When to Consider Radiation Therapy for Your Patient

BERNARD A. TISDALE, M.D.

Chippenham Medical Center and Johnston-Willis Hospitals, Inc.

Richmond, Virginia

Radiation therapy can be an effective treatment modality for both malignant and benign disease. While radiation can be given as primary treatment, it may also be used pre- or postoperatively, with or without other forms of therapy. Radiation therapy is often curative but is sometimes palliative. There are many methods of delivering radiation effectively. Often, patients tolerate irradiation well without significant complications, and organ function is preserved. To ensure that all patients with cancer have the opportunity to consider all treatment options, family physicians should be aware of the usefulness of radiation therapy.

In the United States, approximately one of every two men and one of every three women will have cancer (including skin cancer).¹ Obviously, family physicians play a major role in the care of many of these patients. In this country, approximately 60 percent of all patients with cancer receive radiation therapy each year.² Unfortunately, physicians sometimes direct cancer treatment without considering the option of radiation therapy. Family physicians should be aware of its potential role (Table 1) in order to ensure that patients receive comprehensive cancer management.

TABLE 1 Comparison of Primary Treatment Modalities for Selected Cancers Disease site Expectation Radiation (percentage effective)* Surgery (percentage effective)* Chemotherapy Anal canal Disease-free survival 70 70 With radiation Colostomy-free survival 70 0 Bladder Five-year survival 45 40 With radiation Bladder T2,T3 Bladder preservation 60 0 Breast 10-year survival 70 70 Breast--stage I, stage II Breast preservation 90 0 Esophagus Five-year survival 10 10 With radiation Head and neck--stage I, stage II Larynx Local control 85 85 Oral cavity Local control 85 85 Oropharynx Local control 85 85 Hodgkin's disease--stage I, stage II 10-year survival 90 60 to 85% Lung--stage III Five-year survival 10 <5 With radiation Prostate--stage I, stage II 10-year survival 60 60 Skin, basal cell Local control 95 95 Skin, squamous cell Local control 90 90 Uterine cervix--stage IB, stage IIA Five-year survival 85 85 *--Percentages are approximate.

Radiation Treatment

Mechanism of Action
Radiation therapy is a local treatment modality that works by damaging the DNA of malignant cells. Normal cells have a greater ability to repair this damage than tumor cells. Radiation therapy takes advantage of this difference. It is important to note that since damaged cells do not die immediately after treatment, tumors often persist after successful radiation therapy is completed.

Early effects of radiation therapy are usually related to inflammation; late effects are related to tissue damage with necrosis or scarring. Fatigue is a commonly occurring systemic symptom.

Approach to Treatment Planning
Treatment prescriptions are based on the goals of treatment and the potential for side effects. A course of treatment may be as short as one day or as long as 10 weeks, but a typical duration is between two and seven weeks and usually consists of five daily treatments a week. Patients most commonly receive radiation through a linear accelerator, which accelerates electrons to be used as a treatment beam or to generate x-rays to be used as a treatment beam. Treatment is not painful and often lasts less than five minutes.

The goal of treatment may be curative or palliative. If radiotherapy is potentially curative, the length of treatment is often longer and usually consists of smaller daily doses over a longer period of time. This approach minimizes late side effects. If treatment is intended to be strictly palliative, shorter treatment schedules consisting of larger daily treatment doses over a shorter time period are used. In such cases, late side effects are not likely to occur within the patient's lifetime. Furthermore, a shorter treatment program will negatively affect less of the patient's remaining life.

TABLE 2 Potential Side Effects of Radiation Therapy Site Early effects Late effects Bone Arrest of growth, pain, fracture Bone marrow Pancytopenia Pancytopenia Central nervous system/spinal cord Headache, nausea, seizures, stroke Lhermitte's sign,* paralysis, seizures, coma Ear Otitis, desquamation, hypoacusis, tinnitus Eye Conjunctivitis, keratitis, iritis, blindness, glaucoma, ulceration Cataract, corneal ulcer, glaucoma, blindness Heart Pericarditis, congestive heart failure Pericarditis, coronary artery disease, congestive heart failure Joints Stiffness, fixation Kidney Renal failure, hypertension Larynx Hoarseness, edema, dyspnea Edema, chondritis, necrosis Liver Necrosis, hepatic failure Lower gastrointestinal tract Diarrhea, obstruction, bleeding Diarrhea, obstruction, bleeding, fistula, necrosis Lung Cough, dyspnea, pneumonitis Fibrosis, pneumonitis Mucous membrane Mucositis, ulceration Atrophy, ulceration, telangiectasia Pharynx/esophagus Dysphagia, ulceration, obstruction, perforation, fistula Dysphagia, fibrosis, necrosis, perforation Salivary gland Xerostomia, dysguesia Xerostomia, dysguesia, fibrosis Skin Erythema, epilation, edema, desquamation, ulceration Atrophy, telangiectasia, pigment changes, alopecia, ulceration Soft tissue Inflammation Fibrosis, necrosis Upper gastrointestinal tract Anorexia, nausea, pain, obstruction, bleeding Obstruction, fibrosis, fistula Any area Secondary malignancy: 1 in 1,000 at 10 years after treatment† *--Electric-shock­like sensation felt when the head is flexed. †--Approximation. Adapted with permission from Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) [Editorial]. Int J Radiat Oncol Biol Phys 1995;31:1341-6.

Side Effects of Radiation Therapy

Since radiation is a form of local therapy, side effects are usually limited to the treated area. However, fatigue is one common systemic symptom. Usually, the side effects of radiation are mild, but occasionally they are severe. The side effects can be divided into early and late effects (Table 2).³ Early effects occur during or immediately after treatment and typically resolve within three to six weeks following therapy. Late side effects occur months to years after treatment and are often permanent. These effects are the result of tissue injury that leads to necrosis or scarring and, rarely, to carcinogenesis. The occurrence of malignancies secondary to radiation therapy has become well known. While it is true that many genetic factors predispose some patients to second cancers, radiation also contributes to the increased relative risk.

TABLE 3 Potential Roles of Radiotherapy Radiation therapy as optimal primary treatment • Anal and perianal cancer • Certain Hodgkin's and non-Hodgkin's lymphomas • Early laryngeal cancer • Nasopharyngeal cancer • Nonmelanoma skin cancers in certain sites • Unresectable lung cancer Radiation therapy as optional primary treatment • Bladder cancer • Esophageal cancer • Early head and neck cancer • Advanced lung cancer • Prostate cancer • Uterine cervical cancer Preoperative radiation therapy useful • Certain advanced breast cancers • Certain advanced lung cancers • Certain advanced rectal cancers • Certain sarcomas Postoperative radiation therapy useful • Breast conservation in early stage • Breast-chest wall and lymphatics in advanced stage • Endometrial cancer • Gastric cancer • Gliomas • Advanced head and neck cancer • Pancreatic cancer • Certain advanced rectal cancers • Testicular seminoma Consolidative radiation therapy after chemotherapy • Hodgkin's lymphoma • Non-Hodgkin's lymphoma

Specific Cancers

Radiation therapy has many potential specific indications. It can be given as primary tumor treatment, as pre- or postoperative therapy, or as a component of combination or consolidative therapy (Table 3). Radiotherapy will benefit patients with many different types of cancer. The following discussion highlights some specific potential uses of radiation therapy.

Head and Neck Cancer
In patients with cancer of the head and neck, radiation can be used as primary therapy or as postoperative treatment. Sometimes radiation is given in combination with chemotherapy. One of the most beneficial results of radiotherapy is laryngeal preservation in persons with cancer of the vocal cord.⁴ Because of their location, nasopharyngeal cancers are treated primarily with radiation therapy. Many patients can be re-treated successfully should the tumor recur. Postoperatively, patients with large, extensively invasive tumors or tumors that have positive or close margins, and patients with positive lymph nodes are at high risk for local or regional recurrence. Radiation therapy increases the chance of local control of these tumors and often improves survival in patients with tumors of the head and neck.⁵

Skin Cancer
Skin cancer can be treated primarily or postoperatively with radiation. Generally, primary treatment is reserved for use in areas where the cosmetic result with surgery may not be suitable. Most commonly, these include areas around the nose, ear, upper lip and commissure, eyelid and canthi. Similarly, postoperative irradiation increases local control in high-risk patients.⁶

Central Nervous System Tumors
Sometimes primary radiotherapy is indicated because the tumor location precludes surgery. But most commonly, postoperative radiation is employed. Radiation therapy improves survival in many patients with high-grade gliomas and in some patients with low-grade gliomas.⁷ New methods of conformal and stereotactic therapy, which more precisely focus the treatment beam using a three-dimensional technique, allow higher doses of radiation to be administered safely and accurately. These techniques seem particularly promising for the treatment of brain tumors.

Genitourinary Cancers
In selected patients with invasive bladder cancer, radiation along with chemotherapy may help to preserve the bladder and its function.⁸ Prostate cancer can be treated primarily or postoperatively with radiation. It appears that, stage for stage, radical prostatectomy and primary radiotherapy offer the same chance of disease-free survival for prostate cancer patients.⁹ Recently, androgen blockade has been found to enhance local control and improve survival rates. Radiation therapy is associated with lower morbidity in patients with prostate cancer, particularly when conformal therapy or radioactive seed implants are used. With radiation, it is often possible to avoid the occurrence of impotence and incontinence, which are more common with other therapies.

In patients who have had a prostatectomy and who have a high risk of local recurrence, such as those with tumors with positive margins or a rising level of prostate-specific antigen (PSA), radiation may improve local control and survival. Patients with early-stage testicular seminoma have a very high survival rate when treated with low-dose irradiation following radical orchiectomy.

Radiation, which may be given as either curative or palliative treatment, may be used as primary, pre- or postoperative therapy, or as a component of combination therapy.

Gynecologic Tumors
Early stage (stage I) cervical cancer can be treated with radiotherapy as effectively as with surgery.¹⁰ Later (stages II and III) tumors are best treated with irradiation. Many cervical and endometrial cancers with unfavorable histologic characteristics are better controlled with postoperative radiation. Certain patients with ovarian cancer may benefit from intraperitoneal radioactive phosphorus given postoperatively. Vaginal and vulvar cancers are frequently treated with radiotherapy because the required surgery is often too extensive, and patients are often elderly.

Breast Cancer
Radiation has dramatically altered the management of primary breast cancer. Two national consensus conferences have concluded that breast conservation, using lumpectomy and radiation therapy, is the treatment of choice in early-stage breast cancer.¹¹ Cosmetic results are good in most patients, and survival is not compromised. Attempts are being made to identify patients at low risk who can be managed with lumpectomy alone, but so far, all groups of patients have better local control with added radiation. Many patients with locally advanced breast cancer show improvement in local control with radiotherapy, and recent trials have also shown increased survival following radiation.^12,13

TABLE 4 Important Cancer Syndromes in Which Radiation Therapy Is Palliative Condition Symptoms Treatment Painful bone metastasis Bone pain Analgesics, radiation treatments, hormonal/ medical management, radiopharmaceuticals Spinal cord compression Back pain, especially radicular pain, neurologic deficits, bowel/bladder dysfunction Steroids, then surgery and radiation or radiation alone Superior vena cava syndrome Dyspnea, orthopnea, venous congestion Steroids, diuretics, oxygen, chemotherapy, radiation treatments Brain metastasis Headache, cognitive deficits, focal deficits Multiple metastases: steroids, then whole-brain radiation treatments Single metastasis: steroids, then surgery or stereotactic radiotherapy, and whole-brain radiation treatments

Gastrointestinal Tumors
Esophageal cancer is usually advanced by the time the patient seeks treatment. Radiotherapy, along with chemotherapy, appears to be as effective as surgery in most patients with esophageal cancer.¹⁴ In selected patients, preoperative chemoradiotherapy may offer the best results. Patients with stomach cancer also often present with advanced disease. Some studies suggest the best treatment in these patients is postoperative chemoradiotherapy if the tumor is resectable or chemoradiotherapy alone if it is unresectable.¹⁵ Similarly, postoperative chemoradiotherapy or chemoradiotherapy alone is the preferred treatment for resectable and unresectable pancreatic cancer.¹⁶

TABLE 5 Benign Diseases in Which Radiation Therapy May Be Used • Ameloblastoma • Aneurysmal bone cyst • Angiofibroma • Arteriovenous malformation • Chemodectoma • Chordoma • Craniopharyngioma • Desmoid tumor • Graves' ophthalmopathy • Gynecomastia associated with hormonal management of prostate cancer • Hemangioma • Heterotopic bone formation • Hypersplenism • Keloid • Keratoacanthoma • Meningioma • Peyronie's disease • Pituitary adenoma • Pterygium • Total lymphoid irradiation for autoimmune disease or organ transplantation • Vascular restenosis prevention

Certain high-risk patients with locally advanced colon cancer may have better local control and survival with adjuvant radiation therapy. Preoperative radiotherapy, often administered with chemotherapy, can downstage advanced or low-lying rectal cancers and allow resection and preservation of the sphincter.¹⁷ In high-risk surgical patients, radiation therapy can be helpful postoperatively as well. Anal and perianal cancers are usually treated with combined radiation and chemotherapy because excellent results and sphincter preservation can be obtained.¹⁸

Lung Cancer
Lung cancer should be treated surgically whenever possible. Postoperative radiation improves local control and may improve survival in certain high-risk surgical patients.¹⁹ Unresectable lung cancer can occasionally be made resectable with preoperative radiation. If resection is not possible, an approach combining radiation and chemotherapy is preferred.²⁰ Administration of chemotherapy may precede or coincide with radiotherapy.

Sarcomas
Wide local excision with preservation of function is indicated for soft tissue sarcomas. High-risk patients who receive preoperative or postoperative irradiation show improvement in local control and survival. By shrinking the tumor, preoperative radiation may allow more limited surgery and improvement in local control, which can also be limb sparing.²¹

Lymphomas
Some patients with either non-Hodgkin's or Hodgkin's lymphoma may be best treated with radiotherapy. Many patients with low-grade non-Hodgkin's lymphoma can be treated with radiation alone, with excellent local control. Some patients with higher-grade non-Hodgkin's lymphoma with stage I or stage II disease have better survival with irradiation after chemotherapy.²² Hodgkin's lymphoma in selected patients with early-stage disease should be treated with radiation alone or combined with chemotherapy. Radiation therapy may also help control more advanced Hodgkin's lymphomas.

Pediatric Cancers
Pediatric cancer patients may benefit from radiation of central nervous system tumors (ependymomas, astrocytomas, medulloblastomas, embryonal tumors, brainstem gliomas, craniopharyngiomas, pineal tumors, cerebellar astrocytomas, optic gliomas, retinoblastomas, spinal cord tumors), neuroblastomas, lymphomas, Ewing's sarcoma, rhabdomyosarcomas and Wilm's tumor.

Palliative Care

Most head and neck cancers can be treated either primarily or postoperatively with radiation therapy. Because of their location, nasopharyngeal tumors are treated primarily with radiation therapy.

In patients with metastatic cancer, radiation often improves quality of life and even survival (Table 4). Radiation is excellent for relief of painful bone metastases and may prevent pathologic fracture in weight-bearing bones. Generally, the pain relief afforded by radiation allows a reduction in pain medications and drug side effects. Spinal cord compression as a result of cancer is an emergency that can often be treated effectively with radiotherapy alone. Patients with back pain, weakness of the extremities, or problems with bowel or bladder control should be evaluated immediately to rule out cord compression. Superior vena cava syndrome, another potential emergency, usually responds well to radiotherapy. Patients usually present with dyspnea, orthopnea and venous congestion in the neck and upper extremities. Likewise, airway compression caused by cancer can often be treated effectively with radiotherapy. Short courses of radiation may improve median survival and quality of life in patients with brain metastases. If the only clinical disease is a single brain metastasis, the combined approaches of either surgery and whole-brain irradiation or stereotactic radiation and whole-brain irradiation improve the median survival rate most dramatically.²³

Benign Disease

Radiotherapy can be used to treat certain benign diseases (Table 5). Local strontium application can help prevent the local recurrence of a surgically resected eye pterygium. Superficial low-dose radiation treatment can help prevent local recurrence of surgically resected keloids. Radiation therapy is often used to treat pituitary adenomas successfully with minimal morbidity. Low-dose irradiation can sometimes improve Graves' ophthalmopathy in selected patients in whom other types of therapy have failed. Likewise, keratoacanthomas that fail to respond to other treatment usually respond well to irradiation. Hemangiomas also respond well to low-dose radiation. Radiotherapy can help control high-risk desmoids and Peyronie's disease. In some postoperative orthopedic patients, low-dose radiation can prevent heterotopic bone formation. Finally, arteriovenous malformations of the central nervous system may be eliminated with stereotactic radiotherapy, if the malformations are not surgically accessible.²⁴

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The Author

BERNARD A. TISDALE, M.D.,
is medical director of the Radiation Oncology Center at Chippenham Medical Center and Johnston-Willis Hospitals, Inc., in Richmond, Va. Dr. Tisdale earned a medical degree and completed a residency in family practice at the University of Virginia School of Medicine, Charlottesville. He also completed a residency in radiation oncology at the University of Louisville School of Medicine in Kentucky.

Address correspondence to Bernard A. Tisdale, M.D., Radiation Oncology Center, Johnston-Willis Hospitals, 1401 Johnston-Willis Dr., Richmond, VA, 23235. Reprints are not available from the author.

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