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

OBJECTIVES: Metastasis-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. METHODS: Spine 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. RESULTS: 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 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). CONCLUSIONS: Spine 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.

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

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

Burden of Cardiac Arrhythmias in Patients With Anthracycline-Related Cardiomyopathy.

OBJECTIVES: The objective of this study was to determine the incidence of arrhythmias and device (internal cardiac defibrillator/cardiac resynchronization therapy defibrillator) therapies in patients with a diagnosis of cardiomyopathy and anthracycline exposure. BACKGROUND: The burden of arrhythmias in adult cancer survivors with anthracycline-related cardiomyopathy has not been studied, but might have important implications for clinical management and outcomes. METHODS: Retrospective cohort study of all patients with left ventricular dysfunction (LVD) who underwent internal cardiac defibrillator/cardiac resynchronization therapy defibrillator implantation at the Mayo Clinic from 1990 to 2012. Ninety-five patients were cancer survivors (on average, 5 years), 23 of which had anthracycline-related cardiomyopathy (CA-ACM) and 72 of which had non-anthracycline-related cardiomyopathy (CA-NACM). A second control group of 68 noncancer patients with ischemic heart disease-related LVD or dilated cardiomyopathy (ischemic heart disease [IHD]/DCM) was age- and gender-matched to patients with CA-ACM. All patients were followed for arrhythmias and appropriate ICD therapies, total mortality, heart transplantation, and left ventricular ejection fraction. RESULTS: More than 5.5 ± 3.0 years after device implantation, nonsustained ventricular tachycardia was the most common arrhythmia in patients with CA-ACM followed by atrial fibrillation and sustained ventricular tachycardia or fibrillation (73.9%, 56.6%, and 30.4%, respectively), which was not significantly different from CA-NACM and IHD/DCM. The 5-year rate of ICD therapies was 19.9% in the CA-ACM group versus 22.1% in the CA-NACM group and 32.6% in the IHD/DCM group (p = NS for both). Device therapy-free, heart transplantation-free, and/or overall survival as well as cardiac function dynamics over time were not different in patients with CA-ACM than in patients with CA-NACM and IHD/DCM. CONCLUSIONS: This study indicates that the burden of arrhythmia in patients with anthracycline-related cardiomyopathy is not different from cancer and non-cancer patients with IHD-related LVD or DCM.