Background Bone metastases are considered uncomplicated if they are not causing neurological compromise and have not resulted in and are not at imminent risk for pathological fracture. They are often accompanied by localized pain at the lesion site, which may be controlled at rest but is incident with activity and often difficult to control with analgesics alone. Clinicians may need to advocate for single-fraction radiation therapy courses for seriously ill patients with refractory pain from uncomplicated bone metastases. This Fast Fact provides guidance for the use of single-fraction radiation treatment for painful bone metastases. See Fast Facts #66 and 67 for information on standard courses of palliative radiation.
Efficacy and Toxicity A single-fraction radiation treatment for uncomplicated bone metastases has the potential of offering quicker analgesia and lower patient burden in time, cost, and inconvenience than longer radiation schedules (1). Published data suggests that up to 60-80% of patients treated with single-fraction treatment achieve a partial or complete response in pain, meaning significantly lower patient-reported pain scores and decreased use of opioids (2). Pain relief can start within 24-48 hours of treatment but typically occurs within 2-3 weeks. Peak analgesia may not occur for up to 5-6 weeks (2). Patients with a life expectancy less than 1 month may not have sufficient time to warrant even single fraction radiation therapy for pain relief.
Pediatric Use One study showed that single-treatment radiation courses were well tolerated and associated with rapid pain relief in 37% of pediatric patients (3). They may also reduce the risk of iatrogenic harm by limiting the need for sedation or general anesthesia.
Comparative Evidence At least 25 randomized clinical trials and 4 meta-analyses have demonstrated equivalent analgesia with single-fraction versus multi-fraction radiation schemas without a difference in efficacy, pain recurrence, or toxicity (1,4). The duration of follow-up varies between studies with most being limited to 3-12 weeks after treatment completion. Multiple studies have showed that patients receiving a single treatment were more likely to require re-treatment (up to 20%) (4).
Pain Flare Pain flare is a temporary increase in pain at the treated site and can occur following single-dose radiation treatment or any other radiation schedule. A pain flare develops in 30-40% of patients shortly after treatment and generally resolves within a few days (5). Patients should be given anticipatory guidance about pain flares to avoid misattributions of worsening cancer or a failure of radiation therapy. Anti-inflammatory based medications such as non-steroidal anti-inflammatories and corticosteroids are recognized analgesics for radiation induced pain flares (5,6). A randomized controlled trial of patients receiving single-fraction treatment showed that 8 mg of dexamethasone orally < 1 hour prior to the start of radiation therapy and 8 mg daily 1-4 days thereafter can help prevent radiation induced pain flares (5).
Re-Treatment About 55% of patients who live > 1 year post-treatment develop pain again (typically 18 weeks or more after treatment completion) regardless of the radiation treatment course (7). If bone pain persists or returns, patients treated with any of the common radiation regimens can be considered for an additional single-fraction 8 Gy radiation retreatment to that site 4-6 weeks status post initial treatment (1,4). Patients usually experience moderate pain relief when re-treated (8).
Cost Analysis One study found that single 8-Gy fraction treatment was less expensive than a 10-fraction course (mean cost $998 vs $2316), even when accounting for re-treatment risk and potential survival differences (10). Use of single-fraction radiation therapy can be a cost-effective choice for the palliation of bone metastases, even compared to chemotherapy or other treatments (9-12).
Use Despite the evidence for single-fraction radiation therapy for uncomplicated bone metastases, it is not often used. A 2015 study of nearly 25,000 U.S patients who received radiation therapy for bone metastases from breast, prostate, and lung cancer showed <5% were treated with a single 8 Gy treatment (13). A Choosing Wisely campaign for the American Academy of Hospice and Palliative Medicine recommends that clinicians advocate and pursue single fraction radiation therapy for seriously ill patients with an anticipated prognosis > 1 month and uncomplicated painful bone metastases (14). In Canada, the use of single-fraction radiation therapy is likely higher than in the US, but utilization varies substantially between physicians and centers, from 26-73% (15-16).
- Patients with incident pain from uncomplicated bone metastases may receive palliative benefit from single radiation treatment.
- About 1/3 of patients develop a temporary pain flare which may be alleviated by dexamethasone.
- Re-treatment for pain that is intractable or recurs is common.
- Lutz S, Balboni T, Jones J, et al. Palliative radiotherapy for bone metastases: Update of an ASTRO evidence-based guideline. Pract Radiat Oncol. 2016;pII:S1879-8500.
- Lim PS, Hoskin PJ. “Bone Metastases” in: Handbook of Palliative Radiation Therapy. Johnstone C, Lutz ST. DemosMedical. 2017: New York.
- Deutsch M, Tersak JM. Radiotherapy for symptomatic metastases to bone in children. Am J Clin Oncol. 2004;27:128-131.
- Chow E, Zeng L, Salvo N, et al. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol. 2012;24:112-24.
- Chow E, Meyer RM, Ding K, et al. Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomized placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16:1463-72.
- Ishiwata T, Iwasawa S, Kurimoto R, et al. Comment on: Prophylactic dexamethasone for radiation-induced bone-pain flare. Lancet Oncol. 2016;17:e39-40.
- Van der Linden YM, Steenland E, van Houwelingen HC, et al. Patients with a favourable prognosis are equally palliated with single and multiple fraction radiotherapy: results on survival in the Dutch Bone Metastasis Study. Radiother Oncol. 2006;78:245-53.
- Chow E, van der Linden YM, Roos D, et al. Single versus multiple fractions of repeat radiation for painful bone metastases: a randomized, controlled, non-inferiority trial. Lancet Oncol. 2014;15:164-71.
- Konski A. Radiotherapy is a cost-effective palliative treatment for patients with bone metastasis from prostate cancer. Int J Radiat Oncol Biol Phys. 2004;60:1373-8.
- Konski A, James J, Hartsell W, et al. Economic analysis of radiation therapy oncology group 97-14: Multiple versus single fraction radiation treatment of patients with bone metastases. Am J Clin Oncol. 2009;32:423-8.
- Van den Hout WB, van der Linden YM, Steenland E, et al. Single- versus multiple-fraction radiotherapy in patients with painful bone metastases: Cost-utility analysis based on a randomized trial. J Natl Cancer Inst. 2003;95:222-229.
- Pollicino CA, Turner SL, Roos DE, O’Brien PC. Costing the components of pain management: analysis of Trans-Tasman Radiation Oncology Group trial (TROG 96.05): one versus five fractions for neuropathic bone pain. Radiother Oncol. 2005;76(3):264-269.
- Rutter CE, Yu JB, Wilson LD, Park HS. Assessment of national practice for palliative radiation therapy for bone metastases suggests marked underutilization of single-fraction regimens in the United States. Int J Radiat Oncol Biol Phys. 2015;91:548-55.
- Fischberg D, Bull J, Casarett D, et al. Five things physicians and patients should question in hospice and palliative medicine. J Pain Symptom Manage. 2013;45:595-605.
- Ashworth A, Kong W, Chow E, Mackillop WJ. Fractionation of palliative radiation therapy for bone metastases in Ontario: Do practice guidelines guide practice? Int J Radiat Oncol Biol Phys. 2016;94:31-9.
- Olson RA, Tiwana M, Barnes M, et al. Impact of using audit data to improve the evidence-based use of single-fraction radiation therapy for bone metastases in British Columbia. ? Int J Radiat Oncol Biol Phys. 2016;94:40-7.
Authors’ Affiliations: Mayo Clinic, Jacksonville, FL; Medical College of Wisconsin, Milwaukee, WI
Conflict of Interest: None
Version History: Originally edited by Sean Marks MD; first electronically published in June 2017
Fast Facts and Concepts are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School), with the generous support of a volunteer peer-review editorial board, and are made available online by the Palliative Care Network of Wisconsin (PCNOW); the authors of each individual Fast Fact are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at Palliative Care Network of Wisconsin with contact information, and how to reference Fast Facts.
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