Introduction

When most people think of radiation they envision the type of radiation depicted in movies and on television, the type of radiation that is so powerful it can destroy whole cities, or cause mutations that are either deforming or can invest superhuman powers on its victim.

The reality is that radiation is all around us. Radiation is just energy that travels in waves. Different types of radiation have different energy levels. Radiation is what gives us radios, microwaves, sunburns, and can even kill. Radiation can also be a medical wonder. When utilized properly, by trained individuals, radiation can cure cancer.

Radiation has been used for over a century to treat humans with cancer, and over the years has become more sophisticated. But the basic science behind how and why radiation works hasn't changed. In recent years radiation has become a more common/available therapy for our veterinary patients.

Radiation works by attacking and killing DNA. DNA is the backbone of all of the genes that make us who we are. The pattern of proteins that make up DNA is what makes us a human being, gives fish fins and the ability to breathe underwater and gives cancer cells the drive to divide, metastasis and eventually kill their host.

The DNA in a cancer cell is different from the DNA in the cells that inhabit the same living organism. While the basic backbone is identical, cancer cells have mutations that allow them to divide uninhibited by normal control mechanisms.

In all living organisms cells divide by process called mitosis, dividing into two new daughter cells. Prior to dividing, a cell must first replicate its DNA. In order to do this cell goes through an extremely tightly controlled process called the cell cycle. Mitosis makes up only a small portion (approximately 10%) of a cell's lifetime, but is vital to allow for replication. How often a cell divides depends on what type of cell it is. Some cells, such as the ones that make up brain tissue, or bone, divide very slowly. Some cells, such as skin and intestinal mucosa, divide multiple times a day. Cancer cells can divide even faster than this.

Cancer cells can speed up their cell cycle by ignoring cell cycle check points. These are prescheduled rest stops in a cell cycle that allows the body to check for abnormalities in replication of DNA. If an abnormality is detected, a normal cell is stopped at a checkpoint to allow for repair of its DNA. If repair is not possible, that cell commits suicide, in a process called apoptosis. Cell suicide prevents damaged or abnormal cells from progressing through to replication and passing on their inherent problems to their offspring.

Many cancer cells have mutations that allow them to ignore cell cycle check points. Radiation can actually exploit this ability, allowing us to destroy cancerous cells while saving normal cells around it.

Remember that checkpoints are there to allow cells to repair damaged DNA. Because cancer cells do not pause at checkpoints, any damage to the DNA passes through to the point of mitosis. If, at the point of a cell dividing into two daughter cells, the DNA damage is so severe that replication is impossible, cancer cells will die. The goal of radiation is to create damage in the DNA that is this severe.

Now remember that even the normal cells in our body have different rates of replication. So what about quickly dividing skin cells and intestinal mucosal cells that have less time to repair themselves? When we irradiate an area of the body, we do so non-specifically, which means that all the cells in the field get the same dose of radiation. Normal cells that are dividing quickly, will also die. This leads to what we call "Acute Radiation Effects" (ARE). These side effects are seen in the fast dividing cells in our body, and include things like moist desquamation of the skin, diarrhea or mucositis. Luckily, because these cells divide quickly, they can be quickly replaced with new cells moving into the damaged area, or coming from stem cells that have a much higher radiation tolerance.

Normal cells that divide slowly are also affected, but may be able to repair the radiation damage if given enough time before they are irradiated again or go to divide. A brain cell is dividing very slowly, and can spend an extended time at a check point trying to fix radiation damage before it has to decide whether to commit suicide or not. The down side to that is that if the slowly dividing cell either has too much damage, or gets a second dose of radiation before its manage to repair the initial damage, it could be hurt beyond possible recovery. If the slowly dividing cells in the body are damaged they may not be replaced because there is no reserve. It could be a long time before the damage created by this is seen because they will live out their normal life span before realizing they can't divide. Irreparable damage to slowly dividing cells give rise to "Late Radiation Effects" (LRE), which will be seen months to years after a radiation treatment.

As a radiation oncologist we are willing to accept acute radiation effects, because we know that these will heal quickly. Late radiation side effects are to be avoided, because they are irreparable.

Side Effects

Most organs in the body can have both acute and late radiation side effects. As discussed, some degree of radiation side effects are unavoidable. But preventing these side effects from being life limiting or from affecting the quality of life of our patient, is what matters most to a veterinary radiation oncologist.

Skin

 ARE are common and often unavoidable. These effects can range from mild superficial erythema to full thickness moist desquamation.

 Pain control is very important, and usually very aggressive to prevent self-mutilation during this period.

 LRE effects can happen with skin also and are almost never quality of life limiting.

 Vitaligo (whitening of hair).

 Alopecia (loss of hair) along with dermal hyperpigmentation.

 Rarely full thickness fibrosis and ulceration; usually happens if an animal is allowed to chew at ulcerated skin.

Mucosa

 Mucositis is an ARE that is quite common when irradiating oral mucosa or mucocutaneous junctions such as the perineum.

 Topical medications (magic mouthwash, cortisone creams) may help; aggressive pain control is more important.

Intestines

 Diarrhea due to sloughing of intestinal lining is the most common ARE of the intestines.

 This ARE may be mild and controlled easily with medications, or may even progress to life-threatening bacterial translocation and sepsis.

 Degree of ARE depends on dose to intestine, length of intestine irradiated and whether or not it is full circumference radiation.

 If the ARE is severe, fibrosis and stricture may eventually result (i.e., consequential late effect; severity is dependent degree of ARE).

Lungs

 Lungs can have both ARE (pneumonitis) and LRE (fibrosis).

 Lungs are very sensitive to radiation and the best strategy is to just avoid as much lung tissue as possible.

 If approximately ½ of the lungs are untouched by radiation, clinical consequences of radiation are considered unlikely.

Eyes

 The lining of tear ducts are composed of quickly dividing tissues; therefore ARE would include conjunctivitis, erythema and infections as a result of decreased tear production.

 If severe enough this could result in permanent keratoconjunctivitis sicca (KCS; "dry eye").

 The lenses of the eyes develop cataracts and potential blindness as an LRE.

Brain

 Rarely will the brain suffer from ARE if the dose to brain tissue is kept low enough per treatment.

 If ARE occurs, its usually inflammation and edema, which can suddenly worsen neurological signs.

 Usually responsive to steroids.

 More severe is the possibility of a LRE called brain radionecrosis.

 If radiation necrosis occurs, brain cells die off and are never replaced.

 If a large enough number of them die off, this leads to irreparable neurological damage.

 Brain radionecrosis is one of the most severe LRE.

Bladder

 The bladder can rarely develop sterile cystitis (occasionally hemorrhagic) as an ARE.

 At high doses per treatment of radiation the bladder will fibrose as a LRE; then it cannot expand to collect urine and an animal will become incontinent, definitively a quality of life issue.

Secondary Tumor Induction

 A very rare (in veterinary medicine) LRE where radiation treatment damages the normal cells surrounding a radiation treatment field just enough to cause mutations.

 Years down the road this can lead to tumor induction of a second, completely different type of tumor.

 This is most commonly see with brain and bone.

 Usually in veterinary medicine our patients won't live long enough to see this happen.

 Three point four percent (3.4%) of dogs treated for superficial tumors on their distal limbs will develop osteosarcoma in their underlying bones.

 In humans 1.9% of children that undergo brain irradiation will develop a second tumor, usually more than 20 years after their first irradiation.