Practical robustness evaluation in radiotherapy - A photon and proton-proof alternative to PTV-based plan evaluation

Background and purpose: A planning target volume (PTV) in photon treatments aims to ensure that the clinical target volume (CTV) receives adequate dose despite treatment uncertainties. The underlying static dose cloud approximation (the assumption that the dose distribution is invariant to errors) is problematic in intensity modulated proton treatments where range errors should be taken into account as well. The purpose of this work is to introduce a robustness evaluation method that is applicable to photon and proton treatments and is consistent with (historic) PTV-base

Clinical implementation of a knowledge based planning tool for prostate VMAT

Abstract Background A knowledge based planning tool has been developed and implemented for prostate VMAT radiotherapy plans providing a target average rectum dose value based on previously achievable values for similar rectum/PTV overlap. The purpose of this planning tool is to highlight sub-optimal clinical plans and to improve plan quality and consistency. Methods A historical cohort of 97 VMAT prostate plans was interrogated using a RayStation script and used to develop a local model for predicting optimum average rectum dose based on individual anatomy. A preliminary validation study was performed whereby historical plans identified as “optimal” and “sub-optimal” by the local model were replanned in a blinded study by four experienced planners and compared to the original clinical plan to assess whether any improvement in rectum dose was observed. The predictive model was then incorporated into a RayStation script and used as part of the clinical planning process. Planners were asked to use the script during planning to provide a patient specific prediction for optimum average rectum dose and to optimise the plan accordingly. Results Plans identified as “sub-optimal” in the validation study observed a statistically significant improvement in average rectum dose compared to the clinical plan when replanned whereas plans that were identified as “optimal” observed no improvement when replanned. This provided confidence that the local model can identify plans that were suboptimal in terms of rectal sparing. Clinical implementation of the knowledge based planning tool reduced the population-averaged mean rectum dose by 5.6Gy. There was a small but statistically significant increase in total MU and femoral head dose and a reduction in conformity index. These did not affect the clinical acceptability of the plans and no significant changes to other plan quality metrics were observed. Conclusions The knowledge-based planning tool has enabled substantial reductions in population-averaged mean rectum dose for prostate VMAT patients. This suggests plans are improved when planners receive quantitative feedback on plan quality against historical data

Characterization and modulation of anti- αβTCR antibodies and their respective binding sites at the βTCR chain to enrich engineered T cells

T cell engineering strategies offer cure to patients and entered clinical practice with chimeric antibody-based receptors, αβT cell receptors (αβTCR)-based strategies are however lagging behind. To allow a more rapid and successful translation to successful concepts also using αβTCRs for engineering, incorporating a method for the purification of genetically modified T cells, as well as engineered T cell deletion after transfer into patients, could be beneficial. This would allow to increase efficacy, reduce potential side effects, and improve safety of newly, to be tested, lead structures. By characterizing the antigen binding interface of a GMP-grade anti-αβTCR antibody, usually used for depletion of αβT cells from stem cell transplantation products, we developed a strategy which allows for the purification of untouched αβTCR engineered immune cells by changing two amino acids only in the TCR β chain constant domain of introduced TCR chains. Vice versa, we engineered an antibody, which targets an extended mutated interface of nine amino acids in the TCR β chain constant domain, and provides the opportunity to further develop depletion strategies of engineered immune cells

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution

Polyamide 6-polycaprolactone multiblock copolymers : synthesis, characterization, and degradation

This work describes the synthesis and characterization of polyamide 6 (PA 6)-polycaprolactone (PCL) multiblock copolymers. Low molar mass, fully amine end-capped PA 6 was prepared by the addition of a diamine monomer during e-caprolactam polymerization. A low molar mass PCL was selected to be incorporated as the biodegradable block and was fully end-capped with toluene 2,4-diisocyanate. End group analysis and molecular weight characterizations were performed for both end-functionalized polymers by SEC, NMR and titration analysis. Incorporation of PCL into PA 6 was mainly achieved by solution mixing of the two end-functional blocks and, was continued after the removal of the solvent with solid state polymerization (SSP) by gradual heating until about 40 ??C below the melting temperature of the PA 6. Molecular weights started to grow immediately during solution mixing and only increased marginally during the SSP treatment. FTIR and SEC studies confirmed the reaction between the two components. DSC data, in combination with the enhanced molar mass during solution mixing pointed to a blocky microstructure, for which distinct melting and crystallization temperatures were observed for the PCL and the PA 6 blocks. Hydrolytic and enzymatic degradation studies were performed at 25 ??C where the degree of degradation was followed by weight loss analysis, SEM and SEC

Sturen op temperatuur- en vochtverschillen

Wageningen UR Glastuinbouw heeft op twee groente- en twee sierteeltbedrijven een draadloos sensorsysteem uitgeprobeerd. Door met meerdere sensoren te werken krijg je meer informatie over horizontale en verticale verschillen in temperatuur en vochtigheid, dan wanneer je alleen op de meetbox afgaat. Op de deelnemende bedrijven vonden de onderzoekers diverse ‘probleemplekken’. De sensoren zijn goedkoper dan de meetbox. Dat maakt het mogelijk op meer punten te meten en daarop te regelen. Deze aanpak kan daarmee energie besparen

Sturen op temperatuur- en vochtverschillen

Wageningen UR Glastuinbouw heeft op twee groente- en twee sierteeltbedrijven een draadloos sensorsysteem uitgeprobeerd. Door met meerdere sensoren te werken krijg je meer informatie over horizontale en verticale verschillen in temperatuur en vochtigheid, dan wanneer je alleen op de meetbox afgaat. Op de deelnemende bedrijven vonden de onderzoekers diverse ‘probleemplekken’. De sensoren zijn goedkoper dan de meetbox. Dat maakt het mogelijk op meer punten te meten en daarop te regelen. Deze aanpak kan daarmee energie besparen