Editorial: Radiotherapy for prevention for pathological femoral fractures

In this paper, “Prophylactic single fraction radiotherapy for the prevention of pathologic femoral fractures”, Ewongwo et al. discuss the use of conventional, single-dose palliative radiation for prophylaxis of femoral fractures (1). In recent decades, there has been steady progress in our understanding of palliative radiotherapy (RT) for bone metastases. In 2005, Hartsell et al. conducted a phase III, randomized trial comparing long-course palliative RT (30 Gy in 10 fractions) to single fraction treatment (8 Gy in 1 fraction). Of note, they found no difference in pain control between the arms, with a low rate of pathologic fracture (5% vs. 4%, respectively). The major difference between these approaches was the rate of re-treatment, which was higher in the 8 Gy arm (2). With the advent of stereotactic body radiotherapy (SBRT), other investigators looked into this new modality for palliation. While primarily used for bone metastases in the spine, studies thus far have been contradictory regarding the utility of SBRT in this setting. A trial comparing 16–18 Gy in 1 fraction (SBRT) to 8 Gy in 1 fraction (conventional RT) showed no difference in pain scores (3). However, a separate trial comparing 24 Gy in 2 fractions (SBRT) to 20 Gy in 5 fractions (conventional RT) showed a decrease in pain scores for the SBRT arm (4). Specifically for non-spine bone metastases, a phase II trial showed improved pain response for 12–16 Gy in 1 fraction (SBRT) versus 30 Gy in 10 fractions (conventional RT) (5). However, these studies have generally evaluated pain response and local control, whereas pathologic fracture rates and functional outcomes are typically secondary or exploratory endpoints.

In patients without bone pain, there is a lack of evidence to guide radiation oncologists. While there is ongoing study into the utility of RT in the oligometastatic setting, we do not know how to best manage asymptomatic bone metastases with RT for diffuse disease. The authors of this study hypothesize that palliative RT could be used for high-risk bone metastases as prophylaxis against catastrophic pathologic fractures. For example, hip fracture alone can lead to a severe decline in quality of life. Prophylactic RT to prevent such outcomes is therefore worth investigating (6,7). Of the 28 bone lesions treated with 8 Gy in 1 fraction on this study, no subsequent fractures occurred in-field. These findings suggest that palliative RT may have a role in the prevention of pathologic fractures of the femur. However, the authors recognize that the small sample size of 27 patients, as well as the retrospective design, limit the ability to draw firm conclusions or apply these findings to general practice.

In addition to the work by these authors, a similar study was presented in abstract form at the 2022 American Society of Radiation Oncology meeting; the authors of that phase II study found that prophylactic palliative RT to asymptomatic bone metastases decreased skeletal events, such as pathologic fracture (8). While we await the full publication of that study, we expect the outcome of both works to support ongoing research into this application of palliative RT. The next logical step would be a larger, phase III trial to determine the management of high-risk sites of bony metastasis using palliative RT, regardless of symptoms or oligometastatic state.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Therapeutic Radiology and Oncology. The article did not undergo external peer review.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://tro.amegroups.com/article/view/10.21037/tro-23-7/coif). The author has no 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/.

References

1. Ewongwo AN, Skrepnik T, Laughlin BB, et al. Prophylactic single fraction radiotherapy for the prevention of pathologic femoral fractures. Ther Radiol Oncol 2023; [Crossref]
2. Hartsell WF, Scott CB, Bruner DW, et al. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst 2005;97:798-804. [Crossref] [PubMed]
3. Ryu S, Deshmukh S, Timmerman RD, et al. Radiosurgery Compared To External Beam Radiotherapy for Localized Spine Metastasis: Phase III Results of NRG Oncology/RTOG 0631. Int J Radiat Oncol 2019;105:S2-S3. [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;22:1023-33. [Crossref] [PubMed]
5. 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;5:872-8. [Crossref] [PubMed]
6. Papadimitriou N, Tsilidis KK, Orfanos P, et al. Burden of hip fracture using disability-adjusted life-years: a pooled analysis of prospective cohorts in the CHANCES consortium. Lancet Public Health 2017;2:e239-46. [Crossref] [PubMed]
7. Amarilla-Donoso FJ, Roncero-Martin R, Lavado-Garcia JM, et al. Quality of life after hip fracture: a 12-month prospective study. PeerJ 2020;8:e9215. [Crossref] [PubMed]
8. Gillespie EF, Mathis NJ, Marine C, et al. Prophylactic Radiation Therapy vs. Standard-of-Care for Patients with High-Risk, Asymptomatic Bone Metastases: A Multicenter, Randomized Phase II Trial. Int J Radiat Oncol 2022;114:1059. [Crossref]