The optimal radiation therapy modality for spinal metastases: stereotactic body radiation therapy versus conventional external beam radiation therapy

The March 2025 issue of Annals of Palliative Medicine features 4 Original Articles, 4 Review Articles, 1 Brief Report, 1 Editorial Commentary, and a Study Protocol article describing the protocol for the prospective, multicenter observational PRO ASEPT trial on tunnelled catheters for palliative care outcomes, as well as a Meeting Report from the Society for Palliative Radiation Oncology Eleventh Annual Meeting.

This Message from the Editor-in-Chief focuses on the Brief Report by Wong et al. focusing on how recent clinical trials have impacted results of a meta-analysis on the benefits of stereotactic body radiation therapy (SBRT) for spine metastases (1).

Bone metastases remain a common manifestation of advanced malignancies and a major driver in reduced quality of life in this patient population. Spine metastases are particularly impactful, as they can lead to irreversible neurological complications like radiculopathy and spinal cord compression (2). Such spinal lesions have long been managed with conventional external beam radiation therapy.

There has been increasing interest over the past two decades in using SBRT to treat bone and spinal lesions due to its ability to deliver highly conformal and ablative doses of irradiation to the target volume while often better sparing adjacent normal tissues (3). Such delivery with SBRT allows for higher biologically effective doses (BEDs) to be administered to targets, theoretically allowing for superior tumor control and symptomatic response rates.

The value of SBRT to treat spinal metastases has been assessed in several recent trials, and Wong et al. previously conducted a systematic review and meta-analysis of randomized controlled trials comparing SBRT to conventional external beam radiation therapy for spinal metastases (4). In that report published in December 2023 in Radiotherapy and Oncology, trials published through May 2023 were analyzed. Three randomized controlled trials involving 642 patients were analyzed. There were no significant differences identified between the radiation therapy modalities in overall pain response at 3 months or at 6 months, or in local progression or overall survival. However, based on two (5,6) of the three trials reporting on complete pain response rates, SBRT was found to have a statistically significant improvement in complete pain responses compared to conventional external beam radiation therapy at both 3 months [risk ratio (RR) 2.52; 95% confidence interval (CI): 1.58–4.01; P<0.0001] and 6 months (RR 2.48; 95% CI: 1.23–4.99; P=0.01). Overall, toxicities were similar between modalities, although SBRT had fewer radiation dermatitis events (RR 0.17; 95% CI: 0.03–0.96; P=0.04). Based on the findings, the authors concluded that SBRT is a safe treatment option for spine metastases that may provide superior complete pain response, although additional trials are needed (4).

In their Annals of Palliative Medicine Brief Report, those authors have now updated the results of their prior meta-analysis with regard to complete pain response. The recently reported North American-based NRG Oncology RTOG 0631 randomized trial did not show a difference in complete pain response at 3 or 6 months between arms (1,7). Additionally, a recently reported European-based phase 3 randomized controlled trial found a higher proportion of patients with clinically significant pain reduction at 6 months following SBRT relative to conventional external beam radiation therapy (69.4% vs. 41.9%, P=0.02), but no differences in complete pain responses at either 3 months (19.4% vs. 16.1%, P=0.73) or 6 months (22.2% vs. 29.0%; P=0.53) (8).

When combining these two new results (7,8) with the two prior trials reporting on complete pain response (5,6), complete pain responses on the updated meta-analysis at 3 and 6 months were no longer statistically significantly different between SBRT and conventional external beam radiation therapy (1). It is noteworthy that the authors found a significant heterogeneity in the newly updated meta-analysis that they hypothesized was due to different baseline patient characteristics and SBRT dose fractionations delivered between the studies. As a result, the authors conducted a network meta-analysis to evaluate the relative efficacy of various SBRT dose fractionation regimens, although no clear relationship between higher BED and rates of complete pain response in 3 months was identified.

It is possible that pain relief from tumor control with higher SBRT doses could have been offset by new pain from vertebral fractures, as some of the included studies suggest that SBRT might be associated with a higher risk of symptomatic vertebral fractures compared to conventional external beam radiation therapy, and that this risk increases when radiation therapy doses exceed 20 Gy in a single fraction (9). A definitive assessment has been limited by many of the trials included in the meta-analysis failing to assess the pain response specifically at the treated spine and to clearly document if vertebral compression fractures were attributable to treatment or if they occurred concurrently with local tumor progression.

Of note, the definitions of pain response and study inclusion criteria varied between the studies included in the meta-analysis. Such variability in the efficacy outcome measures and differences in baseline pain scores across trials may have limited the interpretation of the pooled result in the meta-analyses.

In addition to updating the results of the meta-analysis, in their Brief Report, the authors discuss different study endpoints and the development of the International Consensus Pain Response Endpoints (ICPRE) for bone metastases trials (10,11). This measure has helped to standardize study endpoints and allowed for more valid comparison and consistencies in reporting across studies, and we await the updated third version of that consensus that is currently underway and is expected to establish endpoints specifically for SBRT clinical trials.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Palliative Medicine. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-25-49/coif). The author serves as the co-Editor-in-Chief of Annals of Palliative Medicine from April 2014 to April 2027. The author has no other conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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