Spine Stereotactic Body Radiotherapy Research Articles

Assessment of minimum target dose as a predictor of local failure after spine SBRT

ObjectivesMetastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. MethodsSpine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20–24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27–36 Gy and 21–24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. Results522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3–54.4). The cumulative incidence of local failure was 10.5 % (7.4–13.4) at 1 year and 16.3 % (12.6–19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 – 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6–9.4) vs. 14.2 % (8.3–19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). ConclusionsSpine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14–15.3 Gy with single fraction SBRT is recommended whenever possible.

Utility of molecular markers in predicting local control specific to lung cancer spine metastases treated with stereotactic body radiotherapy.

We report outcomes following spine stereotactic body radiotherapy (SBRT) in metastatic non-small cell lung cancer (NSCLC) and the significance of programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR) mutation and timing of immune check point inhibitors (ICI) on local failure (LF). 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, overall survival (OS) and vertebral compression fracture (VCF). Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. The median follow-up and OS were: 13.0months (range, 0.5-95.3months) and 18.4months (95% CI 11.4-24.6). 52.1% were male and 76.4% had adenocarcinoma. Of the 389 segments, 30.3% harboured an EGFR mutation and 17.0% were PD-L1 ≥ 50%. The 24months LF rate in PD-L1 ≥ 50% vs PD-L1 < 50% was 10.7% vs. 38.0%, and in EGFR-positive vs. negative was 18.1% vs. 30.0%. On MVA, PD-L1 status of ≥ 50% (HR 0.32, 95% CI 0.15-0.69, p = 0.004) significantly predicted for lower LF compared to PD-L1 < 50%. Lower LF trend was seen with ICI administration peri and post SBRT (HR 0.41, 95% CI 0.16-1.05, p = 0.062). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84-5.85, p < 0.0001) and ECOG ≥ 2 (HR 1.87, 95% CI 1.16-3.02, p = 0.011) significantly predicted for worse OS and absence of baseline VCF predicted for lower VCF rate (HR 0.20, 95% CI 0.10-0.39, p < 0.0001). We report a significant association of PD-L1 ≥ 50% status on improved LC rates from spine SBRT in NSCLC patients.

Intrafractional motion detection for spine SBRT via X-ray imaging using ExacTrac Dynamic

PurposeDue to its close vicinity to critical structures, especially the spinal cord, standards for safety for spine stereotactic body radiotherapy (SBRT) should be high. This study was conducted, to evaluate intrafractional motion during spine SBRT for patients without individualized immobilization (e.g., vacuum cushions) using high accuracy patient monitoring via orthogonal X-ray imaging. MethodsIntrafractional X-ray data were collected from 29 patients receiving 79 fractions of spine SBRT. No individualized immobilization devices were used during the treatment. Intrafractional motion was monitored using the ExacTrac Dynamic (ETD) System (Brainlab AG, Munich, Germany). Deviations were detected in six degrees of freedom (6 DOF). Tolerances for repositioning were 0.7 mm for translational and 0.5° for rotational deviations. Patients were repositioned when the tolerance levels were exceeded. ResultsOut of the 925 pairs of stereoscopic X-ray images examined, 138 (15 %) showed at least one deviation exceeding the predefined tolerance values. In all 6 DOF together, a total of 191 deviations out of tolerance were recorded. The frequency of deviations exceeding the tolerance levels varied among patients but occurred in all but one patient. Deviations out of tolerance could be seen in all 6 DOF. Maximum translational deviations were 2.6 mm, 2.3 mm and 2.8 mm in the lateral, longitudinal and vertical direction. Maximum rotational deviations were 1.8°, 2.6° and 1.6° for pitch, roll and yaw, respectively. Translational deviations were more frequent than rotational ones, and frequency and magnitude of deviations showed an inverse correlation. ConclusionIntrafractional motion detection and patient repositioning during spine SBRT using X-ray imaging via the ETD System can lead to improved safety during the application of high BED in critical locations. When using intrafractional imaging with low thresholds for re-positioning individualized immobilization devices (e.g. vacuum cushions) may be omitted.

Re-irradiation spine stereotactic body radiotherapy following high-dose conventional radiotherapy for metastatic epidural spinal cord compression: a retrospective study.

We aimed to evaluate the efficacy and safety of re-irradiation stereotactic body radiation therapy (SBRT) in patients with metastatic epidural spinal cord compression (MESCC) following high-dose conventional radiotherapy. Twenty-one patients met the following eligibility criteria: with an irradiation history of 50 Gy2 equivalent dose in 2-Gy fractions (EQD2) or more, diagnosed MESCC in the cervical or thoracic spines, and treated with re-irradiation SBRT of 24Gy in 2 fractions between April 2018 and March 2023. Prior treatment was radiotherapy alone, not including surgery. The primary endpoint was a 1-year local failure rate. Overall survival (OS) and treatment-related adverse events were assessed as the secondary endpoints. Since our cohort includes one treatment-related death (TRD) of esophageal perforation, the cumulative esophageal dose was evaluated to find the dose constraints related to severe toxicities. The median age was 68, and 14 males were included. The primary tumor sites (esophagus/lung/head and neck/others) were 6/6/7/2, and the median initial radiotherapy dose was 60 Gy2 EQD2 (range: 50-105 Gy2, 60-70/ > 70 Gy2 were 11/4). Ten patients underwent surgery followed by SBRT and 11 SBRT alone. At the median follow-up time of 10.4months, 17 patients died of systemic disease progression including one TRD. No radiation-induced myelopathy or nerve root injuries occurred. Local failure occurred in six patients, with a 1-year local failure rate of 29.3% and a 1-year OS of 55.0%. Other toxicities included five cases of vertebral compression fractures (23.8%) and one radiation pneumonitis. The cumulative esophageal dose was recommended as follows: Dmax < 203, D0.035cc < 187, and D1cc < 167 (Gy3 in biological effective dose). Re-irradiation spine SBRT may be effective for selected patients with cervical or thoracic MESCC, even with high-dose irradiation histories. The cumulative dose assessment across the original and re-irradiated esophagus was recommended to decrease the risk of severe esophageal toxicities.

Robotic Stereotactic Body Radiotherapy for Spine Metastasis Pain Relief

Spinal metastasis may occur in 40–70% of patients with cancer. Symptoms can vary from pain to spinal cord compression (SCC) and can affect their quality of life (QoL). Stereotactic body radiotherapy (SBRT) allows dose escalation of spinal tumor metastases, minimizing doses to organs at risk and improving pain control. The aim of this study is to retrospectively describe our institution’s experience with robotic SBRT (CyberKnife®, Accuray Incorporated, Sunnyvale, CA, USA) for spinal metastases, in terms of feasibility, oncological results, toxicities, and pain relief observed. In total, 25 patients with 43 lesions were assessed, most of them with dorsal metastases (48.8%). The median total dose was 27 Gy (16–35 Gy), the median number of fractions administered was 3 (1–5), and the median dose per fraction was 9 Gy. Pain was evaluated using the visual analogue scale at baseline and at the end of treatment. The statistically significant reduction in pain (p &lt; 0.01) was associated with the total dose of radiotherapy delivered (p &lt; 0.01). Only one patient developed grade 3 dermatitis. Female gender, adenocarcinoma tumors, and lack of previous surgery were associated with better response to SBRT (p &lt; 0.05). Robotic spine SBRT is feasible, well-tolerated, and improves patients’ QoL through a statistically significant reduction in pain, so it should be offered to patients at an early stage in their process.

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.

Stereotactic Body Radiotherapy for Treatment of Spinal Metastasis: A Systematic Review of the Literature

Abstract Advances in local and systemic therapies continue to improve overall survival for patients with cancer, resulting in an increase in the incidence of spine metastases. Metastases to the spine are the most common bony metastasis. Up to 15% of patients with solid tumors develop spinal metastases. Spinal metastases can be particularly devastating for quality of life given the potential pain, neurological deficits from spinal cord compression or cauda equina syndrome, spinal instability, and pathological fractures that may result. Stereotactic body radiotherapy (SBRT) with or without the addition of less invasive surgical techniques for stabilization or separation has gained favor. SBRT uses smaller, more precise treatment volumes, allowing for higher doses per fracture, thus increasing ablative abilities. In this systematic review we discuss the literature regarding SBRT’s effectiveness in providing local control and pain control for patients with metastatic disease to the spine. This remains true for patients with spinal cord compression managed with surgical separation followed by postoperative spine SBRT. While not all patients are appropriate candidates for SBRT, careful consideration of appropriate frameworks which take into account the patient’s overall prognosis can guide a multidisciplinary team towards the patients who will benefit the most from this treatment modality.

Stereotactic Body Radiation Therapy for Sacral Metastases: Deviation From Recommended Target Volume Delineation Increases the Risk of Local Failure

PurposeAlthough spine stereotactic body radiotherapy (SBRT) is considered a standard of care in the mobile spine, mature evidence reporting outcomes specific to sacral metastases is lacking. Furthermore, there is a need to validate the existing sacral SBRT international consensus contouring guidelines to define the optimal contouring approach. We report mature rates of local failure (LF), adverse events, and the impact of contouring deviations in the largest experience to date specific to sacrum SBRT. Methods/MaterialsConsecutive patients who underwent sacral SBRT from 2010-2021 were retrospectively reviewed. Primary endpoint was magnetic resonance imaging-based LF with a specific focus on adherence to target volume contouring recommendations. Secondary endpoints included vertebral compression fracture (VCF) and neural toxicity. ResultsOf the 215 sacrum segments treated in 112 patients, most received 30 Gy/4 fractions (51%), 24 Gy/2 fractions (31%), or 30 Gy/5 fractions (10%). Sixteen percent of segments were non-adherent to the consensus guideline with a more restricted target volume (under-contoured). The median follow-up was 21.4 months (range, 1.5-116.9). The cumulative incidence of LF at 1 and 2 years was 18.4% and 23.1%, respectively. In those with guideline adherent vs. non-adherent contours, the LF rate at 1 year was 15.1% vs. 31.4% and at 2 years 18.8% vs. 40.0% (HR=2.5, 95% CI 1.4-4.6, p=0.003), respectively. On multivariable analysis, guideline non-adherence (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) predicted for an increased risk of LF. The cumulative incidence of VCF was 7.1% at 1 year and 12.3% at 2 years. Seven patients (6.3%) developed peripheral nerve toxicity, of which 4/7 had been previously radiated. ConclusionsSacral SBRT is associated with high efficacy rates and an acceptable toxicity profile. Adhering to consensus guidelines for target volume delineation is recommended to reduce the risk of LF.

Efficacy of flattening filter-free beams with the acuros XB algorithm in thoracic spine stereotactic body radiation therapy

This study aimed to determine the dosimetric value of flattening filter-free (FFF) beams compared to flattening filter (FF) beams using different algorithms in the treatment planning of thoracic spine stereotactic body radiation therapy (SBRT). A total of 120 plans were created for 15 patients using the Anisotropic Analytical Algorithm (AAA) and the Acuros External Beam (AXB) algorithm with FF and FFF beams at 6 MV and 10 MV energies. Various dosimetric parameters were evaluated, including target coverage, dose spillage, and organs-at-risk sparing of the spinal cord and esophagus. Treatment delivery parameters, such as the monitor units (MUs), modulation factors (MFs), beam-on time (BOT), and dose calculation time (DCT), were also collected. Significant differences were observed in the dosimetric parameters when AXB was used for all energies (P < 0.05). 6 XFFF energy was the best option for target coverage, dose spillage, and organs-at-risk sparing. In contrast, dosimetric parameters had no significant difference when using the AAA. The AAA and AXB calculations showed that the 6 XFFF beam had the shortest DCT. The treatment delivery parameters indicated that 10 XFF beam required the fewest MUs and MFs. In addition, the 10 XFFF beam demonstrated the shortest BOT. For effective treatment of the thoracic spine using SBRT, it is recommended to use the 10 XFFF beam because of the short BOT. Moreover, the AXB algorithm should be used because of its accurate dose calculation in regions with tissue heterogeneity.

Dosimetric impact of CT metal artifact reduction for spinal implants in stereotactic body radiotherapy planning.

Metal artifacts due to spinal implants may affect the accuracy of dose calculation for radiotherapy. However, the dosimetric impact of metal artifact reduction (MAR) for spinal implants in stereotactic body radiotherapy (SBRT) plans has not been well studied. The objective of this study was to evaluate the dosimetric impact of MAR in spinal SBRT planning with three clinically common dose calculation algorithms. Gammex phantom and 10 patients' computed tomography (CT) images were studied to investigate the effects of titanium implants. A commercial orthopedic MAR algorithm was employed to reduce artifacts. Dose calculations for SBRT were conducted on both artifact-corrected and uncorrected images using three commercial algorithms [analytical anisotropic algorithm (AAA), Acuros XB (AXB), and Monte Carlo (MC)]. Dose discrepancies between artifact-corrected and uncorrected cases were appraised using a dose-volume histogram (DVH) and 3-dimensional (3D) gamma analysis with different distance to agreement (DTA) and dose difference criteria. The gamma agreement index (GAI) was denoted as G(∆D, DTA). Statistical analysis of t-test was utilized to evaluate the dose differences of different algorithms. The phantom study demonstrated that titanium metal artifacts can be effectively reduced. The patient cases study showed that dose differences between the artifact-corrected and uncorrected datasets were small evaluated by gamma index and DVH. Gamma analysis found that even the strict criterion local G(1,1) had average values ≥93.9% for the three algorithms. For all DVH metrics, average differences did not exceed 0.7% in planning target volume (PTV) and 2.1% in planning risk volume of spinal cord (PRV-SC). Statistical analysis showed that the observed dose differences of MC method were significantly larger than those of AAA (P<0.01 for D98% of PTV and P<0.001 for D0.1cc of spinal cord) and AXB methods (P<0.001 for D98% and P<0.0001 for D0.1cc). Dosimetric impact of artifacts caused by titanium implants is not significant in spinal SBRT planning, which indicates that dose calculation algorithms might not be very sensitive to CT number variation caused by titanium inserts.

ESTRO clinical practice guideline: Stereotactic body radiotherapy for spine metastases

Background and purposeRecent progress in diagnostics and treatment of metastatic cancer patients have improved survival substantially. These developments also affect local therapies, with treatment aims shifting from short-term palliation to long-term symptom or disease control. There is consequently a need to better define the value of stereotactic body radiotherapy (SBRT) for the treatment of spinal metastases. MethodsThis ESTRO clinical practice guideline is based on a systematic literature review conducted according to PRISMA standards, which formed the basis for answering four key questions about the indication and practice of SBRT for spine metastases. ResultsThe analysis of the key questions based on current evidence yielded 22 recommendations and 5 statements with varying levels of endorsement, all achieving a consensus among experts of at least 75%. In the majority, the level of evidence supporting the recommendations and statements was moderate or expert opinion, only, indicating that spine SBRT is still an evolving field of clinical research. Recommendations were established concerning the selection of appropriate patients with painful spine metastases and oligometastatic disease. Recommendations about the practice of spinal SBRT covered technical planning aspects including dose and fractionation, patient positioning, immobilization and image-guided SBRT delivery. Finally, recommendations were developed regarding quality assurance protocols, including description of potential SBRT-related toxicity and risk mitigation strategies. ConclusionsThis ESTRO clinical practice guideline provides evidence-based recommendations and statements regarding the selection of patients with spinal metastases for SBRT and its safe implementation and practice. Enrollment of patients into well-designed prospective clinical trials addressing clinically relevant questions is considered important.

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.

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

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

Predicting vertebral compression fracture prior to spinal SBRT using radiomics from planning CT.

The purpose of the study was to develop a predictive model for vertebral compression fracture (VCF) prior to spinal stereotactic body radiation therapy (SBRT) using radiomics features extracted from pre-treatment planning CT images. A retrospective analysis was conducted on 85 patients (114 spinal lesions) who underwent spinal SBRT. Radiomics features were extracted from pre-treatment planning CT images and used to develop a predictive model using a classification algorithm selected from nine different machine learning algorithms. Four different models were trained, including clinical features only, clinical and radiomics features, radiomics and dosimetric features, and all features. Model performance was evaluated using accuracy, precision, recall, F1-score, and area under the curve (AUC). The model that used all features (radiomics, clinical, and dosimetric) showed the highest performance with an AUC of 0.871. The radiomics and dosimetric features model had the superior performance in terms of accuracy, precision, recall, and F1-score. The developed predictive model based on radiomics features extracted from pre-treatment planning CT images can accurately predict the likelihood of VCF prior to spinal SBRT. This model has significant implications for treatment planning and preventive measures for patients undergoing spinal SBRT. Future research can focus on improving model performance by incorporating new data and external validation using independent data sets.

Patients with progression of spinal metastases who present to the clinic have better outcomes compared to those who present to the emergency department.

As cancer therapies have improved, spinal metastases are increasingly common. Resulting complications have a significant impact on patient's quality of life. Optimal methods of surveillance and avoidance of neurologic deficits are understudied. This study compares the clinical course of patients who initially presented to the emergency department (ED) versus a multidisciplinary spine oncology clinic and who underwent stereotactic body radiation therapy (SBRT) secondary to progression/presentation of metastatic spine disease. We performed a retrospective analysis of a prospectively maintained database of adult oncologic patients who underwent spinal SBRT at a single hospital from 2010 to 2021. Descriptive statistics and survival analyses were performed. We identified 498 spinal radiographic treatment sites in 390 patients. Of these patients, 118 (30.3%) presented to the ED. Patients presenting to the ED compared to the clinic had significantly more severe spinal compression (52.5% vs. 11.7%; p < 0.0001), severe pain (28.8% vs. 10.3%; p < 0.0001), weakness (24.5% vs. 4.5%; p < 0.0001), and difficulty walking (24.5% vs. 4.5%; p < 0.0001). Patients who presented to the ED compared to the clinic were significantly more likely to have surgical intervention followed by SBRT (55.4% vs. 15.3%; p < 0.0001) compared to SBRT alone. Patients who presented to the ED compared to the clinic had a significantly quicker interval to distant spine progression (5.1 ± 6.5 vs. 9.1 ± 10.2 months; p = 0.004), systemic progression (5.1 ± 7.2 vs. 9.2 ± 10.7 months; p < 0.0001), and worse overall survival (9.3 ± 10.0 vs. 14.3 ± 13.7 months; p = 0.002). The establishment of multidisciplinary spine oncology clinics is an opportunity to potentially allow for earlier, more data-driven treatment of their spinal metastatic disease.

Assessment of Minimum Dose as a Strong Predictor of Local Failure after Spine SBRT

Stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). Even so, a wide range of dose-fractionation schemes are used in clinical practice. We seek to assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. From a large institutional database, spine SBRT treatments with subsequent imaging follow-up to assess local control were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, generally delivering 20-24 Gy in 1 fraction to the high dose volume and 16 Gy to the low dose volume (or 30-36 Gy and 24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. Statistical analyses included Cox proportional hazards analyses and the robust log-rank statistic for cut-point analysis. The cumulative incidence of local failure with death as a competing risk was considered as the primary endpoint. A total of 522 eligible spine SBRT treatments (68% single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95% confidence interval: 34.3-54.4). The cumulative incidence of local failure was 19.3% (15.3-23.2) at 1 year and 25.6% (21.1-29.9) at 2 years. Univariate analysis identified that the minimum dose (normalized for the prescription dose) was a strong predictor of local failure (p = 0.0093). Among patients treated with a single fraction, statistical significance was maintained (p = 0.024). No other dosimetric factors were predictive of local failure. In a cut point analysis, the log-rank statistic was maximized at 15.8 Gy minimum dose for single-fraction treatment (HR = 0.51, 95% CI: 0.34 - 0.75, p = 0.0009). Cumulative incidence of local failure was 15.1% (9.8-20.2) vs. 24.7% (17.2-31.5) at 1 year using this cut-off. Comparable local control was demonstrated with a minimum dose of 14 Gy (HR = 0.57, 95%: 0.37 - 0.87, p = 0.009), with reduced local control with lower minimum doses. Among a range of clinical factors assessed, only epidural and soft tissue involvement were predictive of local failure (HR = 1.80 and 1.98, respectively). Multivariable analyses incorporating soft tissue involvement, epidural extension, and multilevel disease confirmed the 15.8 Gy cutoff for single fraction cases (HR = 0.58, 95% CI: 0.38-0.88, p = 0.011). Spine SBRT offers favorable local control using a range of dose-fractionation schemes; however, minimum dose has a strong association with local control, unlike any other dosimetric factors tested. Furthermore, statistical significance was maintained even when considering epidural extension and potential limitations from dose to the spinal cord. Our data suggests that the minimum dose should be prioritized during treatment planning, ideally to at least 14 - 15.8 Gy for single fraction.

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 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 for Posterior Element Only Spinal Metastases: Outcomes and Validation of Recommended Clinical Target Volume Delineation Practice

Spine stereotactic body radiotherapy (SBRT) results in improved local control and pain response compared to conventional external beam radiotherapy. Consensus stipulates MRI-based delineation of the clinical target volume (CTV) is critical and is based on spine segment sector involvement. The applicability of these contouring guidelines to metastases confined to the posterior elements is unknown. The purpose of this study was to determine the patterns of failure, as well as the safety of treating posterior element metastases when the vertebral body was intentionally excluded from the CTV. A retrospective review of a prospectively maintained database of 605 patients and 1412 spine segments treated with spine SBRT was performed. Only treated segments involving the posterior elements alone were included for the analyses. The primary outcome was local failure, as per SPINO recommendations, and secondary outcomes included patterns of failure, toxicities. Clinical and tumor factors were reported with descriptive statistics. The cumulative risk of local failure was estimated using the Fine-Gray method, accounting for death before local failure as a competing risk. A total of 24/605 patients and 31/1412 segments within the database were treated to the posterior elements only. Local failure occurred in 11/31 segments. The cumulative rate of local recurrence was 9.7% at 12 months and 30.8% at 24 months. Amongst local failures, the most common histologies were renal cell carcinoma (36.4%) and non-small cell lung cancer (36.4%). At baseline, 4/11 (36.4%) segments with local failure (36.4%) had epidural disease and 8/11 (72.7%) had paraspinal disease. Most local failures were treated in the de novo setting (8/11, 72.7%). 6/11 (54.5%) failed exclusively within treated CTV sectors and 5/11 (45.5%) with both treated and adjacent untreated sectors. Of these five, four had disease progression within the untreated vertebral body. No failures occurred exclusively within the untreated vertebral body. One patient (4.2%) experienced a grade 4 skin toxicity and one patient (4.2%) developed an iatrogenic Grade 1 vertebral compression fracture. Posterior element alone metastases are rare. Our analyses support SBRT consensus contouring guidelines such that the vertebral body can be excluded from CTV in spinal metastases confined to the posterior elements.

Dosimetric Impact of Radiolucent Carbon Fiber Hardware for Post-Operative Spine Stereotactic Body Radiation Therapy

The spine is the most common site of osseous metastases. In the non-operative setting, there is growing support for stereotactic body radiation therapy (SBRT) over conventional radiation therapy for improved pain relief and local control. Hybrid therapy consisting of separation surgery and post-operative SBRT is considered in patients with biomechanical instability and epidural cord compression. Surgery traditionally requires titanium (Ti) implants, which introduce artifacts on post-operative imaging in addition to increased uncertainty and beam attenuation. Use of radiolucent carbon fiber reinforced polyetheretherketone (CFR-PEEK) hardware has been shown to provide safe and comparable surgical outcomes as compared to Ti. Our primary objective is to assess the dosimetric impact of Ti versus carbon fiber implants in spine SBRT. Single institution retrospective series of post-operative spine SBRT from 2019-2020. Re-irradiation cases were excluded. The electronic medical record and treatment planning systems (TPS) were queried. Dosimetric analyses compared original Ti plans with reoptimized plans, replacing Ti hardware electronic density with carbon fiber. Maintaining clinical goals, dose calculations were performed in a treatment planning system using a collapsed cone algorithm. All treatments used step and shoot intensity modulated radiation therapy to avoid beam angles with significant metal along the beam path. Metallic artifacts were contoured and assigned the appropriate tissue density. A D'Agostino-Pearson test was used to assess data for normality. We used paired Student's t-tests to compare three dosimetric outcomes in the setting of Ti and carbon fiber implants. Planning target volume (PTV) coverage was represented by the volume receiving at least the prescribed dose (%), the maximum point dose (dmax, cGy) to the spinal cord planning risk volume (PRV, 2 mm margin), and the overall hot spot intensity (plan dmax). A series of 14 consecutive SBRT cases were evaluated (dose 27-30 Gy in 3-5 fractions). All dosimetric outcomes were normally distributed (p>0.05). We found a statistically significant difference in PTV coverage between the original SBRT treatment plans with Ti hardware (mean 85.1 ± 7.9%) and reoptimized carbon fiber hardware (87.3 ± 6.6%; p = 0.002). There was no significant difference in mean spinal cord PRV dmax between Ti and carbon fiber plans (1846 ± 483 cGy vs. 1842 ± 495 cGy; p>0.05). We observed a nonsignificant increase in mean overall dmax from 3932 ± 416 cGy in the Ti cohort to 4111 ± 906 cGy in the carbon fiber cohort (p>0.05). Carbon fiber implants provide a significant increase in SBRT target coverage, without impacting the overall plan and spinal cord PRV dmax in this retrospective series. In addition to improved post-operative imaging and reduced uncertainty, carbon fiber hardware may offer dosimetric advantages as compared to traditional Ti spinal implants, and warrants further investigation in a larger cohort.