Risk Of Vertebral Compression Fractures Research Articles

The association between body mass index and bone mineral density in older adults: a cross-sectional study of community population in Beijing

BackgroundOlder subjects have a higher risk for vertebral compression fracture. Maintaining a higher bone mineral density (BMD) at this age can protect individuals from osteoporosis-related events. Body mass index (BMI) has been found to have a robust association with BMD. However, excessive BMI is detrimental to bone health and may cause systemic disorders. Therefore, the present study aimed to determine the association between BMI and BMD, and identify a reasonable BMI range.MethodsA total of 961 participants were recruited from community-dwelling residents between August 2021 and May 2022. A weighted multivariate linear regression model was applied to identify the relationship between BMI and BMD. Meanwhile, subgroup stratified analysis by BMI quartile and gender was also performed. A non-linear relationship and threshold value were determined based on the smooth curve fittings and threshold effects analysis model.ResultsA robust relationship was found between BMI and BMD, which remained significant in subgroups stratified by gender and BMI quartile. The BMI inflection point values in lumbar BMD and femoral neck BMD were 25.2 kg/m2 and 27.3 kg/m2, respectively. For individuals with BMI < 25.2 kg/m2, an increase in BMI was related to an increase in lumbar BMD. For BMI > 25.2 kg/m2, an increase in BMI was associated with a decrease in lumbar BMD. For subjects with BMI < 27.3 kg/m2, the femoral neck BMD rose by 0.008 kg/m2 for each unit rise in BMI. However, when BMI exceeded 27.3 kg/m2, the femoral neck BMD increased only by 0.005 kg/m2. Fracture risk assessment based on the spinal deformity index (SDI) failed to determine the optimal BMI range.ConclusionsThis study found an inflection point between BMI and lumbar/ femoral neck BMD in older community-dwelling subjects. An appropriate BMI but not an excessive BMI may allow older adults to have a better BMD.

Comparative Analysis of Stereotactic Radiation Therapy and Conventional Radiation Therapy in Cancer Pain Control: A Systematic Review and Meta-Analysis

AimsApproximately 55% of patients diagnosed with primary or metastatic cancer endure pain directly attributable to the disease. Consequently, it becomes imperative to address pain management through a comparative analysis of stereotactic radiotherapy (SRT) and conventional radiation therapy (CRT), especially in light of the less efficacious improvement achieved solely through pharmacological interventions. Materials and methodsA systematic exploration was undertaken on PubMed, the Cochrane Library, and Elsevier's ScienceDirect databases to identify studies that compare Stereotactic Radiotherapy to Conventional radiation therapy for pain management in individuals with metastatic bone cancer. The analyses were executed utilizing the random-effects model. ResultsA cohort of 1152 participants with metastatic bone cancer was analyzed, demonstrating significantly higher complete pain relief in the Stereotactic Radiotherapy group during both early and late follow-up (RR: 1.61; 95% CI: 1.17, 2.23, p-value: 0.004; I2: 0%). Stereotactic Radiotherapy also showed a non-significant increase in the incidence of partial pain relief (RR: 1.07; 95% CI: 0.85, 1.34, p-value: 0.56; I2: 18%). Furthermore, Stereotactic Radiotherapy was associated with a significantly reduced risk of stationary pain throughout follow-up (RR: 0.61; 95%CI: 0.48, 0.76, p-value: <0.0001; I2: 0. The incidence of progressive pain was non-significantly reduced with Stereotactic Radiotherapy during both early and late follow-up (RR: 0.77; 95% CI: 0.50, 1.17, p-value: 0.22; I2: 0%). Secondary outcomes exhibited a non-significant trend favoring Stereotactic Radiotherapy for dysphagia, esophagitis, pain, and radiodermatitis, while a non-significant increase was observed for nausea, fatigue, and vertebral compression fracture. ConclusionIn summary, stereotactic radiation therapy (SRT) has improved in achieving complete pain relief while exhibiting a decreased probability of delivering stationary pain compared to conventional radiation therapy (CRT). Nevertheless, it is crucial in future research to address a noteworthy limitation, specifically, the risk of vertebral compression fracture.

Associations betweenco‑exposure toheavy metals and vertebral compression fracture, as well as femoral neck bone mineral density: A cross-sectional study from NHANES data.

Accumulating evidence showed that exposure to heavy metals was harmful to human health. Little is known regarding the mixing effects of multiple metal exposures on vertebral compression fracture (VCF) and femoral neck bone mineral density (BMD). This study aimed to explore the individual and joint effects of four heavy metals [manganese (Mn), lead (Pb), cadmium (Cd) and mercury (Hg)] on VCF risk and femoral neck BMD. This cross-sectional study included 1,007 eligible individuals with vertebral fractures from National Health and Nutrition Examination Survey 2013-2014. The outcome was the risk of VCF and femoral neck BMD. Weighted multivariate logistic regression was used to explore the individual effect of four heavy metals on the VCF risk, separately. Weighted multivariate linear regression was used to explore the individual effect of four heavy metals on the femoral neck BMD, separately. Adopted bayesian kernel machine regression (BKMR) model and quantile-based g computation (qgcomp) to examine the joint effects of four heavy metals on the VCF risk and femoral neck BMD. Among the population, 57 individuals developed VCF. After adjusting covariates, we found no statistical differences regarding the individual effects of four heavy metals on the risk of VCF. BKMR model and qgcomp indicated that there were no statistical differences regarding the joint effects between four heavy metals on the VCF risk. In addition, we found that Cd was associated with femoral neck BMD, and an increase in the mixture of heavy metal exposures was associated with a decreased risk of femoral neck BMD. No significant correlation was observed between co-exposure to Mn, Pb, Cd and Hg and VCF risk. But co-exposure to Mn, Pb, Cd and Hg may be associated with femoral neck BMD.

Vertebral Compression Fracture After Spine Stereotactic Body Radiotherapy: The Role of Vertebral Endplate Disruption.

Vertebral compression fracture (VCF) is a common, but serious toxicity of spinal stereotactic body radiotherapy (SBRT). Several variables that place patients at high risk of VCF have previously been identified, including advanced Spinal Instability Neoplastic Score (SINS), a widely adopted clinical decision criterion to assess spinal instability. We examine the role of tumoral endplate (EP) disruption in the risk of VCF and attempt to incorporate it into a simple risk stratification system. This study was a retrospective cohort study from a single institution. Demographic and treatment information was collected for patients who received spinal SBRT between 2013 and 2019. EP disruption was noted on pre-SBRT computed tomography scan. The primary end point of 1-year cumulative incidence of VCF was assessed on follow-up MRI and computed tomography scans at 3-month intervals after treatment. A total of 111 patients were included. The median follow-up was 18 months. Approximately 48 patients (43%) had at least one EP disruption. Twenty patients (18%) experienced a VCF at a median of 5.2 months from SBRT. Patients with at least one EP disruption were more likely to experience VCF than those with no EP disruption (29% vs 6%, P < .001). A nomogram was created using the variables of EP disruption, a SINS of ≥7, and adverse histology. Patients were stratified into groups at low and high risk of VCF, which were associated with 2% and 38% risk of VCF ( P < .001). EP disruption is a novel risk factor for VCF in patients who will undergo spinal SBRT. A simple nomogram incorporating EP disruption, adverse histology, and SINS score is effective for quickly assessing risk of VCF. These data require validation in prospective studies and could be helpful in counseling patients regarding VCF risk and referring for prophylactic interventions in high-risk populations.

Local Control after Re-Irradiation of Spinal Metastases with Stereotactic Body Radiation Therapy

Determine local control (LC) rate and risk of vertebral compression fractures (VCFs) and radiation myelitis (RM) for patients receiving re-irradiation of spinal metastases (SMs) using stereotactic body radiation therapy (SBRT) from large single-institutional experience with long follow-up. Retrospectively identified patients receiving re-irradiation SBRT (rSBRT, 1, 3, or 5 fractions) to SMs previously treated with radiation therapy (RT) and having follow up imaging to assess local control. 1 fraction patients typically received 20-24 Gy and 16-18 Gy to the high- and low-risk planning target volumes (PTVs), respectively, and 27-39 Gy and 21-24 Gy for the 3 fraction patients, with a single level of 50 Gy for 5 fractions. Patient and treatment characteristics for previous RT (pRT) and rSBRT were collected, including histology and dose-volume histogram statistics (DVH). Kaplan-Meier estimates of overall survival (OS), and cumulative incidence (competing with death) of local failure with death as a competing risk was computed for the whole cohort and stratified by radioresistance of histology, and risk of VCF for RM (for treatments at L1 and above) and 95% confidence intervals. Equivalent dose in 2 Gy fractions (EQD2) for PTV and spinal cord (SC) DVH statistics was computed for each individual course and cumulatively, using a/b = 10 Gy for tumor and 2 Gy for SC. Identified 107 lesions in 91 patients. 48 (45%) had radioresistant histologies. For all patients, at 1 and 2 years, respectively OS was 64% (55-74%) and 43% (34-55%), LC was 88% (81-94%) and 85% (78-91%) with median follow-up of 52 months (Table 1). OS and LC were not significantly different between radiosensitivity groups (p>0.05). Risk of VCF at 1 and 2 years was 7% (3-13%) and 9% (4-16%). RM was identified in 1 patient, who received 30 Gy in 5 fractions to T1, and had 1-fraction rSBRT 21 months later. SC Dmax was 31.5 Gy for pRT and 10.4 Gy, for rSBRT, resulting in total SC EQD2 of 73 Gy. RM was confirmed on MRI 8 months after rSBRT. Cumulative RM risk at 8 months after rSBRT was estimated at 1% (0-4%). Median EQD2 for the minimum dose to the high and low risk PTVs were 17.7 Gy (interquartile range, IQR, 13.0-27.6 Gy) and 13.7 Gy (IQR, 10.8-19.3 Gy) for rSBRT, and maximum EQD to SC for previous RT, rSBRT, and cumulatively was 38 Gy (IQR, 30-41 Gy), 27 Gy (IQR, 22-36 Gy), and 65 Gy (IQR, 54-73 Gy).Re-irradiation of spinal metastasis with SBRT can be delivered safely and provide high rates of local control, including for radioresistant tumors, as demonstrated with the longest reported follow-up in this setting. Re-irradiation of SM with SBRT provides high rates of LC even for radioresistant tumors, and low risk of VCF and RM, based on the longest reported follow-up in this setting.

Vertebral Compression Fracture Post Spine Stereotactic Body Radiotherapy: The Role of Vertebral Endplate

Maintaining hydrostatic pressure -via Pascal's Principle- between vertebral bodies is essential to decrease the chance of vertebral compression fracture (VCF). Vertebral endplates (EP) play an essential role in this matter through maintaining the mechanical environment as well as the proper nutrition of avascular discs. The purpose of this study is to establish the correlation of VCF with disrupted EP by tumor involvement. A retrospective analysis of de novo spine metastases treated with stereotactic body radiotherapy (SBRT) between 2013-2019. Patients (pts) with previous surgical intervention were excluded. VCF defined as new or progression of existing loss of vertebral body height. The vertebral EP region defined in relation to the vertebral body as superior EP vs inferior EP. Kaplan-Meier curves used to analyze the variables. A multivariate proportional hazard model used to assess the risk of all covariates. A total of 111 pts were treated with SBRT with a median dose of 27 Gy (10-35 Gy). Median follow-up was 18 months (1.2-107). The median age was 60 years (24-87) and 59 were males (53%) and 52 were females (47%). The median body mass index (BMI) was 27 kg/m2 (16-47). Almost 9 pts diagnosed with osteoporosis prior radiation. Twelve pts received prolonged steroids. Twenty pts received bisphosphonate and 8 pts received denosumab. The median PTV was 50cc (8-465) and median Conformity Index was 1.05 (0.42-1.4). Almost 75% of pts received >95% of the dose covering 100% of the PTV. The most common histopathologies were renal cell carcinoma (25%), lung (13%) and breast (11%). Most of the pts (77%) had SINS score of 7 or less. 48 pts (43%) had either superior or inferior EP disruption secondary to the tumor at the time of radiation. Twenty pts (18%) had both superiorly and inferiorly disrupted EP. Around 20 pts (18%) developed VCF. The median time to VCF was 5.2 months (1.1-57.4). The one-year cumulative incidence of VCF was 18%. The 1-year cumulative incidence of VCF with either superiorly and/or inferiorly disrupted EP was 29% vs 6%, p value <0.001. The 1-year cumulative incidence of VCF with both superiorly and inferiorly disrupted EP was 57% vs 7% (p value <0.001). The median time to VCF was earlier in pts with both disrupted EP (2.4 months vs 5.7 months, p value <0.05). Other risk factors like SINS score of >7 and local recurrence (LR) associated with higher risk of VCF. On multivariate analysis, LR (HR 8.2 [CI 2.4-28, p- value <0.001]), tumor disrupting the EP (HR 4.5 [CI 1.3-16, p-value<0.018]) and SINS score of seven and above (HR 1.7 [CI 1.3-2.25, p-value <0.001]) correlated with the VCF risk. In this retrospective analysis, tumor disrupting the EP, disease recurrence and high SINS score increased the risk of VCF. Cement augmentation either prophylactically or immediately following SBRT is currently being studied in a prospective trial within our institution.

Phase II Randomized Trial of Single- vs. Two-Fraction Spine Stereotactic Radiosurgery for the Treatment of Vertebral Metastases

As systemic therapies improve significantly, more patients with limited metastatic disease are undergoing spine stereotactic radiosurgery (sSRS). High dose (≥24 Gy) single fraction sSRS has been associated with a vertebral compression fracture (VCF) risk of up to 40%. Comparatively, lower dose (16-18 Gy) single fraction sSRS is associated with a fracture risk of 15-20%, with the risk increasing as the dose increases. To mitigate the risk of VCF, while optimizing higher dose delivery, some have advocated utilizing two-fraction sSRS regimen. Therefore, we designed a phase II randomized trial in which we hypothesized that single fraction sSRS is non-inferior to two-fraction sSRS with respect to VCF but offers patients greater convenience. Inclusion criteria include age ≥18, Karnofsky performance score ≥70, vertebral metastasis from C3 to L5, maximum of three separate sites of metastases, limited paraspinal extension (<5 cm), and no rapid neurological decline. Patients must also be either Recursive Partitioning Analysis Class 1 (KPS >70 AND controlled systemic disease) or Class 2 (KPS >70, uncontrolled systemic disease OR KPS ≤70, age ≥54, no visceral metastases). Exclusion criteria include multiple primary cancers, primary neoplasm of the spine, prior surgery at the site of sSRS, spinal cord compression, bony retropulsion resulting in neurologic deficit, inability to undergo/contraindication to MRI, or diffuse multi-level metastatic spine disease. Our primary hypothesis is that single fraction sSRS (experimental arm - 16-18 Gy) is non-inferior to two fraction sSRS (standard arm - 24 Gy). Furthermore, we hypothesize that both treatment arms will have similar local control, pain control, quality of life and toxicity profiles. The primary endpoint of this trial is the development or progression of VCF at 6 months. Secondary endpoints include local control, pain control, quality of life and toxicity all of which will be assessed at 12 months. For the sample size calculation, we assumed a VCF risk of 17% in the experimental arm and a 7% risk in the standard arm. Based on these calculations, we aim to enroll 130 patients, 65 in each arm. This trial is currently enrolling patients actively, and approximately 30% of expected enrollment has been completed to date. This trial is registered on clinicaltrials.gov: NCT04218617. Pending full accrual. Pending full accrual.

Dosimetric Analysis of Local Failure Outcomes and Vertebral Compression Fracture Risk in Single-Fraction Spine Stereotactic Radiosurgery for Metastatic Sarcoma

Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and their inherent radioresistance. We sought to analyze dosimetric parameters impacting local failure and vertebral compression fracture outcomes in a homogenously treated cohort of patients with SSM treated with single-fraction spine stereotactic radiosurgery (SSRS). A retrospective review was conducted on a cohort of patients with SSM treated with definitive SSRS at a single tertiary institution. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to local failure (LF). The log-rank test was utilized to examine group differences. Patients were censored at time of last follow-up or death. Cox proportionate hazards modeling was used to determine hazard ratios (HR) and their respective 95% confidence intervals (CI). A total of 66 patients with 96 lesions underwent SSRS for SSM. Median follow-up was 17 months (IQR 8-28). Median age was 55 years (IQR 41-63). The most common histological subtype was leiomyosarcoma (41%) followed by liposarcoma (9%). 81 lesions received 24 Gy to the GTV, 12 received 18 Gy and 3 received 16 Gy. Median GTV and CTV volume was 13.6cc (IQR 5-27) and 51.6cc (IQR 30-80) respectively. 27% of patients had Bilsky 1b or greater disease. 16 of 96 lesions demonstrated progression representing a crude local failure rate of 17% with median time to failure of 8 months (IQR 5-18). The 1-year actuarial progression free survival (PFS) was 89% with a median PFS of 13 months (IQR 16-63). Median overall survival (OS) was 15 months (IQR 8-28) from SSRS. 8% of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). Every 1 Gy increase in GTV minimum dose (DMin) across the range (5.8-25cc) was associated with a reduced risk of local failure (HR = 0.875 [95% CI 0.787-0.974], p = 0.01). Stratifying thresholds for GTV DMin, a local control benefit was seen as low as 12 Gy and higher (HR = 0.329 [95% CI 0.11-0.97, p = 0.044) with a significantly greater magnitude benefit seen at 14 Gy (HR = 0.267 [95% CI 0.09-0.77, p = 0.014) and above 15 Gy (HR = 0.091 [95% CI 0.03-0.41], p = 0.0018). There were no other queried variables besides GTV Dmin associated with local control including: GTV: volume, mean, Dmax, D90, CTV: volume, Dmin, Dmean, Dmax, or D90. There was an increased risk of VCF with increasing CTV DMean (HR = 2.4 [95% CI 1.4-4.1], p = 0.002) and CTV D90 (HR = 2.2 [95% CI 1.2-4.0], p = 0.01); however, no association with GTV parameters. This study represents one of the most homogenously treated and the largest cohorts of patients with sarcoma spinal metastases treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates. Increasing GTV minimum dose is significantly associated with superior local control with no corresponding increased risk of VCF.

Stereotactic Body Radiotherapy (SBRT) for Breast Cancer Spinal Metastases is Associated with Low Rates of Long-Term Local Failure (LF) and Vertebral Compression Fracture (VCF) Independent of Molecular Status

There is limited outcome data specific to breast cancer spinal metastases following spine SBRT. This study aims to report outcomes specific to breast cancer spinal metastases receiving spine SBRT and determine the implication of biomarker status. We have been maintaining a prospective database since the inception of the spine SBRT program. A retrospective review identified 168 breast cancer patients with 409 spinal segments treated with spine SBRT between January 2008 and January 2023. Molecular subtypes were grouped based on luminal A, luminal B, basal, and HER2 enriched. Patients were followed with q3-monthly full-spine MRI and a clinical assessment. The primary endpoint was MRI-based local failure (LF), and secondary endpoints were overall survival (OS) and vertebral compression fracture (VCF). The median follow-up was 33 months (range, 3.3-123 months). Amongst the 168 patients, the majority were ECOG 0 or 1 (95%), neurologically intact (94%), polymetastatic (74%), and either luminal A (71%) or luminal B (8%). A total of 17% of patients were HER2+ve versus 83% HER2-ve. Of 409 treated segments the majority (76%) had no prior radiation or surgery (de novo), were SINS stable (60%), had either no or low-grade epidural disease (86%) and treated with 24-28 Gy in 2 fractions (73%). The LF and OS rates at 1, 3, and 5 years were 5%, 11%, and 14%, respectively, and 91%, 65%, and 45%, respectively, independent of molecular subtype on univariate analyses. The cumulative risk of VCF at 2 and 5 years was 7% and 10%, respectively. We observe, in the largest breast cancer spine cohort to date, excellent long-term local control rates independent of molecular sub-group, and acceptable VCF rates.

Stereotactic Body Radiotherapy (SBRT) for Sacral Metastases: Deviation from Recommended Target Volume Delineation Predicts Higher Risk of Local Failure

A international consensus recommendation was published to guide target volume delineation specific to sacral stereotactic body radiotherapy (SBRT). We report outcomes after sacrum SBRT, focusing on the impact of contouring deviation on local failure (LF) risk, with an aim to validate this guideline. All patients who underwent SBRT to any level between S1 and S5 from 2010 to 2021 were identified from a prospectively maintained institutional database. The primary outcome was magnetic resonance-based LF. Secondary outcomes included vertebral compression fracture (VCF) and overall survival (OS). Cumulative LF and VCF rates were calculated per segment using the competing risk analysis method. Kaplan Meier analysis was used to estimate OS per patient. Cox proportional hazards model was used to assess predictive factors of LF, VCF, and OS. A total of 215 treated sacral segments in 112 patients were retrospectively reviewed. The median follow-up was 13 months (range, 0.4-116.9). The median age was 64 years (range, 18-86), and 56% were male. Most patients (52%) had treatment to a single segment. The median clinical target volume (CTV) was 129.2 cc (range, 5.8-753.5). Most segments were treated with 30 Gy/4 fractions (51%), 24 Gy/2 fractions (31%), or 30 Gy/5 fractions (10%). Thirty-one percent of segments were of radioresistant histology (gastrointestinal, kidney, melanoma, sarcoma, or thyroid primary), and 51% had extraosseous disease. Sixteen percent of segments were under-contoured per consensus guidelines, with incomplete coverage of the involved sector (71%), omission of the adjacent uninvolved sector (17%), or both (11%) as the causes for deviation. The cumulative incidence of LF was 18.4% (95% CI 13.5-24.0) at 12-months and 23.1% (95% CI 17.6-29.0) at 24-months. On multivariate analysis (MVA), under-contouring (HR 2.4, 95% CI 1.3-4.7, p = 0.008), radioresistant histology (HR 2.4, 95% CI 1,4-4.1, p = 0.001), and extraosseous extension (HR 2.5, 95% CI 1.3-4.7, p = 0.005) were predictors of increased risk of LF. The LF rates at 12/24-months were 15.1%/18.8% for segments contoured per guideline versus 31.4%/40.0% for those under-contoured. The cumulative incidence of VCF was 7.1% (95% CI 4.1-11.1) at 12-months and 12.3% (95% CI 8.2-17.2) at 24-months. On MVA, female gender was the only risk factor for VCF (HR 2.3, 95% CI 1.1-5.2, p = 0.04). The median OS was 29.5 months (95% CI 17.5-59.2). On MVA, primary kidney (HR 4.7, 95% CI 1.7-12.5, p = 0.002) or lung histology (HR 3.4, 95% CI 1.3-8.5, p = 0.010), the presence of liver (HR 2.8, 95% CI 1.2-6.4, p = 0.016) or lung (HR 2.5, 95% CI 1.3-5.1, p = 0.008) metastases, ECOG performance status 2 or 3 (HR 3.3, 95% CI 1.2-8.2, p = 0.013), and the presence of sensory or motor deficit (HR 2.6, 95% CI 1.2-5.4, p = 0.012) were prognostic for worse OS. Sacral SBRT is associated with high rates of efficacy and an acceptable VCF risk. Adherence to target volume delineation consensus guidelines reduces the risk of LF.

Fracture rate after conventional external beam radiation therapy to the spine in multiple myeloma patients

Background ContextConventional external beam radiation therapy (cEBRT) is used in multiple myeloma (MM) to treat severe pain, spinal cord compression, and disease-related bone disease. However, radiation may be associated with an increased risk of vertebral compression fractures (VCFs), which could substantially impair survival and quality of life. Additionally, the use of the Spinal Instability Neoplastic Score (SINS) in MM is debated in MM. PurposeTo determine the incidence of VCFs after cEBRT in patients with MM and to assess the applicability of the SINS score in the prediction of VCFs in MM. Study DesignRetrospective multicenter cohort study. Patient SampleMM patients with spinal myeloma lesions who underwent cEBRT between January 2010 and December 2021. Outcome MeasuresFrequency of new or progressed VCFs and subdistribution hazard ratios for potentially associated factors. MethodsPatient and treatment characteristics were manually collected from the patients’ electronic medical records. Computed tomography (CT) scans from before and up to 3 years after the start of radiation were used to score radiographic variables at baseline and at follow-up. Multivariable Fine and Gray competing risk analyses were performed to evaluate the diagnostic value of the SINS score to predict the postradiation VCF rate. ResultsA total of 127 patients with 427 eligible radiated vertebrae were included in this study. The mean age at radiation was 64 years, and 66.1% of them were male. At the start of radiation, 57 patients (44.9%) had at least one VCF. There were 89 preexisting VCFs (18.4% of 483 vertebrae). Overall, 39 of 127 patients (30.7%) reported new fractures (number of vertebrae (n)=12) or showed progression of existing fractures (n=36). This number represented 11.2% of all radiated vertebrae. Five of the 39 (12.8%) patients with new or worsened VCFs received an unplanned secondary treatment (augmentation [n=2] or open surgery [n=3]) within 3 years. Both the total SINS score (SHR 1.77; 95% confidence interval (CI) 1.54–2.03; p<.001) and categorical SINS score (SHR 10.83; 95% CI 4.20–27.94; p<.001) showed an independent association with higher rates of new or progressed VCFs in adjusted analyses. The use of bisphosphonates was independently associated with a lower rate of new or progressed VCFs (SHR 0.47 [95% CI 0.24–0.92; p=.027]). ConclusionsThis study demonstrated that new or progressed VCFs occurred in 30.7% of patients within 3 years, in a total of 11.2% of vertebrae. The SINS score was found to be independently associated with the development or progression of VCFs and could thus be applied in MM for fracture prediction and possibly prevention.

30 GY IN 4 STEREOTACTIC BODY RADIOTHERAPY (SBRT) FRACTIONS FOR COMPLEX SPINAL METASTASES: MATURE OUTCOMES SUPPORTING THIS NOVEL REGIMEN

Abstract We designed a 30 Gy in 4 fractions stereotactic body radiotherapy (SBRT) protocol, as an alternative option to our standard 2-fraction approach, for primarily large volume, multilevel, or previously radiated spinal metastases. We report imaging-based outcomes of this novel fractionation scheme. MATERIALS AND METHODS: Retrospective analysis of all patients who underwent 30 Gy/4 fractions from 2010-2021 identified from an institutional database. Primary outcomes were magnetic resonance-based vertebral compression fracture (VCF) and local failure (LF). RESULTS: We reviewed 245 treated segments in 116 patients. The median number of consecutive segments within the treatment volume was 2 (range, 1-6) and clinical target volume (CTV) was 126.2 cc (range, 10.4-863.5). Fifty-four percent had received at least one prior course of radiotherapy. The cumulative incidence of LF was 10.7% (95% CI 7.1-15.2) at 1 year and 16% (95% CI 11.5-21.2) at 2 years. The cumulative incidence of VCF was 7.3% (95% CI 4.4-11.2) at 1 and 11.2% (95% CI 7.5-15.8) at 2 years. On multivariable analysis, age ≥68 years (p=0.038), CTV volume ≥72 cc (p=0.021), and no prior surgery (p=0.021) predicted for VCF. The risk of VCF for CTV volumes &amp;lt;72 cc/≥72 cc was 1.8%/14.6% at 2 years. No case of radiation-induced myelopathy was observed. CONCLUSION: 30 Gy in 4 fractions was safe and efficacious despite a population at increased risk of toxicity. The lower risk of VCF in previously stabilized segments highlights the potential for a multi-modal treatment approach for complex metastases, especially for those with CTV volume ≥72 cc.

STEREOTACTIC BODY RADIOTHERAPY (SBRT) FOR SACRAL METASTASES: DEVIATION FROM RECOMMENDED TARGET VOLUME DELINEATION PREDICTS HIGHER RISK OF LOCAL FAILURE

Abstract Report outcomes after sacrum SBRT, focusing on the impact of contouring deviation on local failure (LF) risk, with an aim to validate the contouring consensus guidelines. METHODS/MATERIALS: Patients who underwent sacral SBRT from 2010- 2021 were identified from a prospectively maintained institutional database. Primary outcomes were magnetic resonance-based LF and vertebral compression fracture (VCF). RESULTS: A total of 215 treated sacral segments in 112 patients were reviewed. Most segments were treated with 30 Gy/4 fractions (51%), 24 Gy/2 fractions (31%), or 30 Gy/5 fractions (10%). Thirty-one percent of segments were of radioresistant histology (gastrointestinal, kidney, melanoma, sarcoma, or thyroid primary), and 51% had extraosseous disease. Sixteen percent of segments were under-contoured per consensus guidelines. The cumulative incidence of LF was 18.4% (95% CI 13.5-24.0) at 12-months and 23.1% (95% CI 17.6-29.0) at 24-months. On multivariate analysis (MVA), under- contouring (HR 2.4, 95% CI 1.3-4.7, p=0.008), radioresistant histology (HR 2.4, 95% CI 1,4-4.1, p=0.001), and extraosseous extension (HR 2.5, 95% CI 1.3-4.7, p=0.005) were predictors of increased risk of LF. The LF rates at 12/24-months were 15.1%/18.8% for segments contoured per guideline versus 31.4%/40.0% for those under-contoured. The cumulative incidence of VCF was 7.1% (95% CI 4.1-11.1) at 12-months and 12.3% (95% CI 8.2-17.2) at 24-months. On MVA, female gender predicted increased VCF risk (HR 2.3, 95% CI 1.1-5.2, p=0.04). CONCLUSIONS: Sacral SBRT is associated with high rates of efficacy and an acceptable VCF risk. Adherence to target volume delineation consensus guidelines reduces the risk of LF.

Vertebral compression fracture after stereotactic ablative radiotherapy in patients with oligometastatic bone lesions from hepatocellular carcinoma.

Stereotactic ablative radiotherapy (SABR) is popularly used to treat bone metastasis. Despite its efficacy, adverse events, including vertebral compression fracture (VCF), are frequently observed. Here, we investigated VCF risk after SABR for oligometastatic vertebral bone metastasis from hepatocellular carcinoma. A total of 84 patients with 144 metastatic bone lesions treated at three institutions between 2009 and 2019 were retrospectively reviewed. The primary endpoint was VCF development, either new or progression of a pre-existing VCF. VCFs were assessed using the spinal instability neoplastic score (SINS). Among 144 spinal segments, 26 (18%) had pre-existing VCF and 90 (63%) had soft tissue extension. The median biologically effective dose (BED) was 76.8Gy. VCF developed in 14 (12%) of 118 VCF-naïve patients and progressed in 20 of the 26 with pre-existing VCF. The median time to VCF development was 6months (range, 1-12months). The cumulative incidence of VCF at 12months with SINS class I, II and III was 0%, 26% and 83%, respectively (p<0.001). Significant factors for VCF development were pre-existing VCF, soft tissue extension, high BED, and SINS class in univariate analysis, and pre-existing VCF in multivariate analysis. Of the six components of SINS, pain, type of bone lesion, spine alignment, vertebral body collapse, and posterolateral involvement were identified as predictors of VCF development. SABR for oligometastatic vertebral bone lesions from HCC resulted in a substantial rate of new VCF development and pre-existing VCF progression. Pre-existing VCF was significant risk factor for VCF development, which require special attention in patient care. Patients with SINS class III should be considered surgical treatment rather than upfront SABR.

30 Gy in 4 Stereotactic Body Radiotherapy Fractions for Complex Spinal Metastases: Mature Outcomes Supporting This Novel Regimen.

We designed a 30 Gy in 4 fractions stereotactic body radiotherapy protocol, as an alternative option to our standard 2-fraction approach, for primarily large volume, multilevel, or previously radiated spinal metastases. We report imaging-based outcomes of this novel fractionation scheme. The institutional database was reviewed to identify all patients who underwent 30 Gy/4 fractions from 2010 to 2021. Primary outcomes were magnetic resonance-based vertebral compression fracture (VCF) and local failure per treated vertebral segment. We reviewed 245 treated segments in 116 patients. The median age was 64 years (range, 24-90). The median number of consecutive segments within the treatment volume was 2 (range, 1-6), and the clinical target volume (CTV) was 126.2 cc (range, 10.4-863.5). Fifty-four percent had received at least 1 previous course of radiotherapy, and 31% had previous spine surgery at the treated segment. The baseline Spinal Instability Neoplastic Score was stable, potentially unstable, and unstable for 41.6%, 51.8%, and 6.5% of segments, respectively. The cumulative incidence of local failure was 10.7% (95% CI 7.1-15.2) at 1 year and 16% (95% CI 11.5-21.2) at 2 years. The cumulative incidence of VCF was 7.3% (95% CI 4.4-11.2) at 1 year and 11.2% (95% CI 7.5-15.8) at 2 years. On multivariate analysis, age ≥68 years ( P = .038), CTV volume ≥72 cc ( P = .021), and no previous surgery ( P = .021) predicted an increased risk of VCF. The risk of VCF for CTV volumes <72 cc/≥72 cc was 1.8%/14.6% at 2 years. No case of radiation-induced myelopathy was observed. Five percent of patients developed plexopathy. 30 Gy in 4 fractions was safe and efficacious despite the population being at increased risk of toxicity. The lower risk of VCF in previously stabilized segments highlights the potential for a multimodal treatment approach for complex metastases, especially for those with a CTV volume of ≥72 cc.

Stereotactic Body Radiation Therapy for Spinal Metastases: Benefits and Limitations

Progress in biological cancer characterization, targeted systemic therapies and multimodality treatment strategies have shifted the goals of radiotherapy for spinal metastases from short-term palliation to long-term symptom control and prevention of compilations. This article gives an overview of the spine stereotactic body radiotherapy (SBRT) methodology and clinical results of SBRT in cancer patients with painful vertebral metastases, metastatic spinal cord compression, oligometastatic disease and in a reirradiation situation. Outcomes after dose-intensified SBRT are compared with results of conventional radiotherapy and patient selection criteria will be discussed. Though rates of severe toxicity after spinal SBRT are low, strategies to minimize the risk of vertebral compression fracture, radiation induced myelopathy, plexopathy and myositis are summarized, to optimize the use of SBRT in multidisciplinary management of vertebral metastases.

Dose-Escalated 2-Fraction Spine Stereotactic Body Radiation Therapy: 28 Gy Versus 24 Gy in 2 Daily Fractions

Stereotactic body radiation therapy (SBRT) for spine metastases improves pain response rates compared with conventional external beam radiation therapy; however, the optimal fractionation schedule is unclear. We report local control and toxicity outcomes after dose-escalated 2-fraction spine SBRT. A prospectively maintained institutional database of over 600 patients and 1400 vertebral segments treated with spine SBRT was reviewed to identify those prescribed 28 or 24 Gy in 2 daily fractions. The primary endpoint was magnetic resonance imaging based local failure (LF), and secondary endpoints included overall survival and vertebral compression fracture (VCF). A total of947 treated vertebral segments in 482 patients were identified, of which 301 segments in 159 patients received 28 Gy, and 646 segments in 323 patients received 24 Gy in 2 fractions. Median follow-up per patient was 23.5 months, and median overall survival was 49.1 months. In the 28 Gy cohort, the 6-, 12-, and 24-month cumulative incidences of LF were 3.5%, 5.4%, and 11.1%, respectively, versus 6.0%, 12.5%, and 17.6% in the 24 Gy cohort, respectively (P=.008). On multivariable analysis, 24 Gy (hazard ratio [HR], 1.525; 95% confidence interval, 1.039-2.238; P=.031), paraspinal disease extension (HR, 1.422; 95% confidence interval, 1.010-2.002; P=.044), and epidural extension in either radioresistant or radiosensitive histologies (HR, 2.117 and 1.227, respectively; P=.003) were prognostic for higher rates of LF. Risk of VCF was 5.5%, 7.6%, and 10.7% at 6, 12, and 24 months, respectively, and was similar between cohorts (P=.573). Spinal malalignment (P < .001), baseline VCF (P=.003), junctional spine location (P=.030), and greater minimum dose to 90% of planning target volume were prognostic for higher rates of VCF. Dose escalation to 28 Gy in 2 daily fractions was associated with improved local control without increasing the risk of VCF. The 2-year local control rates are consistent with those predicted by the HypofractionatedTreatment Effects in the Clinic spine tumor control probability model, and these data will inform a proposed dose escalation randomized trial.

Dose-Escalated Two-Fraction Spine Stereotactic Body Radiotherapy: 28 Gy vs. 24 Gy in 2 Daily Fractions

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) for spine metastases improves pain response rates and local control compared to conventional external beam radiotherapy, however, the optimal fractionation schedule is unclear. We report local control and toxicity outcomes after dose-escalated two-fraction spine SBRT. <h3>Materials/Methods</h3> A prospectively maintained institutional database of over 600 patients and 1400 vertebral segments treated with spine SBRT, using an established treatment technique, was reviewed to identify those treated with 28 Gy or 24 Gy in two daily fractions. The primary endpoint was MRI-based local failure (LF), and secondary endpoints included overall survival (OS) and vertebral compression fracture (VCF). <h3>Results</h3> A total of 947 treated vertebral segments in 482 patients were identified, of which 159 patients (301 segments, 31.8%) received 28 Gy and 323 patients (646 segments, 68.2%) received 24 Gy in 2 fractions. Median follow-up was 23.5 months and median OS was 49.1 months. In the 28 Gy cohort, the 6-, 12-, and 24-month cumulative incidences of local failure were 3.5%, 5.4% and 11.1%, respectively, vs. 6.0%, 12.5% and 17.6% in the 24 Gy cohort, respectively (p=0.0075). On multivariable analysis, 24 Gy (HR: 1.572, 95%CI: 1.08-2.30, p=0.0196), epidural disease (HR: 1.522, 95%CI: 1.10-2.10, p=0.0108), and paraspinal extension (HR: 1.517, 95%CI: 1.08-2.12, p=0.0151) predicted for greater rates of local failure. Risk of VCF was 5.5%, 7.6% and 10.7% at 6-, 12- and 24-months, respectively, and similar between the two cohorts (p=0.573). Spinal malalignment (p<0.001), baseline vertebral body collapse (p=0.0027), junctional spine location (p=0.0296), and a greater PTVD90 predicted for greater rates of VCF. <h3>Conclusion</h3> 28 Gy in 2 daily fractions was associated with improved local control without increasing the risk of VCF, and the 2-year local control rates fit the HYTEC spine tumor control probability model.

Impact of Dosimetric Factors on Local Failure in Patients with Spine Metastasis after Stereotactic Body Radiotherapy: A Multi-Institutional Study

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is increasingly utilized in the treatment of spine metastasis. Preliminary data suggest that higher doses may improve local control, but may also increase risk of toxicity including vertebral compression fracture (VCF). Our single institution study recently found that a minimum dose of at least 21 Gy to 80% of planning target volume (PTV D80%) in 2 fractions was associated with higher risk of VCF. The purpose of this study is to assess this variable's relationship with local failure (LF) and VCF in an international, multi-institutional cohort. <h3>Materials/Methods</h3> Patients with radiation naïve solid tumor spine metastases treated with SBRT at 5 international institutions from 2010 - 2020 were included. Patients with surgical stabilization were excluded. LF was defined per spine response assessment in neuro-oncology criteria. Variables examined included spinal instability neoplastic score (SINS) factors and dosimetric/volumetric characteristics of radiation planning. All fractionation scheme doses were converted to 2-fraction equivalent doses (2fxED) using the linear quadratic model with an alpha/beta of 3 and used in analyses of PTV D80%. Univariate and multivariate Cox proportional hazard models for LF and VCF were constructed using the Fine and Gray competing risk method. <h3>Results</h3> 357 vertebral segments from 234 patients were treated with SBRT. Common primary tumor types were prostate (n = 50, 22%), non-small cell lung cancer (n = 42, 18%), breast (n = 35, 15%), and kidney (n = 25, 11%). Most (n = 199 pts, 242 segments) were treated with 2 or 3 fractions with a median prescription dose of 24 Gy or 27 Gy, respectively (range: 14-45 Gy in 1-5 fractions). Median follow was 21.1 months (0.6-88.4 mo). LF was 12.6% and 18.1% at 1- and 2-years, respectively. Variables associated with increased LF on univariate analysis were lower PTV D80% at 2fxED ≤21 Gy (HR 0.36, 95% CI 0.20-0.65, p = 0.001) and lower prescription dose BED3 (HR 0.98 as continuous variable, CI 0.97-0.99, p = 0.03). On multivariate analysis, only PTV D80% at 2fxED ≤21 Gy remained associated with increased risk of LF (HR 0.46, CI 0.24-0.85, p = 0.01). VCF incidence was low, at 4.2% and 6.7% at 1- and 2-years, respectively. Higher SINS was predictive of VCF (HR 1.22, CI 1.1-1.36, p <0.001). Patients with higher PTVD80% at 2fxED>21 Gy had a higher, albeit non-significant, risk of VCF (HR 3.30, CI 0.80-13.6, p = 0.10), consistent with our previous single institution study. <h3>Conclusion</h3> This multi-institutional, international study suggests that a PTV D80% at 2fxED ≤21 Gy may increase the risk of LF, while >21 Gy may increase the likelihood of VCF. Prospective studies are needed to further explore this complex relationship and identify the dose/fractionation schedule that best balances local control with normal tissue toxicity including VCF.

The association between coronary artery disease and osteoporosis: a population-based longitudinal study in Taiwan

PurposeThis large population-based study is the first to analyze the association between coronary artery disease (CAD) and osteoporosis (OP) from the National Health Insurance Research Database (NHIRD) in Taiwan to determine if CAD is associated with OP.MethodsData from NHIRD, a national, population-based, retrospective, matched cohort study of 23 million patients, were collected to recruit two matched cohorts: with (n = 192,367) and without (n = 192,367) CAD. The Cox model was used to compare the incidence rate ratio and crude hazard ratio (HR) between the two cohorts for osteoporotic fracture and OP.ResultsThe CAD cohort had a significantly increased risk for vertebral compression fracture, with an adjusted HR of 1.74 (95% CI, 1.60–1.89). The cumulative incidence of OP was also statistically higher in the cohort versus without CAD (11.6% vs. 5.6%; p ≤ 0.0001, log-rank) during the 10-year follow-up period. The Cox model showed a 2.04-fold increase in the incidence of OP in the CAD cohort, with an adjusted HR of 2.04 (95% confidence interval [CI], 1.99–2.08).ConclusionsA positive association exists between CAD and development of subsequent osteoporotic fracture and OP. Patients with CAD have a significantly increased risk of developing vertebral compression fracture and a higher incident rate ratio of OP.Trial registrationIRB approval number: No. C108094 on February 19, 2020.