Simplifying post-operative radiotherapy for bone metastases
Review Article | Palliative Medicine and Palliative Care for Incurable Cancer

Simplifying post-operative radiotherapy for bone metastases

Emily Keit, Daniel E. Oliver, Hsiang-Hsuan M. Yu, Peter A. S. Johnstone

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

Contributions: (I) Conception and design: PAS Johnstone; (II) Administrative support: PAS Johnstone; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: E Keit; (V) Data analysis and interpretation: E Keit; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Emily Keit, MD. Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Drive, Tampa, FL 33612, USA. Email: Emily.Keit@moffitt.org.

Abstract: The delivery of post-operative radiotherapy (PORT) for solid tumor bone metastases is a well-established practice that aims to enhance patient outcomes following surgical intervention. Surgery for osseous metastases serves to stabilize bone, alleviate pain, reduce tumor volume, and relieve pressure on critical neurological components. Radiotherapy complements surgery by addressing residual malignant disease and cancer-induced pain. Together, they serve to improve local control, maximize functional outcomes, control pain, and improve patients’ overall quality of life. Despite the prevalence of non-spine bone metastases (NSBMs) necessitating operative intervention, structured guidelines for palliative PORT are limited. This is, in part, due to a paucity of research specific to this topic. As such, a wide array of doses are deemed acceptable, leading to varied practice patterns. Conversely, there is more extensive literature available, including prospective trials, for the management of post-operative spine bone metastases (SBMs). This includes advances such as stereotactic body radiotherapy (SBRT), separation surgery, and the utilization of simultaneous integrated boosts that enable evidence driven, safe dose escalation. This mini-review aims to provide a summary of the existing literature on palliative postoperative radiotherapy for both NSBMs and SBMs. By offering historical context and summarizing current evidence, this article seeks to aid clinical decision-making and highlight areas for future research to enhance treatment standardization and patient care.

Keywords: Post-operative radiotherapy (PORT); bone metastases; palliative radiation

Submitted Dec 03, 2024. Accepted for publication Feb 27, 2025. Published online Mar 27, 2025.

doi: 10.21037/apm-24-168

Introduction

The paradigm that radiotherapy should often follow operative stabilization of bone metastases is well-established and widely implemented within the field of oncology. Surgery serves to stabilize bone, debulk tumor, and relieve compression on neurological structures. Radiotherapy then treats metastatic and residual disease and aids in future stabilization of hardware. Together, surgery and radiotherapy reduce pain, improve functional status, and achieve a better a quality of life for patients.

However, despite the prevalence of solid tumor bone metastases requiring operative fixation, there exists little in the way of structured guidelines to aid radiation oncologists in the management of palliative post-operative radiotherapy (PORT). In May of 2024, the American Society for Radiation Oncology (ASTRO) updated their evidence-based guidelines for the management of symptomatic bone metastases (1). While providing guidance for the management of bone metastases as a whole, the piece provided little information specifically for the post-operative setting; this is likely due to the paucity of randomized data on this topic. The post-operative management recommendations included delivery of adjuvant radiotherapy regardless of whether surgery was reactionary or prophylactic, although a specific dose could not be recommended. Doses from 800 cGy in a single fraction up to 4,500 cGy with conventional fractionation appear acceptable. Additionally, the guidelines comment that there is a wide variety of target volumes used in practice. This paper intends to serve as a condensed review of the existing palliative PORT literature for both non-spine bone metastases (NSBMs) and spine bone metastases (SBMs), with the goal of providing context and aid in clinical decision making.

NSBMs

Operative indications for NSBMs include fracture or impending fracture. The risk of impending fracture may be calculated via the Mirels’ score, which considers the site of the lesion, degree of pain, lesion type, and percentage of bone diameter the lesion occupies. A score of 8 indicates a 15% risk of fracture with radiotherapy alone and often warrants surgical intervention (2).

The first data specifically assessing the benefit of PORT on NSBMs was published by Townsend et al. in 1995 (3). This retrospective study was relatively small (64 surgical stabilization procedures) and included PORT doses ranging from 800 to 4,500 cGy, with a median dose of 3,000 cGy. This was the first study to demonstrate that PORT on weight-bearing bones was associated with improved functional status, reduced rates of re-operation, and even an improvement in overall survival (OS). Our review has revealed six other peer-reviewed studies specifically analyzing PORT in NSBMs since this landmark study (Table 1) (4-9). While improved OS was not re-demonstrated, many of these studies reiterated the importance of PORT for improving functional status, reducing re-operation rates, and improving local control (LC) (3-9).

Table 1

Studies investigating post-operative radiotherapy for non-spine bone metastases

Study (citation) Year published Treatment(s) investigated Treated lesions (n) Dose (Gy/fraction) End point(s) Median FU (mo) LF Significant factors associated with LC MVA
Townsend et al. (3) 1995 Surgery vs. surgery + PORT 64 Median: 30/10 (range, 8–45 Gy) Functional status, OS, re-operation rate 9 Not reported PORT associated with fewer rates of re-operation (P=0.02)
Epstein-Peterson et al. (4) 2015 Surgery + PORT 82 Median: 30/10 (range, 8–50/1–25) Local progression 4.3 17% Improved LC with increasing coverage of the hardware by RT fields (P=0.03) and reduced time to PORT (P=0.01); BED ≥39 Gy not associated with LC (P=0.51)
Drost et al. (5) 2017 Surgery + PORT 74 8/1, 20/5, 30/10, unspecified “other” Re-operation rate, re-RT rate, radiographic changes 4.5 17% Not reported
Adamietz et al. (6) 2018 Surgery + PORT 68 30/10, 40/20, 35/14 Functional status, re-operation rate, OS 16.3 Not reported Not reported
Elhammali et al. (7) 2019 Involved site vs. all hardware PORT 40 20/8, 20/10, 25/10 LF 25.7 12.50% MVA not performed, >80% hardware coverage associated with improved LC (P=0.04) on UVA
Rosen et al. (8) 2021 Surgery + PORT 145 Median: 30 Gy LF 29.5 30% Whole hardware coverage was not associated with LC on MVA (P=0.19) but was associated on propensity score matching (P=0.0326)
Kraus et al. (9) 2022 Single fraction PORT vs. multi-fraction PORT 99 Median: 8/1 vs. 30/10 LF, OS, re-RT rate, re-operation rate, complication rate 13 15% vs. 19% (P=0.62) MVA not performed, fractionation scheme not associated with LF on UVA (P=0.86)

BED, biological effective doses; FU, follow-up; LC, local control; LF, local failure; mo, months; MVA, multivariate analysis; OS, overall survival; PORT, post-operative radiotherapy; RT, radiation therapy; UVA, univariate analysis.

The only two factors of PORT that have been demonstrated in multivariate analyses (MVAs) to improve LC were coverage of the entirety of the surgical hardware (4,8) and time from surgery to radiation (4). While increased dose and number of fractions initially showed signal for significance on several univariate analyses (UVAs), this signal did not persist on MVAs or propensity score matching (3,4,8). The study published by Kraus et al. specifically compared 800 cGy in a single fraction vs. 3,000 cGy over 10 fractions and found no association with worse LC, re-irradiation, or re-operation at the median follow up of 30 months (9). Similarly, other authors demonstrated that increased doses were not associated with improved functional status or limb function on MVA or UVA (3,6).

While multifaction regimens are commonly used in the post-operative NSBM setting in the United States (1), this is not necessarily evidence-driven when analyzing the current literature specific to PORT of NSBMs (3-9). Despite this, 3,000 cGy over 10 fractions remains common practice in the United States (1). It is important to note that the available literature is retrospective, contain small cohorts, do not routinely report histology types, and have relatively short median follow-up times (range, 4.3–29.5 months). With continued improvements in systemic therapy, these short follow-up times may not accurately depict modern oncology patients’ expected survivals following operative fixation. A plethora of studies in other contexts have shown higher biological effective doses (BEDs) are associated with improved LC. Many providers therefore find it reasonable to extrapolate and utilize dose-fractionation with higher BEDs in selected patients that have limited bone metastases and are estimated to have survival many years after palliative PORT. Despite common practice patterns in the U.S., 800 cGy in a single fraction remains a viable option for NSBM PORT as demonstrated in the literature. With a wide range of acceptable dose and fractionation regimens endorsed by ASTRO and the literature, radiation oncologists can provide more personalized treatment depending on the patient’s performance status, estimated prognosis, and personal goals.

There is a paucity of literature related to stereotactic body radiotherapy (SBRT) for NSBM PORT. Delivery of such high, hypofractionated doses over large volumes for coverage of hardware is not safely feasible. Ramadan et al. speculate that dose escalation may be feasible with simultaneous integrated boost (SIB) plans where higher doses are delivered to the surgical cavity, and a lower dose is employed for coverage of the hardware (10). While this appears feasible, there are currently no published reports in this setting. As patients with metastatic cancers continue to live longer with improvements in systemic therapies, this may be a future avenue of research in benefiting select patient population.

Thus, the literature specific to PORT of NSBMs demonstrates a wide variety of conventional dose and fractionation schedules that are available for personalized treatment of individuals. The following can be surmised from the available literature for PORT for NSBMs:

  • Doses as low as 800 cGy in a single fraction are appropriate; however, it may be reasonable to extrapolate from studies beyond the palliative PORT of NSBMs and use higher doses for patients with long estimated survivals and/or radioresistant histology types. It may also be reasonable to extend coverage beyond the bone if there was pre-operative disruption of the cortex or extraosseous extension to account for microscopic disease.
  • Radiation should not be delayed beyond 4–5 weeks post-operatively for improved LC (4).
  • The entirety of the surgical hardware should be covered for improved LC (4,7,8).

SBMs

In contrast to post-operative NSBM management, there are numerous publications—including randomized controlled trials—investigating optimal radiotherapy regimens for postoperative SBMs. This greater degree of interest may stem from observing worse outcomes with delayed treatment of SBMs, or because inferior LC rates may lead to paralysis and/or incontinence. In contrast to NSBMs, target volumes are smaller and often require precision (e.g., re-irradiation, tumor abutting spinal cord). This has led to an interest in single and multifraction spine SBRT, which necessitates more studies to validate the increased effort in treatment setup and evaluate the possible risk of increased toxicity. As such, there has been a shift with older literature focusing on patient tolerability of treatment and general improvement while more recent research focuses on toxicity and LC.

Operative indications for SBMs most commonly include mechanical instability of the spine or spinal cord/cauda equina compression. The Spinal Instability Neoplastic Score (SINS) is a tool that aids in determining whether a metastasis is leading to a stable, potentially unstable, or unstable spine. Parameters involved in scoring include location within the vertebral column, degree of pain, lesion type, spinal alignment, vertebral body collapse, and involvement of posterolateral elements (11). A score of at least seven indicates possible need for surgical fixation and neurosurgical evaluation.

The earliest trial demonstrating the utility of decompressive surgery for SBMs in combination with PORT was published by Patchell et al. in 2005 (12). In patients presenting with cord compression, surgical decompression followed by post-operative 3,000 cGy over 10 fractions resulted in more patients regaining the ability to walk (62% vs. 19%, P=0.01), maintained the ability to walk (94% vs. 74%, P=0.02), and a reduced need for analgesics (mean daily morphine equivalent dose of 0.4 vs. 4.8 mg, P=0.002) when compared to 3,000 cGy over 10 fractions of radiotherapy alone.

ASTRO guidelines endorse a wide array of doses that are acceptable for PORT of SBMs including regimens spanning from 800 cGy in a single fraction to 4,500 cGy with conventional fractionation and SBRT over one to five fractions (1). Similar to NSBMs, there exist a wide variety of PORT dose regimens to personalize treatment based on the individual patient’s needs.

Due to the possible sequalae of morbidity with poor LC within the spinal canal, small target volumes, and common need for re-irradiation near the spinal cord, SBM PORT lends itself well to stereotactic techniques in carefully selected patient populations. Faruqi et al. identified 12 studies evaluating SBM PORT (13). Two phase I/II and one phase II prospective postoperative SBM SBRT trials have been reported (Table 2) (14-16). Among these studies, the factors associated with reduced LC were failure to achieve durable pain response (P=0.04), sarcoma histology (P=0.04), and a larger pre-operative tumor volume (P=0.006). Overall, LC rates were excellent (>85% at 12 months) and post-operative SBRT to SBM appears safe. Notably, Redmond et al. reported all local failures to have occurred within the epidural space, indicating that coverage of this region with prescription dose is crucial (16).

Table 2

Prospective studies investigating post-operative radiotherapy for spinal metastases

Study (citation) Year published Study type Treatment investigated Lesions treated (n) Dose (Gy/fraction) Local control Median FU (mo) Factors associated with worse local control on MVA
Patchell et al. (12) 2005 Phase III RT +/− debulking 101 30/10 Not reported 3 Not reported
Garg et al. (14) 2012 Phase I/II SBRT 63 16–24/1 88% at 18 mo 20 Failure to achieve durable pain control at 6 mo (P=0.04)
Tao et al. (15) 2016 Phase I/II SBRT 69 16–24/1, 30/5, 27/3 85% at 12 mo 30 Sarcoma histology (P=0.04), larger pre-operative tumor volume (P=0.006)
Redmond et al. (16) 2020 Phase II SBRT 33 30/5 90% at 12 mo 10.5 Not reported

FU, follow-up; mo, months; MVA, multivariate analysis; RT, radiation therapy; SBRT, stereotactic body radiation therapy.

The International Stereotactic Radiosurgery Society (ISRS) Guidelines Committee provide guidance for patient selection, timing from surgery to SBRT, and treatment volume guidelines (13). It is known that deviation from spine SBRT contouring guidelines results in inferior LC in the non-post-operative setting (17). As such, we strongly encourage review of these guidelines for any provider who is considering introducing SBM PORT into his or her practice.

Because of rigid spinal cord dose constraints, dose-escalation with SBRT may not be safely feasible in patients who have a significant degree of epidural extension, due to concerns of violating the cord’s constraint or introducing reduced coverage of the segment of planning target volume (PTV) abutting/extending into the cord. To circumvent this conundrum, minimally invasive separation surgery has been gaining popularity in patients who may benefit from dose-escalation to SBMs (e.g., oligometastatic disease, radioresistant histology). By surgically introducing space between the spinal cord and the tumor, the dose to the tumor can be safely escalated while not sacrificing target coverage (18,19). Even with the assistance of separation surgery, it may be difficult to deliver the needed doses for effective SBRT while staying within the rigid spinal cord dose constraints. This is of particular concern as the most common site of failure in these patients is within the epidural space (13,15,16,20).

In order to meet cord tolerance, Garg et al. employed dose painting techniques (e.g., 2,400 cGy to the GTV and 1,600 cGy to the CTV over one fraction) (14). Dose painting or SIBs have been well-described in the literature and are an alternate strategy for achieving ablative doses within the tumor while maintaining rigid cord constraints (14).

Data demonstrate post-operative SBRT should be delivered no sooner than 8–14 days post-operatively to allow for healing (13,21), and LC suffers with SBRT delivered >4 weeks post-operatively (22). As spinal surgery often involves the placement of hardware in unaffected, healthy vertebral bodies for stability above and below the unstable vertebrae or level of spinal cord compression, coverage of post-operative hardware is not necessary and may result in needlessly large treatment volumes (13). In contrast to NSBMs, SBM PORT only requires coverage of the hardware that traverses tumor to sufficiently account for tumor seeding. Metal hardware needs to be considered prior to treatment planning when dose escalating. For metal such as titanium implants, Hounsfield units cannot be reliably calculated with accuracy. As such, if this is not corrected prior to treatment planning, the maximum dose (Dmax) and location may be inaccurate with some calculations estimating >10% differences in Dmax when using photons (13,23). With the ablative doses required for SBRT, this could result in injury to the cord. To correct this, simply contour the metal hardware and re-assign the proper density prior to treatment planning. Carbon fiber hardware is being used more frequently as its density does not interfere with treatment planning and require this additional attention (24).

The following can be summarized from the current literature for PORT of SBMs:

  • Phase III data showed improved functional status with surgery followed by postoperative conventional radiotherapy for patients with spinal cord compression (12).
  • A variety of dose and fractionation schemes exist that are appropriate depending on the individual patient’s case and goals. These include single and multi-fraction conventional radiotherapy and SBRT (1).
  • Post-operative SBRT an emerging option for select patient populations including those with oligometastatic disease, radioresistant tumor types, paraspinal tumor extension, and in the setting of re-irradiation. Due to local failures occurring most commonly within the epidural space, contouring guidelines specific to PORT for SBM SBRT should be followed (13).
  • In contrast to NSBMs, the entirety of the surgical hardware does not require treatment coverage (13).

Conclusions

Overall, a wide array of dosing schema and radiation techniques are acceptable for PORT of NSBMs and SMBs as there is a lack of robust evidence to guide providers towards an optimal dose and fractionation technique. As it currently stands, the variability in dosing schedules offers flexibility to tailor treatments for individual patient needs. The choice of radiation technique and dose should consider factors such as tumor histology, patient performance status, and goals of care to maximize therapeutic efficacy. Future studies are essential to refine these strategies, enhance evidence-based practices, and ultimately improve the quality of life for patients undergoing radiotherapy for bone metastases. While randomized controlled trials are the gold standard for investigating causal relationships and changing practice, with such limited data specific to PORT of bone metastases, even large retrospective studies of modern oncology patients would be valuable in this space. With more data, dose and fractionation choice may become more standardized in the future for optimal patient outcomes and cost-effective care.

Acknowledgments

This manuscript is an adaptation of the 2024 American Society for Radiation Oncology (ASTRO) panel presentation entitled “Simplifying Bone Metastases”.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Candice Johnstone and Michael Shing Fung Lee) for the series “Palliative Radiotherapy Column”, published in Annals of Palliative Medicine. The article has undergone external peer review.

Peer Review File: Available at https://apm.amegroups.com/article/view/10.21037/apm-24-168/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-24-168/coif). The series “Palliative Radiotherapy Column” was commissioned by the editorial office without any funding sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are 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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Cite this article as: Keit E, Oliver DE, Yu HHM, Johnstone PAS. Simplifying post-operative radiotherapy for bone metastases. Ann Palliat Med 2025;14(2):189-195. doi: 10.21037/apm-24-168

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