radiation is incoherent (being emitted randomly by various atoms). There's no interference at play.
My impression is that the knife works by spreading the X-rays over multiple paths, which all cross at the target. No path gets very much radiation, but the intersection point gets the accumulation from all paths. One can imagine it in part like traffic flowing into a city's downtown. If all the traffic flows down one path into the city, that path is a complete mess. If the traffic flows down a bunch of different roads into the downtown, only the downtown is a mess!
An excellent post, though!
BaldApe wrote: "It's a powerful magnetic field that keeps the electrons from flip-flopping their spins. As the field is relaxed, some of the electrons start switching spins, and others don't..."
Accurate, except that it's the spin of the nucleus that is affected, not the spin of the electrons, hence the "nuclear" in NMR. Your broader point is correct, though; "nuclear" refers to "nucleus", not to "nuclear power", which is how people often interpret it.
Thanks, gg, I'll fix that. Yes, of course the "nuclear" in NMR does not refer to ionizing radiation, but it still scares folks cuz its teh nucular!@!!!
This makes me excited about becoming an oncologist when I finish Med school (still a long way)
How does brachytherapy compare to proton therapy? A family member of mine was a physicist who worked on one of the early projects and later was treated with it, so he is a big fan. However, I've heard that it prohibitly expensive to do in many locations.
Proton therapy is still fairly new to me. The nearest one to me is several hundred miles away, but they're building one nearby, so I'll be reading about it. I've been told it has certain advantages in certain situations, but I haven't read up much yet.
Brief correction to 2:
It's not the electron spins which are flipped, but the spins of the protons in the nuclei of (usually) hydrogen atoms. That's why it's _nuclear_ magnetic resonance, not electronic magnetic resonance.
That's mostly it. But there are two parts to NMR (it is still called that in chemistry, and it's THE tool of choice for the organic chemist).
One is the powerful magnetic field (for high-res. NMR, that is made with a supraconducting, cryocooled magnet), which serves to create energy differences between different nuclear spin states.
The other is the probing with high intensity radio waves (the wavelenghts are close to those used in TV transmission; I was told that prior to activation of the newer machine my former lab has, verifications had to be made with one local TV station).
The intensity is such that sitting near an NMR spectrometer for long stretches of time makes you feel hot despite a quite cool room temperature. You are also strongly discouraged from going near the machine if you happen to have a pace-maker.
The energy from the radio wave makes the nuclear spins shift against the magnetic field; it is afterwards released, as radio waves of various frequencies, when the spins relax to their former state. It is those reemitted radio waves which constitute the signal in NMR.