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3-D Conformal Radiation therapy for Lung Cancer: Potential Side Effects and Management
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Submitted By: Feng-Ming Kong MD PhD
Three Dimensional Conformal Radiation therapy for Lung Cancer: a Brief Discussion of
Potential Side Effects and Management
Article authored by Shaneli Fernando MD, and Feng-Ming Kong MD PhD
Introduction
Lung cancer is among the most common malignancies for men and women in the United States. Despite the use of multiple modalities of treatment including surgery, chemotherapy and radiation therapy, the 5 year survival is less than 15%. Radiation therapy is widely used in patients who have locally advanced disease, as well as in patients who are medically inoperable. Radiation can also be given to relieve symptoms such as pain or coughing up blood and to open airways obstructed by tumors. Many lung cancer patients will undergo radiation at some point during their treatment. For non-small cell lung cancer patients, 64.3% ± 4.7% will require radiation therapy at least once during the disease course (1). This article will describe radiation treatment technique and address the potential short and long term side effects of lung radiation.
External Beam Radiation Therapy
Most radiation for lung cancer is delivered through high energy photons beams produced by machines called linear accelerators. This type of radiation is external beam since radiation is delivered from outside of the body. One of the major challenges of this type of treatment in lung cancer is to deliver sufficient amount of radiation to the tumor and lymph nodes but to spare as much normal lung as possible. This becomes increasingly important since many people with lung cancer have poor lung functions because of prior smoking or chronic obstructive pulmonary disease (COPD). In addition to normal lung, there are other structure in the radiation field that could be affected, such as the esophagus, spinal cord, and heart. The dose and duration of radiation will be dependent on the type of lung cancer and the overall condition of the patient.
Radiation Treatment Planning Using CT and PET
The amount of radiation to normal tissues can be limited by 3D conformal planning and treatment (Figure 1).
Multiple radiation beams are used to deliver a high dose of radiation to the tumor while minimizing the dose to normal tissue. Planning begins with a computed tomography (CT) simulation in which a patient undergoes CT scan in the same position that he or she will be in for treatment. The CT images are used to localize the tumor as well as normal lung and create a 3D representation of tumor volume and normal structures. The dose of radiation to each of these structures can then be planned and modified. Functional imaging modalities such as positron computed tomography (PET) can be used to define areas that are affected by cancer (2). Figure 2 and 3 show comparisons of a PET and CT image. PET shows areas that are uptaking the compound fluorodeoxyglugose (FDG), indicating metabolic activity. These active areas are more likely to be tumor than areas that use less FDG. Figure 2 shows an example of PET differentiating the tumor from collapsed normal lung, while Figure 3 shows that PET detects an active lymph node in mediastinum which is not remarkable on CT.
PET scan help radiation oncologist to outline the target more accurately for radiation therapy planning and to spare as much normal tissue as possible.
Side Effects of Lung Radiation
Fatigue
The majority of lung cancer patients report fatigue that is greater than normal during radiation treatment. This becomes more common during the latter part of treatment. The fatigue is occasionally related to low red blood cells counts in patients undergoing chemotherapy, but it is more often a direct result of radiation treatment.
Like the other acute effects, the fatigue will improve once treatment is complete. It often takes patients several weeks to get back to their baseline energy level. During treatment, patients are advised to pace themselves at home and work. They may need to take more frequent brakes to avoid overexertion.
Skin Reactions
Radiation treatment for lung cancer rarely causes severe skin reactions such as redness or peeling. However if the lymph nodes above the collar bone or supraclavicular area are treated, patients may experience increased skin reactions. The use of chemotherapy can also add to the skin reactions. Body hair in the treatment area will be lost about two to three weeks after beginning treatment, but the hair does grow back after the completion of treatment.
There are several precautions that patients can take to further minimize skin reactions. Patients are advised to keep the skin in the area of radiation clean and dry. The use of creams or lotions shortly before treatment can make skin reactions worse. If a cream such as Aquaphor or silvadiene is suggested by the physician, it should be applied at least four hours before treatment. If a cream is applied less than four hour before treatment, the area should be cleaned before daily radiation is delivered. Direct sun exposure to the area should also be avoided during radiation treatment. After radiation is complete, the skin in the radiation field may be more prone to sun burns so sunscreen should be applied.
Esophagitis
Since the esophagus has a central location in the chest, it receives a significant amount of radiation during lung cancer treatment, especially if the lung tumor is in the center of the chest or there is mediastinal node involvement. Esophagitis is the irritation and inflammation of the lining of the esophagus. Patients experience pain or difficulty swallowing as a result of this process. Although changes to the esophageal mucosa can be seen as early as the first week, symptoms do not become bothersome until the third to forth week of radiation treatment. Chemotherapy, with such agents as cisplatin, 5- and flurouracil, can increase the severity of esophagitis (3). Since the mucosa of the esophagus can quickly regenerate after radiation, symptoms usually resolve over several weeks after radiation is completed.
The goal in the management of esophagitis is to relieve pain and discomfort so patients can continue treatment while maintaining adequate nutrition and hydration. The first step would be adjustment of dietary habit such as switching to soft food and liquid nutritional supplements as well as eating smaller, more frequent meals. Avoidance of acidic or spicy food and alcohol is also recommended during treatment. While over the counter mouthwashes may be harmful, gargling with a mixture of warm water, salt and baking soda can help with irritation. Mixtures of nystatin, Maalox, and lidocaine (a topical numbing medication) can be taken 5-10 minutes before swallowing food. Treatment of more severe esophagitis can be accomplished with narcotic pain mediations. The pain medication is often better tolerated if it is given in liquid form, such as Tylenol #3 elixir and liquid morphine. Another effective way to deliver pain medication is a patch applied to the skin of the arm or back. The patch delivers long acting pain medication that is used along with short acting medication. When patients are still unable to eat and drink adequately despite the above measures to control pain, a feeding tube may be placed directly into the stomach for nutritional support.
Radiation Pneumonitis
One of the most significant radiation complications is radiation pneumonitis. Pnemonitis or ˙radiation pneumonia˙ can develop between 1-9 months after radiation therapy, but it is more common between 1-3 months after radiation (4). Patients often experience nonproductive cough, low grade fevers, shortness of breath, chest pain, and generalized fatigue. A classic finding on chest x-ray is an infiltrative pattern in the area of radiation although chest x-rays can appear normal in the early phase (5). Chest CTs are more sensitive at detecting radiation pnemonitis in the early phase and show changes that are confined to the radiation field (6). The symptoms of pneumonitis occur in 5-30% of patients treated for lung cancer.
Although most cases of radiation pneumonitis resolve on its own, the condition can be life-threatening. The most common treatment is high doses of the steroid, prednisone for several weeks, followed by a slow taper of the medication over several months. Predisone relieves many of the symptoms associated with pneumonitis including shortness of breath and cough. Prednisone works by reducing the inflammatory response and damage to the lining of blood vessels after radiation (7).
Another medication, amifostine (Ethyol), is used by some physicians in the prevention and treatment of radiation pneumonitis. Amifostine has been shown to protect normal tissue from the effects of chemotherapy and radiation treatment. It acts as a scavenger of free radicals, which are the damaging agents produced by radiation. One study of lung cancer patients showed a decrease in the rates of radiation pneumonitis in patients that were receiving amiphostine compared to those that did not receive the medication with radiation (8).
Pulmonary Fibrosis
Pulmonary fibrosis is a process of scar tissue formation in the lung as a result of tissue injury by radiation. While the symptoms of pneumonitis resolve with treatment, pulmonary fibrosis may become chronic leading to permanent decrease in lung function. The severity of pulmonary fibrosis depends on the degree of injury to the tissue. This process is mediated by chemical molecules called cytokines that are released into the blood. Cytokines recruit other cells which lead to scarring or fibrosis (9). Up to 70% of lung cancer patients who have received radiation will have radiographic findings consistent with pulmonary fibrosis.
There is no effective treatment for radiation fibrosis. Some medications have been tried in animal and patients. Pentoxifylline inhibits platelets and enhances blood flow in the small vessels of the lung. A clinical trial of breast and lung cancer patients undergoing radiation showed that lung injury was less in the group that received pentoxifylline compared to placebo (10). Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been shown in animal models to reduce lung fibrosis. However, there is less evidence to support effectiveness of captopril in preventing fibrosis in patients who have undergone radiation (11).
Damage to nerves and other organs
When planning radiation treatment, one of the critical structures to which radiation is minimized is the spinal cord. There is also a collection of nerves known as the brachial plexus which control arm and hand movement. Damage to the spinal cord or brachial plexus could lead to numbness, weakness or even paralysis in the most severe cases. However, the incidence of these side effects is extremely low due to the use of conformal radiation therapy techniques.
Since the heart is the thorax, or chest cavity, it may also receive some radiation. However, the amount of radiation to the heart is minimized The dose to using 3-dimensional radiation techniques including the use of multiple beams that avoid the heart.
Conclusion
Although most patients undergoing radiation treatment for lung cancer will experience side effects during radiation, most of these symptoms can be managed with medication and supportive care. The acute effects of radiation often improve several weeks after the treatment has been completed. The long term effects of radiation are potentially more serious, but only occur in 5-15% of lung cancer patients who have undergone radiation.
It is important for lung cancer patients not to be overwhelmed by what may happen as a result of radiation treatment since it is an integral part of cancer therapy. This article is focused on making patients aware of side effects so they will be less anxious about undergoing radiation therapy.
Acknowledgement
We are grateful to Daniel Tatro for helping the figure preparation.
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References
1. Tyldesley, S., Boyd C., Schulze K. Estimating the need for radiotherapy for lung cancer: an evidence based epidemiologic approach. Int J Rad Oncol Biol Phys 2001; 49:973.
2. Munley, M.T., Marks, L.B., Scarfone C., et al. Multimodality nucler imaging in three-dimensional radiation treatment planning for lung cancer: challenges and prospects. Lung Cancer 1999; 23:105.
3. Choy, H. Esophagitis in combined modality therapy for locally advanced non-small cell lung cancers. Semin Radiat Oncol 1999; 9:90.
4. Abratt, Q.P., Morgan, G.W., Lung toxicity following chest irradiation in patients with lung cancer. Lung Cancer 2002; 35:109.
5. Marks, L.B., The pulmonary effects of thoracic radiation. Oncology 1994; 8:89.
6. Ikezoe, J., Takashima, S., Morimoto, S., et al. CT appearance of acute radiation induced injury in the lung. Am J Roentgenol 1988; 150:765.
7. Arbetter, K.R., Prakash U.B., Tazelaar, H.D., et al. Radiation induced pnemonitis in the ˙non-irradiated˙ lung. Mayo Clin Proc 1999; 74:27.
8. Antonadou, D., Coliarakis, N., Syndoinou, M., et al. Randomized phase III trial of radiation treatment +/- amifostine in patients with advanced stage lung cancer. Int J Rad Oncol Biol Phys 2001; 51:915.
9. Rubin P., Johnston C.J., Williams J.P., McDonald S., et a. A perpetual cascade of cytokines post-irradiation lead to pulmonary fibrosis. Int J Rad Oncol Biol Phys 1995; 33:99.
10. Ozturk, B., Egehan, I., Atavci, S., et al. Pentoxyifylline in prevention of radiation induced lung toxicity in patients with breast and lung cancer: a double blind randomized trial. Int J Rad Oncol Biol Phys 2004; 58:213.
11. Wang, L.W., Fu X.L., Clough, R. et al. Can angiotensin converting enzyme inhibitors protect against symptomatic radiation pneumonitis?. Radiat Res 2000; 153:405.
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