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Radiation Therapy

Radiation therapy is treatment of cancer with ionizing radiation.

In the most basic sense, ionizing radiation damages the DNA of cells as they try to divide and replicate. Cells that are dividing and replicating faster are more susceptible to DNA damage from radiation therapy. Therefore, since cancer cells are rapidly dividing, they are more likely to be destroyed by radiation than normal cells in the body.

However, some normal cells in the body divide and replicate more frequently than other normal cells in the body; for example, cells lining the mouth and throat are constantly regenerating, as are skin cells. This is why when you are treated with radiation for a cancer inside the mouth or throat, one of the major side effects is mucositis, or inflammation of the mouth and throat lining.

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One advantage of radiation over surgery is that it can be administered on an outpatient basis, which means you will not have to be admitted to the hospital. Also, it avoids the risks of general anesthesia during surgery, which is particularly important in patients with many medical problems or even just one severe medical problem. Also, radiation therapy as a treatment allows for the possibility of organ preservation; for example, patients can be treated for cancer of the larynx (voice box) without the need to remove the larynx.

One disadvantage of radiation is that patients need to come into a treatment facility five days per week for six to eight weeks (though this schedule can vary). Also, there are a number of side effects, both immediate and long-term, that need to be considered.

When is radiation therapy used?

The selection of the best treatment for you is a decision that is made after a discussion with your doctor. The decision will depend on many factors, including the type of cancer, the location of cancer, previous treatments and your other medical problems.

In general, radiation therapy is used for head and neck cancer in a variety of settings:

  • Definitive radiation therapy (with or without chemotherapy): Definitive radiation therapy means that the treatment of the cancer is radiation. It can be combined with chemotherapy, which is called definitive chemoradiation therapy. The advantage of this approach is that it allows for organ preservation in some cases. If there is evidence of persistent cancer, or if the cancer returns in that very location, the next step for treatment will be surgery to remove the cancer.
  • Adjuvant radiation therapy (with or without chemotherapy): This is the use of radiation therapy after surgical removal of all of the obvious cancer. Carefully planned radiation after surgical resection has been shown to decrease the chance of the cancer coming back. This is probably because the radiation kills any microscopic cancer cells that were not obvious during the surgical resection. In some cases, post-operative radiation might be combined with post-operative chemotherapy to further decrease the chance of cancer returning after surgery.
  • Neoadjuvant radiation therapy (with or without chemotherapy): This strategy is used mainly in clinical trials or certain cases of advanced disease. In neoadjuvant radiation therapy (with or without chemotherapy), the non-surgical treatment is given, and then surgery is done afterwards. This allows pathologists to study the response, and if there is any cancer remaining, a surgeon can remove it.
  • Palliation of symptoms: When cancer has spread to distant sites, or when all standard treatment measures have failed and additional surgery is not an option, radiation can be used to palliate symptoms (which means make a person feel better or prevent a major complication that could impact quality of life). An example of this might be cancer that has spread to the bones of the spine; this can be quite painful, and radiation can treat the tumor there without making a patient go through a surgery.

Types of radiation therapy delivery methods

There are a number of different ways to administer radiation therapy. The two main techniques for most head and neck cancers are external beam radiation therapy and brachytherapy.

  • Standard external beam radiation therapy: This is the main form of radiation therapy for head and neck cancer. Either X-rays or gamma rays are used in standard external beam radiation therapy. The current standard of care in delivering external beam radiation for head and neck cancer is to use intensity-modified radiation therapy (IMRT). In a basic sense, this is a way to adjust the dose delivered in over 100 thin beams of energy in a three-dimensional space. By adjusting each beam individually, a radiation oncologist can design a plan that gives little radiation to normal tissue and maximal radiation to cancerous tissue. This decreases, but does not eliminate, side effects of radiation therapy when normal tissue is affected.

A few weeks prior to starting radiation therapy, you will undergo a simulation session. In this session, you will lie on a hard flat bed and undergo a CT scan. Contrast might be injected into your veins for this scan. A technician may make some markings on your skin. During this session, a special mask will also be created just for you; this is to make sure your positioning is consistent each day you come for treatment, and the radiation is administered as accurately as possible.

The images from the CT scan will be analyzed by your radiation oncologist and a team of scientists so they can design a treatment and dosage plan personalized for you and your tumor. These plans are created and checked a number of times to ensure they are correct. It can take about a week to create the right plan for you.

The exact frequency and length of time of your treatment visits will be determined by your radiation oncologist, but a typical treatment will be five days per week for approximately six weeks. Each visit takes less than fifteen minutes inside the machine.

  • Brachytherapy: This is a form of radiation in which the source of radiation, usually a tiny radioactive “seed,” is implanted very close to or actually within the cancerous mass. In contrast to external beam radiation therapy, in which beams of photons are shot through your skin, brachytherapy uses needles (catheters) placed through your skin to the target area. The radioactive implants can be temporary or permanent.

The main advantages of brachytherapy are that more of the radiation can be delivered to the targeted tumor while sparing normal tissue, and that the radiation is administered continuously, which is better for slow-growing cancers. The disadvantages of brachytherapy are that the tumor must be well defined because radiation cannot be delivered as effectively to poorly defined growths.

Brachytherapy catheters or seeds are placed in the operating room while the patient is completely asleep. They are positioned such that the area of each implant that emits radiation sits immediately next to the targeted cancerous tissue.

For the placement of brachycatheters, a surgeon might perform a tracheotomy once the patient is under anesthesia; this is just a precaution in case there is any significant swelling or bleeding that might cause difficulty breathing. This is commonly performed when treating cancers in the base of tongue. The tracheotomy tube is typically removed after a few days. Once the patient is asleep, the radiation oncologist will proceed with placing the catheters. The catheters are placed through the skin and positioned in such a way that the area that emits radiation is positioned within the area of interest. Once the required number of catheters is in place, the patient will awaken and be taken to the recovery room. The next step will be to load the catheters with a radiation source. This will be done in a private room to limit exposure of the clinical staff or other patients to radiation. Currently, for the head and neck, the brachytherapy catheters can be left in place for about five to seven days to deliver a substantial dose of radiation, or they can be used as a boost to a very specific area for about two to three days after giving external beam radiation.

Some additional types of radiation therapy that you might encounter include:

  • Intra-operative radiation therapy (IORT): This type of external beam radiation therapy is a high dose of very targeted therapy directed at a specific area that is at risk of harboring microscopic cancer cells after all the obvious disease has been removed surgically. In the head and neck it is used in a few select centers, mostly in patients who have extensive cancer that has returned after previous radiation therapy, or less commonly in very locally advanced cancers that are at high risk of recurring despite maximal surgery and external beam radiation.1Hu KS, Enker WE, Harrison LB. High-dose-rate intraoperative irradiation: current status and future directions. Seminars in Radiation Oncology. 2002;12(1):62-80. In this technique, after surgical removal of all obvious cancer, the radiation oncologist will enter the operating room and place an applicator in the area where microscopic cancer cells are likely to be. Along with a team of scientists, the radiation oncologist will devise a treatment plan and use a mobile linear accelerator to administer the radiation over a period of about 30 minutes. This must be done in a special shielded room with cameras to monitor the patient asleep on the operating room table. Intra-operative radiation is generally considered safer than administering an additional dose of external beam radiation therapy. This is because normal tissue all around the tumor bed can be pushed out of the way, retracted, and shielded. Also, the radiation in IORT is administered to a very focused area where there is concern for residual tumor. There is no standard dosage that is administered with IORT, but it typically ranges from 10 to 20 Gy.2Perry DJ, Chan K, Wolden S, Zelefsky MJ, Chiu J, Cohen G, Zaider M, Kraus D, Shah J, Lee, N. High-dose-rate intraoperative radiation therapy for recurrent head-and-neck cancer. International Journal of Radiation Oncology * Biology * Physics. 2010;76(4):1140-1146. Taken together, in highly selected cases, the ultimate goal of IORT with salvage surgery is to give the best chance of curing recurrent cancer while lowering the risks of a major complication. This is not standard care at this time. Studies are ongoing to determine the exact role of IORT for recurrent cancer in the Head and Neck.3Chen AC, Bucci MK, Singer MI, Garcia J, Kaplan MJ, Chan AS, Phillips TL, Intraoperative radiation therapy for recurrent head and neck cancer: the UCSF experience. Int J Radiat Oncol Biol Phys; 2007; 67(1):122-129.
  • Neutron beam radiation therapy: This type of external beam radiation is only available at a few sites in the United States. In theory, the higher energy neutron beams (as opposed to the lower energy photon beams) have greater cell killing capability per dose and might be better in overcoming radioresistence. This is particularly important in large tumors with areas of low oxygen and in large slow-growing tumors. For head and neck cancer, neutron beam radiation therapy remains experimental and can be considered for a select few unresectable salivary gland cancers (such as adenoid cystic carcinoma).
  • Proton beam radiation therapy: This type of external beam radiation is only available at a few centers around the world, including approximately 11 in the United States. Proton beam radiation therapy uses protons (instead of photons) to kill cancer cells. The advantage of using protons (as opposed to X-rays or gamma rays in the photons of standard external beam radiation) is that they allow for more precise delivery of radiation than even standard X-ray-based external beam radiation with IMRT. This should result in less damage to normal tissue and thereby decrease side effects. This is still an extremely expensive technology that needs more study before it will become mainstream for treatment of head and neck cancers.
  • Radiosurgery: Though called radio-“surgery,” this is really delivery of very tight beams of radiation from multiple different directions to focus on a very specific target area. It goes by various names, including Cyberknife®, Gamma Knife® and LINAC. It is used mainly for benign disease, including brain tumors. It is not a major form of treatment for head and neck cancers.
  • Radioactive iodine: This is a form of radiation that is NOT external beam. This is used to treat certain stages of well-differentiated thyroid cancer (as well as some cases of benign thyroid disease). It works on the premise that thyroid cells use iodine, so when a patient drinks a radioactive form of iodine, the thyroid cells will take up the iodine and be destroyed. In theory, this should destroy thyroid cells anywhere in the body. For this to be effective for thyroid cancer, any thyroid tissue that can be removed surgically should be removed prior to administering radioactive iodine. Radioactive iodine is administered as a drink or a capsule. Radioactive iodine should not destroy normal tissue because most normal tissues do not take up iodine. Side effects of radioactive iodine might include dry mouth, nausea and fatigue; some patients also complain of a metallic taste in the mouth. In addition, you will need to take some special precautions after treatment.
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Side effects of radiation therapy

There are number of side effects of radiation therapy. The likelihood and severity of complications depends on a number of factors, including the total dose of radiation delivered, over what time it was delivered and what parts of the head and neck received radiation.

  • Xerostomia (dry mouth): The most common long-term side effect of radiation therapy for the treatment of head and neck cancer is xerostomia (dry mouth). It occurs when salivary glands are radiated or in the line of radiation. Aside from being bothersome to patients, including making it difficult to eat and speak, there is great risk of dental cavities and dental disease because saliva helps prevent dental disease. While the incidence of xerostomia is lower with new technologies such as intensity modulated radiation therapy (IMRT), in which the radiation therapist can more precisely control how much radiation is given to different parts, this complication still remains. Patients learn to manage with this in a number of ways, including frequent drinking of liquids and using artificial saliva preparations. Also, certain medications given around the time of radiation might lessen the severity of xerostomia (e.g. pilorcarpine, amifostine).
  • Osteoradionecrosis (bone death): This is necrosis (or death) of bone that has been exposed to radiation. The bone often becomes exposed through the skin or mucosa and can progress to an actual fracture of the bone. Osteoradionecrosis (ORN) can cause severe pain as well as chronic and persistent infections. In ORN, trauma (such as removal of bad teeth within a jaw bone that has poor blood supply from radiation) can lead to all the symptoms of ORN. If you need dental work after head and neck radiation, you should consider seeing a dentist who is familiar with the treatment of ORN.

The main treatment of ORN is really prevention. All head and neck cancer patients who will receive radiation should see a dentist before treatment to make sure the teeth are in the best possible shape; any diseased teeth should be removed approximately three weeks or more before starting radiation treatment. After radiation, patients should take very good care of their mouths, including frequent cleaning and fluoride treatments. Once ORN sets in, treatment might include antibiotics, frequent debridement, and sometimes even hyperbaric oxygen dives. At some point, you might require a major resection of all diseased bone with a reconstruction using a microvascular free flap.

  • Odynophagia (and mucositis): This is pain with swallowing. It can be caused as the mouth and throat lining starts sloughing off and becomes inflamed (mucositis). It can be treated by swishing and swallowing liquids that numb the pain, or in some cases with strong pain medication. Rarely, if a patient is not able to eat or drink for an extended period of time, a doctor might suggest placement of a feeding tube until the patient gets through the painful phase.
  • Skin changes: Patients will usually lose hair in the region that received radiation. Also, there may be some slight color changes to the skin or mild swelling.
  • Hypothyroidism: The thyroid gland is located immediately in front of many parts of the throat. Therefore, damage to the thyroid gland can occur following radiation for head and neck cancers. This will result in hypothyroidism, or an underactive thyroid, which can actually be quite delayed in its presentation. The doctor should routinely check thyroid function tests, especially with new symptoms such as new onset tiredness and significant weight gain. This can be effectively treated by taking a thyroid hormone substitute pill once a day.
  • Pharyngoesophageal stenosis: This can be another delayed problem caused by radiation. Pharyngoesophageal (PE) stenosis is an area of narrowing in the pharynx or esophagus. This narrowing can make it difficult to eat, particularly solid food. If the PE segment becomes completely closed off, the patient won’t be able to eat or drink anything by mouth and will require a feeding tube placed directly into the stomach (gastric tube). Treatment of this complication might include frequent placement of dilating catheters down the throat to stretch open the narrowed segment or surgical removal of the blocked segment with flap reconstruction.
  • Secondary cancers: Paradoxically, even though radiation is used to treat cancer, years later it can actually result in new cancers appearing. The risk increases with high dosage and greater time since treatment. The secondary cancer can be quite different from the original and could include lymphomas, sarcomas and leukemias. Secondary cancer is very rare, and your radiation oncologist will talk to you about this risk, particularly if you are a young patient with head and neck cancer.

References

1 Hu KS, Enker WE, Harrison LB. High-dose-rate intraoperative irradiation: current status and future directions. Seminars in Radiation Oncology. 2002;12(1):62-80.

2 Perry DJ, Chan K, Wolden S, Zelefsky MJ, Chiu J, Cohen G, Zaider M, Kraus D, Shah J, Lee, N. High-dose-rate intraoperative radiation therapy for recurrent head-and-neck cancer. International Journal of Radiation Oncology * Biology * Physics. 2010;76(4):1140-1146.

3 Chen AC, Bucci MK, Singer MI, Garcia J, Kaplan MJ, Chan AS, Phillips TL, Intraoperative radiation therapy for recurrent head and neck cancer: the UCSF experience. Int J Radiat Oncol Biol Phys; 2007; 67(1):122-129.