23 research outputs found

    Quality of life in lung cancer survivors treated with tyrosine-kinase inhibitors (TKI) : results from the multi-centre cross-sectional German study LARIS

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    Purpose We aimed at exploring the quality of life (QOL) of lung cancer survivors with proven tyrosine-kinase receptor (RTK) genetic alterations and targeted tyrosine-kinase inhibitors (TKI) therapy, compared to lung cancer survivors with no-RTK alterations and no-TKI therapy. Methods Data were collected in a cross-sectional multi-centre study. Primary lung cancer survivors were asked about their socio-demographic and clinical information, QOL, symptom burden, and distress. QOL and symptom burden were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and distress with the Patient Health Questionnaire-4 (PHQ-4). Demographic and clinical characteristics were reported in absolute and relative frequencies, QOL, and symptom burden using mean scores. Diferences in mean scores with relative 95% confdence intervals were used for comparison. Results Three groups of survivors were defned: group A with proven RTK alterations, TKI therapy at any time during therapy, and stage IV lung cancer at diagnosis (n=49); group B: non-TKI therapy and stage IV lung cancer (n=121); group C: non-TKI therapy and stage I–III lung cancer (n=495). Survivors in group A reported lower QOL (mean score diference=-11.7 vs. group B) and symptom burden for dyspnoea (diference=-11.5 vs. group C), and higher symptom burden for appetite loss (diference= +11.4 vs. group C), diarrhoea and rash (diferences= +25.6,+19.6 and+13.2,+13.0, respectively, vs. both groups). Conclusions Our results suggest that the specifc side efects of TKI therapy can impair QOL among lung cancer survivors. Therefore, specifc focus towards the optimal management of these side efects should be considered

    Aryl hydrocarbon receptor is required for optimal B-cell proliferation

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    The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up‐regulated upon B‐cell receptor (BCR) engagement and IL‐4 treatment. Addition of a natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is functional in B cells. AhR‐deficient (Ahr (−/−)) B cells proliferate less than AhR‐sufficient (Ahr (+/+)) cells following in vitro BCR stimulation and in vivo adoptive transfer models confirmed that Ahr (−/−) B cells are outcompeted by Ahr (+/+) cells. Transcriptome comparison of AhR‐deficient and AhR‐sufficient B cells identified cyclin O (Ccno), a direct target of AhR, as a top candidate affected by AhR deficiency

    Efficacy and Toxicity of Different Chemotherapy Protocols for Concurrent Chemoradiation in Non-Small Cell Lung Cancer—A Secondary Analysis of the PET Plan Trial

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    (1) Background: The optimal chemotherapy (CHT) regimen for concurrent chemoradiation (cCRT) is not well defined. In this secondary analysis of the international randomized PET-Plan trial, we evaluate the efficacy of different CHT. (2) Methods: Patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume definition and received isotoxically dose-escalated cCRT using cisplatin 80 mg/m2 (day 1, 22) and vinorelbin 15 mg/m2 (day 1, 8, 22, 29) (P1) or cisplatin 20 mg/m2 (day 1–5, 29–33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P2) or carboplatin AUC1 (day 1–5, 29–33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P3) or other CHT at the treating physician’s discretion. (3) Results: Between 05/2009 and 11/2016, 205 patients were randomized and 172 included in the per-protocol analysis. Patients treated in P1 or P2 had a better overall survival (OS) compared to P3 (p = 0.015, p = 0.01, respectively). Patients treated with carboplatin had a worse OS compared to cisplatin (HR 1.78, p = 0.03), but the difference did not remain significant after adjusting for age, ECOG, cardiac function creatinine and completeness of CHT. (4) Conclusions: Carboplatin doublets show no significant difference compared to cisplatin, after adjusting for possibly relevant factors, probably due to existing selection bias

    Report on a Plus-Energy District with Low-Temperature DHC Network, Novel Agrothermal Heat Source, and Applied Demand Response

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    District heating and cooling networks can pose the possibility of including a variety of renewable energy sources as well as waste heat into a district’s heat supply concept. Unfortunately, low demand densities as they increasingly occur through higher building energy standards and in rural areas render conventional heating and cooling networks inefficient. At the same time, power-to-heat is becoming more and more important to make use of a larger amount of renewable energy sources on the electrical side by providing more flexibility by means of demand response and demand-side management. Within this work, a rural Plus-Energy settlement is presented addressing those topics by a low-temperature district heating and cooling network connected to a novel agrothermal collector supplying 23 residential buildings with decentralized heat pumps and PV systems. The collector, the network, and six of the buildings are equipped with comprehensive monitoring equipment. Within those buildings, forecast and optimization algorithms are implemented to adapt their heat pump operation to enable an increase of self-consumption, to include flexible electricity tariffs, and also to participate in power markets. Thereby, for the low-temperature district heating and cooling network, it has been shown that the concept can operate in the future at competitive heat costs. On the building level, up to 50% of cost savings could be achieved under ideal conditions with the optimization of the self-consumption of PV electricity. However, to ensure optimal results, the individual system components have to be dimensioned for this task

    Pediatric craniospinal irradiation with a short partial-arc VMAT technique for medulloblastoma tumors in dosimetric comparison

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    Background!#!This study aimed to contrast four different irradiation methods for pediatric medulloblastoma tumors in a dosimetric comparison regarding planning target volume (PTV) coverage and sparing of organs at risk (OARs).!##!Methods!#!In sum 24 treatment plans for 6 pediatric patients were realized. Besides the clinical standard of a 3D-conformal radiotherapy (3D-CRT) treatment plan taken as a reference, volumetric modulated arc therapy (VMAT) treatment plans ('VMAT_AVD' vs. 'noAVD' vs. 'FullArc') were optimized and calculated for each patient. For the thoracic and abdominal region, the short partial-arc VMAT_AVD technique uses an arc setup with reduced arc-length by 100°, using posterior and lateral beam entries. The noAVD uses a half 180° (posterior to lateral directions) and the FullArc uses a full 360° arc setup arrangement. The prescription dose was set to 35.2 Gy.!##!Results!#!We identified a more conformal dose coverage for PTVs and a better sparing of OARs with used VMAT methods. For VMAT_AVD mean dose reductions in organs at risk can be realized, from 16 to 6.6 Gy, from 27.1 to 8.7 Gy and from 8.0 to 1.9 Gy for the heart, the thyroid and the gonads respectively, compared to the 3D-CRT treatment method. In addition we have found out a superiority of VMAT_AVD compared to the noAVD and FullArc trials with lower exposure to low-dose radiation to the lungs and breasts.!##!Conclusions!#!With the short partial-arc VMAT_AVD technique, dose exposures to radiosensitive OARS like the heart, the thyroid or the gonads can be reduced and therefore, maybe the occurrence of late sequelae is less likely. Furthermore the PTV conformity is increased. The advantages of the VMAT_AVD have to be weighed against the potentially risks induced by an increased low dose exposure compared to the 3D-CRT method

    ORIGINAL ARTICLE Correcting False Gene Expression Measurements From Degraded RNA Using RTQ-PCR

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    Abstract: This paper describes a method allowing correcting false gene expression measured on highly degraded RNA using real-time quantitative reverse transcription-polymerase chain reaction (RTQ-PCR). RNA was isolated from different models (in vitro cell lines, in vivo models of human and dog) and different tissue types. In vitro RNA degradation and modeling of in vivo degradation were applied on intact and degraded total RNA. Gene expression (eg, Bcl-2, GAPDH, PGK, PSME3, RAB2, BAX) was measured using RTQ-PCR. 18S rRNA proved to be the most constant house-keeping gene. Less than 10-fold degraded RNA can be quantified correctly when using 18S rRNA for normalization purposes. Higher-fold degraded RNA can be quantified correctly up to a precision that is comparable to RTQ-PCR measurements on intact RNA when simulating the RNA-species and tissue-specific degradation kinetic. Key Words: RNA degradation, RTQ-PCR, correction of false gene expression measurements, house-keeping genes, simulation of RNA degradation (Diagn Mol Pathol 2007;16:38–49) With the advent of molecular biologic methods, it became desirable to apply these potent methods to archival paraffin-embedded tissue samples. Isolation of RNA in particular seemed to be interesting, because expression alterations caused by gene abnormalities like deletions, structural alterations, rearrangements, and amplifications are associated with certain diseases suc

    Heart atlas for retrospective cardiac dosimetry: a multi-institutional study on interobserver contouring variations and their dosimetric impact

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    Purpose!#!Cardiac effects after breast cancer radiation therapy potentially affect more patients as survival improves. The heart's heterogeneous radiation exposure and composition of functional structures call for establishing individual relationships between structure dose and specific late effects. However, valid dosimetry requires reliable contouring which is challenging for small volumes based on older, lower-quality computed tomography imaging. We developed a heart atlas for robust heart contouring in retrospective epidemiologic studies.!##!Methods and materials!#!The atlas defined the complete heart and geometric surrogate volumes for six cardiac structures: aortic valve, pulmonary valve, all deeper structures combined, myocardium, left anterior myocardium, and right anterior myocardium. We collected treatment planning records from 16 patients from 4 hospitals including dose calculations for 3D conformal tangential field radiation therapy for left-sided breast cancer. Six observers each contoured all patients. We assessed spatial contouring agreement and corresponding dosimetric variability.!##!Results!#!Contouring agreement for the complete heart was high with a mean Jaccard similarity coefficient (JSC) of 89%, a volume coefficient of variation (CV) of 5.2%, and a mean dose CV of 4.2%. The left (right) anterior myocardium had acceptable agreement with 63% (58%) JSC, 9.8% (11.5%) volume CV, and 11.9% (8.0%) mean dose CV. Dosimetric agreement for the deep structures and aortic valve was good despite higher spatial variation. Low spatial agreement for the pulmonary valve translated to poor dosimetric agreement.!##!Conclusions!#!For the purpose of retrospective dosimetry based on older imaging, geometric surrogate volumes for cardiac organs at risk can yield better contouring agreement than anatomical definitions, but retain limitations for small structures like the pulmonary valve
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