Management of the neck in T1 and T2 buccal squamous cell carcinoma.

Buccal squamous cell carcinoma (SCC) appears to behave more aggressively than other oral subsites, in particular with regards to regional disease at presentation and regional recurrence. Adequate management of the neck is of the utmost importance but is still the subject of debate. An international multicentre retrospective review of 101 patients treated for T1-T2 buccal SCC was performed. Twenty-four were staged clinical node positive (cN+) and underwent therapeutic neck dissection, while 77 were node negative (cN0), with 32 undergoing elective neck dissection (END), with an occult nodal metastasis rate of 28.1%. Depth of invasion (DOI) < 4 mm was associated with a significantly lower rate of cervical nodal metastasis (87.5% versus 12.5%; P = 0.033). END demonstrated a non-significantly lower regional recurrence rate compared to observation (6.3% versus 8.9%, P = 0.670). Regional recurrence was more common in pN+ (24%) and undissected cases (8.9%) than in pN0 patients (0%) (P = 0.011) and was associated with DOI > 5 mm (P = 0.002). Regional recurrence resulted in a reduction in survival (24 versus 93 months, P < 0.001). In the pT2cN0 group, END improved survival (123 versus 26 months, P = 0.009). It is suggested that END be performed in cT2N0 buccal SCC, particularly for tumours with DOI > 4 mm.

Blanket antimicrobial resistance gene database with structural information, BOARDS, provides insights on historical landscape of resistance prevalence and effects of mutations in enzyme structure.

Antimicrobial resistance (AMR) in pathogenic bacteria poses a significant threat to public health, yet there is still a need for development in the tools to deeply understand AMR genes based on genetic or structural information. In this study, we present an interactive web database named Blanket Overarching Antimicrobial-Resistance gene Database with Structural information (BOARDS, sbml.unist.ac.kr), a database that comprehensively includes 3,943 reported AMR gene information for 1,997 extended spectrum beta-lactamase (ESBL) and 1,946 other genes as well as a total of 27,395 predicted protein structures. These structures, which include both wild-type AMR genes and their mutants, were derived from 80,094 publicly available whole-genome sequences. In addition, we developed the rapid analysis and detection tool of antimicrobial-resistance (RADAR), a one-stop analysis pipeline to detect AMR genes across whole-genome sequencing (WGSs). By integrating BOARDS and RADAR, the AMR prevalence landscape for eight multi-drug resistant pathogens was reconstructed, leading to unexpected findings such as the pre-existence of the MCR genes before their official reports. Enzymatic structure prediction-based analysis revealed that the occurrence of mutations found in some ESBL genes was found to be closely related to the binding affinities with their antibiotic substrates. Overall, BOARDS can play a significant role in performing in-depth analysis on AMR.IMPORTANCEWhile the increasing antibiotic resistance (AMR) in pathogen has been a burden on public health, effective tools for deep understanding of AMR based on genetic or structural information remain limited. In this study, a blanket overarching antimicrobial-resistance gene database with structure information (BOARDS)-a web-based database that comprehensively collected AMR gene data with predictive protein structural information was constructed. Additionally, we report the development of a RADAR pipeline that can analyze whole-genome sequences as well. BOARDS, which includes sequence and structural information, has shown the historical landscape and prevalence of the AMR genes and can provide insight into single-nucleotide polymorphism effects on antibiotic degrading enzymes within protein structures.

What does "Advanced" mean in 2023? reflecting on 10 years of the ESTRO advanced Skills in modern radiotherapy course.

The roles and responsibilities of radiation therapists (RTTs) are many and varied. Professional expectations are influenced by the technology available, as well as the level of autonomy RTTs have in their daily practice. This professional range requires RTTs to possess a unique set of ever evolving skills, posing challenges from an educational perspective. Teaching these "advanced skills" has been the ambition the ESTRO Advanced Skills in Modern Radiotherapy course. In the 10th year of this course, the Faculty look back and reflect on how our programme has evolved and what it has achieved.

Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

Quality improvements of healthcare trajectories by learning from aggregated patient-reported outcomes: a mixed-methods systematic literature review.

BACKGROUND: In healthcare, analysing patient-reported outcome measures (PROMs) on an aggregated level can improve and regulate healthcare for specific patient populations (meso level). This mixed-methods systematic review aimed to summarize and describe the effectiveness of quality improvement methods based on aggregated PROMs. Additionally, it aimed to describe barriers, facilitators and lessons learned when using these quality improvement methods. METHODS: A mixed-methods systematic review was conducted. Embase, MEDLINE, CINAHL and the Cochrane Library were searched for studies that described, implemented or evaluated a quality improvement method based on aggregated PROMs in the curative hospital setting. Quality assessment was conducted via the Mixed Methods Appraisal Tool. Quantitative data were synthesized into a narrative summary of the characteristics and findings. For the qualitative analysis, a thematic synthesis was conducted. RESULTS: From 2360 unique search records, 13 quantitative and three qualitative studies were included. Four quality improvement methods were identified: benchmarking, plan-do-study-act cycle, dashboards and internal statistical analysis. Five studies reported on the effectiveness of the use of aggregated PROMs, of which four identified no effect and one a positive effect. The qualitative analysis identified the following themes for facilitators and barriers: (1) conceptual (i.e. stakeholders, subjectivity of PROMs, aligning PROMs with clinical data, PROMs versus patient-reported experience measures [PREMs]); (2a) methodological-data collection (i.e. choice, timing, response rate and focus); (2b) methodological-data processing (i.e. representativeness, responsibility, case-mix control, interpretation); (3) practical (i.e. resources). CONCLUSION: The results showed little to no effect of quality improvement methods based on aggregated PROMs, but more empirical research is needed to investigate different quality improvement methods. A shared stakeholder vision, selection of PROMs, timing of measurement and feedback, information on interpretation of data, reduction of missing data, and resources for data collection and feedback infrastructure are important to consider when implementing and evaluating quality improvement methods in future research.

The complementary value of intraoperative fluorescence imaging and Raman spectroscopy for cancer surgery: combining the incompatibles.

A clear margin is an important prognostic factor for most solid tumours treated by surgery. Intraoperative fluorescence imaging using exogenous tumour-specific fluorescent agents has shown particular benefit in improving complete resection of tumour tissue. However, signal processing for fluorescence imaging is complex, and fluorescence signal intensity does not always perfectly correlate with tumour location. Raman spectroscopy has the capacity to accurately differentiate between malignant and healthy tissue based on their molecular composition. In Raman spectroscopy, specificity is uniquely high, but signal intensity is weak and Raman measurements are mainly performed in a point-wise manner on microscopic tissue volumes, making whole-field assessment temporally unfeasible. In this review, we describe the state-of-the-art of both optical techniques, paying special attention to the combined intraoperative application of fluorescence imaging and Raman spectroscopy in current clinical research. We demonstrate how these techniques are complementary and address the technical challenges that have traditionally led them to be considered mutually exclusive for clinical implementation. Finally, we present a novel strategy that exploits the optimal characteristics of both modalities to facilitate resection with clear surgical margins.

Assessment of the association between dust storms and COVID-19 infection rate in southwest Iran.

This study assesses a plausible correlation between a dust intrusion episode and a daily increase in COVID-19 cases. A surge in COVID-19 cases was observed a few days after a Middle East Dust (MED) event that peaked on 25th April 2020 in southwest Iran. To investigate potential causal factors for the spike in number of cases, cross-correlations between daily combined aerosol optical depths (AODs) and confirmed cases were computed for Khuzestan, Iran. Additionally, atmospheric stability data time series were assessed by covering before, during, and after dust intrusion, producing four statistically clustered distinct city groups. Groups 1 and 2 had different peak lag times of 10 and 4-5 days, respectively. Since there were statistically significant associations between AOD levels and confirmed cases in both groups, dust incursion may have increased population susceptibility to COVID-19 disease. Group 3 was utilized as a control group with neither a significant level of dust incursion during the episodic period nor any significant associations. Group 4 cities, which experienced high dust incursion levels, showed no significant correlation with confirmed case count increases. Random Forest Analysis assessed the influence of wind speed and AOD, showing relative importance of 0.31 and 0.23 on the daily increase percent of confirmed cases, respectively. This study may serve as a reference for better understanding and predicting factors affecting COVID-19 transmission and diffusion routes, focusing on the role of MED intrusions.

Laboratory Evaluation of Mechanical Properties of Modified Asphalt and Mixture Using Graphene Platelets (GnPs).

Recently, nanomaterials have attracted attention in the field of pavement construction as modifiers to endure heavy loads and climate changes. In this study, conventional asphalt (bitumen) of penetration grade AC (60/70) was modified with graphene platelets (GnPs) at three different contents: 0.5%, 1.0%, and 1.5% by weight of asphalt content. Kinematic viscosity, softening point, penetration, and dynamic shear rheology tests were performed to evaluate the mechanical properties of modified binder. The results showed that adding GnPs improves the mechanical properties of asphalt binder; the kinematic viscosities, softening points, and rutting parameters increased but penetrations decreased with the contents of GnPs. Hot mix asphalt specimens with GnPs-modified asphalt were prepared and characterized with Marshall tests, thermal stress restrained specimen tests (TSRST), wheel tracking tests, and indirect tensile tests. Similar to the results of asphalt binder, the mechanical properties of asphalt mixture were improved by GnPs. Marshall stability increased by 21% and flow decreased by 24% with accepted value of 2.8 mm in penetration when the mixture was modified with 1.0 wt% of GnPs. At the same GnPs content, modified asphalt mixture led to lower failure temperature by 2 °C in comparison with unmodified asphalt mixture and the cryogenic failure stress was improved by 12%. The wheel tracking tests showed that GnPs-modified asphalt mixture has outstanding deformation resistance in comparison with unmodified asphalt mixtures: after 5000 cycles, 1.0 wt% of GnPs reduced the rut depth of asphalt mixture by 60%-the rut depth of unmodified asphalt mixture was 6.9 mm compared to 2.75 mm for modified asphalt mixture. After 10,000 cycles, the modified asphalt mixture showed rut depth of 3.24 mm in comparison with 8.12 mm in case of unmodified asphalt mixture. Addition of GnPs into asphalt mixture significantly improved the indirect tensile strength: 1.0 wt% of GnPs increased the indirect tensile strength of unmodified asphalt mixture from 0.79 to 1.1 MPa recording ~40% increment. The results of this study can confirm that graphene platelets enhance the mechanical properties of asphalt mixture and its performance.

Reasons for not reaching or using web-based self-management applications, and the use and evaluation of Oncokompas among cancer survivors, in the context of a randomised controlled trial.

INTRODUCTION: The web-based self-management application Oncokompas was developed to support cancer survivors to monitor health-related quality of life and symptoms (Measure) and to provide tailored information (Learn) and supportive care options (Act). In a previously reported randomised controlled trial (RCT), 68% of 655 recruited survivors were eligible, and of those 45% participated in the RCT. Among participants of the RCT that were randomised to the intervention group, 52% used Oncokompas as intended. The aim of this study was to explore reasons for not participating in the RCT, and reasons for not using Oncokompas among non-users, and the use and evaluation of Oncokompas among users. METHODS: Reasons for not participating were assessed with a study-specific questionnaire among 243 survivors who declined participation. Usage was investigated among 320 participants randomised to the intervention group of the RCT via system data and a study-specific questionnaire that was assessed during the 1 week follow-up (T1) assessment. RESULTS: Main reasons for not participating were not interested in participation in scientific research (40%) and not interested in scientific research and Oncokompas (28%). Main reasons for not being interested in Oncokompas were wanting to leave the period of being ill behind (29%), no symptom burden (23%), or lacking internet skills (18%). Out of the 320 participants in the intervention group 167 (52%) used Oncokompas as intended. Among 72 non-users, main reasons for not using Oncokompas were no symptom burden (32%) or lack of time (26%). Among 248 survivors that activated their account, satisfaction and user-friendliness were rated with a 7 (scale 0-10). Within 3 (IQR 1-4) sessions, users selected 32 (IQR 6-37) topics. Main reasons for not using healthcare options in Act were that the information in Learn was already sufficient (44%) or no supportive care needs (32%). DISCUSSION: Main reasons for not reaching or using Oncokompas were no symptom burden, no supportive care needs, or lack of time. Users selected many cancer-generic and tumour-specific topics to address, indicating added value of the wide range of available topics.

Statistical and Reliability Study on Shear Strength of Recycled Coarse Aggregate Reinforced Concrete Beams.

The consumption of structural concrete in the construction industry is rapidly growing, and concrete will remain the main construction material for increasing urbanization all over the world in the near future. Meanwhile, construction and demolition waste from concrete structures is also leading to a significant environmental problem. Therefore, a proper sustainable solution is needed to address this environmental concern. One of the solutions can be using recycled coarse aggregates (RCA) in reinforced concrete (RC) structures. Extensive research has been conducted in this area in recent years. However, the usage of RCA concrete in the industry is still limited due to the absence of structural regulations appropriate to the RCA concrete. This study addresses a safety margin of RCA concrete beams in terms of shear capacity which is comparable to natural coarse aggregates (NCA) concrete beams. To this end, a database for reinforced concrete beams made of recycled coarse aggregates with and without shear reinforcement was established, collecting the shear specimens available from various works in the existing literature. The database was used to statistically identify the strength margin between RCA and NCA concrete beams and to calculate its safety margin based on reliability analysis. Moreover, a comparability study of RCA beams was conducted with its control specimens and with a database for conventional RC beams.

B-cell clusters at the invasive margin associate with longer survival in early-stage oral-tongue cancer patients.

In oral-cancer, the number of tumor-infiltrating lymphocytes (TILs) associates with improved survival, yet the prognostic value of the cellular composition and localization of TILs is not defined. We quantified densities, localizations, and cellular networks of lymphocyte populations in 138 patients with T1-T2 primary oral-tongue squamous cell carcinoma treated with surgical resections without any perioperative (chemo)radiotherapy, and correlated outcomes to overall survival (OS). Multiplexed in-situ immunofluorescence was performed for DAPI, CD4, CD8, CD20, and pan-cytokeratin using formalin-fixed paraffin-embedded sections, and spatial distributions of lymphocyte populations were assessed in the tumor and stroma compartments at the invasive margin (IM) as well as the center of tumors. We observed a high density of CD4, CD8, and CD20 cells in the stroma compartment at the IM, but neither lymphocyte densities nor networks as single parameters associated with OS. In contrast, assessment of two contextual parameters within the stroma IM region of tumors, i.e., the number of CD20 cells within 20 µm radii of CD20 and CD4 cells, termed the CD20 Cluster Score, yielded a highly significant association with OS (HR 0.38; p = .003). Notably, the CD20 Cluster Score significantly correlated with better OS and disease-free survival in multivariate analysis (HR 0.34 and 0.47; p = .001 and 0.019) as well as with lower local recurrence rate (OR: 0.13; p = .028). Taken together, our study showed that the presence of stromal B-cell clusters at IM, in the co-presence of CD4 T-cells, associates with good prognosis in early oral-tongue cancer patients.

Identification of IgG1 isotype phosphorylcholine antibodies for the treatment of inflammatory cardiovascular diseases.

BACKGROUND: Phosphorylcholine (PC) is an important pro-inflammatory damage-associated molecular pattern. Previous data have shown that natural IgM anti-PC protects against cardiovascular disease. We aimed to develop a monoclonal PC IgG antibody with anti-inflammatory and anti-atherosclerotic properties. METHODS: Using various techniques PC antibodies were validated and optimized. In vivo testing was performed in a femoral artery cuff model in ApoE3*Leiden mice. Safety studies are performed in rats and cynomolgus monkeys. RESULTS: A chimeric anti-PC (PC-mAb(T15), consisting of a human IgG1 Fc and a mouse T15/E06 Fab) was produced, and this was shown to bind specifically to epitopes in human atherosclerotic tissues. The cuff model results in rapid induction of inflammatory genes and altered expression of genes associated with ER stress and choline metabolism in the lesions. Treatment with PC-mAb(T15) reduced accelerated atherosclerosis via reduced expression of endoplasmic reticulum stress markers and CCL2 production. Recombinant anti-PC Fab fragments were identified by phage display and cloned into fully human IgG1 backbones creating a human monoclonal IgG1 anti-PC (PC-mAbs) that specifically bind PC, apoptotic cells and oxLDL. Based on preventing macrophage oxLDL uptake and CCL2 production, four monoclonal PC-mAbs were selected, which to various extent reduced vascular inflammation and lesion development. Additional optimization and validation of two PC-mAb antibodies resulted in selection of PC-mAb X19-A05, which inhibited accelerated atherosclerosis. Clinical grade production of this antibody (ATH3G10) significantly attenuated vascular inflammation and accelerated atherosclerosis and was tolerated in safety studies in rats and cynomolgus monkeys. CONCLUSIONS: Chimeric anti-PCs can prevent accelerated atherosclerosis by inhibiting vascular inflammation directly and through reduced macrophage oxLDL uptake resulting in decreased lesions. PC-mAb represents a novel strategy for cardiovascular disease prevention.

The eHealth self-management application 'Oncokompas' that supports cancer survivors to improve health-related quality of life and reduce symptoms: which groups benefit most?

BACKGROUND: Oncokompas is a web-based self-management application that supports cancer survivors to monitor their health-related quality of life (HRQOL) and symptoms, and to obtain personalised feedback and tailored options for supportive care. In a large randomised controlled trial among survivors of head and neck cancer, colorectal cancer, and breast cancer and (non-)Hodgkin lymphoma, Oncokompas proved to improve HRQOL, and to reduce several tumour-specific symptoms. Effect sizes were however small, and no effect was observed on the primary outcome patient activation. Therefore, this study aims to explore which subgroups of cancer survivors may especially benefit from Oncokompas. MATERIALS AND METHODS: Cancer survivors (n = 625) were randomly assigned to the intervention group (access to Oncokompas, n = 320) or control group (6 months waiting list, n = 305). Outcome measures were HRQOL, tumour-specific symptoms, and patient activation. Potential moderators included socio-demographic (sex, age, marital status, education, employment), clinical (tumour type, stage, time since diagnosis, treatment modality, comorbidities), and personal factors (self-efficacy, personal control, health literacy, Internet use), and patient activation, mental adjustment to cancer, HRQOL, symptoms, and need for supportive care, measured at baseline. Linear mixed models were performed to investigate potential moderators. RESULTS: The intervention effect on HRQOL was the largest among cancer survivors with low to moderate self-efficacy, and among those with high personal control and those with high health literacy scores. Cancer survivors with higher baseline symptom scores benefitted more on head and neck (pain in the mouth, social eating, swallowing, coughing, trismus), and colorectal cancer (weight) specific symptoms. DISCUSSION: Oncokompas seems most effective in reducing symptoms in head and neck cancer and colorectal cancer survivors who report a higher burden of tumour-specific symptoms. Oncokompas seems most effective in improving HRQOL in cancer survivors with lower self-efficacy, and in cancer survivors with higher personal control, and higher health literacy.

Cost-utility of an eHealth application 'Oncokompas' that supports cancer survivors in self-management: results of a randomised controlled trial.

PURPOSE: The eHealth self-management application 'Oncokompas' was developed to support cancer survivors in monitoring health-related quality of life (HRQOL) and symptoms, and obtaining personalized feedback and options for supportive care. The aim of this study was to assess the cost-utility of Oncokompas compared with care as usual (CAU) among cancer survivors. METHODS: Survivors were randomly allocated to the intervention or control group. Direct (non-)medical, indirect non-medical costs, and HRQOL were measured at 3- and 6-month follow-up, using iMTA Medical Consumption and Productivity Costs and the EuroQol-5D questionnaires. Mean cumulative costs and quality-adjusted life-years (QALYs) were compared between both groups. RESULTS: In total, 625 survivors were randomized into intervention (n = 320) or control group (n = 305). Base case analysis showed that incremental costs from a societal perspective were - €163 (95% CI, - 665 to 326), and incremental QALYs were 0.0017 (95% CI, - 0.0121 to 0.0155) in the intervention group compared with those in the control group. The probability that, compared with CAU, Oncokompas is more effective was 60%, less costly 73%, and both more effective and less costly 47%. Sensitivity analyses showed that incremental costs vary between - €40 and €69, and incremental QALYs vary between - 0.0023 and - 0.0057. CONCLUSION: Oncokompas is likely to be equally effective on utilities, and not more expensive than CAU, and will therefore contribute to sustainable cancer survivorship care in a (cost-)effective manner. IMPLICATIONS FOR CANCER SURVIVORS: Oncokompas seems to improve HRQOL and reduces the burden of several tumour-specific symptoms, while costs from a societal perspective are similar to CAU.

Evaluation of Ultra-low-dose Paediatric Cone-beam Computed Tomography for Image-guided Radiotherapy.

AIMS: In image-guided radiotherapy, daily cone-beam computed tomography (CBCT) is rarely applied to children due to concerns over imaging dose. Simulating low-dose CBCT can aid clinical protocol design by allowing visualisation of new scan protocols in patients without delivering additional dose. This work simulated ultra-low-dose CBCT and evaluated its use for paediatric image-guided radiotherapy by assessment of image registration accuracy and visual image quality. MATERIALS AND METHODS: Ultra-low-dose CBCT was simulated by adding the appropriate amount of noise to projection images prior to reconstruction. This simulation was validated in phantoms before application to paediatric patient data. Scans from 20 patients acquired at our current clinical protocol (0.8 mGy) were simulated for a range of ultra-low doses (0.5, 0.4, 0.2 and 0.125 mGy) creating 100 scans in total. Automatic registration accuracy was assessed in all 100 scans. Inter-observer registration variation was next assessed for a subset of 40 scans (five scans at each simulated dose and 20 scans at the current clinical protocol). This subset was assessed for visual image quality by Likert scale grading of registration performance and visibility of target coverage, organs at risk, soft-tissue structures and bony anatomy. RESULTS: Simulated and acquired phantom scans were in excellent agreement. For patient scans, bony atomy registration discrepancies for ultra-low-dose scans fell within 2 mm (translation) and 1° (rotation) compared with the current clinical protocol, with excellent inter-observer agreement. Soft-tissue registration showed large discrepancies. Bone visualisation and registration performance reached over 75% acceptability (rated 'well' or 'very well') down to the lowest doses. Soft-tissue visualisation did not reach this threshold for any dose. CONCLUSION: Ultra-low-dose CBCT was accurately simulated and evaluated in patient data. Patient scans simulated down to 0.125 mGy were appropriate for bony anatomy set-up. The large dose reduction could allow for more frequent (e.g. daily) image guidance and, hence, more accurate set-up for paediatric radiotherapy.

Structural brain differences in pre-adolescents who persist in and recover from stuttering.

BACKGROUND: Stuttering is a complex speech fluency disorder occurring in childhood. In young children, stuttering has been associated with speech-related auditory and motor areas of the brain. During transition into adolescence, the majority of children who stutter (75-80%) will experience remission of their symptoms. The current study evaluated brain (micro-)structural differences between pre-adolescents who persisted in stuttering, those who recovered, and fluently speaking controls. METHODS: This study was embedded in the Generation R Study, a population-based cohort in the Netherlands of children followed from pregnancy onwards. Neuroimaging was performed in 2211 children (mean age: 10 years, range 8-12), of whom 20 persisted in and 77 recovered from stuttering. Brain structure (e.g., gray matter) and microstructure (e.g., diffusion tensor imaging) differences between groups were tested using multiple linear regression. RESULTS: Pre-adolescents who persisted in stuttering had marginally lower left superior frontal gray matter volume compared to those with no history of stuttering (ß -1344, 95%CI -2407;-280), and those who recovered (ß -1825, 95%CI -2999;-650). Pre-adolescents who recovered, compared to those with no history of stuttering, had higher mean diffusivity in the forceps major (ß 0.002, 95%CI 0.001;0.004), bilateral superior longitudinal fasciculi (ß 0.001, 95%CI 0.000;0.001), left corticospinal tract (ß 0.003, 95%CI 0.002;0.004), and right inferior longitudinal fasciculus (ß 0.001, 95%CI 0.000;0.001). CONCLUSION: Findings suggest that relatively small difference in prefrontal gray matter volume is associated with persistent stuttering, and alterations in white matter tracts are apparent in individuals who recovered. The findings further strengthen the potential relevance of brain (micro-)structure in persistence and recovery from stuttering in pre-adolescents.

Online adaptive radiotherapy compared to plan selection for rectal cancer: quantifying the benefit.

BACKGROUND: To compare online adaptive radiation therapy (ART) to a clinically implemented plan selection strategy (PS) with respect to dose to the organs at risk (OAR) for rectal cancer. METHODS: The first 20 patients treated with PS between May-September 2016 were included. This resulted in 10 short (SCRT) and 10 long (LCRT) course radiotherapy treatment schedules with a total of 300 Conebeam CT scans (CBCT). New dual arc VMAT plans were generated using auto-planning for both the online ART and PS strategy. For each fraction bowel bag, bladder and mesorectum were delineated on daily Conebeam CTs. The dose distribution planned was used to calculate daily DVHs. Coverage of the CTV was calculated, as defined by the dose received by 99% of the CTV volume (D99%). The volume of normal tissue irradiated with 95% of the prescribed fraction dose was calculated by calculating the volume receiving 95% of the prescribed fraction or more dose minus the volume of the CTV. For each fraction the difference between the plan selection and online adaptive strategy of each DVH parameter was calculated, as well as the average difference per patient. RESULTS: Target coverage remained the same for online ART. The median volume of the normal tissue irradiated with 95% of the prescribed dose dropped from 642 cm3 (PS) to 237 cm3 (online-ART)(p < 0.001). Online ART reduced dose to the OARs for all tested dose levels for SCRT and LCRT (p < 0.001). For V15Gy of the bowel bag the median difference over all fractions of all patients was - 126 cm3 in LCRT, while the average difference per patient ranged from - 206 cm3 to - 40 cm3. For SCRT the median difference was - 62 cm3, while the range of the average difference per patient was - 105 cm3 to - 51 cm3. For V15Gy of the bladder the median difference over all fractions of all patients was 26% in LCRT, while the average difference per patient ranged from - 34 to 12%. For SCRT the median difference of V95% was - 8%, while the range of the average difference per patient was - 29 to 0%. CONCLUSIONS: Online ART for rectal cancer reduces dose the OARs significantly compared to a clinically implemented plan selection strategy, without compromising target coverage. TRIAL REGISTRATION: Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center (W19_357 # 19.420; Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands).

Dosimetric benefit of an adaptive treatment by means of plan selection for rectal cancer patients in both short and long course radiation therapy.

BACKGROUND: To compare target coverage and dose to the organs at risk in two approaches to rectal cancer: a clinically implemented adaptive radiotherapy (ART) strategy using plan selection, and a non-adaptive (non-ART) strategy. METHODS: The inclusion of the first 20 patients receiving adaptive radiotherapy produced 10 patients with a long treatment schedule (25x2Gy) and 10 patients with a short schedule (5X5Gy). We prepared a library of three plans with different anterior PTV margins to the upper mesorectum, and selected the most appropriate plan on daily Conebeam CT scans (CBCT). We also created a non-adaptive treatment plan with a 20 mm margin. Bowel bag, bladder and target volume were delineated on CBCT. Daily DHVs were calculated based on the dose distribution of the selected and non-adaptive plans. Coverage of the target volume was compared per fraction between the ART and non-ART plans, as was the dose to the bladder and small bowel, assessing the following dose levels: V15Gy, V30Gy, V40Gy, V15Gy and V95% for long treatment schedules, and V15Gy and V95% for short ones. RESULTS: Target volume coverage was maintained from 98.3% (non-ART) to 99.0% (ART)(p = 0.878). In the small bowel, ART appeared to have produced significant reductions in the long treatment schedule at V15Gy, V40Gy, V45Gy and V95% (p <  0.05), but with small absolute differences. The DVH parameters tested for the short treatment schedule did not differ significantly. In the bladder, all DVH parameters in both schedules showed significant reductions (p <  0.05), also with small absolute differences. CONCLUSIONS: The adaptive treatment maintained target coverage and reduced dose to the organs at risk. TRIAL REGISTRATION: Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center, W19_194 # 19.233.

Demographic, clinical and lifestyle-related correlates of accelerometer assessed physical activity and fitness in newly diagnosed patients with head and neck cancer.

Introduction: Objective measurements of levels of physical activity and fitness in patients with head and neck cancer (HNC) are lacking. Furthermore, demographic, clinical and lifestyle-related correlates of low levels of physical activity and fitness in patients with HNC are unknown. This study aims to investigate the levels of accelerometer that assessed physical activity and fitness in patients with HNC and to identify their demographical, clinical and lifestyle-related correlates.Methods: Two hundred and fifty-four patients who were recently diagnosed with HNC and participated in the NETherlands QUality of life and Biomedical cohort studies In head and neck Cancer (NET-QUBIC) study were included. Physical activity (accelerometer), cardiorespiratory fitness (Chester Step Test), hand grip strength (hand dynamometer) and lower body muscle function (30-second chair-stand test) were assessed. Multivariable linear regression analyses with a stepwise forward selection procedure were used.Results: Patients spent 229 min/d in physical activity of which 18 min/d in moderate-to-vigorous physical activity. The mean predicted VO2max was 27.9 ml/kg/min, the mean hand grip strength was 38.1 kg and the mean number of standings was 14.3. Patients with lower educational level, more comorbidity and higher tumor stage spent significantly less time in physical activity. Older patients, females and patients with a higher tumor stage had significantly lower cardiorespiratory fitness levels. Older patients, females, patients with more comorbidity, patients with normal weight and patients who have never smoked had significantly lower hand grip strength. Older patients, patients with lower educational level, smokers and patients with more comorbidity had a significantly lower function of lower body muscle.Conclusions: Pre-treatment levels of physical activity, cardiorespiratory fitness and lower body muscle function are low in patients with HNC. Based on this study, exercise programs targeted and tailored to patients with low levels of physical activity and fitness can be developed.