Single fraction treatment of painful bone metastases is as effective as multi-fraction regimens, less costly, and more convenient for patients. It should be the standard of care for the palliation of bone metastases. ASTRO favored shorter treatment rather than single fraction in its “Choosing Wisely” program, while the American Academy of Hospice and Palliative Medicine included the recommendation, saying “Although it results in a higher incidence of later need for retreatment (20% vs 8% for multi-fraction regimens), the decreased patient burden usually outweighs any considerations of long-term effectiveness for those with a limited life expectancy”. But instead of just reading policy statements, let’s look at the evidence.
1. Efficacy. In the RTOG trial comparing 8 Gy in1 fraction to 30 Gy in 10 fractions showed no difference in the rate for complete and partial pain relief (overall 66% in each group). At 3 months, 33% of the 898 patients no longer required narcotic pain medication, and this did not differ between treatment arms. The multi-fraction treatment had greater grade 2-4 toxicity (17% vs 10%). The rate of retreatment was higher (18% vs 9%), but it had nothing to do with efficacy – physicians were re-irradiating their single fraction treated patients basically because they could – even though their patients were just as likely to have pain control and not need narcotics.
A Dutch trial comparing 8 Gy in 1 fraction to 24 Gy in 6 fraction in 1171 patient had similar results – equal efficacy, with a higher retreatment rate (24% vs 7%). After controlling for the influence of re-treatment, they found that single fraction and multi-fraction treatment provided equal palliation, but although there was no greater acute toxic toxicity, there was a small increase in the number of pathologic fractures (not demonstrated in other trials). The predictors for retreatment were not uncontrolled pain or increased use of narcotics in single fraction treated patients. The randomization arm itself significantly predicted re-treatment.
The British/New Zealand trial compared 8 Gy/1 fx, 20 Gy/5 fx, 30 Gy/10 fx, at 12 months for 765 patients, There were no differences in pain end points amongst the three groups – all had a 78% response rate and no difference in toxicity. Time to first improvement in pain, time to complete pain relief, and time to first increase in pain were similar in all arms. All studies confirmed RTOG’s results for retreatment – it was based on physician comfort to retreat, not lack of efficacy.
2. Cost. The RTOG re-analyzed the data to evaluate cost-effectiveness of single fraction treatment. The expected mean cost for a course of single fraction treatment was $1009 versus $2322 for a course of multi-fraction treatment. However, they did not report the outcome including the additional cost of re-treatment. The Dutch group also reviewed the costs and found that even when accounting for re-treatment, the single fraction course was less costly – $2438 vs $3311.
3. Convenience. I calculated how many fractions the average patient treated with single fraction versus multi-fraction treatment, including the retreatment. To make it as fair as possible, the presumed retreatment schema for single fraction patients would be 30 Gy in 10 fractions, while those re-treated after 30 Gy in 10 fractions would receive a single fraction of 8 Gy. Looking at all three trials, the “average” single fraction patient would like receive 2.8-3.8 fractions compared to 10.1 fractions for the multi-fraction approach.
Keep in mind, this data may not apply for all bone metastases. If there is spinal epidural disease or a significant soft tissue mass from the tumor, that’s a different story. Maybe that’s why ASTRO hedged. But if it’s a simple problem, the solution should be simple, too.
The evidence reveals that single fraction palliative radiation is equally effective, less costly and more convenient. So why isn’t it standard of care? What do we need to do to make it the standard?