Background To determine if a machine learning approach optimizes survival estimation for patients with symptomatic bone metastases (SBM), we developed the Bone Metastases Ensemble Trees for Survival (BMETS) to predict survival using 27 prognostic covariates. To establish relative clinical utility, we compared BMETS to two simpler Cox regression models used in this setting. Methods and materials For 492 bone sites in 397 patients evaluated for palliative radiation therapy (RT) for SBM from 1/2007-1/2013, data for 27 clinical variables were collected. These covariates and the primary outcome of time from consultation to death were used to build BMETS utilizing random survival forests. https://www.selleckchem.com/products/hoipin-8.html We then performed Cox regressions as per two validated models Chow's 3-item (C-3) and Westhoff's 2-item (W-2) tools. Model performance was assessed using cross-validation procedures and measured by time-dependent area under the curve (tAUC) for all three models. For temporal validation, a separate dataset comprised of 104 bone sites treated in 85 patients in 2018 was used to estimate tAUC from BMETS. Results Median survival was 6.3 months. Variable importance was greatest for performance status, blood cell counts, recent systemic therapy type, and receipt of concurrent non-bone palliative RT. tAUC at 3-, 6-, and 12-months was 0.83, 0.81, and 0.81, respectively, suggesting excellent discrimination of BMETS across post-consultation time points. BMETS outperformed simpler models at each time, with respective tAUC at each time of 0.78, 0.76, and 0.74 for the C-3 model and 0.80, 0.78, and 0.77 for the W-2 model. For the temporal validation set, respective tAUC was similarly high at 0.86, 0.82, and 0.78. Conclusions For patients with SBM, BMETS improved survival predictions versus simpler traditional models. Model performance was maintained when applied to a temporal validation set. To facilitate clinical use, we developed a web platform for data entry and display of BMETS predicted survival probabilities.Purpose After radiotherapy for painful bone metastases up to 44% of patients report a pain flare (PF). Our study compared two dose schedules of dexamethasone versus placebo to prevent PF. Methods and materials This double-blind, randomized, placebo-controlled trial allocated patients with painful bone metastases from solid tumors randomly to receive A 8 mg dexamethasone before radiotherapy, followed by three daily doses, B 8 mg dexamethasone followed by three doses of placebo, or C four doses of placebo. Patients reported worst pain scores, study medication side effects and opioid intake before treatment and thereafter daily for 14 days and on day 28. PF was defined as at least a two-point increase on a 0-10 pain scale with no decrease in opioid intake, or a 25% or greater increase in opioid intake with no decrease in pain score, followed by a return to baseline or below. The primary analysis was by intention-to-treat with patients with missing data classified as having a PF. Results From January 2012 to April 2016, 295 patients were randomized. PF incidence was 38% for A, 27% for B, and 39% for C (p= 0.07). Although patients in group B had the lowest PF-incidence, a relatively high percentage did not return to baseline pain levels indicating pain progression. The mean duration of PF was 2.1 days for A, 4.5 days for B and 3.3 days for C (p= 0.0567). Dexamethasone postponed PF occurrence in A, 52% occurred on day 2-5 vs. 73% in B and 99% in C (p=0.02). Patients in group A reported lower mean pain scores on days 2-5 than in B or C (p less then 0.001). Side effects were similar. Conclusions There was insufficient evidence that dexamethasone reduced the incidence of radiation-induced PF. However, dexamethasone postponed the occurrence of PF and led to lower mean pain scores on day 2-5.Purpose CD19-targeting chimeric antigen receptor T-cell (CART) therapy has emerged as a promising treatment for relapsed/refractory aggressive B-cell lymphoma (r/rABL), culminating in two FDA-approved therapies, tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Following leukapheresis and in preparation for CART infusion, contemporary bridging and lymphodepletion regimens rely mostly on cytotoxic chemotherapy. Here, in a cohort of patients treated with commercial tisa-cel and axi-cel, we show that bridging radiation therapy (bridging-RT) may offer a supplemental approach. Methods and materials Thirty-one patients receiving commercial tisa-cel (n=13) or axi-cel (n=18) between August 2018 and February 2019 for r/rABL were retrospectively reviewed. Patients were divided into two groups a) bridging-RT within 30 days (d) of CART infusion or b) non-bridging-RT (NBRT), where patients received either remote RT greater than 30d before CART infusion or no prior RT. Results Five patients received bridgi larger patient numbers are required to elucidate significant associations. Future work to prospectively assess the value of bridging-RT is warranted.Chronic cerebral hypoperfusion is a common cause of cerebral small vascular disease (CSVD). White matter (WM) lesions are the typical pathological manifestation of CSVD and contribute to cognitive decline. Epimedium flavonoids (EF) are the main component in Epimedium brevicornu Maxim., which is commonly used in traditional Chinese medicine. The purpose of this study was to investigate the effects of EF on cognitive impairment and the underlying mechanisms in a CSVD rat model induced with chronic cerebral hypoperfusion. The model was established by permanent bilateral common carotid artery occlusion (2VO) in rats. EF (50, 100, and 200 mg/kg) was intragastrically administered once a day for 12 weeks starting 2 weeks after 2VO surgery. The learning and memory capacity of the rats were measured using the Morris water maze and step-through tests. WM lesions were observed by MRI-diffusion tensor imaging, transmission electron microscopy, and LFB staining. Oligodendrocytes were detected by immunohistochemistry. Western blotting assay was used to determine the level of protein expression. The results showed that EF significantly improved learning and memory impairment, alleviated WM nerve fiber injuries and demyelination, and increased the number of mature oligodendrocytes in the corpus callosum, subcortical WM, and periventricular WM in 2VO rats. Mechanistically, EF reduced the expression of Lingo-1 and ROCK2 and increased the levels of phosphorylated (p-) Fyn, brain-derived neurotrophic factor (BDNF), TrkB, neuregulin-1 (NRG-1), p-ErbB4, PI3K p85 and p110α, p-Akt, and p-CREB in the corpus callosum of 2VO rats. These results suggest that EF may improve cognitive impairment and WM lesions induced by chronic cerebral hypoperfusion through inhibiting the Lingo-1/Fyn/ROCK pathway and activating the BDNF/TrkB, NRG-1/ErbB4, and the downstream PI3K/Akt/CREB pathways in WM. Thus, EF can be used as a potential neuroprotective agent in CSVD therapy.