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Purpose: To identify frequency, clinical relevance and risk factors for vertebral compression fracture (VCF) after spine stereotactic body radiation therapy (SBRT) with long-term follow up (FU)., Methods: From 2012 to 2015, 61 lesions (56 patients) were treated within a prospective multicenter phase 2 study (NCT01594892) of SBRT for painful vertebral metastases. Post-SBRT VCF were identified. Anatomical segments, normal and tumor tissue of treated vertebrae were segmented for volumetric analyses. Predictive factors for VCF were identified by logistic regression., Results: Median clinical and radiological FU for all patients was 16.2 months (range, 0-68.2) and 7.8 months (range, 0-66.9), respectively. Local metastasis control was observed in 82% of lesions at last imaging FU. Post-SBRT VCF occurred in 21 lesions (34.4%): 16.4% showed a progressive VCF, while a new VCF occurred in 18.0%. 3/56 (5.4%) patients developed painful VCF defined as pain increase by ≥2 on the visual analogue scale (VAS) and 2 (3.6%) patients required surgical stabilization. Pre-SBRT VCF, localization in the thoracic spine, Bilsky score >0, SINS score, pre-SBRT osteolytic volume and metastatic vertebral body (VB) involvement were predictive factors for VCF on univariate analysis. Relative VB involvement, osteolytic volume and pre-SBRT VCF remained in the multivariate logistic regression model that had AUC = 0.930, 83.3% sensitivity and 96.6% specificity., Conclusion: Spine SBRT resulted in favorable long-term pain and local metastasis control. Despite post-SBRT VCF being observed after one third of treatments, this was symptomatic in only 5% of patients. Predictive factors for developing VCF were identified which could contribute to better selection of patients for spine SBRT., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To investigate if a local dose-effect (LDE) relationship for perfusion loss improves the NTCP model fit for SBRT induced radiation pneumonitis (RP) compared to conventional LDEs., Methods and Materials: Multi-institutional data of 1015 patients treated with SBRT were analyzed. Dose distributions were converted to NTD with α/β = 3 Gy. The Lyman-Kutcher-Burman NTCP model was fitted to the incidence grade ≥2 RP by maximum likelihood estimation with mean lung dose (MLD), equivalent uniform doses (EUD) using three LDE functions (power-law (EUD power ), logistic with 2 free parameters (EUD log-free ) and logistic with fixed parameters describing local perfusion loss (EUD Perfusion )) and volume above a threshold dose (V x ). Models were compared with the Akaike weights (Aw) derived from the Akaike information criteria (AIC)., Results: The median time to grade ≥2 RP was 4.2 months and plateaued after 17 months at 5.4%. A strong dose-effect relationship for RP incidence was observed. The EUD Perfusion based NTCP model had the lowest AIC. The Aw were 0.53, 0.19, 0.11, 0.11, 0.05 for the EUD Perfusion , V x , MLD, EUD log-free and EUD power LDEs respectively., Conclusion: A LDE for perfusion loss provided modest improvement in NTCP model fit for SBRT induced radiation pneumonitis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Purpose: To investigate potential associations between dose to heart (sub)structures and non-cancer death, in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT)., Methods: 803 patients with early stage NSCLC received SBRT with predominant schedules of 3×18Gy (59%) or 4×12Gy (19%). All patients were registered to an average anatomy, their planned dose deformed accordingly, and dosimetric parameters for heart substructures were obtained. Multivariate Cox regression and a sensitivity analysis were used to identify doses to heart substructures or heart region with a significant association with non-cancer death respectively., Results: Median follow-up was 34.8months. Two year Kaplan-Meier overall survival rate was 67%. Of the deceased patients, 26.8% died of cancer. Multivariate analysis showed that the maximum dose on the left atrium (median 6.5Gy EQD2, range=0.009-197, HR=1.005, p-value=0.035), and the dose to 90% of the superior vena cava (median 0.59Gy EQD2, range=0.003-70, HR=1.025, p-value=0.008) were significantly associated with non-cancer death. Sensitivity analysis identified the upper region of the heart (atria+vessels) to be significantly associated with non-cancer death., Conclusions: Doses to mainly the upper region of the heart were significantly associated with non-cancer death. Consequently, dose sparing in particular of the upper region of the heart could potentially improve outcome, and should be further studied., (Copyright © 2017 Elsevier B.V. All rights reserved.)