Radical radiotherapy for paediatric solid tumour metastases:An overview of current European protocols and outcomes of a SIOPE multicenter survey

Purpose/objective: About 20% of children with solid tumours (ST) present with distant metastases (DM). Evidence regarding the use of radical radiotherapy of these DM is sparse and open for personal interpretation. The aim of this survey was to review European protocols and to map current practice regarding the irradiation of DM across SIOPE-affiliated countries. Materials/methods: Radiotherapy guidelines for metastatic sites (bone, brain, distant lymph nodes, lung and liver) in eight European protocols for rhabdomyosarcoma, non-rhabdomyosarcoma soft-tissue sarcoma, Ewing sarcoma, neuroblastoma and renal tumours were reviewed. SIOPE centres irradiating >= 50 children annually were invited to participate in an online survey. Results: Radiotherapy to at least one metastatic site was recommended in all protocols, except for high-risk neuroblastoma. Per protocol, dose prescription varied per site, and information on delineation and treatment planning/delivery was generally missing. Between July and September 2019, 20/27 centres completed the survey. Around 14% of patients were deemed to have DM from ST at diagnosis, of which half were treated with curative intent. A clear cut-off for a maximum number of DM was not used in half of the centres. Regardless of the tumour type and site, conventional radiotherapy regimens were most commonly used to treat DM. When stereotactic radiotherapy was used, a wide range of fractionation regimens were applied. Conclusion: Current radiotherapy guidelines for DM do not allow a consistent approach in a multicentre setting. Prospective (randomised) trials are needed to define the role of radical irradiation of DM from paediatric ST. (C) 2020 The Author(s). Published by Elsevier Ltd

Mycobacterium abscessus-Induced Granuloma Formation Is Strictly Dependent on TNF Signaling and Neutrophil Trafficking

Mycobacterium abscessus is considered the most common respiratory pathogen among the rapidly growing non-tuberculous mycobacteria. Infections with M. abscessus are increasingly found in patients with chronic lung diseases, especially cystic fibrosis, and are often refractory to antibiotic therapy. M. abscessus has two morphotypes with distinct effects on host cells and biological responses. The smooth (S) variant is recognized as the initial airway colonizer while the rough (R) is known to be a potent inflammatory inducer associated with invasive disease, but the underlying immunopathological mechanisms of the infection remain unsolved. We conducted a comparative stepwise dissection of the inflammatory response in S and R pathogenesis by monitoring infected transparent zebrafish embryos. Loss of TNFR1 function resulted in increased mortality with both variants, and was associated with unrestricted intramacrophage bacterial growth and decreased bactericidal activity. The use of transgenic zebrafish lines harboring fluorescent macrophages and neutrophils revealed that neutrophils, like macrophages, interact with M. abscessus at the initial infection sites. Impaired TNF signaling disrupted the IL8-dependent neutrophil mobilization, and the defect in neutrophil trafficking led to the formation of aberrant granulomas, extensive mycobacterial cording, unrestricted bacterial growth and subsequent larval death. Our findings emphasize the central role of neutrophils for the establishment and maintenance of the protective M. abscessus granulomas. These results also suggest that the TNF/IL8 inflammatory axis is necessary for protective immunity against M. abscessus and may be of clinical relevance to explain why immunosuppressive TNF therapy leads to the exacerbation of M. abscessus infections

Prognostication and monitoring of mesothelioma using biomarkers:a systematic review

Background: Radiological markers of treatment response and prognostication in malignant pleural mesothelioma have limitations due to the morphology of the disease. Serum or pleural fluid biomarkers that could act as an adjunct to radiological assessment would be of significant value. The aim of this review was to collate and summarise the literature relating to this topic. Methods: A systematic review was performed on the databases Pubmed and EMBASE to identify relevant studies. Two independent researchers read the abstracts and used the Quality in Prognostic Studies tool to assess the quality of the evidence. Results: Forty-five studies were identified from the current literature. Twenty studies investigated the role of serum soluble mesothelin with majority suggesting that it has variable utility as a baseline test but when measured serially correlates with treatment response and prognosis. Several studies demonstrated that serum osteopontin correlated with survival at baseline. Other biomarkers have shown prognostic utility in individual studies but are yet to be reproduced in large cohort studies. Conclusions: From the available literature no serum or pleural fluid biomarker was identified that could be recommended currently for routine clinical practice. However, a falling serum soluble mesothelin might correlate with treatment response and improved survival

Characterization of Fe-Nb-B Base Hardfacing of Steel

Recently hardfacing by welding has become a commonly used technique for improvement of material performance in extreme (high temperature, impact/abrasion, erosion, etc.) conditions. In the present study, three different alloy compositions of the Fe-Nb-B were used for hardfacing of the AISI 1020 steel by tungsten inert gas welding process and analyzed. The coatings were produced from a mixture of ferrous niobium, ferrous boron and iron powders in the range of - 45 μm particle size with different ratio. The coatings' thickness was set to 2-3 mm on the substrate. Microstructure, phase analysis and hardness of the manufactured hardfacing alloys were characterized. Deposition results indicate good quality thick coating and porosity free of the hardfacings. X-ray diffraction analyses showed that the alloyed layers include iron borides, FeNbB and iron phases. It was shown that surface alloyed layer has composite structure including steel matrix and well distributed boride phases

The incidence of mesothelioma has not decreased for the last twenty years in Southeast region of Anatolia

Background: Malignant pleural Mesothelioma (MPM) is a very rarely encountered tumor in the normal population. Objectives: To investigate the variations in incidence of MPM in Southeast region of Turkey. Methods: We retrospectively investigated the data of 161 MPM patients who were diagnosed from January 2000 to December 2009. The residential areas were determined according to asbestos exposure which plays a role in MPM etiology; previously reported as having asbestos (Region 1) and asbestos has not been determined previously (Region 2). Results: One hundred nine (109) of the patients (67.7%) included from the Region 1 and 52 of them (32.3%) included from the Region 2. MPM incidence of the last decade was 3.9/100,000 person/year for the whole region. In Region 1, 20002004 incidences was 12.6/100,000 person/year and 2005-2009 incidences was 14.9/100,000 person/year. In Region 2, 2000- 2004 incidences was 0.4/100,000 person/year and 2005-2009 incidences was 1.0/100,000 person/year. According to the recently conducted incidence studies in our region, MPM incidence increased in region 1 and decreased in region 2. The number of patients applying to our hospital has increased in the last three years. Conclusion: This increase, in Region 1 may be associated with continuous use of asbestos