Efficacy
Dose fractionation schedules have been under investigation for some time. Current evidence shows that when comparing single fraction regimens vs multiple fraction regimens, there is no significant difference found in regards to pain control, neuropathic pain, pain flare, pathological fracture, overall response rates and cord compression between the two groups. A significant difference has been demonstrated in re-treatment rates between the single fraction regimens vs multiple fraction regimens as detailed below.
The evidence supporting this protocol is provided by a meta-analysis by Chow et al. 2019 of 29 trials that involved a total of 5617 patients.r These trials included patients with painful bony metastases of any primary site and endpoint was pain control. All studies compared a single fraction (SF) regimen with a multiple fraction (MF) regimen. Overall response rates for SF and MF radiation therapy were 61% (1867 out of 3059) and 62% (1890 out of 3040) respectively, with a pooled odds ratio (OR) of 0.98 and a 95% confidence interval (CI) from 0.95-1.02. This was not statistically significant (p = 0.36). Higher re-treatment rates 20% (497 out of 24820) vs 8% (192 out of 2468) were reported in the SF arm vs the MF arm, respectively, with a pooled OR of 2.42 (95% CI:1.87-3.12). This was statistically significant with a p <0.01. This analysis included 12 studies, representing 4632 random assignments. Twelve trials reported pathological fracture rates at the sites treated. There was no trend favouring either arm (p = 0.42). In total, 4% and 3% of the SF and MF arms, respectively, experienced a pathological fracture. Pooled OR was 1.12 (95% CI:0.76-1.95). Six trials reported spinal cord compression rates in 2886 random assignments. 2.8% (41 out of 1443) and 1.9% (28 out of 1443) of SF and MF arms, respectively, developed spinal cord compression. Overall OR was 1.44 (95% CI:0.73–2.67), and was not significant (p = 0.13). Chow 2019 provided no new evidence over the 2012 publication.
Table 1. Single vs multi fraction meta-anlysis outcomesr
Response rates |
Re-treatment rates |
Pathological fracture rates* |
Spinal cord compression rates |
Single fx |
Multi fx |
Single fx |
Multi fx |
Single fx |
Multi fx |
Single fx |
Multi fx |
61% |
62% |
20% |
8% |
4% |
3% |
2.8% |
1.9% |
*Pathological fracture can be a result of disease progression, as well as a response to treatment.
Re-irradiation
Chow et al. 2014 published results of an international multicentre, non-blinded, randomised, controlled trial of 425 patients with painful bone metastases that had previous radiation therapy to the same site.r Patients were randomised to receive either 8 Gy in a single fraction or 20 Gy in multiple fractions. Patients were stratified by treatment centre, previous radiation fraction schedule and response to initial radiation treatment. In the intention-to-treat analysis, 118 (28%) patients allocated to 8 Gy treatment and 135 (32%) allocated to 20 Gy treatment, had an overall pain response. The study concluded that in the setting of re-irradiation for patients with painful bone metastases, treatment with 8 Gy in a single fraction is non-inferior and less toxic than 20 Gy in multiple fractions, however, there may be trade-offs between efficacy and toxicity.
Post-operative radiation
There is a lack of high-level evidence, and some conflicting data, for the benefits of post-operative radiation therapy for bony metastases.rr There is uncertainty regarding optimal treatment field design but covering the full surgical implant may minimise the risk of tumour progression.r