•5 patients with pelvic lymph node metastases received SBRT using a 1.5 T MR-linac.•Session time was <60 min for all 25 treatment fractions.•All quality assurance tests were passed (dose calculations ...& film measurements).
Online adaptive radiotherapy using the 1.5 Tesla MR-linac is feasible for SBRT (5 × 7 Gy) of pelvic lymph node oligometastases. The workflow allows full online planning based on daily anatomy. Session duration is less than 60 min. Quality assurance tests, including independent 3D dose calculations and film measurements were passed.
•We developed an online adaptive radiotherapy (oART) workflow.•The oART workflow is cone-beam computed tomography-guided.•The oART workflow can be performed on a standard C-arm linac.•The first ...patients with bladder cancer were successfully treated with the workflow.
Current online adaptive radiotherapy (oART) workflows require dedicated equipment. Our aim was to develop and implement an oART workflow for a C-arm linac which can be performed using standard clinically available tools. A workflow was successfully developed and implemented. Three patients receiving palliative radiotherapy for bladder cancer were treated, with 33 of 35 total fractions being delivered with the cone-beam computed tomography (CBCT)-guided oART workflow. Average oART fraction duration was 24 min from start of CBCT acquisition to end of beam on. This work shows how oART could be performed without dedicated equipment, broadening oART availability for application at existing treatment machines.
Chemoradiotherapy (CRT) is the standard of care in inoperable non–small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in ...responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe.
The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy.
Out of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO ≥2 (P = .006), and TNM IIIC (P = .031). The multivariable analysis for acute toxicity was significant for cCRT (P = .015), WHO ≥2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality.
In this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.
In this national lung cancer audit of inoperable NSCLC patients, acute toxicity and 3-month mortality of curative chemoradiation was analyzed. Another important question was whether concurrent chemoradiation for elderly stage III NSCLC patients is safe. The results showed that 3-month toxicity was significantly higher in patients treated with concurrent chemoradiation, higher TNM stage IIIC and poor performance (WHO≥2) patients.
Glioblastoma multiforme is the most common and aggressive primary brain tumor. Valproate has been used as an anti-epileptic drug and mood stabilizer for decades. Recently, it was found to inhibit the ...proliferation of various cancers including glioblastoma multiforme.
We provide a comprehensive review of the mechanisms of action of valproate in gliomas, of its potential side effects and of the published clinical results obtained with this drug in glioblastomas. Valproate inhibits a subset of histone deacetylases and cellular kinases, and affects gene transcription through histone hyperacetylation, DNA hypomethylation and the modulation of several transcription factors. As a result, VPA induces differentiation of glioma cells, can prevent their invasion in surrounding tissues and may inhibit tumor angiogenesis. VPA can also inhibit DNA repair, thereby potentiating cytotoxic treatments such as chemotherapies or radiation therapy. Based on these mechanisms and case reports of glioblastoma remissions following VPA treatment, several clinical studies currently assess the therapeutic potential of VPA in glioma therapy.
The combination of VPA treatment with chemotherapy and radiotherapy in glioblastoma appears a rational option that deserves well-designed prospective clinical trials that assess the efficacy and the molecular characteristics of the responding tumors in these patients.
Purpose. To systematically examine the state of research on sexuality and amputees.
Methods. A total of five publication databases were searched: Pubmed, Cinahl, Embase, Psychinfo and Recall.
...Results. A total of 11 eligible studies was found. The studies were characterised by a diversity of study populations, sampling methods, gender and age distributions, assessment methods, and outcomes measures. The use of the terminology regarding sexuality was ambiguous. All studies found an impact of the amputation of a limb on some part of sexual functioning (or concerns about) to some degree.
Conclusions. Studies on sexuality and amputees are very diverse and terminology is ambiguous. Amputation of a limb has an impact on sexual functioning. Amputees complain that there is little support from professionals. The authors recommend the use of the ICF terminology. Suggestions for future research are given.
In a previous study, the authors demonstrated an association between prenatal famine in middle to late gestation and major affective disorders requiring hospitalization. In this study, they sought to ...examine the association by using newly identified cases from the Dutch birth cohort used previously to examine the gender specificity of the association and to assess whether this relation is present for both unipolar and bipolar affective disorders.
The authors compared the risk of major affective disorder requiring hospitalization in birth cohorts who were and were not exposed, in each trimester of gestation, to famine during the Dutch Hunger Winter of 1944-1945. These cases of major affective disorder requiring hospitalization were newly ascertained from a national psychiatric registry. A larger data set from this registry was used for analysis by gender and diagnostic subtype.
For the newly ascertained cases, the risk of developing major affective disorder requiring hospitalization was increased for subjects with exposure to famine in the second trimester and was increased significantly for subjects with exposure in the third trimester, relative to unexposed subjects. For the cases from the entire period of ascertainment, the risk of developing affective disorder was significantly increased for those exposed to famine during the second and the third trimesters of gestation. The effects were demonstrated for men and women and for unipolar and bipolar affective disorders.
These results provide support for the authors' previous findings on the association between middle to late gestational famine and affective disorder.
Abstract
The last decade has witnessed a substantial increase of multi‐centre, public health‐oriented clinical trials in poor countries. However, non‐commercial research groups have less staff and ...financial resources than traditional commercial sponsors, so the trial teams have to be creative to comply with Good Clinical Practices (
GCP
) requirements. According to the recent experience of a large multicentre trial on antimalarials, major challenges result from the complexity of multiple ethical review, the costs of in‐depth monitoring at several sites, setting up an adequate Good Clinical Laboratory Practices (
GCLP
) framework, lack of insurers in host countries, and lack of adequate non‐commercial data management software. Public research funding agencies need to consider these challenges in their funding policies. They also could support common spaces where North‐South collaborative research groups may share critical information, such as on research insurance and open‐source,
GCP
‐compliant software.
WHO
should update its
GCP
guidelines, which date back to 1995, to incorporate the perspectives and needs of non‐commercial clinical research.
Objectif
Explorer les moyens de lutter contre
C
hrysomya putoria
, la mouche africaine des latrines, dans les latrines à fosse. Comme les latrines sont une source importante de production pour ces mouches, l’élimination de ces sites de reproduction importants est susceptible de réduire les populations de mouches du village et peut réduire la propagation des agents pathogènes diarrhéiques.
Méthodes
Nous avons traité 24 latrines dans un village gambien: six avec soit (1) du pyriproxyfène, une formulation imitant une hormone juvénile des insectes appelée Sumilarv
®
0.5G, à granules de 0,5% de pyriproxyfène, (2) des billes de polystyrène gonflées (
EPB
), (3) du savon local ou (4) aucun traitement i.e. témoins. Les mouches ont été recueillies à l'aide de pièges de sortie placés au dessus des orifices des fosses, chaque semaine pendant cinq semaines. Dans une autre étude, nous avons testé si les latrines pouvaient servir également comme pièges à mouches efficaces en utilisant les odeurs fécales comme attractifs. Nous avons construit six latrines à fosse chacune avec un piège à mouche intégré et avons testé leur efficacité de capture par rapport à six pièges appâtés sous forme de boîtes de poisson placées à 10 m de la latrine. Des discussions de groupe focalisées ont été menées par la suite pour évaluer l'acceptabilité des latrines attrape‐mouche.
Résultats
Le nombre de
C
. putoria
émergents a été réduit de 96,0% (
IC
95%: 94,5 à 97,2%) 4 à 5 semaines après le traitement avec le pyriproxyfène, de 64,2% (
IC
95%: 51,8 à 73,5%) après traitement avec du savon local, de 41,3% (
IC
95%: 24,0 à 54,7%) 3 à 5 semaines après traitement avec des
EPB
. Les pièges à mouches placés sur latrines ont collecté
C
. putoria
et étaient jugés acceptables par les collectivités locales.
Conclusions
Sumilarv 0,5 G est prometteur comme agent de lutte chimique, tandis que les pièges appâtés aux odeurs de latrines peuvent s'avérer une méthode utile non chimique pour lutter contre les mouches. Les deux méthodes justifient un développement supplémentaire afin de pouvoir réduire la production de mouches à partir des latrines à fosse. Une combinaison des interventions peut s'avérer efficace pour le contrôle des mouches des latrines et des maladies qu'elles transmettent.
Objetivo
Explorar las formas de controlar
C
hrysomya putoria
, la mosca Africana de letrinas, en letrinas de hoyo seco. Puesto que las letrinas de hoyo seco son una fuente importante de estas moscas, eliminar estos lugares de reproducción puede reducir las poblaciones de la mosca y por lo tanto reducir la diseminación de patógenos diarreicos.
Métodos
Hemos tratado 24 letrinas en un poblado de Gambia: cada grupo de seis se trató con una de las siguientes (1) piriproxifen, que mimetiza una hormona juvenil del insecto formulada como Sumilarv
®
0.5G, y piriproxifen granulado al 0.5%, (2) pastillas de poliestireno expandido (
PPE
), (3) jabón local (4) sin tratamiento como controles. Las moscas se recolectaron utilizando trampas de salida localizadas sobre los orificios de entrada, semanalmente, durante cinco semanas. En un estudio separado evaluamos si las letrinas también funcionaban como trampas eficientes utilizando los olores fecales como atrayentes. Construimos seis letrinas de fosa, cada una con una trampa para moscas incluida, y evaluamos su eficiencia para atrapar las moscas en comparación con seis cajas‐trampa con pescado como cebo, localizadas a 10 m de la letrina. Se llevaron a cabo grupos de discusión focalizada después para evaluar la aceptación de las letrinas con trampas para moscas.
Resultados
El número de
C
. putoria
emergentes se redujo en un 96.0% (
IC
95%: 94.5–97.2%) 4–5 semanas después del tratamiento con piriproxifen; en un 64.2% (
IC
95%: 51.8–73.5%) después del tratamiento con jabón local; en un 41.3% (
IC
95% = 24.0–54.7%) tras el tratamiento con
PPE
, 3–5 semanas después del tratamiento. Las trampas de moscas localizadas en las letrinas recolectaron
C
. putoria
y fueron consideradas como aceptables por las comunidades locales.
Conclusiones
El Sumilarv 0.5G parece ser prometedor como agente de control químico, mientras que las letrinas con trampas de olor podrían ser útiles como método no químico para el control de las moscas. Ambos métodos garantizan un mayor desarrollo para reducir la producción de moscas de las letrinas de fosas. Una combinación de intervenciones podría ser efectiva para el control de las moscas de letrinas y la enfermedad que transmiten.
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