Implementation of state-of-the-art (chemo)radiation for advanced cervix cancer in the Netherlands: A quality improvement program

Purpose: To report on the “Dutch Quality Improvement Project” regarding external beam (EBRT) and brachytherapy (BT) contouring and treatment planning for locally advanced cervical cancer (LACC). Material and methods: Two rounds of three workshops were organized. Data from two patients with LACC were made available for homework exercises. Contouring and treatment planning was asked for according to the EMBRACE-II protocol. The submissions were analysed and the results were addressed during the workshops. Results: Almost all invited centres participated. EBRT contouring guidelines were followed within acceptable range, with major effort needed with regard to the ITV concept. BT contouring was of good quality, with especially small discrepancies for centres already participating in EMBRACE.EBRT treatment planning results improved between workshops with more centres being able to fulfil the planning aims. Guidance was especially necessary to improve the coverage probability planning for affected nodes.For BT planning prioritizing between target coverage and OAR sparing improved over time; the variation in dose to vaginal points remained considerable, as did variation in loading patterns and spatial dose distribution.The project was highly appreciated by all participants. Conclusion: Homework and workshop activities provide a suitable platform for discussion, exchange of experience and improvement of quality and conformity. Due to this project, radiotherapy for LACC can be administered with better and more comparable quality throughout the Netherlands. Keywords: Quality assurance, Quality improvement, Education & trainin

Direct Observation of Chaperone-Induced Changes in a Protein Folding Pathway

How chaperone interactions affect protein folding pathways is a central problem in biology. With the use of optical tweezers and all-atom molecular dynamics simulations, we studied the effect of chaperone SecB on the folding and unfolding pathways of maltose binding protein (MBP) at the single-molecule level. In the absence of SecB, we find that the MBP polypeptide first collapses into a molten globulelike compacted state and then folds into a stable core structure onto which several α helices are finally wrapped. Interactions with SecB completely prevent stable tertiary contacts in the core structure but have no detectable effect on the folding of the external a helices. It appears that SecB only binds to the extended or molten globulelike structure and retains MBP in this latter state. Thus during MBP translocation, no energy is required to disrupt stable tertiary interactions.