Chow, E., van der Linden, Y.M., Roos, D., Hartsell, W.F., Hoskin, P., Wu, J.S., . . . Wong, R.K. (2014). Single versus multiple fractions of repeat radiation for painful bone metastases: A randomised, controlled, non-inferiority trial. The Lancet Oncology, 15, 164–171. 

To assess two different radiation therapy fractionation approaches in patients with painful bone metastases needing repeat radiation therapy

Patients with radiologically confirmed bone metastases that had previously been treated with radiation were randomized to receive 8 Gy in a single fraction or 20 Gy in multiple fractions. Those getting 20 Gy received treatment in five fractions unless the target field was the spine or whole pelvis. Bone-modifying agents and systemic therapy were allowed at the discretion of the physician. Overall response to treatment was the primary endpoint at two months after beginning treatment. Pain assessments were done at days 7 and 14, monthly for 6 months, and at 9 and 12 months after radiation therapy. A difference of 10% with treatment response was established to determine noninferiority.

• N = 521 per protocol (850 in intention-to-treat [ITT] analysis)
• MEAN AGE = 65 years
• MALES: 58.7%, FEMALES: 41.3%
• KEY DISEASE CHARACTERISTICS: Prostate, breast, and lung were the most frequent diagnoses. Other cancer types were included. 
• OTHER KEY SAMPLE CHARACTERISTICS: Average worst pain at baseline was 7–10. Baseline average morphine equivalent daily dose was 40–47.5 in the 20 Gy and 8 Gy groups, respectively.

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: International

• PHASE OF CARE: Late-effects, survivorship
• APPLICATIONS: Palliative care

Unblinded, randomized, controlled noninferiority trial

• Brief Pain Inventory (BPI)
• Complete response was defined as a worst pain score of 0 with no increase in daily morphine equivalent.
• Partial response was defined as pain with either a worst pain score reduction of at least two points and no increase in daily morphine equivalents or no increase in pain with a reduction of daily opioid consumption by at least 25%.
• Pain progression was defined as either an increase in worst pain score by two or more points with no change in opioid consumption or no change in worst pain score with increased opioid consumption.

In the ITT analysis, 28% in the 8 Gy group had response, and 32% of those in the 20 Gy group had overall response with a confidence interval that did not meet the noninferiority margin. In the per-protocol analysis, 45% of patients in the 8 Gy group and 51% in the 20 Gy group had overall response with a 95% confidence interval that met the 10% noninferiority margin. Patients in the 20 Gy group had more skin reddening and more frequent and severe anorexia, vomiting, and diarrhea (p < .05).

The per-protocol analysis showed that multiple fractionation was associated with slightly better pain response to treatment, but was also associated with more side effects.

• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: Differences in use of bone-modifying agents are not reported in this manuscript. This study reports overall pain response but not complete or partial response data.

Radiation therapy to areas of painful bone metastases is effective in reducing pain. Though a higher total dose was slightly more effective, it was also associated with more side effects. Nurses can use this knowledge to educate patients and to monitor appropriate patients for treatment side effects.