Radiation therapy uses high-energy x-rays to kill cancer cells, thereby shrinking the cancer growth. The objective of radiation therapy is to maximize the probability of cure with a minimum of side effects. Radiation therapy is considered a local treatment because only the cancer cells in the area of the body where the radiation is delivered are killed. If cancer exists outside the radiation field, those cancer cells are not affected by the radiation. Radiation therapy is used alone or in combination with surgery and chemotherapy for the treatment of head and neck cancers. Therefore, it is important for patients with cancers of the head and neck to be treated by physicians at a specialty medical center who are part of a multidisciplinary team.
The two most common ways in which radiation therapy is delivered are externally, through external beam radiation therapy and internally, by brachytherapy. External beam radiation therapy (EBRT) involves the delivery of radiation via a machine that aims x-rays at the body. During brachytherapy, or interstital implantation, a physician places small pellets or seeds of radioactive material directly into the cancer. Most patients receive one or the other kind of radiation and some patients receive both.
External Beam Radiation Therapy
Modern radiation therapy for cancers of the head and neck is usually administered with machines called linear accelerators, which produce high-energy external radiation beams. This beam of radiation penetrates the tissues and delivers the radiation dose deep in the area of the body where the cancer resides. These modern machines and other state-of-the-art techniques have enabled radiation oncologists to significantly reduce side effects while improving the capacity to deliver radiation to the cancer.
Simulation: After an initial consultation with a radiation oncologist, a planning session called a “simulation” is conducted. Areas that will be radiated, called the treatment fields, are determined during the simulation. This session is conducted by the radiation oncologist, aided by one or more radiation technologists and often a dosimetrist, who performs calculations necessary in the treatment planning. The simulation may last anywhere from fifteen minutes to an hour or more, depending on the complexity of the treatment regimen that is being planned.
During simulation, patients lay on a table similar to that used for a CT scan, and a machine called a “simulator” is used to establish the treatment fields. The dimensions and movements of the simulator closely match that of a linear accelerator. But rather than delivering radiation treatment, the simulator lets the radiation oncologist and technologists see the area to be treated. Using an X-ray beam, the radiologist is able to observe the patient’s internal anatomy. The table can be raised and lowered and rotated around a central axis. The lights are usually dimmed while treatment fields are being set. Temporary marks may be made on the patient’s skin with magic markers.
Once the dimensions of the treatment fields are determined, they are marked on the patient’s body with tattoos. These tattoos consist of only small pinpricks with a small amount of ink, appearing like a small freckle. The use of tattoos enables the radiation technologist to set up the treatment fields each day with precision, while allowing the patient to wash and bathe without obscuring the treatment fields.
Radiation treatment is usually given in another room separate from the simulation room. The treatment plans and treatment fields resulting from the simulation session are transferred over to the treatment room. The treatment plan is verified and treatment started only after the radiation oncologist and technologists have rechecked the treatment field and calculations, and are thoroughly satisfied with the setup.
Treatment Schedules: A typical course of radiation for cancer of the head and neck lasts 3-5 weeks with daily treatments on Monday through Friday. The actual treatment with radiation generally last no more than a few minutes. Anesthesia is not needed for radiation treatments, since the patient is unlikely to feel any discomfort. Patients generally have few restrictions on activities during radiation therapy. Many patients continue to work during the weeks of treatment. Patients are encouraged, however, to carefully evaluate how they feel and not overexert themselves.
However, rapidly growing cancers are poorly controlled if radiation is given in daily doses over a long period of time. Therefore, delivery of radiation can be accelerated and given in two or more treatments per day (hyperfractionation) for certain rapidly growing head and neck cancers, such as nasopharyngeal cancers.
Side Effects and Complications: A radiation dose which causes some discomfort in one patient may cause no side effects in another patients. It is not unusual for some patients to report fatigue and changes in sleep or rest patterns. If side effects occur, the patient should inform the technologists and radiation oncologist because treatment is almost always available and effective.
The most significant immediate side effects of radiation for head and neck cancers are mucositis, inflammation of the mucous membranes of the mouth or throat, or dry mouth (xerostomia). These side effects may be further complicated by damage to the salivary glands, resulting in a lack of saliva. These problems can be mild or lead to severe malnutrition.
One of the frequently encountered complications of radiation therapy for head and neck cancer is abnormally low levels of thyroid hormone, referred to as hypothyroidism. Signs and symptoms of hypothyroidism include weight gain, tiredness, depression, constipation, brittle nails, and pale color. These symptoms are subtle and may occur very late; therefore, it is important for patients who have received radiation therapy to be tested on a regular basis.
Another major side effect of radiation therapy is the development of a second cancer. Treatment with radiation can damage healthy tissues to the point that a second cancer, separate from the cancer being treated, may develop. Second cancers often take years to develop. In the head and neck area, radiation treatment for a primary cancer is a frequent cause of second cancers. Thus, the risk of receiving radiation therapy must be carefully weighed with the benefit.
Blood counts can be affected by radiation therapy, though this is not a common complication for patients with cancers of the head and neck. Nonetheless, many radiation therapy institutions make it a policy to check the blood counts at least once during the radiation treatments.
Internal delivery of radiation by the use of implants is called brachytherapy. With brachytherapy, high radiation doses may be delivered to specific cancer cells, without damaging adjacent normal tissues. The radioactive implants are needles or tubes containing a radioactive substance. Such implantations, if carefully performed, are effective, safe, and have a low risk of complications. Brachytherapy can be a useful addition to external beam irradiation in the treatment of patients with head and neck cancer.
Removable implants are especially important in the treatment of cancers of the mouth, tongue, throat, and nasopharynx where they are given as intracavitary boosts following external beam radiation therapy. The implants are placed in the area of the cancer and removed when the appropriate dose is administered. The most commonly used radioactive substance in removable implants is iridium 192.
In some cases, permanent placement of radioactive sources may be necessary. Instances in which permanent implants are effective include recurrent nasophayngeal malignancies, for palliation of accessible recurrences of primary sites in the mouth and throat, or for cervical lymph node metastases. Iodine 125 and palladium 103 are the radioactive substances used for permanent implants.
Another way to deliver radiation internally is linked to elements or monoclonal antibodies that home to specific areas in the body. For example, thyroid cancer is treated with iodine linked to an isotope and injected into a vein. The thyroid gland preferentially takes up iodine from the blood, resulting in a concentration of radiation. Monoclonal antibodies are also used to deliver radioactive substances. These are laboratory produced proteins that can locate cancer cells in the body. When attached to a radioactive substance, they serve as a delivery system that targets cancer cells while sparing normal cells.
Combined Radiation and Chemotherapy
Combined modality therapy plays a central role in the management of head and neck cancers. Clinical studies have suggested that combining chemotherapy with radiation is better than using either treatment alone for the treatment of head and neck cancers. For example, three large studies involving patients with throat cancer have shown that treatment with radiation plus chemotherapy lead to longer survival rates and a lower rate of recurrence than treatment with radiation alone. Currently, clinical trials are ongoing to determine the optimal chemotherapy combinations and sequencing of radiation.
Effects of treatment with radiation and chemotherapy vs radiation alone in three studies of patients with throat cancer
|Europe (226 patients)||Japan (130 patients)||Germany (226 patients)|
|3-year survival||Survival w/out recurrence||2-year survival||5-year survival||5-year survival||Control of local cancer||Recurrence Rate|
|Radiation plus Chemo.||51%||42%||68%||46%||51%||66%||58%|
Strategies to Improve Radiation Treatment of Head and Neck Cancers
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new radiation treatment strategies. Future progress in the treatment of head and neck cancers will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active exploration to improve radiation treatment of head and neck cancers include the following:
Three-Dimensional Conformal Radiation: Three-dimensional conformal radiation therapy is a promising approach for the treatment of head and neck cancers because it decreases the exposure of normal tissues to radiation. Using computerized tomography (CT) scans and other imaging techniques, radiation oncologists have developed methods for determining the 3-dimensional size and shape of the cancer. This allows high-dose external beam radiation therapy to be delivered primarily to the cancer with less damage to normal cells. The technique is particularly useful in the treatment of head and neck cancers near the midline of the body because conventional radiotherapy usually damages the salivary glands resulting in xerostomia, or dry mouth.
Clinical studies have demonstrated that the saliva glands could be spared from radiation damage with the conformal radiation technique. Patients with cancers of the throat and larynx treated with simple three-dimensional conformal radiotherapy technique resulted in significantly less radiation to the saliva glands and improved doses of radiation delivered to the target cancer cells compared to conventional external beam radiation therapy.
Acceleration of Radiation Dose: Another strategy in the treatment of head and neck cancers is to administer radiation therapy at more frequent and intensive doses. Patients with cancer of the head and neck may benefit from higher doses of radiation therapy that are administered twice daily compared to standard therapy consisting of lower doses administered once a day. However the current standard therapy is to administer radiation only once a day.
One of the largest clinical trials of the past 2 decades involving the treatment of head and neck cancer showed that the risk of a local cancer recurrence may be reduced in patients with locally advanced head and neck cancer by using increased frequency and doses of radiation therapy. In this study, over 1,000 patients with locally advanced head and neck cancer received radiation therapy either once daily or twice daily. Higher doses of radiation were delivered to the group of patients receiving treatment twice daily, whereas standard doses of radiation were delivered to the group of patients receiving treatment once daily. Two years following treatment, 56% of patients receiving radiation treatment twice daily were free of cancer recurrence, compared with 46% of patients who received radiation once daily.
Research indicates that accelerated boost radiation therapy can also be effective in elderly patients with cancer of the head and neck who are healthy enough to tolerate this more aggressive treatment. In one study, accelerated boost radiation therapy was administered to 45 patients, age 70 or older, with cancer of the mouth, throat, or larynx. The results were compared to a similar group of patients who were younger than 70 years of age. Among the older patients, 68% lived 3 years or longer after treatment, compared to 62% for the younger patients. The local cancer was controlled in 73% of the older patients and 68% of the younger patients.
Intensity Modulated Radiation Therapy (Tomotherapy): Tomotherapy delivers varying intensity radiation with a rotating device. The intensity is varied by the placement of “leaves” which either block or allow the passage of radiation. The rotating component of this technique allows for more specific targeting of the cancer. In conventional radiation therapy, the beam is usually delivered from several different directions, possibly 5-10. The greater the number of beam directions, the more the dose will be confined to the target cancer cells, sparing normal cells from exposure. Tomotherapy delivers radiation from every point on a helix, or spiral, instead of from just a few points.
Tomotherapy is similar to CT scanning. In CT, a beam rotates around the patient, creating a sequence of cross-sectional images. Tomotherapy also uses a rotating beam, except the beam delivers radiation. Tomography also delivers treatment one cross-section at a time. Tomotherapy-based intensity-modulated radiation therapy appears to be a promising and more precise approach for the treatment of head and neck cancers because it spares normal tissue from radiation damage.
Neutron Radiation Therapy: Neutron radiation therapy utilizes a beam of high-energy neutrons to treat a variety of cancers. Neutrons are electrically neutral particles that are part of all atoms. Modern neutron machines and the use of three-dimensional treatment planning systems are now available in a few institutions and may further reduce the side effects of neutron radiation therapy. Neutron radiation therapy was once considered purely experimental, but it has now become the treatment of choice for certain cancers.
Results from a clinical trial of neutron radiotherapy demonstrated that this technique was effective in salivary gland cancers. This study included 72 patients with carcinoma of the salivary glands. Sixty-six were treated with neutrons after surgery and 6 were treated without surgery because their cancer was not operable. Following neutron therapy, the cancer was eliminated in 28 patients and was partially eliminated in 35 patients. Two years after completion of treatment, 85% of patients survived, 81% without cancer recurrence. Five years after completion of treatment, 58% of patients survived, 53% without cancer.
Radiosensitizers: Radiosensitizers are drugs that make cancer cells more susceptible to damage by radiation therapy. These drugs act by increasing the normally low level of oxygen in the cancer cells. Cancers with low levels of oxygen are less sensitive to radiation than cancers with normal or high levels. At this time, the US Food and Drug Administration (FDA) has not approved the use of radiosensitizer drugs. Thus, treatment with these drugs is only available through clinical trials.
Two radiosensitizer drugs have been investigated. Preliminary experiments have shown that a radiosensitizer called RSR 13, binds to hemoglobin increasing the level of oxygen in cancers. RSR 13 has not yet been evaluated in humans. Another radiosensitizer drug, nimorazole, significantly improved the effect of radiotherapeutic management of cancers of the larynx and pharynx without major side effects. In this clinical trial 144 patients with pharynx and larynx carcinoma were treated. Half the patients received the radiosensitizer and half received placebo. All patients received conventional radiotherapy. Overall, the group that received the radiosensitizer experienced significantly better local and regional control of cancer and lived longer. Drug-related side effects were minor and tolerable, the most common of which were transient nausea and vomiting.
Radiation Protectors: Radiation protectors are drugs that selectively protect normal tissues from radiation treatment, while exposing cancer cells. Over the past 50 years, many radiation protectors have been tested in the laboratory for prevention of radiation damage to normal cells and tissues. Ethyol® is one of these and the only drug that has been approved by the FDA for use in patients receiving radiation therapy for cancers of the head and neck. Clinical trials have demonstrated that Ethyol® can reduce both early and late radiation-induced side effects.
Treatment with Ethyol® resulted in fewer and less severe cases of xerostomia. Xerostomia can greatly impair a patient’s ability to speak, chew, swallow, and taste and therefore, has a negative effect on a patient’s quality of life. In a large multi-center clinical trial, 300 patients with cancer of the head and neck received either radiation therapy combined with Ethyol® or radiation therapy alone. Xerostomia occurred in 51% of patients receiving Ethyol®, compared to 78% for patients receiving radiation therapy without Ethyol®. One year following completion of radiation therapy, only 35% of patients who had received Ethyol® were still experiencing symptoms of xerostomia, whereas 57% of patients who had received radiation therapy alone were still experiencing symptoms.
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