Citations

AbstractPurposeDue to the employment of quadratic programming using soft constraints to implement dose volume constraints and the “trial‐and‐error” procedure needed to achieve a clinically acceptable plan, conventional dose volume constraints (upper limit) are not adequately effective in controlling small and isolated hot spots in the dose/linear energy transfer (LET) distribution. Such hot spots can lead to adverse events. In order to mitigate the risk of brain necrosis, one of the most clinically significant adverse events in patients receiving intensity‐modulated proton therapy (IMPT) for base of skull (BOS) cancer, we propose per‐voxel constraints to minimize hot spots in LET‐guided robust optimization.Methods and materialsTen BOS cancer patients treated with IMPT were carefully selected by meeting one of the following conditions: (1) diagnosis of brain necrosis during follow‐up; and (2) considered high risk for brain necrosis by not meeting dose constraints to the brain. An optimizing structure (BrainOPT) and an evaluating structure (BrainROI) that both contained the aforementioned hot dose regions in the brain were generated for optimization and evaluation, respectively. Two plans were generated for every patient: one using conventional dose‐only robust optimization, the other using LET‐guided robust optimization. The impact of LET was integrated into the optimization via a term of extra biological dose (xBD). A novel optimization tool of per‐voxel constraints to control small and isolated hot spots in either the dose, LET, or combined (dose/LET) distribution was developed and used to minimize dose/LET hot spots of the selected structures. Indices from dose‐volume histogram (DVH) and xBD dose‐volume histogram (xBDVH) were used in the plan evaluation. A newly developed tool of the dose‐LET‐volume histogram (DLVH) was also adopted to illustrate the underlying mechanism. Wilcoxon signed‐rank test was used for statistical comparison of the DVH and xBDVH indices between the conventional dose‐only and the LET‐guided robustly optimized plans.ResultsPer‐voxel constraints effectively and efficiently minimized dose hot spots in both dose‐only and LET‐guided robust optimization and LET hot spots in LET‐guided robust optimization. Compared to the conventional dose‐only robust optimization, the LET‐guided robust optimization could generate plans with statistically lower xBD hot spots in BrainROI (VxBD,50 Gy[RBE], p = 0.009; VxBD,60 Gy[RBE], p = 0.025; xBD1cc, p = 0.017; xBD2cc, p = 0.022) with comparable dose coverage, dose hot spots in the target, and dose hot spots in BrainROI. DLVH analysis indicated that LET‐guided robust optimization could either reduce LET at the same dose level or redistribute high LET from high dose regions to low dose regions.ConclusionPer‐voxel constraint is a powerful tool to minimize dose/LET hot spots in IMPT. The LET‐guided robustly optimized plans outperformed the conventional dose‐only robustly optimized plans in terms of xBD hot spots control.

Introduction: Short-term use of Mechanical Circulatory Support (MCS) has the potential to benefit the patients undergoing Transcatheter Aortic Valve Replacement (TAVR) who may be high-risk or suffer complications. The present study was conducted to address the contemporary use of MCS in TAVR procedures. Methods: The study included a total of 1794 TAVR procedures in the years 2011-2012 from Nationwide Inpatient Sample (NIS) database. Use of MCS was identified using ICD-9-CM codes. The patients were divided based on use of MCS devices. The primary outcome of the study was in-hospital mortality and the secondary outcomes were complications, length of stay (LOS) and cost. Multi-variate simple logistic regression models were used to identify independent predictors of the outcomes. Results: Out of total 1794 TAVR procedures, 190 (10.6 %) utilized a MCS device (MCS group) and 1,604 (89.4%) did not (non-MCS group). The use of MCS devices with TAVR was associated with increase in the in-hospital mortality (14.9% vs. 3.5%, p<0.01) with same results obtained in multi-variate models. The rates of complications were significantly higher in MCS group so as the mean length of stay (11.8±0.8 vs. 8.1±0.2 days, p<0.01) and cost ($68,997±3,656 vs. $55,878±653, p=0.03). Conclusion: Use of MCS in TAVR predicts increase in-hospital mortality, complications, LOS and cost of care.

Background: Contemporary outcome data regarding effects of atherectomy in lower extremity arterial revascularization is lacking. Methods: We queried HCUP’s Nationwide Inpatient Sample (NIS) for 2012 using the appropriate primary ICD 9-CM diagnostic code for peripheral vascular disease and procedural codes 39.90 (bare metal stent - BMS), 00.55 (drug eluting stent - DES), 17.56 (peripheral artherectomy) and 39.50 for angioplasty. Only procedures performed in patients >= 18 years were included. Hierarchical mixed effects logistic regression models were generated to evaluate multivariate predictors of outcomes. Results: In total 13,206 (weighted: 66,030) lower extremity arterial revascularization were analyzed (65.5% white, 56.2% Male & 97.4% angioplasty). Atherectomy utilization (23.2%) was associated with significant reduction in amputation (11.5% vs 13.4%), any complications (13.2% vs 16.3%) and in hospital morality (0.8% vs 1.4%) compared to no atherectomy group (p < 0.001). Multivariate analysis showed similar results with decrease amputation (OR, 95% CI; p - value) (0.83, 0.71 - 0.97, p = 0.02) and in hospital mortality/any complication (0.79, 0.69 - 0.90, p = 0.001) with atherectomy (similar results were observed with propensity score matching). “Atherectomy only” was utilized only in 2.3%. post-hoc analysis also shows better outcomes when atherectomy was used with either angioplasty or stenting (figure a & b). subgroup multivariate analysis shows significant reduction in amputation when atherectomy was utilized in chronic limb ischemia (0.74, 0.59 - 0.93, p = 0.01) and with angioplasty (0.72, 0.60 - 0.87, p = 0.001) and trend towards advantage while used along with stents but not reaching statistical significant. Conclusion: Lower extremity atherectomy utilization was associated with significant reduction in amputation and overall complication. We observed better outcomes when atherectomy was used in conjunction with angioplasty.

Introduction: With the technical advancements and expanding indications, utilization of TAVR is on the rise among various institutions in the United States .While appropriate patient selection and better techniques are essential to improving outcomes, the impact of institutional design (or hospital setting) on outcomes with TAVR has yet to be examined. Objective: The objective of our study is to compare TAVR complication rates among teaching vs non-teaching centers in the United States Methods: We used Healthcare Cost and Utilization Project - National Inpatient Sample (NIS) data , the largest all payer database of hospital inpatient stay available in United States, to identify patients (age ≥18 years) who underwent TAVR from Jan-Dec 2012. We constructed multivariable models to determine independent predictors (age, sex, race, Charlson’s comorbidity index, hospital size, hospital location and TAVR approach) of TAVR-associated complications. Statistical analysis was performed using Stata IC 11.0 (Stata-Corp, College Station, TX). Results: We identified 7,405 TAVR procedures performed in the United States in 2012. 88% of TAVR were performed in teaching centers. There was no difference in mortality following TAVR between teaching and non-teaching centers. The occurrence of any in-hospital complication was lower in teaching centers as compared to non-teaching centers (42% vs. 50%, p<0.001). Rates of individual complications in teaching vs. non-teaching centers are illustrated in the figure. In adjusted analysis, hemorrhage requiring transfusion (13.2% vs. 20.8%, p<0.001), renal complications requiring dialysis (1.2% vs. 2.3%, p=0.009), respiratory complications (7.5% vs. 11%, p<0.001) and complications requiring open-heart surgery (2% vs. 4.6%, p<0.001) were lower in teaching centers as compared to non-teaching centers. Vascular access site complications, pacemaker insertion, pericardial and neurological complications were similar between teaching and non-teaching centers (Figure). Conclusion: Institutional design impacts TAVR complication rates albeit no difference in mortality. In general, complication rates are lower in teaching centers compared to non-teaching centers.

Background: Brain metastases (BM) from differentiated thyroid cancer are rare. Stereotactic radiosurgery (SRS) is commonly used for the treatment of BMs; however, the experience with SRS for thyroid cancer BMs remains limited. The goal of this international, multi-centered study was to evaluate the efficacy and safety of SRS for thyroid cancer BMs. Methods: From 10 institutions participating in the International Radiosurgery Research Foundation, we pooled patients with established papillary or follicular thyroid cancer diagnosis who underwent SRS for histologically confirmed or radiologically suspected BMs. We investigated patient overall survival (OS), local tumor control, and adverse radiation events (AREs). Results: We studied 42 (52% men) patients who underwent SRS for 122 papillary (83%) or follicular (17%) thyroid cancer BMs. The mean age at SRS was 59.86 ± 12.69 years. The mean latency from thyroid cancer diagnosis to SRS for BMs was 89.05 ± 105.49 months. The median number of BMs per patient was 2 (range: 1–10 BMs). The median SRS treatment volume was 0.79 cm 3 (range: 0.003–38.18 cm 3 ), and the median SRS prescription dose was 20 Gy (range: 8–24 Gy). The median survival after SRS for BMs was 14 months (range: 3–58 months). The OS was significantly shorter in patients harboring ≥2 BMs, when compared with patients with one BM (Log-rank = 5.452, p = 0.02). Two or more BMs (odds ratio [OR] = 3.688; confidence interval [CI]: 1.143–11.904; p = 0.03) and lower Karnofsky performance score at the time of SRS (OR = 0.807; CI: 0.689–0.945; p = 0.008) were associated with shorter OS. During post-SRS imaging follow-up of 25.21 ± 30.49 months, local failure (progression and/or radiation necrosis) of BMs treated with SRS was documented in five (4%) BMs at 7.2 ± 7.3 months after the SRS. At the last imaging follow-up, the majority of patients with available imaging data had stable intracranial disease (33%) or achieved complete (26%) or partial (24%) response. There were no clinical AREs. Post-SRS peritumoral T2/fluid attenuated inversion recovery signal hyperintensity was noted in 7% BMs. Conclusion: The SRS allows durable local control of papillary and follicular thyroid cancer BMs in the vast majority of patients. Higher number of BMs and worse functional status at the time of SRS are associated with shorter OS in patients with thyroid cancer BMs. The SRS is safe and is associated with a low risk of AREs.

ABSTRACTRadiation therapy (RT) is an integral part of the management of many pediatric tumors; however, it is associated with both acute and permanent adverse events that can significantly impact a child's quality of life, lead to treatment delays, and potentially affect outcomes of cancer therapy. Prevention, early detection, and optimal management of these adverse effects will help reduce their impact on the patients’ quality of life and overall well‐being. Unfortunately, there has not been a coordinated effort to study the etiology, evaluate risk factors, and explore novel treatments for these conditions. Studies of supportive care for children undergoing RT are often small and uncontrolled. This review will focus on the impact of irradiation on the different organ systems and their current management. Further studies are required to improve our understanding of the contributing factors and explore novel treatment options for these adverse effects and to enable children and their families to better cope with some of the unavoidable toxicities following multimodality therapy.

Staphylococcus argenteus is a newly described species, formerly known as S. aureus clonal complex 75 (CC75). Here, we describe the largest collection of S. argenteus isolates in North America, highlighting identification challenges.

OBJECTIVE Radiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs. METHODS From 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS. RESULTS Fifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm 3 , and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4–195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3–45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm 3 predicted progression (HR 8.226, 95% CI 1.028–65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS. CONCLUSIONS SRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.