Background
Brain metastases occur when cancer cells spread from their original site to the brain and are a frequent cause of morbidity and death in people with cancer. They occur in 20% to 40% of ...people during the course of their disease. Brain metastases are also the most frequent type of brain malignancy. Single and solitary brain metastasis is infrequent and choosing the most appropriate treatment is a clinical challenge. Surgery and stereotactic radiotherapy are two options. For surgery, tumour resection is performed using microsurgical techniques, while in stereotactic radiotherapy, external ionising radiation beams are precisely focused on the brain metastasis. Stereotactic radiotherapy may be given as a single dose, also known as single dose radiosurgery, or in a number of fractions, also known as fractionated stereotactic radiotherapy. There is uncertainty regarding which treatment (surgery or stereotactic radiotherapy) is more effective for people with single or solitary brain metastasis.
Objectives
To assess the effectiveness and safety of surgery versus stereotactic radiotherapy for people with single or solitary brain metastasis.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, March 2018), MEDLINE and Embase up to 25 March 2018 for relevant studies. We also searched trials databases, grey literature and handsearched relevant literature.
Selection criteria
We included randomised controlled trials (RCTs) comparing surgery versus stereotactic radiotherapy, either a single fraction (stereotactic radiosurgery) or multiple fractions (fractionated stereotactic radiotherapy) for treatment of single or solitary brain metastasis.
Data collection and analysis
Two review authors screened all references, evaluated the quality of the included studies using the Cochrane tool for assessing risk of bias, and performed data extraction. The primary outcomes were overall survival and adverse events. Secondary outcomes included progression‐free survival and quality of life . We analysed overall survival and progression‐free survival as hazard ratios (HRs) with 95% confidence intervals (CIs), and analysed adverse events as risk ratios (RRs). For quality of life we used mean difference (MD).
Main results
Two RCTs including 85 participants met our inclusion criteria. One study included people with single untreated brain metastasis (n = 64), and the other included people with solitary brain metastasis (22 consented to randomisation and 21 were analysed). We identified a third trial reported as completed and pending results this may be included in future updates of this review. The two included studies were prematurely closed due to poor participant accrual. One study compared surgery plus whole brain radiotherapy (WBRT) versus stereotactic radiosurgery alone, and the second study compared surgery plus WBRT versus stereotactic radiosurgery plus WBRT. Meta‐analysis was not possible due to clinical heterogeneity between trial interventions. The overall certainty of evidence was low or very low for all outcomes due to high risk of bias and imprecision.
We found no difference in overall survival in either of the two comparisons. For the comparison of surgery plus WBRT versus stereotactic radiosurgery alone: HR 0.92, 95% CI 0.48 to 1.77; 64 participants, very low‐certainty evidence. We downgraded the certainty of the evidence to very low due to risk of bias and imprecision. For the comparison of surgery plus WBRT versus stereotactic radiosurgery plus WBRT: HR 0.53, 95% CI 0.20 to 1.42; 21 participants, low‐certainty evidence. We downgraded the certainty of the evidence to low due to imprecision. Adverse events were reported in both trial groups in the two studies, showing no differences for surgery plus WBRT versus stereotactic radiosurgery alone (RR 0.31, 95% CI 0.07 to 1.44; 64 participants) and for surgery plus WBRT versus stereotactic radiosurgery plus WBRT (RR 0.37, 95% CI 0.05 to 2.98; 21 participants). Most of the adverse events were related to radiation toxicities. We considered the certainty of the evidence from the two comparisons to be very low due to risk of bias and imprecision.
There was no difference in progression‐free survival in the study comparing surgery plus WBRT versus stereotactic radiosurgery plus WBRT (HR 0.55, 95% CI 0.22 to 1.38; 21 participants, low‐certainty evidence). We downgraded the evidence to low certainty due to imprecision. This outcome was not clearly reported for the other comparison. In general, there were no differences in quality of life between the two studies. The study comparing surgery plus WBRT versus stereotactic radiosurgery plus WBRT found no differences after two months using the QLQ‐C30 global scale (MD ‐10.80, 95% CI ‐44.67 to 23.07; 14 participants, very low‐certainty evidence). We downgraded the certainty of evidence to very low due to risk of bias and imprecision.
Authors' conclusions
Currently, there is no definitive evidence regarding the effectiveness and safety of surgery versus stereotactic radiotherapy on overall survival, adverse events, progression‐free survival and quality of life in people with single or solitary brain metastasis, and benefits must be decided on a case‐by‐case basis until well powered and designed trials are available. Given the difficulties in participant accrual, an international multicentred approach should be considered for future studies.
Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate ...COVID-19 is not well studied.
To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19.
Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C).
Aspirin use within the first day of hospitalization.
The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.
Among the 2 446 650 COVID-19-positive patients who were screened, 189 287 were hospitalized and 112 269 met study inclusion. For the full cohort, Median age was 63 years (IQR, 47-74 years); 16.1% of patients were African American, 3.8% were Asian, 52.7% were White, 5.0% were of other races and ethnicities, 22.4% were of unknown race and ethnicity. In-hospital mortality occurred in 10.9% of patients. After inverse probability treatment weighting, 28-day in-hospital mortality was significantly lower in those who received aspirin (10.2% vs 11.8%; odds ratio OR, 0.85; 95% CI, 0.79-0.92; P < .001). The rate of pulmonary embolism, but not deep vein thrombosis, was also significantly lower in patients who received aspirin (1.0% vs 1.4%; OR, 0.71; 95% CI, 0.56-0.90; P = .004). Patients who received early aspirin did not have higher rates of gastrointestinal hemorrhage (0.8% aspirin vs 0.7% no aspirin; OR, 1.04; 95% CI, 0.82-1.33; P = .72), cerebral hemorrhage (0.6% aspirin vs 0.4% no aspirin; OR, 1.32; 95% CI, 0.92-1.88; P = .13), or blood transfusion (2.7% aspirin vs 2.3% no aspirin; OR, 1.14; 95% CI, 0.99-1.32; P = .06). The composite of hemorrhagic complications did not occur more often in those receiving aspirin (3.7% aspirin vs 3.2% no aspirin; OR, 1.13; 95% CI, 1.00-1.28; P = .054). Subgroups who appeared to benefit the most included patients older than 60 years (61-80 years: OR, 0.79; 95% CI, 0.72-0.87; P < .001; >80 years: OR, 0.79; 95% CI, 0.69-0.91; P < .001) and patients with comorbidities (1 comorbidity: 6.4% vs 9.2%; OR, 0.68; 95% CI, 0.55-0.83; P < .001; 2 comorbidities: 10.5% vs 12.8%; OR, 0.80; 95% CI, 0.69-0.93; P = .003; 3 comorbidities: 13.8% vs 17.0%, OR, 0.78; 95% CI, 0.68-0.89; P < .001; >3 comorbidities: 17.0% vs 21.6%; OR, 0.74; 95% CI, 0.66-0.84; P < .001).
In this cohort study of US adults hospitalized with moderate COVID-19, early aspirin use was associated with lower odds of 28-day in-hospital mortality. A randomized clinical trial that includes diverse patients with moderate COVID-19 is warranted to adequately evaluate aspirin's efficacy in patients with high-risk conditions.
To assess management patterns and outcome in patients with glioblastoma multiforme (GBM) treated during 2008-2010 in Spain.
Retrospective analysis of clinical, therapeutic, and survival data ...collected through filled questionnaires from patients with histologically confirmed GBM diagnosed in 19 Spanish hospitals.
We identified 834 patients (23% aged >70 years). Surgical resection was achieved in 66% of patients, although the extent of surgery was confirmed by postoperative MRI in only 41%. There were major postoperative complications in 14% of patients, and age was the only independent predictor (Odds ratio OR, 1.03; 95% confidence interval CI,1.01-1.05; P = .006). After surgery, 57% received radiotherapy (RT) with concomitant and adjuvant temozolomide, 21% received other regimens, and 22% were not further treated. In patients treated with surgical resection, RT, and chemotherapy (n = 396), initiation of RT ≤42 days was associated with longer progression-free survival (hazard ratio HR, 0.8; 95% CI, 0.64-0.99; P = .042) but not with overall survival (HR, 0.79; 95% CI, 0.62-1.00; P = .055). Only 32% of patients older than 70 years received RT with concomitant and adjuvant temozolomide. The median survival in this group was 10.8 months (95% CI, 6.8-14.9 months), compared with 17.0 months (95% CI, 15.5-18.4 months; P = .034) among younger patients with GBM treated with the same regimen.
In a community setting, 57% of all patients with GBM and only 32% of older patients received RT with concomitant and adjuvant temozolomide. In patients with surgical resection who were eligible for chemoradiation, initiation of RT ≤42 days was associated with better progression-free survival.
Background
Non‐small cell lung cancer is one of the leading causes of death in developed countries. Brain metastases are often seen in non‐small cell lung cancer patients and although they are ...frequently multiple, a subset of patients with a solitary brain metastasis is regularly seen. Treatment of solitary brain metastasis has been surgery, when possible, but radiotherapy techniques, such as stereotactic radiotherapy using a linear accelerator or a high precision device of 201 cobalt‐60 sources (gamma knife) have provided new treatment options.
Objectives
To determine the effectiveness of surgery compared to radiosurgery, either combined with whole brain irradiation or administered alone, for patients with a solitary brain metastasis from successfully treated non‐small cell lung cancer.
Search methods
For this update we performed a new search in March 2009, using the following search strategy designed in the original review: Cochrane Central Register of Controlled Trials (CENTRAL) (accessed through The Cochrane Library, 2004, Issue 2), MEDLINE (accessed through PubMed), EMBASE and CINAHL (both accessed through Ovid). We also searched the Cochrane Lung Cancer Specialised Register.
Selection criteria
We considered for inclusion randomised trials comparing surgery (with or without whole brain irradiation) with all types of radiosurgery (with or without whole brain irradiation) for solitary brain metastasis from non‐small cell lung cancer.
Data collection and analysis
Two review authors independently screened the search results to identify suitable trials.
Main results
Despite extensive searching we found no randomised trials suitable for inclusion.
Authors' conclusions
Based on the available evidence a meaningful conclusion cannot be reached. The term "single brain metastasis" is used to describe a brain metastasis found in patients presenting with an inoperable lung cancer or from an uncontrolled primary tumour some time after diagnosis, and the term "solitary brain metastasis" is used when the brain metastasis is diagnosed some time after radical, potentially curative treatment. In the evaluated studies, we found that the criteria for the definition of solitary brain metastasis were not consistent. Some series combined patients with single and solitary brain metastasis. Some of the single arm or cohort studies came from single institutions where the availability of both techniques (radiosurgery and surgery) was not described. Therefore, it is possible that the most accessible technique might be used preferentially, reinforced by a general belief that the techniques are equivalent. This has prevented an appropriate treatment comparison, which should be made through a well designed phase III clinical trial.
This is the protocol for a review and there is no abstract. The objectives are as follows:
To assess the effectiveness and safety of surgery versus radiosurgery for people with single or solitary ...brain metastases.
This work deals with the design and analysis of a controller for a shunt active power filter. The design is based on combined feedforward and feedback actions, the last using odd-harmonic repetitive ...control, and aims at obtaining good closed-loop performance in spite of the possible frequency variations that may occur in the electrical network. As these changes affect the performance of the controller, the proposal includes a compensation technique consisting of an adaptive change of the sampling time of the digital controller according to the network frequency variation. However, this implies structural changes in the closed-loop system that may eventually destabilize it. Hence, this article is also concerned with closed-loop stability of the resulting system, which is analyzed using a robust control approach that takes advantage of the small gain theorem. Experimental results reporting good performance of the closed-loop system are provided.
The asp Leuciscus aspius (L.), a large piscivorous cyprinid fish, is reported for the first time in the Iberian Peninsula. Six individuals were captured in July 2017 and many other were observed in ...the Darnius-Boadella Reservoir (Muga river basin, NE Spain). Our observations suggest that the asp has established in the reservoir, representing a potential threat to the native species of the Muga River. As it has been the case with several other alien fish species, the asp is likely to be illegally spread to other Iberian river basins if current management measures do not change.
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