Adjuvant radiotherapy (RT) after surgical resection of World Health Organization (WHO) grade II meningioma, also known as atypical meningioma (AM), is a topic of controversy. The purpose of this ...study is to compare overall survival (OS) with or without adjuvant RT after subtotal resection (STR) or gross total resection (GTR) in AM patients diagnosed according to the 2007 WHO classification.
The National Cancer Database was used to identify 2515 patients who were diagnosed with AM between 2009 and 2012 and underwent STR or GTR with or without adjuvant RT. Propensity score matching was first applied to balance covariates including age, year of diagnosis, sex, race, histology, and tumor size in STR or GTR cohorts stratified by adjuvant RT status. Multivariate regression according to the Cox proportional hazards model and Kaplan-Meier survival plots with log-rank test were then used to evaluate OS difference associated with adjuvant RT.
GTR is associated with improved OS compared with STR. In the subgroup analysis, adjuvant RT in patients who underwent STR demonstrated significant association with improved OS compared with no adjuvant RT (adjusted hazard ratio AHR 0.590, P = .045); however, adjuvant RT is not associated with improved OS in patients who underwent GTR (AHR 1.093, P = .737).
Despite the lack of consensus on whether adjuvant RT reduces recurrence after surgical resection of AM, our study observed significantly improved OS with adjuvant RT compared with no adjuvant RT after STR.
Introduction:
The improved survival of patients even with metastatic cancer has led to an increase in the incidence of spine metastases, suggesting the need for a more aggressive palliative treatment ...than conventional external beam radiation therapy (cEBRT). Consequently, spinal stereotactic body radiation therapy (SBRT) has increased in popularity over the past decade. However, there has been no comparison of patterns of usage of cEBRT versus SBRT in the treatment of spinal metastases in the US.
Methods:
The National Cancer Data Base (NCDB) from 2004-2013 was used for analysis. cEBRT was defined as 30 Gy in 10 fractions, 20 Gy in 5 fractions, or 8 Gy in 1 fraction. SBRT was defined as 25-32 Gy infive5 fractions, 24-32 Gy in 4 fractions, 20-32 Gy in three fractions, 14-32 Gy in 2 fractions, or 14-24 Gy in 1 fraction. Single and multivariable associations between patient demographic and cancer characteristics and type of radiation were performed.
Results:
From 2004-2013, 23,181 patients with spinal metastases in the United States received cEBRT, while 1,030 received SBRT as part of their first course of treatment. Most patients (88%) received 10 fractions of radiation. Multivariable analysis suggested that non-Medicare or private insurance (adjusted OR 0.4-0.7), African-American race (adjusted OR = 0.8, 95%CI = 0.7-1.0), age 65+ (adjusted OR = 0.8), living in a region with lower population (adjusted OR 0.7), earlier year of diagnosis (OR = 0.9), and receiving treatment in a non-academic/research facility (adjusted OR 0.6) were associated with cEBRT. After controlling for other variables, regional education level was no longer significantly associated with cEBRT.
Conclusions:
Most patients with spine metastases were treated with cEBRT, usually with 10 fractions. Receipt of SBRT was significantly associated with race, insurance, geography, population, type of treatment facility, and year of diagnosis, even after controlling for other factors. These findings raise questions about disparities in access to and delivery of care that deserve further investigation.
Although glycogen synthase kinase-3 beta (GSK-3β) was originally named for its ability to phosphorylate glycogen synthase and regulate glucose metabolism, this multifunctional kinase is presently ...known to be a key regulator of a wide range of cellular functions. GSK-3β is involved in modulating a variety of functions including cell signaling, growth metabolism, and various transcription factors that determine the survival or death of the organism. Secondary to the role of GSK-3β in various diseases including Alzheimer’s disease, inflammation, diabetes, and cancer, small molecule inhibitors of GSK-3β are gaining significant attention. This paper is primarily focused on addressing the bifunctional or conflicting roles of GSK-3β in both the promotion of cell survival and of apoptosis. GSK-3β has emerged as an important molecular target for drug development.
Metastatic progression defines the final stages of tumor evolution and underlies the majority of cancer-related deaths. The heterogeneity in disseminated tumor cell populations capable of seeding and ...growing in distant organ sites contributes to the development of treatment resistant disease. We recently reported the identification of a novel tumor-derived cell population, circulating hybrid cells (CHCs), harboring attributes from both macrophages and neoplastic cells, including functional characteristics important to metastatic spread. These disseminated hybrids outnumber conventionally defined circulating tumor cells (CTCs) in cancer patients. It is unknown if CHCs represent a generalized cancer mechanism for cell dissemination, or if this population is relevant to the metastatic cascade. Herein, we detect CHCs in the peripheral blood of patients with cancer in myriad disease sites encompassing epithelial and non-epithelial malignancies. Further, we demonstrate that in vivo-derived hybrid cells harbor tumor-initiating capacity in murine cancer models and that CHCs from human breast cancer patients express stem cell antigens, features consistent with the potential to seed and grow at metastatic sites. Finally, we reveal heterogeneity of CHC phenotypes reflect key tumor features, including oncogenic mutations and functional protein expression. Importantly, this novel population of disseminated neoplastic cells opens a new area in cancer biology and renewed opportunity for battling metastatic disease.
Pre-residency peer-reviewed publications (PRP) have been associated with subsequent resident choice of academic versus private practice career. The evolution of PRP prevalence among radiation ...oncology resident classes has yet to be examined. A list of radiation oncology residents from the graduating classes of 2016 and 2022 were obtained, and PRP was compiled as the number of publications a resident had listed in PubMed as of the end of the calendar year of residency application. Statistical analysis was conducted using Fisher's exact test. Analysis of 163 residents from the 2016 class compared with 195 from the 2022 class revealed that the proportion of residents with zero PRP decreased from 46.6% to 23.6% between the 2016 to 2022 classes (p<0.0001), while that of residents with one PRP increased from 17.8% to 19.0% (p>0.05) and with at least two PRP increased from 35.6% to 57.4% (p<0.0001). Residents with a PhD were more likely to have at least two PRP in each class (p<0.0001). As with the class of 2016, there remained no significant difference in PRP by gender for the class of 2022. Over the past six years, PRP has become more prevalent among incoming radiation oncology residents. Residents in the class of 2016 were 180% less likely than the class of 2022 to have at least one PRP, and 60% less likely to have at least two PRP. These findings are indicative of the increasing pressure on medical students to enter residency with a publication background.
Medically refractory tremor treatment has evolved over the past half-century from intraoperative thalamotomy to deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM). Within ...the past 15years, unilateral radiosurgical VIM thalamotomy has emerged as a comparably efficacious treatment modality.
An extensive literature search of VIM DBS series was performed; the total cost of VIM DBS was calculated from hospitals geographically representative of the entire United States using current procedural terminology and work relative value unit (RVU) codes. The 2016 Medicare Ambulatory Payment Classification for stereotactic radiosurgery (SRS) was added to the work RVU to determine the total cost of VIM SRS for both Gamma Knife and linear accelerator SRS. Cost estimates assumed that VIM DBS was performed without intraoperative microelectrode recording.
The mean unilateral VIM DBS cost was $17,932.41 per patient. For SRS VIM, the total costs for Gamma Knife ($10,811.77) and linear accelerator ($10,726.40) were 40% less expensive than for unilateral VIM DBS.
Radiosurgery of the VIM is 40% less expensive than unilateral VIM DBS in treatment of medically refractory tremor, regardless of radiosurgical modality. This finding argues for increased radiation oncology involvement in the management of medically refractory tremor patients.
Autophagy has been reported to be increased in irradiated cancer cells resistant to various apoptotic stimuli. We therefore hypothesized that induction of autophagy via mTOR inhibition enhances ...radiosensitization in apoptosis-inhibited H460 lung cancer cells in vitro and in a lung cancer xenograft model. To test this hypothesis, combinations of Z-DEVD (caspase-3 inhibitor), RAD001 (mTOR inhibitor) and irradiation were tested in cell and mouse models. The combination of Z-DEVD and RAD001 more potently radiosensitized H460 cells than individual treatment alone. The enhancement in radiation response was not only evident in clonogenic survival assays, but also was demonstrated through markedly reduced tumor growth, cellular proliferation (Ki67 staining), apoptosis (TUNEL staining), and angiogenesis (vWF staining) in vivo. Additionally, upregulation of autophagy as measured by increased GFP-LC3-tagged autophagosome formation accompanied the noted radiosensitization in vitro and in vivo. The greatest induction of autophagy and associated radiation toxicity was exhibited in the tri-modality treatment group. Autophagy marker, LC-3-II, was reduced by 3-methyladenine (3-MA), a known inhibitor of autophagy, but further increased by the addition of lysosomal protease inhibitors (pepstatin A and E64d), demonstrating that there is autophagic induction through type III PI3 kinase during the combined therapy. Knocking down of ATG5 and beclin-1, two essential autophagic molecules, resulted in radiation resistance of lung cancer cells. Our report suggests that combined inhibition of apoptosis and mTOR during radiotherapy is a potential therapeutic strategy to enhance radiation therapy in patients with non-small cell lung cancer.
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