Pain is a frequent complication of cancer. It can be a presenting symptom of the disease, a sign of local recurrence of tumor after prior treatment, or a symptom of metastatic disease. Palliative radiation therapy became a mainstay of nonsurgical cancer treatment soon after the discovery of x-rays. Radiation, delivered by external beam, implantation (placement of radioactive sources within the tumor), or systemic radiopharmaceutical can be effective in the management of cancer pain. Radiation therapy can relieve pain related to either metastatic disease or symptoms from local extension of primary disease. This chapter focuses on the treatment of pain related to metastatic disease. It is worth emphasizing that radiation therapy can complement analgesic drug or other therapies and may enhance their effectiveness because this therapy directly targets the cause of pain.

In principle, ionizing radiation is delivered to the tumor with the intent of reducing or eliminating viable cancer cells while maintaining normal tissue integrity. It is most commonly given as megavoltage external beam photons produced by a linear accelerator. Electrons, which have a more limited range in tissue defined by their energy, also can be produced by linear accelerators and can be very useful in the treatment of superficial tumors, with the additional benefit of sparing normal tissues below the tumor. Systemically administered radiopharmaceuticals, such as strontium-89 (⁸⁹Sr) or samarium-153 (¹⁵³Sm), have a role in the treatment of patients with symptomatic metastatic disease involving multiple bones, whereas iodine-131 (¹³¹I) is appropriate for the treatment of patients with metastatic thyroid cancers that are iodine avid. Brachytherapy (implantation of radioactive sources into tumor) is a useful mode of radiation delivery because of the physical advantage of very high radiation doses
applied to the tumor compared to the surrounding normal tissue and the biologic advantage of low dose rate (which differentially spares the normal tissue). Brachytherapy is usually used in the management of the primary tumor; it is less commonly used for palliation of metastatic disease.

External beam radiation is prescribed by absorbed radiation dose (the SI unit is the Gray; 1 Gy is equal to 100 rads) per unit volume in a selected field. The total dose, the number of daily fraction, and the volume of tissue irradiated are determined by considering the needs and the likely benefit for each patient.

The primary indications for radiotherapy in the management of cancer pain are listed in Table 1. These indications include bone pain from metastases (with or without pathologic fracture), spinal cord compression, tumor infiltration of nerve plexus, blockage of hollow viscera, and reduction in space-occupying lesions (particularly cerebral metastases). Radiotherapy also can be very useful in palliation of bleeding from tumors, cough or dyspnea secondary to tumor invading bronchus, and superior vena cava syndrome.

When making decisions about the use of radiation therapy, physicians should consider the type of neoplasm, the relative effectiveness of available treatment modalities, the patient’s prior treatment, and the extent of his or her disease (i.e., single or limited versus multiple metastatic sites), as well as the patient’s performance status, length of expected survival, and bone marrow reserve.
The efforts of the radiation oncologist should be closely coordinated with those of other physicians and health care personnel. Patients with particularly difficult pain problems may benefit from presentation at a tumor board or other appropriate multidisciplinary conference to allow for input and discussion among the varying specialists with expertise in the management of cancer pain.

The intent of palliative treatment is rapid and durable pain relief. Ideally such treatment should maintain symptom control for the remainder of the patient’s life, with minimal associated morbidity. Radiation therapy can arrest local tumor growth that might otherwise lead to intractable pain, cord compression, airway obstruction, uncontrolled bleeding, or pathologic fracture. For some patients, the resultant elimination of or reduction in the need for narcotic pain medications can improve quality of life. Reduction in pain also can improve ambulation.

Treatment should be tailored to the patient’s clinical condition and overall prognosis. Patients with good performance status and with a limited burden of metastatic disease near crucial structures such as the spinal cord or brachial plexus may benefit from radiation treatment programs that give a higher total radiation dose delivered in multiple fractions. Although such a program may require more initial visits to the radiotherapy clinic, it is likely to result in more durable palliation in the patient with a longer life expectancy. In contrast, patients with widely metastatic disease and limited life expectancy should be considered for rapid, limited-fraction treatment courses.

For a single site or a limited number of sites of bone metastases, external beam radiation therapy is appropriate and may relieve symptoms for an extended period. For patients with symptomatic bone metastases at multiple sites, it is more appropriate to institute analgesics along with available systemic chemotherapy or endocrine therapy and bisphosphonates. If symptoms persist, consider systemic radiopharmaceuticals, localized external radiotherapy to the most symptomatic areas, or hemibody irradiation.

Most patients referred for palliation of metastatic bone pain have the most frequently occurring types of primary tumors, namely, breast, prostate, or lung tumors. Eighty to 90% of these patients experience pain relief following radiation therapy, with 50% of these patients obtaining complete relief. Most patients experience some pain relief within 10 to 14 days after the start of therapy. Seventy percent of patients have pain relief by 2 weeks after the completion of treatment; 90% have relief within 1 to 3 months. Pain relief after radiation therapy is durable in 55% to 70% of patients.

Although it has been assumed that tumor shrinkage is responsible for pain relief in this setting, the exact mechanism of pain relief is poorly understood; patients often experience pain relief at radiation doses that are well below that is necessary to induce a complete regression of the tumor.

Several small studies did not report any clear differences in overall response rates among patients with different tumor histologies. However, a large, randomized radiation therapy oncology group (RTOG) study that looked at different radiation fractionation schemes reported a higher percentage of complete pain relief in patients with breast and prostate primaries compared to patients with lung and other types of primary tumors. Sites of metastases do not correlate with the degree of pain relief. Severe and frequent pain indicates a poor prognosis. A sudden increase in pain during treatment should raise concerns about a pathologic fracture, and appropriate radiographs and orthopaedic evaluation should be performed.