Single-Fraction Radiation Treatment for Uncomplicated Bone Metastases #335

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 suggest 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 five to six weeks. ² Patients with a life expectancy less than one month may not have sufficient time to warrant even single-fraction radiation therapy for pain relief.

Pediatric Use

One study showed that single-fraction 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 multifraction 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 shown that patients receiving a single-fraction treatment were more likely to require retreatment (up to 20%). ⁴

Pain Flare

Pain flare is a temporary increase in pain at the treated site and can occur after 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 nonsteroidal 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 before the start of radiation therapy and 8 mg daily one to four days thereafter can help prevent radiation-induced pain flares. ⁵

Retreatment

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 four to six weeks after initial treatment.^1,4 Patients usually experience moderate pain relief when retreated. ⁸

Cost Analysis

One study found that single 8 Gy fraction treatment was less expensive than a 10 Gy fraction course (mean cost $998 vs. $2316), even when accounting for retreatment risk and potential survival differences. ⁹ Use of single-fraction radiation therapy can be a cost-effective choice for the palliation of bone metastases, even when compared with 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 United States, but utilization varies substantially between physicians and centers, from 26% to 73%.^15,16

Summary