INTRODUCTION — Bone metastases are a common manifestation of distant relapse from many types of solid cancers, especially those arising in the lung, breast, and prostate. As many as 80 percent of patients with solid tumors will develop painful bone metastases to the spine, pelvis, and extremities during the course of their illness [1].
The goals of palliative treatment of bone metastases are pain relief, preservation of function, and maintenance of skeletal integrity. When bone pain is limited to a single or limited number of sites, local field external beam radiation therapy (EBRT) to the painful sites can provide pain relief in approximately 60 to 85 percent of cases, with complete pain response reported in 15 to 58 percent [2]. If symptomatic lesions are widespread, radiopharmaceuticals or hemibody radiation may provide useful palliative alternatives. Although treatment can be effective for patients with mild, moderate, or severe pain, early intervention may be useful in maintaining quality of life and minimizing the side effects of analgesic medications [3].
The use of RT for palliation of painful bone metastases will be reviewed here. Overviews of the clinical presentation and diagnosis of bone metastases and of the treatment approaches for bone metastases are presented separately, as are other aspects of cancer pain management, including the management of patients with epidural spinal cord compression, the use of image-guided thermal ablation for patients with pain from bone metastases that persists or recurs after RT, and management of patients with pathologic or impending pathologic fractures, including the role of kyphoplasty and vertebroplasty for patients with pathologic vertebral fractures. (See "Epidemiology, clinical presentation, and diagnosis of bone metastasis in adults" and "Overview of therapeutic approaches for adult patients with bone metastasis from solid tumors" and "Cancer pain management: General principles and risk management for patients receiving opioids" and "Treatment and prognosis of neoplastic epidural spinal cord compression" and "Image-guided ablation of skeletal metastases" and "Clinical presentation and evaluation of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma" and "Management of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma".)
EXTERNAL BEAM RADIATION THERAPY — For most patients with a single or limited number of areas of painful bone metastases, we recommend external beam RT (EBRT). RT is effective in partially or completely relieving pain in a majority of patients with bone metastases, although a transient worsening of pain may occur in some patients [4]. This typically occurs in the first few days after RT, and the pain generally lasts one to two days.
One setting in which stereotactic body RT (SBRT) may be preferred over EBRT is in the definitive treatment of patients with symptomatic bone metastases from relatively radioresistant neoplasms (eg, renal cell cancer, melanoma, sarcoma), especially in the setting of vertebral metastases with epidural extension but no high-grade epidural spinal cord compression. This subject is discussed in detail elsewhere. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Stereotactic body radiotherapy' and "Overview of therapeutic approaches for adult patients with bone metastasis from solid tumors", section on 'Stereotactic body radiation therapy'.)
Another setting in which SBRT may be considered as an alternative to EBRT is in patients with oligometastatic bone metastases in whom the primary is controlled and who have an estimated survival of greater than six months. Nomograms to assist in estimating survival in patients with metastatic cancer referred for RT for bone metastases are available [5,6]. (See 'Stereotactic radiation therapy' below.)
Single-dose versus fractionated treatment — For most patients with uncomplicated painful bone metastases (ie, without a substantial soft tissue component or fracture/impending fracture), we suggest using a single fraction of 8 Gy to the involved area. This approach provides equal palliation with improved patient convenience and cost-effectiveness compared with fractionated schedules, although retreatment is needed more frequently. For patients with a relatively long life expectancy (such as six months or more), a fractionated regimen (such as 30 Gy in 10 fractions or 20 Gy in five fractions) is a reasonable alternative because of the reduced need for retreatment.
This recommendation is in keeping with evidence-based guidelines from the American Society for Radiation Oncology (ASTRO), which support single-fraction EBRT at a dose of 8 Gy to provide palliation for relief of pain from bone metastases [2]. This approach is more convenient and cost-effective compared with fractionated schedules, and there is no evidence that the use of a single-fraction regimen is associated with an increase in acute or late toxicity. However, retreatment is necessary in a higher number of those initially treated with a single fraction compared with those initially managed with a fractionated regimen (approximately 20 versus 8 percent).
The similar effectiveness of a single fraction of 8 Gy compared with longer fractionated courses has been shown in multiple large randomized trials [7-10] and several meta-analyses [11-14], all of which concluded that single-fraction RT results in similar rates of pain control and treatment-related toxicity compared with multiple-fraction RT, but a higher rate of retreatment. As examples:
●In a Dutch multicenter trial, 1171 patients with painful bone metastases were randomly assigned to 8 Gy in a single dose or to 24 Gy in six fractions [7,8]. The palliative benefit was similar in both groups (overall pain relief in 72 and 69 percent of patients, respectively), as were the time to response (median three weeks in both groups) and the rates of treatment-related toxicity. However, retreatment was required by significantly more patients treated with a single fraction (25 versus 7 percent).
●In the Radiation Therapy Oncology Group (RTOG) trial 9714, 949 patients with prostate or breast cancer and painful bone metastases were randomly assigned to 8 Gy in a single fraction or to 30 Gy in 10 fractions [9]. Patients with evidence of cauda equina syndrome or epidural spinal cord compression were excluded. There were no significant differences in the rates for complete and partial pain relief (overall 66 percent in each group), the use of narcotics, or the incidence of subsequent pathologic fractures. However, patients treated with a single fraction were twice as likely to require retreatment (18 versus 9 percent).
Despite these data, a year 2015 assessment of national practice suggests marked underutilization of single-fraction treatment approaches [15].
Dose of single-fraction radiation — A single 8 Gy dose of RT is more effective than lower doses at providing pain relief [16].
In a representative multicenter trial, 651 patients with painful bone metastases were randomly assigned to treatment with either 8 or 4 Gy as a single dose [17]. The main tumor types represented in the trial were breast, lung, and prostate cancer (35, 35, and 17 percent, respectively). The overall response rate was higher at 4, 8, and 52 weeks with the 8 Gy dose of radiation (83 versus 71, 91 versus 83, and 93 versus 82 percent, respectively). The retreatment rate was significantly lower in those given 8 Gy (14 versus 22 percent).
Time course of relief and incidence of pain flare — The majority of patients receiving a single fraction of EBRT for a painful bone metastasis derive pain relief, and relief is often rapid. This was shown in an analysis of data from the National Cancer Institute of Canada (NCIC) symptom control trial SC.23, which examined the benefit of dexamethasone to prevent pain flare in patients receiving EBRT [18]. A total of 122 out of 298 patients (41 percent) had a beneficial response by day 10, while an additional 116 patients (39 percent) responded by day 42. These data provide support for the view that a single dose of RT should be offered to all patients with painful bone metastases, even those with poor expected survival.
A transient worsening of pain ("pain flare") occurs in approximately 30 to 40 percent of patients undergoing RT for a painful bone metastasis [4,19]. This typically occurs in the first few days after RT, and the flare in pain generally lasts one to two days.
Treatment with dexamethasone may reduce the frequency or severity of pain flare, although the data are somewhat contradictory:
●In a double-blind trial, in which 298 patients with painful bone metastases were randomly assigned to either dexamethasone (8 mg daily for five days beginning one hour before a single dose of 8 Gy radiation) or placebo, the incidence of pain flare was decreased with dexamethasone compared with placebo (26 versus 35 percent, p = 0.05) [19].
Similarly, benefit was suggested in a trial of 120 patients with symptomatic vertebral metastases treated with 30 Gy in three fractions; those randomly assigned to a single dose of methylprednisolone prior to treatment had a lower incidence of pain flare (6.6 versus 20 percent in the placebo group, relative risk reduction 72 percent) [20].
●On the other hand, a Dutch trial that randomized 295 patients with painful bone metastases from a solid tumor to multiday dexamethasone (8 mg before RT, followed by three daily doses), single-dose dexamethasone (8 mg dexamethasone followed by three days of placebo), or placebo daily for four days, the pain flare incidence was 38, 27, and 39 percent for the three groups, respectively [21]. Although the incidence of pain flare was not significantly different, patients receiving four days of dexamethasone reported lower mean pain scores on days 2 through 5 than did those receiving a single daily dose of dexamethasone or placebo.
●A systematic review of four clinical trials (including two of the three described above) and one prospective cohort study concluded that a short course of a glucocorticoid (eg, oral dexamethasone 8 mg once daily from day 1 through day 5) was effective in preventing pain flare during radiation therapy for bone metastases [22]. The overall incidence of pain flare was significantly less in the prophylaxis group (21 versus 37 percent, 43 percent relative risk reduction). When the analysis was limited to the two placebo-controlled phase III trials [19,20], the risk for pain flare was 21 versus 31 percent (relative risk 0.67, 95% CI 0.48-0.93).
While the administration of a short course of glucocorticoids may decrease flare, this benefit must be carefully weighed against the risks of toxicity (hyperglycemia, gastrointestinal irritation, and insomnia). We do prescribe glucocorticoids to patients with epidural spinal cord compression. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Glucocorticoids'.)
Need for surgery — Surgical fixation may be indicated prior to EBRT to decrease pain and facilitate rehabilitation in symptomatic bone metastases causing a pathologic fracture involving the long bones or other weight-bearing bones. In other cases, prophylactic fixation to prevent pathologic fractures, or surgical stabilization of an unstable spine may be recommended prior to EBRT for an impending fracture.
Mirels scoring system was developed to address the void in objective criteria for predicting fracture risk in the setting of metastatic disease to long bones, and it is outlined in the table and discussed in more detail separately (table 1) [23]. In general, we request orthopedic consultation for patients with long bone metastases and a Mirels score of 8 or higher. A separate assessment, the Spinal Instability Neoplastic Score (SINS), has been developed for vertebral metastases (table 2). (See "Clinical presentation and evaluation of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma", section on 'Assessing the risk of fracture' and "Clinical presentation and evaluation of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma", section on 'Assessing spinal stability'.)
Patients with inoperable fractures and those who are physically debilitated may achieve pain relief from palliative EBRT alone.
STEREOTACTIC RADIATION THERAPY — In our view and that of others [2], stereotactic body RT (SBRT) should be reserved mostly for patients who have persistent or recurrent bone pain after a standard course of external beam RT (EBRT). This view is in keeping with evidence-based guidelines on palliative RT for bone metastases from the American Society for Radiation Oncology (ASTRO) [2].
One setting in which SBRT may be preferred over EBRT is in the definitive treatment of patients with symptomatic bone metastases from relatively radioresistant neoplasms (eg, renal cell cancer, melanoma, sarcoma), especially in the setting of vertebral metastases with epidural extension but no high-grade epidural spinal cord compression.
Another setting in which SBRT may be considered is in patients with oligometastatic bone metastases in whom the primary is controlled and who have an estimated survival of greater than six months. Nomograms to assist in estimating survival in patients with metastatic cancer referred for RT for bone metastases are available [5,6].
SBRT utilizes precisely targeted radiation to the tumor while minimizing radiation to adjacent normal tissue, allowing the treatment of small- or moderate-sized tumors in either a single or limited number of dose fractions. SBRT may have a role in treating selected patients with painful bone metastases. However, there are few published randomized trials directly comparing both approaches [24-26]:
●In a randomized phase II study of 99 patients with cancer of a variety of primary tumors and up to five metastatic lesions to any site (65 had bone metastases), when compared with palliative care alone (which included standard-fractionation RT with or without systemic chemotherapy), SBRT demonstrated a nonsignificant trend towards better overall survival (41 versus 28 months; hazard ratio 0.57, 95% CI 0.30-1.10) [24].
●These data must be tempered with the potential increase in treatment-related acute and late morbidity in patients treated with SBRT. However, these risks appear to be low overall. In a meta-analysis of data from 21 single-arm studies evaluating ablative stereotactic radiotherapy for patients with oligometastatic cancer (943 patients and 1290 oligometastases, 45 percent in bone), acute grade 3 to 5 toxic effect rates were 1.2 percent (95% CI 0-3.8%) and, at a median follow-up of 16.9 months, late grade 3 to 5 toxic effect rates were 1.7 percent (95% CI 0.2-4.6%) [27]. Although these data seem reassuring, higher rates of late grade 3 or 4 toxicities are reported by others with longer follow-up [28], and phase III confirmatory trials are needed to confirm the safety and efficacy of this approach.
●The better outcomes of single-fraction SBRT over multiple-fraction EBRT can also be illustrated by the results of a phase II noninferiority trial in which 160 patients with painful bone metastases were randomly assigned to single-fraction SBRT (12 Gy for a ≥4 cm lesion, 16 Gy for a <4 cm lesion) or EBRT (30 Gy in 10 fractions) [25]. The single-fraction SBRT group had a higher fraction of complete responders at all time points post-treatment (eg, 77 versus 46 percent at nine months), and there were no local failures at 24 months of follow-up (versus 10 percent local failures in the EBRT group).
●A systematic review of 57 studies addressing the role of SBRT for bone metastases (one randomized phase II trial, the remainder retrospective or prospective cohort studies) concluded that, while there might be potential benefit for SBRT over conventional palliative RT for pain response and local tumor control, there was a high risk of selection bias in the observational studies, there was marked heterogeneity in the study populations and delivered treatments, and few studies used consensus endpoint definitions of pain response [29].
In addition to the lack of high-quality comparative data, at least in the spine, the use of SBRT might be associated with a higher risk of vertebral compression fracture (VCF), which is an early acute or subacute side effect:
●In a series of 252 patients in which 410 spinal segments were treated with SBRT, 57 VCFs (14 percent) were observed, 27 of which were new and 30 of which were a progression of preexisting fractures [30]. Multivariate analysis suggested that the risk was greatest in those treated with a single fraction of 20 Gy or greater and in those with a baseline fracture, lytic tumor, or spinal deformity.
●In another report of 448 patients (1070 vertebral bodies), 127 VCFs (11.9 percent) in 97 patients were potentially SBRT induced [31]. In multivariate analysis, patients with prior VCF, primary hematologic malignancy, thoracic spine lesions, and lytic lesions had increased rates of developing fracture. Patients treated with fraction sizes >18 Gy seemed to have a higher rate of fracture than did those treated at 16 to 18 Gy (3 of 31 versus 33 of 1030). The median time to develop a VCF was 2.7 months.
Whether SBRT is better than EBRT for symptom control remains unclear based on preliminary data presented only in abstract form:
●SBRT was not significantly better than EBRT for symptom control in a multicenter randomized phase III study (Radiation Therapy Oncology Group [RTOG] 0631) presented at the ASTRO Annual Meeting in 2019 [32]. In this trial, 339 patients with one to three sites of spine metastases were randomized to receive either SBRT (n = 209) at 16 or 18 Gy in a single fraction or EBRT (n = 130) at 8 Gy in a single fraction. In this preliminary report, there was no significant difference in pain response between SBRT and EBRT at three months (40.3 versus 47.9 percent, one-sided p = 0.99). Long-term outcomes have not yet been reported.
●On the other hand, a preliminary report of a phase II/III Canadian Cancer Trials Group/Trans-Tasman Radiation Oncology Group trial, presented at the ASTRO Annual Meeting in 2020, which randomly assigned 229 patients with painful spine metastases to SBRT (24 Gy in two fractions) or EBRT (20 Gy in five fractions), concluded that SBRT was superior to conventional EBRT at significantly improving the complete response rate for pain at both three (36 versus 14 percent) and six months (33 versus 16 percent) [33]. There were 20 (17 percent) versus 12 (11 percent) post-RT VCFs, and two versus zero patients progressed to epidural spinal cord compression in the EBRT and SBRT arms, respectively.
One setting in which SBRT may be preferred over EBRT is in the definitive treatment of patients with symptomatic bone metastases from relatively radioresistant neoplasms (eg, renal cell cancer, melanoma, sarcoma), especially in the setting of vertebral metastases with epidural extension but no high-grade epidural spinal cord compression. This subject is discussed in detail elsewhere. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Stereotactic body radiotherapy' and "Overview of therapeutic approaches for adult patients with bone metastasis from solid tumors", section on 'Stereotactic body radiation therapy'.)
The efficacy of SBRT for relatively radioresistant neoplasms can be illustrated by a large series in which SBRT (12.5 to 25 Gy, median 20 Gy) was used to treat 393 patients (including 93 with renal cell and 38 with melanoma metastases), 69 percent of whom had received prior RT [34]. Long-term pain improvement was experienced by 86 percent of all patients, including 94 percent of those with renal cell cancer and 96 percent of those with melanoma. Long-term tumor control was achieved in 90 percent of lesions treated with stereotactic radiosurgery as the primary treatment modality, including 87 percent of patients with renal cell cancer and 75 percent of those with melanoma. Of the 32 patients with a progressive neurologic deficit prior to treatment, 27 (84 percent) improved clinically.
TREATMENT OF RECURRENT OR PERSISTENT PAIN — Options for patients who have persistent or recurrent bone pain following treatment with external beam RT (EBRT) include repeat irradiation with fractionated treatment (especially if single-fraction EBRT was initially used), stereotactic RT, image-guided local thermal ablation, or radiopharmaceuticals. (See 'Stereotactic radiation therapy' above and "Image-guided ablation of skeletal metastases" and 'Bone-targeted radioisotopes' below.)
Reirradiation — Reirradiation may be a useful option for patients with painful bone metastases if the initial treatment fails to adequately relieve bone pain or there is a subsequent relapse after an initial response. A meta-analysis of seven studies that included 2694 patients who were initially treated with RT for painful bone metastases found that reirradiation was subsequently used in 527 (20 percent) [35]. Retreatment produced some benefit in terms of pain relief in 58 percent (95% CI 49-67).
There are only limited data on the optimal schedule and dose for patients in whom reirradiation is indicated. The most extensive data come from a trial in which 850 patients were randomly assigned to either a single fraction of 8 Gy or 20 Gy divided in eight fractions of 2.5 Gy [36]:
●Overall, 521 patients (61 percent) received the assigned treatment and were assessable for a pain response two months after completion of reirradiation. Within the per-protocol subset, there was no statistically significant difference in pain response (28 percent of those given a single 8 Gy fraction versus 32 percent of those given 20 Gy in eight fractions); this difference was within the predetermined noninferiority limits. There was no statistically significant difference in the incidence of pathologic fractures or spinal cord compression, although there was a trend toward a decreased incidence in those given the longer schedule.
●Acute toxicity was significantly higher in the 20 Gy arm one week after treatment in terms of loss of appetite, incidence of vomiting, diarrhea, and skin reddening. There was no difference in patient-reported global quality of life two months after treatment.
MANAGEMENT OF PATIENTS WITH DIFFUSE BONE PAIN — Some patients with multiple bone metastases have diffuse pain that is not easily managed by focal radiation. There are two options in such circumstances: bone-targeted radioisotopes and hemibody irradiation.
Bone-targeted radioisotopes — Bone-targeting radioisotopes (eg, the beta-emitting agents strontium-89, samarium-153 lexidronam, and rhenium-186, and alpha-emitting radium-223) localize to areas of osteoblastic activity and are indicated for the treatment of bone pain in patients with predominantly osteoblastic metastases. Because these agents are systemically administered, they are most appropriate for patients with multiple painful bone lesions. The vast majority of the efficacy data are in patients with metastatic prostate cancer. Data on other tumor types are limited [37-39] but show promise, especially for metastatic breast cancer. Clinical trials are underway examining the efficacy of radium-223 in a variety of solid tumor types. (See "Bone metastases in advanced prostate cancer: Management", section on 'Bone-targeted radioisotopes'.)
Radium-223 dichloride is an alpha-particle-emitting radiotherapeutic drug that mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover; it is approved only for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. Radium-223 was approved based on a double-blind, randomized, placebo-controlled trial in patients with metastatic castration-resistant prostate cancer who had symptomatic bone metastases and no known visceral metastatic disease [40]. Radium-223 significantly improved overall survival and had a beneficial effect on delaying bone pain, with the time to having to undergo external beam RT (EBRT) for bone pain being significantly longer for patients receiving radium-223 than for those receiving placebo. The recommended dose and schedule for radium-223 dichloride is 50 kBq/kg (1.35 microcuries/kg) administered by slow intravenous injection over one minute every four weeks for six doses. Pain relief has been reported in approximately 71 percent of treated patients by week 8, although some pain relief may be evident as early as week 2 [41]. Radium-223 can be administered with EBRT, and is safe whether administered concurrently or sequentially [42]. However, concurrent use with abiraterone has been associated with increased fracture risk, especially when bone health agents are not employed. (See "Bone metastases in advanced prostate cancer: Management", section on 'Radium-223'.)
Hemibody irradiation — Hemibody irradiation refers to treating a large portion of the body with external beam irradiation and can provide rapid pain relief when multiple sites of symptomatic bone metastases are present [2,43]. The use of hemibody irradiation has largely been replaced by the administration of radiopharmaceuticals, which offer a similar degree of pain relief and may be associated with less toxicity. Hemibody irradiation may retain a role when access to radiopharmaceuticals is limited. While there are limited data, historical doses of 6 Gy in one fraction to the upper torso and 8 Gy in one fraction to the lower body have been used [44,45]. (See 'Bone-targeted radioisotopes' above.)
SUPPORTIVE CARE — For all patients with painful bone metastases, supportive care should include adequate analgesia and the use of osteoclast inhibitors to enhance analgesia and to reduce the risk of skeletal-related events (including the need for radiation or surgery to bone, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy).
Opioid therapy is the first-line approach for moderate or severe pain in populations with active cancer, including those with symptomatic bone metastases. Patients with multifocal bone pain usually are managed with a nonsteroidal anti-inflammatory agent (NSAID), unless they have a specific contraindication to use of these agents, in conjunction with an opioid and usually with an adjuvant analgesic (ie, osteoclast inhibitors, glucocorticoids) used specifically for bone pain. (See "Cancer pain management with opioids: Optimizing analgesia" and "Cancer pain management: Role of adjuvant analgesics (coanalgesics)", section on 'Patients with bone pain'.)
Osteoclast inhibitors (including bisphosphonates and denosumab) are indicated for the management of metastatic bone disease for most patients with solid tumors. Osteoclast inhibitors slow or reverse the progression of skeletal metastases and reduce the likelihood of skeletal-related events. In addition, they also have some analgesic benefit, although it is modest.
The vast majority of the data regarding the benefits of osteoclast inhibitors for prostate cancer were generated in the castration-resistant state; hence, for men with bone metastases from prostate cancer, the use of osteoclast inhibitors is generally restricted to those with castration-resistant disease. (See "Bone metastases in advanced prostate cancer: Management", section on 'Castration-resistant disease'.)
For patients in whom skeletal-related events are unlikely (eg, those with minimal bone tumor burden) and for those with a limited expected survival (eg, in the setting of widespread and progressive visceral metastases), treatment with osteoclast inhibitors should be considered on a case-by-case basis. This subject, as well as other adjuvant analgesics, is discussed in detail elsewhere. (See "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors" and "Cancer pain management: Role of adjuvant analgesics (coanalgesics)", section on 'Patients with bone pain'.)
Finally, prophylactic antiemetics are very useful when treating metastases in the lumbar spine or pelvic bones when the radiation field includes the stomach or intestines.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of bone metastases in solid tumors".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Bone metastases (The Basics)")
SUMMARY AND RECOMMENDATIONS
●For most patients with a single or limited number of areas of painful bone metastases, we recommend external beam radiation therapy (EBRT) (Grade 1A). (See 'External beam radiation therapy' above.)
•For most patients, we suggest using a single fraction of 8 Gy to the involved area (Grade 2A). This approach provides equal palliation with improved patient convenience and cost-effectiveness compared with fractionated schedules, although retreatment is needed more frequently. (See 'Single-dose versus fractionated treatment' above.)
•For patients with a relatively long life expectancy (six months or longer), a fractionated regimen (such as 30 Gy in 10 fractions or 20 Gy in five fractions) is a reasonable alternative.
•A transient worsening of pain ("pain flare") occurs in approximately 30 to 40 percent of patients undergoing RT for a painful bone metastasis. Treatment with dexamethasone may reduce the frequency of pain flare. (See 'Time course of relief and incidence of pain flare' above.)
●In our view, stereotactic body RT (SBRT) should be reserved mostly for patients who have persistent or recurrent bone pain after a standard course of EBRT. This view is in keeping with evidence-based guidelines on palliative RT for bone metastases from the American Society for Radiation Oncology (ASTRO).
One setting in which SBRT may be preferred over EBRT is in the definitive treatment of patients with symptomatic bone metastases from relatively radioresistant neoplasms (eg, renal cell cancer, melanoma, sarcoma), especially in the setting of vertebral metastases with epidural extension but no high-grade epidural spinal cord compression. For patients with oligometastatic bone disease, a controlled primary site, and a long estimated life expectancy, SBRT is also a reasonable approach. (See 'Stereotactic radiation therapy' above.)
●Surgical consultation for fixation should be obtained prior to the institution of RT for high-risk bone metastases involving the long bones or other weight-bearing bones to treat or prevent a pathologic fracture. In general, we request orthopedic consultation for patients with a Mirels score of 8 or higher (table 1). (See 'Need for surgery' above and "Management of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma", section on 'Management principles'.)
●Options for patients who have persistent or recurrent bone pain following treatment with EBRT include repeat irradiation with fractionated treatment (especially if single-fraction EBRT was initially used), SBRT, image-guided local thermal ablation, kyphoplasty/vertebroplasty for vertebral compression fractures, or radiopharmaceuticals. (See 'Treatment of recurrent or persistent pain' above.)
Reirradiation may be indicated if there is an incomplete response to initial treatment or if severe pain recurs and the patient's overall condition permits. Clinical trials data suggest that acceptable regimens include a single fraction of 8 Gy or a brief fractionated regimen of 20 Gy, although the latter can be associated with higher acute toxicity. For selected patients with a good performance status and recurrence in the spine, SBRT is another option, where available. (See 'Reirradiation' above and 'Stereotactic radiation therapy' above.)
●Some patients with multiple bone metastases have diffuse pain that is not easily managed by focal radiation. There are two options in such circumstances: systemic administration of a bone-targeted radioisotope, and hemibody irradiation. (See 'Management of patients with diffuse bone pain' above.)
●For all patients with painful bone metastases, supportive care should include adequate analgesia and the use of osteoclast inhibitors to enhance analgesia and reduce the risk of skeletal-related events (including the need for radiation or surgery to bone, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy). (See 'Supportive care' above.)
