Effects of Single-Dose Versus Hypofractionated Focused Radiation on Vertebral Body Structure and Biomechanical Integrity: Development of a Rabbit Radiation-Induced Vertebral Compression Fracture Model

Perdomo‐Pantoja, Alexander; Holmes, Christina; Lina, Ioan; Liauw, Jason; Puvanesarajah, Varun; Goh, Brian C.; Achebe, Chukwuebuka C.; Cottrill, Ethan; Elder, Benjamin D.; Grayson, Warren L.; Redmond, Kristin J.; Hur, Soojung; Witham, Timothy F.

doi:10.1016/j.ijrobp.2021.04.050

Cited by 9 publications

(5 citation statements)

References 39 publications

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“…We hypothesize that epidural extension also weakens the bone secondary to the breakthrough of disease through the cortex. The resulting alterations in the bone microstructure may be associated with increased susceptibility to VCF, as supported by animal models …”

Section: Discussionmentioning

confidence: 88%

Development and Assessment of a Predictive Score for Vertebral Compression Fracture After Stereotactic Body Radiation Therapy for Spinal Metastases

et al. 2022

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IMPORTANCEVertebral compression fracture (VCF) is a potential adverse effect following treatment with stereotactic body radiation therapy (SBRT) for spinal metastases.OBJECTIVE To develop and assess a risk stratification model for VCF after SBRT. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study conducted at a high-volume referral center included 331 patients who had undergone 464 spine SBRT treatments from December 2007 through October 2019. Data analysis was conducted from November 1, 2020, to August 17, 2021. Exclusions included proton therapy, prior surgical intervention, vertebroplasty, or missing data.EXPOSURES One and 3 fraction spine SBRT treatments were most commonly delivered. Single-fraction treatments generally involved prescribed doses of 16 to 24 Gy (median, 20 Gy; range, 16-30 Gy) to gross disease compared with multifraction treatment that delivered a median of 30 Gy (range, 21-50 Gy). MAIN OUTCOMES AND MEASURESThe VCF and radiography components of the spinal instability neoplastic score were determined by a radiologist. Recursive partitioning analysis was conducted using separate training (70%), internal validation (15%), and test (15%) sets. The log-rank test was the criterion for node splitting. RESULTSOf the 331 participants, 88 were women (27%), and the mean (IQR) age was 63 (59-72) years. With a median follow-up of 21 months (IQR, 11-39 months), we identified 84 VCFs (18%), including 65 (77%) de novo and 19 (23%) progressive fractures. There was a median of 9 months (IQR, 3-21 months) to developing a VCF. From 15 candidate variables, 6 were identified using the backward selection method, feature importance testing, and a correlation heatmap. Four were selected via recursive partitioning analysis: epidural tumor extension, lumbar location, gross tumor volume of more than 10 cc, and a spinal instability neoplastic score of more than 6. One point was assigned to each variable, and the resulting multivariable Cox model had a concordance of 0.760. The hazard ratio per 1-point increase for VCF was 1.93 (95% CI, 1.62-2.30; P < .001). The cumulative incidence of VCF at 2 years (with death as a competing risk) was 6.7% (95% CI, 4.2%-10.7%) for low-risk (score, 0-1; 273 [58.3%]), 17.0% (95% CI, 10.8%-26.7%) for intermediate-risk (score, 2; 99 [21.3%]), and 35.4% (95% CI, 26.7%-46.9%) for high-risk cases (score, 3-4; 92 [19.8%]) (P < .001). Similar results were observed for freedom from VCF using stratification. CONCLUSIONS AND RELEVANCEThe results of this cohort study identify a subgroup of patients with high risk for VCF following treatment with SBRT who may potentially benefit from undergoing prophylactic spinal stabilization or vertebroplasty.

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Section: Discussionmentioning

confidence: 88%

Development and Assessment of a Predictive Score for Vertebral Compression Fracture After Stereotactic Body Radiation Therapy for Spinal Metastases

et al. 2022

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“…The alteration in morphology and strength were related to the quantities and the activities of the osteoblast and osteoclast cells. For example, Perdomo-Oantoja et al [ 17 ] studies the effects of 24 Gy given as a single dose or given as three fractions of 8 Gy on the L5 vertebral body of rabbits. The vertebral bodies given one fraction had lower fracture load strengths and lower stiffness compared to the fractionated bones and unirradiated bones.…”

Section: Resultsmentioning

confidence: 99%

The effects of high-dose radiation therapy on bone: a scoping review

Berk

2024

Radiat Oncol J

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Purpose: This scoping review presents the preclinical and clinical data on the effects of high-dose radiation therapy (RT) on bone structure and function. Materials and Methods: An extensive PubMed search was performed for the relevant questions. The data were then synthesized into a comprehensive summary of the available relevant in-vitro, preclinical and clinical literature. Results: In-vitro studies of high-dose RT on cell cultures show considerable damage in the viability and functional capacity of the primary cells of the bones; the osteoclasts, the osteoblasts, and the osteocytes. In-vivo animal models show that high-dose RT induces significant morphological changes to the bone, inhibits the ability of bone to repair damage, and increases the fragility of the bone. Clinical data show that there is an increasing risk over time of damage to the bone, such as fractures, after high-dose RT. Conclusion: These findings suggest that there may be a limit to the safe dose for single-fraction RT, and the long-term consequences of high-dose RT for the patients must be considered.

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“…VCF has been found to be associated with SRS dose in addition to baseline presence of compression fracture >50% of height, spinal misalignment, and lytic tumor [14,32,33,34]. Animal studies suggest that fractionated SRS may be associated with less detrimental effect on microarchitectural, cellular, and biomechanical characteristics in rabbit vertebra than single-fraction SRS [35]. Clinical series seem to support this nding, with VCF observed in only 11% of patients treated with 24 Gy in 2 fractions on the CC.24 trial [6].…”

Section: Discussionmentioning

confidence: 99%

Single- Versus Multi-Fraction Spine Stereotactic Radiosurgery (ALL-STAR) for Patients with Spinal Metastases: a Randomized Phase III Trial

Pratapneni,

Klebaner,

Soltys

et al. 2024

Preprint

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Background: For patients with spine metastases, stereotactic radiosurgery (SRS) provides excellent local control and pain response. Despite increasing use of this treatment modality, there is no consensus on the optimal dose and fractionation of spine SRS for efficacy and toxicity. We have initiated a phase III randomized trial that compares two dose regimens with similar biological equivalent dose (BED) to determine the isolated effect of SRS fractionation on local control. Methods: Patients with one to three cervical, thoracic, or lumbar spine metastases spanning no more than two contiguous vertebral levels in need of radiation will be eligible for enrollment. Patients will be assigned 1:1 to receive either 22 Gy in 1 fraction or 28 Gy in 2 fractions. Biased coin randomization will be used to minimize the size difference between arms, and randomization will incorporate the following strata: gastrointestinal histology (yes/no), paraspinal tissue extension (yes/no), epidural compression (low-/high-grade), and number of sites treated (one to three). The primary endpoint is one-year local control, defined per Spine Response Assessment in Neuro-Oncology (SPINO) criteria. The secondary endpoints include patient-reported health-related quality of life (HRQOL), pain associated with the treated site, vertebral compression fracture (VCF), and two-year local control. Patients will be followed for these outcomes at one to two weeks, one month, three months, and six months after treatment, and every six months thereafter until 24 months after treatment. Discussion: The studies published thus far comparing the single- and multi-fraction SRS are lacking long-term local control outcomes and are limited by selection bias as well as single-fraction arms with higher BED, which is correlated with improved local control. Our study will compare one-year local control in patients treated with 28 Gy in 2 fractions and the biologically equivalent single-fraction dose of 22 Gy. We will additionally compare the two arms with respect to two-year local control, pain response, adverse events, VCF, and HRQOL.

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Effects of Single-Dose Versus Hypofractionated Focused Radiation on Vertebral Body Structure and Biomechanical Integrity: Development of a Rabbit Radiation-Induced Vertebral Compression Fracture Model

Cited by 9 publications

References 39 publications

Development and Assessment of a Predictive Score for Vertebral Compression Fracture After Stereotactic Body Radiation Therapy for Spinal Metastases

Development and Assessment of a Predictive Score for Vertebral Compression Fracture After Stereotactic Body Radiation Therapy for Spinal Metastases

The effects of high-dose radiation therapy on bone: a scoping review

Single- Versus Multi-Fraction Spine Stereotactic Radiosurgery (ALL-STAR) for Patients with Spinal Metastases: a Randomized Phase III Trial

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