Background
The COVID‐19 outbreak has resulted in collision between patients infected with SARS‐CoV‐2 and those with cancer on different fronts. Patients with cancer have been impacted by deferral, ...modification, and even cessation of therapy. Adaptive measures to minimize hospital exposure, following the precautionary principle, have been proposed for cancer care during COVID‐19 era. We present here a consensus on prioritizing recommendations across the continuum of sarcoma patient care.
Material and Methods
A total of 125 recommendations were proposed in soft‐tissue, bone, and visceral sarcoma care. Recommendations were assigned as higher or lower priority if they cannot or can be postponed at least 2–3 months, respectively. The consensus level for each recommendation was classified as “strongly recommended” (SR) if more than 90% of experts agreed, “recommended” (R) if 75%–90% of experts agreed and “no consensus” (NC) if fewer than 75% agreed. Sarcoma experts from 11 countries within the Sarcoma European‐Latin American Network (SELNET) consortium participated, including countries in the Americas and Europe. The European Society for Medical Oncology‐Magnitude of clinical benefit scale was applied to systemic‐treatment recommendations to support prioritization.
Results
There were 80 SRs, 35 Rs, and 10 NCs among the 125 recommendations issued and completed by 31 multidisciplinary sarcoma experts. The consensus was higher among the 75 higher‐priority recommendations (85%, 12%, and 3% for SR, R, and NC, respectively) than in the 50 lower‐priority recommendations (32%, 52%, and 16% for SR, R, and NC, respectively).
Conclusion
The consensus on 115 of 125 recommendations indicates a high‐level of convergence among experts. The SELNET consensus provides a tool for sarcoma multidisciplinary treatment committees during the COVID‐19 outbreak.
Implications for Practice
The Sarcoma European‐Latin American Network (SELNET) consensus on sarcoma prioritization care during the COVID‐19 era issued 125 pragmatical recommendations distributed as higher or lower priority to protect critical decisions on sarcoma care during the COVID‐19 pandemic. A multidisciplinary team from 11 countries reached consensus on 115 recommendations. The consensus was lower among lower‐priority recommendations, which shows reticence to postpone actions even in indolent tumors. The European Society for Medical Oncology‐Magnitude of Clinical Benefit scale was applied as support for prioritizing systemic treatment. Consensus on 115 of 125 recommendations indicates a high level of convergence among experts. The SELNET consensus provides a practice tool for guidance in the decisions of sarcoma multidisciplinary treatment committees during the COVID‐19 outbreak.
The COVID‐19 pandemic has caused deferral, modification, or cessation of treatment for patients with cancer. This article presents a consensus on prioritizing recommendations across the continuum of sarcoma patient care.
Nonlinear dynamic analysis techniques have made significant progress in the last 20 years, providing powerful tools for assessing structural damage and potential building collapse mechanisms. The ...fact that several reinforced concrete shear wall residential buildings underwent severe structural damage in walls at the lower building levels during the 2010 Maule earthquake (Chile) presents a scientific opportunity to assess the predictive quality of these techniques. The objective of this research is to compare building responses using two completely different three-dimensional nonlinear dynamic models and study in detail the observed damage pattern and wall collapse of one reinforced concrete shear wall building in Santiago, Chile. The first model is a mixed fiber-shell model developed in MATLAB, and the second is a shell finite element model developed in the software DIANA. Results of both models are consistent with the hypothesis that high axial loads trigger a limited ductility failure in critical walls at roof-to-base drift ratios less than 0.34% with little capacity of hysteretic energy dissipation, which contradicts the ductile design philosophy of current code provisions.
Non-cytotoxic therapy has changed the treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients. With unique mechanisms of action, these agents have decidedly improved survival and ...have demonstrated an improved toxicity profile. However, the real-life experience of the patient, which is commonly assessed by health-related quality of life (HRQoL) measurement, is not clearly established with this new generation of lung cancer treatments. The heterogeneity created by specific patient subgroups and different therapeutics calls for a tailored-approach to analyzing patient-reported outcomes. The objective of this systematic review was to assess the methodological quality of HRQoL analysis in Randomized Clinical Trials (RCTs) involving biologic agents to treat NSCLC.
A systematic literature search was performed using Medline, Embase, and Web of Science databases to identify NSCLC RCTs published between January 1st, 2000 and January 1st, 2020 reporting HRQoL measures. Only RCTs that both enrolled previously untreated patients with advanced NSCLC and had HRQoL analysis were included.
4203 abstracts were screened, of which only 85 RCTs met inclusion and exclusion criteria for analysis. The most applied HRQoL assessment tools were the EORTC-QLQ-C30 (47, 55.3 %), and EORTC-QLQ-LC13 (35, 41.2 %). The median number of verified CONSORT-PRO Extension criteria in the included trials was 3, and only in 10 (11.8 %) trials were all criteria well-documented. Notably, only 21 (24.7 %) RCTs performed subgroup analyses to specifically evaluate HRQoL in different patient populations.
QoL reporting in clinical trials is inconsistent and the quality of QoL measures adopted in a majority of trials is suboptimal. Considering the fact that NSCLC is a biologically diverse disease and that the treatments differ based on patient and tumor-specifics, efforts should be pursued to tailor QoL measures for different subsets of this patient population in addition to mandating QoL reporting in clinical trials. We believe that this is necessary to understand the real-life experience of lung cancer patients in the era of personalized medicine.
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•Only two HRQoL instruments were used in 31 % of 85 clinical trials to evaluate PROs.•12 % of the included trials met all CONSORT Extension Criteria for PRO reporting.•Subgroup analysis to evaluate PROs was performed only in 24.7 % of the studies.•Patient heterogeneity supports the incorporation of tailored tools for PRO analysis.
•The model correctly reproduces the cyclic behavior of tested RC walls.•The model predicts the response of a RC wall building damaged in the Maule earthquake.•Results are consistent with a limited ...ductility seismic behavior of the RC building.•The shear transferred through the bending of slabs significantly increases the ALR.•The vertical ground motion and the damping ratio alter the sequence of wall damage.
Buildings with Reinforced Concrete (RC) walls are commonly used to resist lateral forces in seismic countries because they provide high lateral stiffness and strength. In recent earthquakes, shear wall buildings have shown good behavior in general; however, a small percentage underwent severe damage localized typically in lower stories. Several numerical models have been developed and proposed to simulate the failure mechanism and behavior of RC walls. From the existing models, only those denoted as micro-models can accurately simulate the stress and strain distributions. The aim of this research is double: (i) to validate a nonlinear finite element wall model and the associated material stress-strain constitutive relationship using the behavior of a real building during the 2010 Chile earthquake; and (ii) to analyze the uncertainty of the response of the building due to changes in model parameters. To validate the response of the wall model, four experimental benchmark RC wall specimens were studied, and model accuracy was evaluated using five parameters: initial stiffness, peak base-shear, ultimate base-shear, maximum displacement, and dissipated energy. A sensitivity analysis was carried out to study the influence of material parameters in the wall response and its damage. The case-study is a 18-story building with 1 basement, which suffered severe damage during the 2010 Chile earthquake, which has been studied by non-linear response-history analysis. Uncertainty in the building response due to three important modeling assumptions was considered: Rayleigh’s damping model parameters; effective elastic bending stiffness of the structural elements; and effect of the vertical ground motion component. Results showed that the proposed model can predict the seismic response of the building with reasonable accuracy by identifying correctly the damage location. This case-study enabled us to assess also the effect of damping in non-ductile structures, the important influence of the slab stiffness in the response, and the effect of the vertical ground motion component in the sequence of damaged walls.
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•Drug safety investigation is crucial in cancer clinical trials.•We reviewed adverse events (AEs) reporting and attribution process in oncology trials.•Among 60 manuscripts analyzed, ...the majority (66.6 %) presented an incomplete report of AEs attribution.•One-third of the studies did not specify the total frequency of all-grade and grade 3−4 AEs.•Half of the patients suffering from AEs in the placebo arms were misattributed to an inert substance.
We systematically reviewed the quality of AEs reports in published oncology trials analyzing also the bias in the attribution process. We searched MEDLINE, PubMed (2000–2019) selecting randomized, double-blind, placebo-controlled, and phase 3 cancer trials using exclusively targeted therapy or immunotherapy-related drugs. The proportion of publications with complete AE reports (including both all-cause and drug-related AE data) and the AEs attribution ratio (patients with drug-related over all-cause AE) were investigated. Among 60 trials (38,174 patients) included, 40 (66.6 %) presented an incomplete report of AEs attribution. Journals with the lowest impact factor were significantly associated with deficient reports of grade 3−4 AEs (p = 0.02). Under placebo administration, the median incidence of all-grade drug-related AEs was 49 % (IQR 39–56). The median attribution ratio for all-grade AEs in the active and placebo arms was 88.9 % (IQR 79.8–93) and 53.9 % (IQR 43.4–60.9), respectively. The AEs reporting and attribution process appear to be more unreliable than expected.
Malignant melanoma represents the most aggressive type of skin cancer. Modern therapies, including targeted agents and immune checkpoint inhibitors, have changed the dismal prognosis that ...characterized this disease. However, most evidence was obtained by studying patients with frequent subtypes of cutaneous melanoma (CM). Consequently, there is an emerging need to understand the molecular basis and treatment approaches for unusual melanoma subtypes. Even a standardized definition of infrequent or rare melanoma is not clearly established. For that reason, we reviewed this challenging topic considering clinical and molecular perspectives, including uncommon CMs—not associated with classical V600E/K BRAF mutations—malignant mucosal and uveal melanomas, and some unusual independent entities, such as amelanotic, desmoplastic, or spitzoid melanomas. Finally, we collected information regarding melanomas from non-traditional primary sites, which emerge from locations as unique as meninges, dermis, lymph nodes, the esophagus, and breasts. The aim of this review is to summarize and highlight the main scientific evidence regarding rare melanomas, with a particular focus on treatment perspectives.
To describe treatment patterns among patients with stage III melanoma who underwent surgical excision in years 2011–2016, and assess outcomes among patients who subsequently received systemic ...adjuvant therapy versus watch-and-wait.
Chart review of 380 patients from 17 melanoma centers in North America, South America and Europe.
Of 129 (34%) patients treated with adjuvant therapy, 85% received interferon α-2b and 56% discontinued treatment (mostly due to adverse events). Relapse-free survival was significantly longer for patients treated with adjuvant therapy versus watch-and-wait (hazard ratio = 0.63; p < 0.05). There was considerable heterogeneity in adjuvant treatment schedules and doses. Similar results were found in patients who received interferon-based adjuvant therapy.
Adjuvant therapies with better safety/efficacy profiles will improve clinical outcomes in patients with stage III melanoma.
•Uncertainty of modeling assumptions is quantified for RC free-plan buildings.•Uncertainty of shear forces in the wall core is larger than that for the story.•Diaphragm bending stiffness affects ...upper story shears more than in-plane stiffness.•The soil-structure interaction model causes larger uncertainty in basement forces.•Location of the minimum base shear depends on the fixity level of the building model.
Complex building models consider multiple degrees of freedom and modeling assumptions that influence the accuracy of the predicted seismic response. This study evaluates the epistemic uncertainty inherent to modeling assumptions by evaluating the seismic response behavior of six instrumented reinforced concrete free-plan structures in Santiago, Chile. The free-plan structural concept is frequently used in office buildings and consists of a core of shear walls, a perimeter frame, and a flat slab connecting both lateral force resisting systems. Epistemic uncertainties studied in this paper are inherent to the following modeling assumptions: (1) the type of finite elements used in the building models; (2) the in-plane and out-of-plane stiffness of the diaphragms; (3) the interaction between the basement and the surrounding soil; and (4) the decision where to apply base fixity. The response uncertainty was first evaluated by comparing predicted and measured vibration periods using ambient vibrations and aftershock records of the 2010 Maule, Chile earthquake. Additionally predicted global and local seismic response parameters such as story shears, torques, and drifts were compared between a predefined reference model typically used in design and a set of variant models. A statistical evaluation of the modeling uncertainty showed a strong dependency on the response parameter considered. Larger uncertainties were observed for shear force related response parameters, including the influence of soil-structure interaction on base and story shears, while uncertainties for predicting fundamental periods or the depth at which building fixity was assumed had moderate impact on the overall building response. In general, uncertainties identified in core forces were larger than uncertainties in story forces and also larger at the underground stories than in comparison to upper levels.
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