Addendum

Publication Details

A recently published randomized controlled trial (RCT)1 comparing stereotactic body radiation therapy (SBRT) with conventional external beam radiation therapy (EBRT) was brought to the attention of the Evidence-based Practice Center by the American Society for Radiation Oncology (ASTRO) after submission of the final review to the Agency for Healthcare Research and Quality. This addendum briefly summarizes the findings of this RCT and provides limited data abstraction of it in the related appendix (located at https://effectivehealthcare.ahrq.gov/products/radiation-therapy-bone-metastases/research). We briefly summarize evidence for the primary outcomes considered in the full published review.

Study Description

This large, fair quality, government funded RCT (N=353 randomized)1 compared a single 16 Gy or 18 Gy SBRT dose with a single 8 Gy EBRT dose for treatment of spine metastases. Patients were predominately white (80%) and male (54%) with a mean age of 63 years andwith a median Numeric Pain Rating Scale (NPRS) score of 7 (0-10 scale) at baseline; most reported pain medication at baseline (87%). Baseline Zubrod performance score was 0 in 25 percent of patients (0 to 4 scale, 0 being fully functional and asymptomatic). Zubord scores differed between treatment groups; a value of 1 was most common in both treatment groups (53.6% in SBRT vs. 63.8% for EBRT); more SBRT recipients that EBRT recipients had a value of 2 (22% vs. 10.0%). Most metastases were single (76%), and not radioresistant (87%); baseline spinal cord compression or impending fracture were not reported. In the full report, four RCTs (6 publications)2–7compared SBRT with EBRT; mean ages and proportion of males and white participants were similar to this new RCT. SBRT doses varied (12 to 24 Gy in 1 fraction, 24 Gy total in 2 fractions, 30 Gy total in 3 fractions, 35 Gy in 5 fractions) and the most common EBRT dose was 30 Gy (3 Gy x 10); one trial3 primarily used single fraction EBRT (8 Gy) and two trials also used 20 Gy (4 Gy x 5).3,4 One trial2 was in patients with nonspine metastatic bone disease (MBD) only, two RCTs4,6 include patients with only spine MBD, and one3 includes patients with mixed spine and nonspine MBD.

Results

Overall pain response (partial or complete pain relief) was more common with SBRT versus EBRT at 4 weeks (n=246, 64.7% vs. 55.9%, risk ratio [RR] 1.16, 95% confidence interval [CI] 0.93 to 1.43) in patients who had only a single treatment site but was not statistically significant. Overall pain response across all patients was less likely with SBRT versus EBRT at 12 weeks (N=214, 41.3% vs. 60.5%, RR 0.68, 95% CI 0.52 to 0.89). Authors report a risk difference of −19 (95% CI −32.9 to −5.5) favoring EBRT but no difference between techniques using a 1-sided test or for mean change in baseline scores at the index site (−2.98 vs. −3.83, 0-10 scale), suggesting that SBRT was not found to be superior to EBRT. No difference in pain response between SBRT and EBRT was seen at 52 weeks (N=97, 57.7% vs.55.3%, RR 1.04, 95% CI 0.73 to 1.49) across all patients; substantial attrition is noted. In contrast, in the full report, a small likelihood of overall pain improvement with SBRT was seen posttreatment up to 4 weeks (2 RCTs [excluding poor quality], N=325, 60% vs. 48%, RR 1.24, 95% CI 0.98 to 1.57, I2=0%)2,4 and at 12 weeks (4 RCTs, N=408, 59% vs. 44%, RR 1.31, 95% CI 1.05 to 1.61, I2=0%).2–4,6 Differences in response definitions, techniques, patient populations, and MBD characteristics may partially explain differences in findings for this new RCT and those included in the published review.

Authors of the new RCT1 report no difference between SBRT and EBRT for any of the quality-of-life measures evaluated at any time, including Functional Assessment of Cancer Therapy (FACT-G), the Brief Pain Inventory (BPI), and the EuroQol (EQ-5D). This is consistent with findings in the full review.

Treatment-related harms were similar for SBRT and EBRT in the new RCT, and findings are consistent with those in the full review. There was no difference in the proportion of vertebral compression factures (19.5% vs. 21.6%). Authors report that there were no clinical signs of acute or late spinal cord complications. Late Grade 4 toxicities were reported in two SBRT and one EBRT participant (all attributed to sepsis, lymphopenia). Grade 3 pain frequency with SBRT and EBRT was similar (7.9% vs. 4.3%) and was primarily back pain in both groups.

Regarding secondary outcomes, authors report no differences between SBRT and EBRT in the progression of known metastases (34% vs. 42%, p=0.12) or in survival rates at 52 weeks (44.3% vs. 53.1%) or 104 weeks (31.5% for both techniques, hazard ratio 0.91, 95% CI 0.37 to 1.06, timing not reported).

Addendum References

1.
Ryu S, Deshmukh S, Timmerman RD, et al. Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial. JAMA Oncol. 2023 Apr 20doi: 10.1001/jamaoncol.2023.0356. PMID: 37079324. [PMC free article: PMC10119775] [PubMed: 37079324] [CrossRef]
2.
Nguyen QN, Chun SG, Chow E, et al. Single-Fraction Stereotactic vs Conventional Multifraction Radiotherapy for Pain Relief in Patients With Predominantly Nonspine Bone Metastases: A Randomized Phase 2 Trial. JAMA Oncol. 2019 Jun 1;5(6):872–8. doi: 10.1001/jamaoncol.2019.0192. PMID: 31021390. [PMC free article: PMC6487911] [PubMed: 31021390] [CrossRef]
3.
Pielkenrood BJ, van der Velden JM, van der Linden YM, et al. Pain Response After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases-A Phase 2 Randomized Controlled Trial Within a Prospective Cohort. Int J Radiat Oncol Biol Phys. 2021 Jun 1;110(2):358–67. doi: 10.1016/j.ijrobp.2020.11.060. PMID: 33333200. [PubMed: 33333200] [CrossRef]
4.
Sahgal A, Myrehaug SD, Siva S, et al. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. Lancet Oncol. 2021 Jul;22(7):1023–33. doi: 10.1016/S1470-2045(21)00196-0. PMID: 34126044. [PubMed: 34126044] [CrossRef]
5.
Sprave T, Verma V, Forster R, et al. Quality of Life Following Stereotactic Body Radiotherapy Versus Three-Dimensional Conformal Radiotherapy for Vertebral Metastases: Secondary Analysis of an Exploratory Phase II Randomized Trial. Anticancer Res. 2018 Aug;38(8):4961–8. doi: 10.21873/anticanres.12814. PMID: 30061276. [PubMed: 30061276] [CrossRef]
6.
Sprave T, Verma V, Forster R, et al. Randomized phase II trial evaluating pain response in patients with spinal metastases following stereotactic body radiotherapy versus three-dimensional conformal radiotherapy. Radiother Oncol. 2018 Aug;128(2):274–82. doi: 10.1016/j.radonc.2018.04.030. PMID: 29843899. [PubMed: 29843899] [CrossRef]
7.
Sprave T, Verma V, Forster R, et al. Local response and pathologic fractures following stereotactic body radiotherapy versus three-dimensional conformal radiotherapy for spinal metastases - a randomized controlled trial. BMC Cancer. 2018 Aug 31;18(1):859. doi: 10.1186/s12885-018-4777-8. PMID: 30170568. [PMC free article: PMC6119304] [PubMed: 30170568] [CrossRef]