Rate Of Vertebral Compression Fracture Research Articles

Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy for Painful Spinal Metastases: A Comparative Analysis of Randomized Trials and Practical Considerations

IntroductionRecent randomized trials have compared the efficacy and safety of stereotactic body radiation therapy (SBRT) with standard conventional external beam radiotherapy (cEBRT) for the treatment of painful spinal metastases. We conducted a composite analysis of these trials in order to inform current practice using pooled outcomes. MethodsData from each randomized trial were abstracted from the final publications with biologically effective doses (BEDs) recalculated for SBRT and cEBRT. Primary outcome measures were overall (OR) and complete pain response (CR) rates at 1, 3, and 6-months, and rates of vertebral compression fracture (VCF). Random effects models were used to estimate primary outcome measures and meta-regression assessed the effect of BED. ResultsFour prospective randomized clinical trials published between 2018 and 2024 were included, with a total of 686 patients (383 and 303 in the SBRT and cEBRT groups, respectively). Dose and fraction (fx) number for the SBRT group ranged from 24 Gy/ 1 fx to 48.5 Gy/ 10 fx (median BED10 50 Gy), and for the cEBRT group from 8 Gy/ 1 fx to 30 Gy/ 10 fx (median BED10 28 Gy). The 1, 3, and 6-month OR rates for SBRT and cEBRT were similar: 53.6%, 52.4%, 58.8% vs. 48.4%, 47.9%, 43.8%, respectively (p>0.05). The 3-month CR rate was significantly higher for SBRT compared to cEBRT (31.9% vs. 14.8%, RR 2.26; 95% CI, 1.48-3.45, p<0.001), but not the 6-month rate (34.4% vs. 16.3% RR 1.83; 95% CI, 0.74-4.53, p=0.194). VCF rates were similar at 17.3% and 18.4% for SBRT and cEBRT, respectively. No significant dose-dependent effect was observed with increasing BED for any efficacy or safety outcomes. ConclusionsOR pain response rates are similar, but CR pain response rates appear higher with SBRT compared to cEBRT, yet no dose-dependent effects were identified despite approximately 1.8x BED dose with SBRT.

Early Experience With Two-Fraction Spine Stereotactic Body Radiation Therapy in Treating Spinal Metastases.

Spinal metastases are common in metastatic cancer, affecting around 40% of patients. The primary treatment involves radiation therapy, transitioning from conventional external beam radiation therapy (EBRT) to stereotactic body radiation therapy (SBRT) for its superior, durable response. While spine SBRT has gained popularity in the United States, Level I evidence supporting it over EBRT is limited to a Canadian trial using a 2-fraction SBRT regimen. We present our findings from one of the earliest US experiences of 2-fraction spine SBRT for spinal metastases. A retrospective analysis of patients with metastatic spine cancer receiving 2-fraction spine SBRT at a single center was conducted. Patients received treatment based on Level 1 evidence (24Gy in 2 fractions). Follow-up records were assessed for local control outcomes and toxicity. Twenty patients since August 2022 have been treated with 2-fraction spine SBRT. Most patients were treated at 1 (45%) or 2 (40%) spinal levels, with the thoracic (55%) and lumbar (50%) spine being the most common locations. Common primary sites included the lung (30%), breast (20%), esophagus (15%), and prostate (10%). The rate of local control was 100%, while the rate of vertebral compression fracture was 15%. No esophageal or bowel toxicity occurred, and no fractures required intervention. These findings suggest that 2-fraction spine SBRT is safe and effective, consistent with existing Level I evidence. Our local control rate exceeding 95% aligns with the literature, indicating the feasibility and achievability of implementing this approach in the United States over a short period of time.

Molecular Status Predicts for Local Control in Patients with Non-Small Cell Lung Cancer Spinal Metastases Following Spine Stereotactic Body Radiotherapy

We report outcomes after spine stereotactic body radiotherapy (SBRT) in patients with metastatic non-small cell lung cancer (NSCLC), to determine the significance of programmed death-ligand 1 (PD-L1) status and epidermal growth factor (EGFR) mutation on local failure (LF) rate. A total of 165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was LF and secondary outcomes included overall survival (OS) and vertebral compression fracture (VCF) rates. OS was estimated using the Kaplan-Meier method. Cumulative LF and VCF rates were calculated using competing risk analysis method. Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. Median follow-up was 13 months (range, 0.5-95 months). Median OS was 18.4 months (95% CI 11.4-24.6). Median age was 67 years (range, 28.2-89.9). 52% were female, 76% had an adenocarcinoma histology and 61% had a smoking history. 49/165 (29%) had an EGFR mutation. PD-L1 status was analyzed in 109/165 (66%) patients with 16% PD-L1 ≥ 50%, 20% PD-L1 1-49% and 35% PD-L1 <1%. Of 389 segments, 79% were de novo and 21% were previously radiated. At baseline, 35% had a VCF, 27% had epidural disease, 27% had paraspinal extension, and 49% were Spinal Instability in Neoplasia Score (SINS) stable. 239/389 (61%) were treated with either 24 or 28 Gy in 2 SBRT fractions. Within 1 month of SBRT, 39/165 (24%) had a tyrosine kinase inhibitor, 27/165 (16%) immunotherapy (IO) with or without chemotherapy, and 31/165 (19%) chemotherapy alone. LF cumulative incidence at 1- and 2-years was 16.3% (95% CI 12.8-20.3%) and 25.4% (95% CI 20.9%-30%), respectively. EGFR positivity (p<0.0001), PD-L1≥50% (p = 0.013) and treatment with IO within 1 month of SBRT (p = 0.004) predicted for improved local control on MVA. The 1- and 2-year LF rate in EGFR-positive vs. negative patients were 12.9% vs. 16.6% and 17.7% vs. 28.8%, respectively, and in those PD-L1 ≥50% vs PD-L1<50% were 7.8% vs. 19.6% and 7.8% vs. 38.1% respectively. Cumulative incidence of VCF at 1- and 2-years were 6.6% (95% CI 4.4-9.4%) and 8.8% (95% CI 6.1-12.0%). MVA identified prior SBRT to the same treated segment (P<0.0001) and a baseline VCF (p<0.0001) as significant predictors. 18/389 (4.6%) had radiation-induced radiculopathy and no radiation myelopathy events detected. We identify the predictive utility of EGFR mutation and PD-L1 ≥50% status on local control in NSCLC patients with spinal metastases treated with spine SBRT, and a therapeutic benefit with peri-SBRT IO.

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.

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.

Morbidity of single-fraction spine radiosurgery for metastatic disease.

e24116 Background: The optimal management of metastatic spine disease involves radiation therapy, with stereotactic radiosurgery (SRS) utilization having increased in adoption while proving to be efficacious and safe. Spine SRS morbidity (fatigue, dermatitis, nausea and esophagitis) is generally mild and depends on the spinal vertebral level(s) treated. More severe adverse events such as vertebral compression fracture (VCF), radiation-induced myelopathy, and tracheoesophageal (TE) fistula have been documented. The potential benefits of single-fraction SRS (sfSRS) over multi-fraction SRS include increased patient convenience, decreased financial toxicity, and increased treatment completion rates. These benefits may potentially be overshadowed by the morbidity of sfSRS versus multifraction SRS. In this analysis, we perform the first comprehensive examination of sfSRS morbidity in the treatment of spinal lesions. Methods: An extensive search of the PubMed database was undertaken through 2/2/23 to find studies examining spinal sfSRS. Search parameters included the terms “single-fraction, spine, radiation SRS OR SBRT” Articles including multi-fractionated regimens only, reviewed sites outside of the spine, or did not report on clinical outcomes/toxicities were excluded. Results: 17 articles met initial inclusion criteria; 9 were added from references for a total of 26 articles comprising at least 2,699 patients (one study reported the number of tumors, not patients). Dose ranges for single-fraction SRS were 8-26 Gy. Commonly noted toxicities were fatigue, nausea/vomiting, and dermatitis which were no worse than moderate/minimal, not requiring invasive intervention. The overall rate of VCF was 16.2%, with an increased propensity at &gt;20 Gy. The proportion of reported segments requiring surgical intervention (operative stabilization, vertebroplasty/kyphoplasty) for VCF after single-fraction SRS was 20.2% (33/163). The rate of TE fistula at 25 Gy was 8.3%, with an overall rate (dose range = 10-28 Gy) of 1.3% with up to 12-years of follow-up. In patients receiving median dose of 24 Gy, the rate of severe esophagitis was 6.8%, myositis was 1.3% (at 1-year) and 8.3% (at 5-years). The rate of peripheral nervous system injury was 2.5% (at 18-26 Gy) and pain flare was 8% (at 16-24 Gy). The rate of ureteral and esophageal stricture was 1.9% each in patients receiving 12-24 Gy. Conclusions: VCF is the most commonly reported severe adverse events with single-fraction spine SRS, particularly for doses &gt; 20 Gy. 80% of VCFs can be successfully managed without invasive intervention. Other severe adverse events are rare – particularly for &lt; 20 Gy – but require post-SRS monitoring to expediently and efficiently intervene if necessary. These findings indicate that single-fraction spine SRS to &lt; 20 Gy is safe with minimal morbidity. Further study regarding the efficacy of such dosing is being evaluated in ongoing clinical trials.

Mature Outcomes of Stereotactic Body Radiotherapy for Spinal Metastases with 30 Gy in 4 Fractions

<h3>Purpose/Objective(s)</h3> At our institution, 30 Gy in 4 spine stereotactic body radiotherapy (SBRT) fractions is typically delivered for larger volume when multiple segments are included in the treatment volume and/or for the retreatment of spinal metastases. We report MRI-based local failure (LF) and vertebral compression fracture (VCF) rates for patients (pts) treated with 30 Gy/4Fx of spine SBRT. <h3>Materials/Methods</h3> A retrospective analysis of all pts with spine metastases treated with 30 Gy/4Fx from 2010 to 2021 from an institutional registry was performed. Demographic, clinical, dosimetric, and radiological data were summarized, and the primary endpoint was the MRI-based LF rate. Secondary endpoints included the incidence of VCF and overall survival (OS). Kaplan Meier was used to calculate LF and VCF per segment and OS per patient. <h3>Results</h3> Were included 116 pts with 245 treated segments in this analysis. The median number of consecutive segments in the treatment volume was 3 (1-7), and the median clinical target volume (CTV) was 126 cc (range, 10-863). Kidney (25%), lung (20%), breast (19%), prostate (19%), and colon (10%) cancer were the most common primary histologic types. 38% of pts had oligometastatic disease and 24% spine metastases only. 15% (17/116) of the patients were treated with postoperative SBRT. 31% of segments were re-irradiated for conventional palliative radiation, and 26% prior SBRT, failures. 25% of segments had a baseline VCF, 46% epidural disease, and 53% paraspinal tumor extension. The median follow-up per patient was 18.5 (range, 0.1-61) and per segment 10.7 mos (range, 0.1-59). The LF rates at 12 and 24 mos were 10.7% (95% CI 7.1-15.2) and 16% (95% CI 11.5-21.2), and for VCF were 7.3% (95% CI 4.4-11.2) and 11.2% (95% CI 7.5-15.8), respectively. 60% of failures had an epidural, and 23% a paraspinal, component. Age <68y (HR=0.43, 95% CI 0.19-0.95, p=0.038), volume of CTV <72cc (HR=0.09, 95% CI 0.01-0.70, p=0.021), and prior surgical stabilization (HR=0.25, 95% CI 0.07-0.81, p=0.021) were protective predictors for VCF on multivariable analyses (MVA). In particular, the VCF rate at 24 mos was 1.8% for pts with CTV volume <72 vs 14.6% for ≥72cc. Median OS was 20.3 mos (95% CI 14.8-27.1). Low grade or no epidural disease (HR=0.42, 95% CI 0.21-0.84, p=0.014), paraspinal disease (HR=3.07, 95% CI 1.68-5.62, p<0.001) and kidney primary cancer (HR=2.43, 95% CI 1.08-5.44, p=0.031) were predictors for OS on MVA, with a trend for oligometastatic disease (HR=0.56, 95% CI 0.31-1.02, p=0.059). No radiation-induced myelopathy was observed. <h3>Conclusion</h3> This first report for 30 Gy/4Fx as a novel fractionation for spine SBRT suggests high rates of local control and a low rate of VCF, particularly for those target volumes with a CTV<72 cc. However, our rate of VCF in very large treatment volumes (≥72cc) is comparable to the SBRT-induced VCF literature, where optimal management remains an active area of investigation.

Clinical and dosimetric risk factors for vertebral compression fracture after single-fraction stereotactic body radiation therapy for spine metastases

ObjectivesThis analysis was performed to evaluate the incidence of vertebral compression fracture (VCF) and determine the contributing factors for VCF in patients undergoing single-fraction stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM). MethodsA retrospective review of medical records was conducted for patients undergoing SBRT for SBM at our institution between January 2010 and December 2018. Patients who had undergone neither pre-SBRT surgical excision nor post-SBRT prophylactic fixation were included. The effects of clinical and dosimetric parameters were analyzed with respect to VCF risk. The following dosimietric parameters of the planning target volume (PTV) were calculated: mean/minimum/maximum dose, radiation dose to 10–90% volume, and irradiated volume receiving more than 10–25 Gy (PTV_V10 – 25 Gy). ResultsAmong 163 patients (179 vertebrae), 21 (12.8%) experienced VCF. The 1-year and 2-year VCF rates were 12.1% and 13.2%, respectively. Among dosimetric parameters, PTV_V15 Gy was the most significant for VCF prediction. In a univariate analysis, breast or prostate primary, no vertebral body collapse, and PTV_V15 Gy ≤42 cm3 were significantly associated with a lower incidence rate of VCF. In a multivariate analysis, PTV_V15 Gy was the only significant factor for VCF risk. The 1-year VCF rate was 3.8% in patients with PTV_V15 Gy ≤42 cm3, while it was 22.1% in those with PTV_V15 Gy > 42 cm3 (p < 0.01). ConclusionsSBRT-related VCF was found in 12% of patients in our institution. The PTV_V15 Gy is a significant factor for VCF prediction.

Vertebral compression fracture rate following stereotactic ablative body radiotherapy for spine oligometastases: a UK experience

AbstractAim:Stereotactic ablative body radiotherapy (SABR) for spine metastases is associated with a risk of vertebral compression fracture (VCF). The aim of this study was to determine the rate of VCF at one UK institution and evaluate the use of the Spinal Instability Neoplastic Score (SINS) to predict these.Materials and methods:A retrospective analysis of all patients who underwent SABR for spinal metastases between 2014 and 2018 at one UK institution was performed. Basic demographic data were collected, and SINS prior to SABR was calculated. The primary outcome was VCF rate. Secondary outcomes included time to VCF and need for surgical intervention following VCF.Results:A total of 48 oligometastases were treated with a median follow-up of 20·5 months. A maximum of two vertebral bodies were treated. The median baseline SINS was calculated as 3. The median dose was 26 Gy in three fractions. Two patients were reported to have VCF and both were successfully conservatively managed.Findings:SABR for spine oligometastases is being performed safely with low VCF rates which are comparable with those in international publications. This may be as a result of strict adherence to criteria for delivery of SABR with low pre-treatment SINS.

Local control and patterns of failure for "Radioresistant" spinal metastases following stereotactic body radiotherapy compared to a "Radiosensitive" reference.

The concept of a radioresistant (RR) phenotype has been challenged with use of stereotactic body radiotherapy (SBRT). We compared outcomes following SBRT to RR spinal metastases to a radiosensitive cohort. Renal cell, melanoma, sarcoma, gastro-intestinal, and thyroid spinal metastases were identified as RR and prostate cancer (PCA) as radiosensitive. The primary endpoint was MRI-based local failure (LF). Secondary endpoints included overall survival (OS) and vertebral compression fracture (VCF). From a prospectively maintained database of 1394 spinal segments in 605 patients treated with spine SBRT, 173 patients/395 RR spinal segments were compared to 94 patients/185 PCA segments. Most received 24-28Gy in 2 fractions (68.9%) and median follow-up was 15.5months (range, 1.4-84.2months). 1- and 2-year LF rates were 19.2% and 22.4% for RR metastases, respectively, which were significantly greater (p < 0.001) than PCA (3.2% and 8.4%, respectively). Epidural disease (HR: 2.47, 95% CI 1.65-3.71, p < 0.001) and RR histology (HR: 2.41, 95% CI 1.45-3.99, p < 0.001) predicted for greater LF. Median OS was 17.4 and 61.0months for RR and PCA cohorts, respectively. Lung/liver metastases, polymetastatic disease and epidural disease predicted for worse OS. 2-year VCF rates were ~ 13% in both cohorts. Coverage of the CTV V90 (clinical target volume receiving 90% of prescription dose) by ≥ 87% (HR: 2.32, 95% CI 1.29-4.18, p = 0.005), no prior spine radiotherapy (HR: 1.96, 95% CI 1.09-3.55, p = 0.025), and a greater Spinal Instability Neoplasia Score (p = 0.013) predicted for VCF. Higher rates of LF were observed after spine SBRT in RR metastases. Optimization strategies include dose escalation and aggressive management of epidural disease.

Imaging-Based Local Control Rates For “Radioresistant” Spinal Metastases Following Spine Stereotactic Body Radiotherapy Using Prostate Cancer As The “Radiosensitive” Reference

It is thought that stereotactic body radiotherapy (SBRT) challenges the notion of a radioresistant phenotype given the high rates of local control. To determine the impact on local control for those classically considered radioresistant spinal metastases, we compared outcomes following spine SBRT using prostate cancer metastases as the radiosensitive comparator. We retrospectively reviewed a prospectively maintained database of 1394 spinal segments in 605 patients treated with SBRT between January 2009 to December 2018, and identified renal cell carcinoma (RCC), melanoma, sarcoma, colon cancer, and thyroid cancer metastases as the radioresistant cohort and prostate cancer metastases as the radiosensitive cohort. All patients were serially followed with clinic visit and full spine MRI every 2 to 3 months. The primary endpoint was imaging-based local control using the prostate cancer cohort as the comparator, and secondary endpoints included overall survival (OS) and vertebral compression fracture (VCF). 173 patients/395 radioresistant spinal segments were compared to 94 patients/185 prostate cancer spinal segments and median follow-up was 15.5 months (range: 1.4-84.2 months). For the entire cohort, the majority had an ECOG of 0-1 (87.3%), were treated with 24-28 Gy in 2 fractions (71.9%), and half had oligometastatic disease (53.9%). 1- and 2-year local control (LC) rates for the radioresistant cohort were 80.8% and 77.6%, as compared to 96.8% and 91.6% for the prostate cancer cohort. Variation amongst radioresistant histologies was observed with 1-year LC rates of 76.2% for melanoma (41/395), 76.3% for colon cancer (85/395), 81.1% for renal cell carcinoma (225/395), 86.2% for thyroid cancer (29/395), and 100% for sarcoma (15/395). Local failure was associated with presence of epidural disease (HR 2.481, 95% CI: 1.652-3.724, p<0.0001), radioresistant histology (HR 2.318, 95% CI: 1.397-3.848, p = 0.0011), and a lower CTV V90 (p<0.0001). For the radioresistant and prostate cancer cohorts the median OS was 17.4 and 61.0 months and the 2-year OS rates were 37.4% and 81.4%, respectively. Presence of lung, liver and brain metastases, widespread (non-oligometastatic) disease, epidural disease and ECOG ≥ 2 were prognostic for worse OS. Non-significant differences in the 1- and 2-year VCF rates at 9.8% and 14.1%, and 5.1% and 12.7%, were observed in the radioresistant and prostate cancer cohorts, respectively. Coverage of CTV V95 by > 0.87 (HR 2.32, 95% CI: 1.29-4.18, p = 0.005), no-prior radiotherapy at index lesion (HR 1.963, 95% CI: 1.086-3.546, p = 0.0254), and higher SINS score (p = 0.0125) predicted for VCF. Our results confirm a significant difference in local control rates amongst those histologies classically considered radioresistant compared to radiosensitive. Although local control rates are still high, optimization strategies may include dose escalation and more aggressive management of epidural disease.

Commentary: Mature Imaging-Based Outcomes Supporting Local Control for Complex Reirradiation Salvage Spine Stereotactic Body Radiotherapy

Background Upon progression after upfront radiotherapy to spinal metastases, low-dose re-irradiation conventional external beam radiation (cEBRT) provides limited clinical benefit. Spine stereotactic body radiotherapy (SBRT) allows for dose escalation in the salvage setting with the potential for improved local control. Objective To report mature clinical and imaging-based outcomes for salvage SBRT. Methods A retrospective review was undertaken of consecutive patients with spinal metastases treated with re-irradiation spine SBRT having failed either cEBRT (n = 60 with 1 prior course and n = 17 with 2 or more prior cEBRT courses), or prior SBRT (n = 6) to the same spinal segment. The primary outcome was local failure (LF), and secondary outcomes included overall survival (OS) and the rate of vertebral compression fracture (VCF). Results A total of 43 patients with 83 spinal segments treated with salvage SBRT were reviewed. The crude risk of LF was 18%, and actuarial LF rates at 6, 12, and 24 mo were 7%, 14%, and 19%, respectively. The presence of extensive paraspinal disease (hazard ratio [HR] = 7.1, 95% CI 1.5-34) significantly predicted for LF. The median OS was 13.2 (95% CI 6.1-16.3) mo, and the presence of neurological deficits (HR = 4.7, 95% CI 1.8-12.1) and brain metastases (HR = 2.6, 95% CI 1.1-6.3) were significant prognostic factors. The crude risk of VCF was 4%, and radiation myelopathy was not observed. Conclusion These data support the safety and efficacy of spinal re-irradiation with SBRT including patients with prior SBRT and multiple courses of prior cEBRT.

Mature Imaging-Based Outcomes Supporting Local Control for Complex Reirradiation Salvage Spine Stereotactic Body Radiotherapy.

Upon progression after upfront radiotherapy to spinal metastases, low-dose re-irradiation conventional external beam radiation (cEBRT) provides limited clinical benefit. Spine stereotactic body radiotherapy (SBRT) allows for dose escalation in the salvage setting with the potential for improved local control. To report mature clinical and imaging-based outcomes for salvage SBRT. A retrospective review was undertaken of consecutive patients with spinal metastases treated with re-irradiation spine SBRT having failed either cEBRT (n=60 with 1 prior course and n=17 with 2 or more prior cEBRT courses), or prior SBRT (n=6) to the same spinal segment. The primary outcome was local failure (LF), and secondary outcomes included overall survival (OS) and the rate of vertebral compression fracture (VCF). A total of 43 patients with 83 spinal segments treated with salvage SBRT were reviewed. The crude risk of LF was 18%, and actuarial LF rates at 6, 12, and 24 mo were 7%, 14%, and 19%, respectively. The presence of extensive paraspinal disease (hazard ratio [HR]=7.1, 95% CI 1.5-34) significantly predicted for LF. The median OS was 13.2 (95% CI 6.1-16.3) mo, and the presence of neurological deficits (HR=4.7, 95% CI 1.8-12.1) and brain metastases (HR=2.6, 95% CI 1.1-6.3) were significant prognostic factors. The crude risk of VCF was 4%, and radiation myelopathy was not observed. These data support the safety and efficacy of spinal re-irradiation with SBRT including patients with prior SBRT and multiple courses of prior cEBRT.

Normal tissue complication probability of vertebral compression fracture after stereotactic body radiotherapy for de novo spine metastasis

ObjectiveStereotactic body radiotherapy (SBRT) for spine metastases is associated with post-treatment vertebral compression fracture (VCF). The purpose of this study is to identify clinical and radiation planning characteristics that predict post-SBRT VCF through a novel normal tissue complication probability (NTCP) analysis. MethodsPatients with de novo spine metastases treated with SBRT between 2009 and 2018 at a single institution were included. Those who had surgical stabilization or radiation to the same site prior to SBRT were excluded. VCF was defined as new development or progression of existing vertebral body height loss not attributable to tumor growth. Probit NTCP models were constructed and fitted using a maximum likelihood approach. A multivariate proportional hazard model was used to estimate time to VCF using the Fine and Gray method. ResultsThree hundred and two vertebral segments from 193 patients were treated with a median dose of 24 Gy in 3 fractions (range 15–30 Gy in 1–5 fractions). With a median follow up of 13.9 months, local control was 89.3% at 1 year. A total of 26 SBRT-induced VCFs were observed, with 1 and 2-year cumulative incidences of 4.6% and 6.7%. NTCP modeling demonstrated a steep response of VCF risk to the dose to 80% and 50% volume of the planning target volume (PTV D80% and D50%), but not maximum dose or dose to 1 cc or 10% of PTV. D80% of 25 Gy and D50% of 28 Gy in 3 fractions corresponded to 10% VCF risk. On multivariate analysis, lower body mass index (HR 0.90 per unit increase, p = 0.04), total spinal instability neoplastic score (SINS, HR 2.44 unstable vs stable, p = 0.04), and PTV D80% (HR 1.11 for every Gy increase, p = 0.003) were associated with increased VCF risk. ConclusionsSBRT provides excellent tumor control for spinal metastases and is associated with low rate of VCF in our cohort. NTCP modeling suggests that the larger volume of spine receiving lower doses are more closely associated with post-SBRT VCF than high dose regions. Under current target delineation methods, common SBRT regimens such as 24 Gy in 2 fractions or 27 Gy in 3 fractions may be inherently associated with VCF risk of 10% or greater. Consensus contouring guidelines should be reevaluated to minimize the volume of irradiated spine in light of these new data.

Vertebral Compression Fracture Rates after Stereotactic Radiosurgery for Spinal Metastases

Vertebral Compression Fracture Rates after Stereotactic Radiosurgery for Spinal Metastases

Long-Term Outcomes After Stereotactic Radiosurgery for Spine Metastases: Radiation Dose–Response for Late Toxicity

Todocument the 5- and 10-year rates of late toxicity and vertebral compression fracture (VCF) in long-term survivors after stereotactic radiosurgery for spine metastases. A retrospective review was performed on 562 patients treated with SRS for spine metastases between April 2001 and July 2011. Selecting those with at least 5-year survival after SRS, included were 43 patients who collectively underwent 84 treatments at 54 spine sites. Most were treated with single-fraction stereotactic radiosurgery to a median dose of 16Gy (range, 12-24Gy), and 56% of sites had received prior external beam radiation therapy. Late toxicities and VCFs occurring in the absence of tumor progression were recorded. Binary logistic regression was used to identify predictors of late complications. Nine patients (17% of treatment sites) developed grade ≥2 late toxicities at a median time of 12.8months (range, 4.2-59.0months). Actuarial 5- and 10-year rates of grade ≥2 late toxicity were 17% and 17%, respectively. On multivariate analysis, only cumulative biologically effective dose (BED3)>200Gy (or EQD22Gy [2-Gy equivalent dose calculated using an α/β ratio of 2]>130Gy) was associated with grade ≥2 late toxicity (P=.036). Maximum point BED3 > 110Gy (or EQD22Gy>70Gy) to spinal cord or cauda equina was associated with grade ≥2 late neuropathy (P=.017). Nine VCFs (18%) occurred at a median time of 10.2months (range, 3.2-57.2months), with 5- and 10-year VCF rates of 17% and 17%, respectively. Stereotactic radiosurgery for primary treatment and reirradiation of spinal metastases is associated with a moderate risk of late toxicity with 10-year follow-up. Risk of late toxicity significantly increases with cumulative BED3 > 200Gy and spinal cord or cauda equina point BED3 > 110Gy. Patients remain at moderate risk of VCF up to 5years after treatment, with a plateau in incidence thereafter up to 10years.

Re-irradiation of Vertebral Body Metastases: Treatment in the Radiosurgery Era

Vertebral bodies remain one of the most common sites of metastases. In cases where surgical intervention is not indicated or appropriate, conventional external radiation therapy (cEBRT) has been the standard treatment modality. Unfortunately, cEBRT is typically limited, with low complete response and poor local control rates. Disappointing results with re-irradiation using cEBRT highlight the need for innovative salvage therapeutic strategies, such as stereotactic body radiotherapy. A detailed description of this complex treatment strategy is outlined, as is a systematic review of current literature. Although data are limited to single institution series, re-irradiation has consistently been found to be effective with respect to local control (1 year rates range from 66 to 90%) and pain response. Importantly, the treatment is shown to be safe, with the crude rate of radiation myelopathy <1% and a rate of vertebral compression fracture of 12%. As further research and technologic advances continue to refine therapy, stereotactic body radiotherapy is now a recommended option for the treatment of previously irradiated vertebral body metastases.

Radiosurgery for Treatment of Renal Cell Metastases to Spine: A Systematic Review of the Literature.

The incidence of renal cell carcinoma (RCC) continues to increase, and the spine is the most common site for bony metastasis. Radiation therapy is one treatment for spinal RCC metastasis. Stereotactic body radiotherapy (SBRT) is a newer treatment that reportedly has benefits over conventional external beam radiotherapy. This study systematically reviewed the current literature on SBRT for metastatic RCC to spine. A search of PubMed, Embase, and Scopus databases was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Clinical articles evaluating SBRT for RCC metastases were identified. After inclusion and exclusion criteria were applied, the search resulted in 9 articles. Data including pain outcomes, local control, survival outcomes, vertebral compression fracture (VCF), and toxicity were extracted and evaluated. The studies analyzed showed an improvement in pain in 41%-95% of patients. Local control rates after SBRT ranged 71.2%-85.7% at 1 year, a significant improvement when compared with conventional external beam radiotherapy. The rate of VCF after treatment with SBRT ranged 16%-27.5%, with single-fraction therapy being a risk factor for increased incidence. Overall toxicity rates ranged 23%-38.5%, with only 3 cases of grade 3 toxicity (nausea) and no cases of radiation myelitis. Use of SBRT for spinal metastasis from RCC resulted in significant local control and pain outcomes. There is a risk of VCF with SBRT; however, treatment seems to be well tolerated with few serious side effects. There is continued need for long-term prospective studies investigating the optimal role of SBRT in the treatment algorithm of RCC spinal metastases.

Outcomes Following Spine Stereotactic Radiosurgery for the Treatment of Melanoma Spine Metastases

With new targeted and immunotherapies improving survival among patients with metastatic melanoma, the prevalence of metastatic disease within the spine is likely to increase. Spine stereotactic radiosurgery (sSRS) as a palliative treatment strategy for spinal metastasis allows for dose escalation, which may improve the therapeutic ratio of radioresistant tumors such as melanoma. We sought to evaluate the outcomes of patients with spinal metastasis from primary melanoma treated with sSRS. Patients who were diagnosed with metastatic melanoma to the spine and underwent sSRS with at least 1 month of follow-up were included. Clinical and treatment data, including initial consultation notes, disease characteristics, prior surgery and radiotherapy (including sSRS) were collected. The primary outcome was pain relief. Secondary outcomes included pain progression- and radiographic failure-free survival. Actuarial outcomes were assessed with Kaplan-Meier analysis. Cox proportional hazards modeling was utilized to evaluate the association between clinical and treatment factors with treatment outcomes. From our database of over 700 treatments, 36 treatments in 15 patients met inclusion criteria. One patient had metastatic uveal melanoma whereas 14 had metastatic cutaneous melanoma. Median KPS was 80 (range, 70-90). Median prescription dose was 16 Gy (range, 12-30 Gy) in 1 fraction (range, 1-5 fractions) with a median follow-up time of 5 months (range, 2.1-66.1 months). Median time to pain relief was 1.28 months. Cumulative incidence of pain relief at 1, 3, and 12 months were 3.2%, 77.0%, and 92.3%, respectively. Pain progression- and radiographic failure-free survival at 1, 3, and 12 months were 94.4%, 73.9%, and 73.9%, and 100%, 84.8%, and 84.8%, respectively. Overall, 11% of treatments developed radiographic failure with a median time to failure of 2.6 months (range, 1.6-2.8 months). Crude rates of pain flare and vertebral compression fracture after sSRS were 22.2% and 25%, respectively. Univariate analysis did not identify any disease or treatment characteristics that predicted for pain progression or radiographic failure after sSRS. sSRS for metastatic melanoma provides very favorable and durable radiographic and pain control. Due to the limited number of treatments in this series, caution must be utilized in interpreting the pain flare and vertebral compression fracture rates.

Analysis of the Factors Contributing to Vertebral Compression Fractures After Spine Stereotactic Radiosurgery

To determine our institutional vertebral compression fracture (VCF) rate after spine stereotactic radiosurgery (SRS) and determine contributory factors. Retrospective analysis from 2001 to 2013 at a single institution was performed. With institutional review board approval, electronic medical records of 1905 vertebral bodies from 791 patients who were treated with SRS for the management of primary or metastatic spinal lesions were reviewed. A total of 448 patients (1070 vertebral bodies) with adequate follow-up imaging studies available were analyzed. Doses ranging from 10Gy in 1 fraction to 60Gy in 5 fractions were delivered. Computed tomography and magnetic resonance imaging were used to evaluate the primary endpoints of this study: development of a new VCF, progression of an existing VCF, and requirement of stabilization surgery after SRS. A total of 127 VCFs (11.9%; 95% confidence interval [CI] 9.5%-14.2%) in 97 patients were potentially SRS induced: 46 (36%) were de novo, 44 (35%) VCFs progressed, and 37 (29%) required stabilization surgery after SRS. Our rate for radiologic VCF development/progression (excluding patients who underwent surgery) was 8.4%. Upon further exclusion of patients with hematologic malignancies the VCF rate was 7.6%. In the univariate analyses, females (hazard ratio [HR] 1.54, 95% CI 1.01-2.33, P=.04), prior VCF (HR 1.99, 95% CI 1.30-3.06, P=.001), primary hematologic malignancies (HR 2.68, 95% CI 1.68-4.28, P<.001), thoracic spine lesions (HR 1.46, 95% CI 1.02-2.10, P=.02), and lytic lesions had a significantly increased risk for VCF after SRS. On multivariate analyses, prior VCF and lesion type remained contributory. Single-fraction SRS doses of 16 to 18Gy to the spine seem to be associated with a low rate of VCFs. To the best of our knowledge, this is the largest reported experience analyzing SRS-induced VCFs, with one of the lowest event rates reported.