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Meta-Analysis
. 2024 Feb 5;7(2):e2355409.
doi: 10.1001/jamanetworkopen.2023.55409.

Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis

Bas J J Bindels  1 , Carole Mercier  2   3 , Roxanne Gal  4 , Jorrit-Jan Verlaan  1 , Joost J C Verhoeff  5 , Piet Dirix  2   3 , Piet Ost  2   6 , Nicolien Kasperts  5 , Yvette M van der Linden  7   8 , Helena M Verkooijen  4   9 , Joanne M van der Velden  5
Affiliations
Meta-Analysis

Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis

Bas J J Bindels et al. JAMA Netw Open. .

Abstract

Importance: Conventional external beam radiotherapy (cEBRT) and stereotactic body radiotherapy (SBRT) are commonly used treatment options for relieving metastatic bone pain. The effectiveness of SBRT compared with cEBRT in pain relief has been a subject of debate, and conflicting results have been reported.

Objective: To compare the effectiveness associated with SBRT vs cEBRT for relieving metastatic bone pain.

Data sources: A structured search was performed in the PubMed, Embase, and Cochrane databases on June 5, 2023. Additionally, results were added from a new randomized clinical trial (RCT) and additional unpublished data from an already published RCT.

Study selection: Comparative studies reporting pain response after SBRT vs cEBRT in patients with painful bone metastases.

Data extraction and synthesis: Two independent reviewers extracted data from eligible studies. Data were extracted for the intention-to-treat (ITT) and per-protocol (PP) populations. The study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.

Main outcomes and measures: Overall and complete pain response at 1, 3, and 6 months after radiotherapy, according to the study's definition. Relative risk ratios (RRs) with 95% CIs were calculated for each study. A random-effects model using a restricted maximum likelihood estimator was applied for meta-analysis.

Results: There were 18 studies with 1685 patients included in the systematic review and 8 RCTs with 1090 patients were included in the meta-analysis. In 7 RCTs, overall pain response was defined according to the International Consensus on Palliative Radiotherapy Endpoints in clinical trials (ICPRE). The complete pain response was reported in 6 RCTs, all defined according to the ICPRE. The ITT meta-analyses showed that the overall pain response rates did not differ between cEBRT and SBRT at 1 (RR, 1.14; 95% CI, 0.99-1.30), 3 (RR, 1.19; 95% CI, 0.96-1.47), or 6 (RR, 1.22; 95% CI, 0.96-1.54) months. However, SBRT was associated with a higher complete pain response at 1 (RR, 1.43; 95% CI, 1.02-2.01), 3 (RR, 1.80; 95% CI, 1.16-2.78), and 6 (RR, 2.47; 95% CI, 1.24-4.91) months after radiotherapy. The PP meta-analyses showed comparable results.

Conclusions and relevance: In this systematic review and meta-analysis, patients with painful bone metastases experienced similar overall pain response after SBRT compared with cEBRT. More patients had complete pain alleviation after SBRT, suggesting that selected subgroups will benefit from SBRT.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Bindels reported receiving grants from Philips Medical Systems outside the submitted work. Dr Mercier reported receiving grants from Kom op tegen Kanker outside the submitted work. Dr Gal reported receiving grants from the Dutch Cancer Society outside the submitted work. Dr Verlaan reported being a cofounder and stockholder SentryX. Dr Ost reported receiving personal fees from Bayer, Janssen, Novartis, and MSD and grants from Bayer outside the submitted work. Dr Verkooijen reported receiving grants from Elekta outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Pooled Overall Pain Response (OPR) Among the Per-Protocol Population of the 8 Included Randomized Clinical Trials at 1, 3, and 6 Months
The trials compared conventional external beam radiotherapy (cEBRT) with stereotactic body radiotherapy (SBRT).
Figure 2.
Figure 2.. Intention-to-Treat Meta-Analysis on Overall Pain Response (OPR) at 1, 3, and 6 Months After Radiotherapy of the 8 Included Randomized Trials
The trials compared conventional external beam radiotherapy (cEBRT) with stereotactic body radiotherapy (SBRT). Studies were sorted based on the equivalent dose delivered in 2 Gy (EQD2) for SBRT, with the highest dose on top.
Figure 3.
Figure 3.. Intention-to-Treat Meta-Analysis on Complete Pain Response (CR) at 1, 3, and 6 Months After Radiotherapy of the 6 Included Randomized Trials
The trials compared conventional external beam radiotherapy (cEBRT) with stereotactic body radiotherapy (SBRT). Studies were sorted based on the equivalent dose delivered in 2 Gy (EQD2) for SBRT, with the highest dose on top.
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