BE-WEL trial (breast: evaluation of weight and exercise for lymphoedema) testing weight control and exercise programmes for women with breast cancer related lymphoedema: a feasibility trial.

PURPOSE: A combined body weight loss and upper body/arm exercise programme is a potential strategy for managing Breast cancer related lymphoedema (BCRL), but there is limited data on the best method for delivery or its potential efficacy. METHODS: Fifty-seven women with overweight/obesity and BCRL were randomised to a 12 week supervised (n = 12) or home-based combined weight loss and upper body/arm exercise programme (n = 16), a home-based upper-body arm exercise only programme (n = 17) or standard care (n = 12). Primary outcomes were uptake, retention and changes in weight and change in Relative Arm Volume Increase (RAVI) using analysis of covariance (ANCOVA). RESULTS: Sixteen percent of women invited joined the study and 49 completed the trial (85% retention). Reductions in weight occurred in the supervised and home-based weight control and exercise programmes; Mean (95% CI) change compared to standard care - 1.68 (- 4.36 to - 1.00), - 2.47(- 4.99 to - 0.04) Kg. Reductions in perometer assessed RAVI were seen in the supervised and home-based combined weight control and arm exercise groups and the weight stable home-based arm exercise only group: mean (95% CI) change compared to standard care - 2.4 (- 5.0 to + 0.4),- 1.8 (- 4.3 to + 0.7), - 2.5(- 4.9 to - 0.05)%. CONCLUSION: Women with BCRL and overweight and obesity engaged in diet and exercise weight loss programmes. Both weight loss/arm exercise programmes led to modest changes in weight and BCRL. Comparable reductions in BCRL were reported in the weight stable group undertaking arm exercise only. The independent and combined effects of weight loss and exercise on BCRL need further study. TRIAL REGISTRATION: ISRCTN86789850 https://doi.org/10.1186/ISRCTN86789850 , registered 2011.

Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing.

BACKGROUND: Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB). METHODS AND MATERIALS: We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri-hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ-1), 6 to 10 mm (HZ-2), and >10 mm (HZ-3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard-risk patients with MB were planned using either volumetric-modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) plans. RESULTS: Thirty-eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ-1. The crude incidence of peri-hippocampal failure was 8%. Both HA-VMAT and HA-IMPT plans were associated with significantly reduced mean dose to the hippocampi (p < .05). HA-VMAT and HA-IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy. CONCLUSIONS: Peri-hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB. PLAIN LANGUAGE SUMMARY: In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.

Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer.

BACKGROUND: Excess adiposity at diagnosis and weight gain during chemotherapy is associated with tumour recurrence and chemotherapy toxicity. We assessed the efficacy of intermittent energy restriction (IER) vs continuous energy restriction (CER) for weight control and toxicity reduction during chemotherapy. METHODS: One hundred and seventy-two women were randomised to follow IER or CER throughout adjuvant/neoadjuvant chemotherapy. Primary endpoints were weight and body fat change. Secondary endpoints included chemotherapy toxicity, cardiovascular risk markers, and correlative markers of metabolism, inflammation and oxidative stress. RESULTS: Primary analyses showed non-significant reductions in weight (-1.1 (-2.4 to +0.2) kg, p = 0.11) and body fat (-1.0 (-2.1 to +0.1) kg, p = 0.086) in IER compared with CER. Predefined secondary analyses adjusted for body water showed significantly greater reductions in weight (-1.4 (-2.5 to -0.2) kg, p = 0.024) and body fat (-1.1 (-2.1 to -0.2) kg, p = 0.046) in IER compared with CER. Incidence of grade 3/4 toxicities were comparable overall (IER 31.0 vs CER 36.5%, p = 0.45) with a trend to fewer grade 3/4 toxicities with IER (18%) vs CER (31%) during cycles 4-6 of primarily taxane therapy (p = 0.063). CONCLUSIONS: IER is feasible during chemotherapy. The potential efficacy for weight control and reducing toxicity needs to be tested in future larger trials. CLINICAL TRIAL REGISTRATION: ISRCTN04156504.

Reducing Missed Appointments for Patients With HIV: An Evidence-Based Approach.

BACKGROUND: High rates of missed appointments for routine HIV care are associated with unsuppressed viremia, increasing morbidity. LOCAL PROBLEM: The Clinic no-show rate ranged between 30% and 35%, and only 69% of patients were considered retained in care within a 24-month time frame. METHODS: The Woodward Risk Prediction Tool was completed on all patients to stratify patient risk for missing the next appointment. INTERVENTIONS: All patients were offered text message along with standard phone message appointment reminders, and patients who missed appointments were called within 24 hours to reschedule. Medium-risk patients received a previsit planning call to remove barriers to appointment attendance, and high-risk patients received a home visit from the peer navigator. RESULTS: The project resulted in a 3.8% reduction rate in the overall no-show rate in the first 5 months of implementation. Using risk stratification and targeted interventions allowed valuable resources to be allocated where they were needed.

The effectiveness of home versus community-based weight control programmes initiated soon after breast cancer diagnosis: a randomised controlled trial.

BACKGROUND: Breast cancer diagnosis may be a teachable moment for lifestyle behaviour change and to prevent adjuvant therapy associated weight gain. We assessed the acceptability and effectiveness of two weight control programmes initiated soon after breast cancer diagnosis to reduce weight amongst overweight or obese women and prevent gains in normal-weight women. METHODS: Overweight or obese (n = 243) and normal weight (n = 166) women were randomised to a three-month unsupervised home (home), a supervised community weight control programme (community) or to standard written advice (control). Primary end points were change in weight and body fat at 12 months. Secondary end points included change in insulin, cardiovascular risk markers, quality of life and cost-effectiveness of the programmes. RESULTS: Forty-three percent of eligible women were recruited. Both programmes reduced weight and body fat: home vs. control mean (95% CI); weight -2.3 (-3.5, -1.0) kg, body fat -1.6 (-2.6, -0.7) kg, community vs. control; weight -2.4 (-3.6, -1.1) kg, body fat -1.4 (-2.4, -0.5) kg (all p < 0.001). The community group increased physical activity, reduced insulin, cardiovascular disease risk markers, increased QOL and was cost-effective. CONCLUSIONS: The programmes were equally effective for weight control, but the community programme had additional benefits. CLINICAL TRIAL REGISTRATION: ISRCTN68576140.

Can differences in linear energy transfer and thus relative biological effectiveness compromise the dosimetric advantage of intensity-modulated proton therapy as compared to passively scattered proton therapy?

PURPOSE: To investigate the effect of differences in linear energy transfer (LET) and thus the relative biological effectiveness (RBE) between passively scattered proton therapy (PS) and pencil-beam scanning intensity-modulated proton therapy (IMPT). METHODS: IMPT treatment plans were generated for six ependymoma patients, originally treated with PS, using the original plan's computed tomography image sets and beam directions, and its dose-volume values as optimization constraints. Two beam spot sizes and both single-field optimization (SFO) and multi-field optimization (MFO) techniques were used for each patient. Three-dimensional variable-RBE-weighted dose distributions were computed, using Monte Carlo calculated dose and LET distributions, and a linear dose and LET-based RBE model, and were compared between the two delivery methods. RESULTS: Increased target dose coverage and decreased mean and maximum dose to the OARs was achieved with IMPT compared to PS, for constant RBE value of 1.1. Nevertheless, the maximum variable-RBE-weighted dose to the brainstem, was increased up to 6% for the IMPT plans compared to the corresponding PS plans. CONCLUSIONS: IMPT can be dosimetrically superior to PS for ependymoma patients. However, caution should be exercised so that the increased dose conformity is not counteracted by an increase in radiobiological effect in adjacent critical structures.

Statistical shape modelling of hip and lumbar spine morphology and their relationship in the MRC National Survey of Health and Development.

The anatomical shape of bones and joints is important for their proper function but quantifying this, and detecting pathological variations, is difficult to do. Numerical descriptions would also enable correlations between joint shapes to be explored. Statistical shape modelling (SSM) is a method of image analysis employing pattern recognition statistics to describe and quantify such shapes from images; it uses principal components analysis to generate modes of variation describing each image in terms of a set of numerical scores after removing global size variation. We used SSM to quantify the shapes of the hip and the lumbar spine in dual-energy x-ray absorptiometry (DXA) images from 1511 individuals in the MRC National Survey of Health and Development at ages 60-64 years. We compared shapes of both joints in men and women and hypothesised that hip and spine shape would be strongly correlated. We also investigated associations with height, weight, body mass index (BMI) and local (hip or lumber spine) bone mineral density. In the hip, all except one of the first 10 modes differed between men and women. Men had a wider femoral neck, smaller neck-shaft angle, increased presence of osteophytes and a loss of the femoral head/neck curvature compared with women. Women presented with a flattening of the femoral head and greater acetabular coverage of the femoral head. Greater weight was associated with a shorter, wider femoral neck and larger greater and lesser trochanters. Taller height was accompanied by a flattening of the curve between superior head and neck and a larger lesser trochanter. Four of the first eight modes describing lumbar spine shape differed between men and women. Women tended to have a more lordotic spine than men with relatively smaller but caudally increasing anterior-posterior (a-p) vertebral diameters. Men were more likely to have a straighter spine with larger vertebral a-p diameters relative to vertebral height than women, increasing cranially. A weak correlation was found between body weight and a-p vertebral diameter. No correlations were found between shape modes and height in men, whereas in women there was a weak positive correlation between height and evenness of spinal curvature. Linear relationships between hip and spine shapes were weak and inconsistent in both sexes, thereby offering little support for our hypothesis. In conclusion, men and women entering their seventh decade have small but statistically significant differences in the shapes of their hips and their spines. Associations with height, weight, BMI and BMD are small and correspond to subtle variations whose anatomical significance is not yet clear. Correlations between hip and spine shapes are small.

Frailty and bone health in European men.

Background: frailty is associated with an increased risk of fragility fractures. Less is known, however, about the association between frailty and bone health. Methods: men aged 40-79 years were recruited from population registers in eight European centres for participation in the European Male Aging Study. Subjects completed a comprehensive assessment which included quantitative ultrasound (QUS) scan of the heel (Hologic-SAHARA) and in two centres, dual-energy bone densitometry (dual-energy x-ray absorptiometry, DXA). Frailty was defined based on an adaptation of Fried's phenotype criteria and a frailty index (FI) was constructed. The association between frailty and the QUS and DXA parameters was determined using linear regression, with adjustments for age, body mass index and centre. Results: in total, 3,231 subjects contributed data to the analysis. Using the Fried categorisation of frailty, pre-frail and frail men had significantly lower speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) compared to robust men (P< 0.05). Similar results were seen using the FI after categorisation into 'high', 'medium' and 'low' levels of frailty. Using the Fried categorisation, frail men had lower femoral neck bone mineral density (BMD) compared to robust men (P < 0.05), but not lower lumbar spine BMD. Using the FI categorisation, a 'high' level of frailty (FI > 0.35) was associated with lower lumbar spine BMD (P < 0.05) when compared to those with low (FI < 0.2), but not lower femoral neck BMD. When analysed as a continuous variable, higher FI was linked with lower SOS, BUA and QUI (P < 0.05). Conclusions: optimisation of bone health as well as prevention of falls should be considered as strategies to reduce fractures in frail older people.

Prediction of Hip Failure Load: In Vitro Study of 80 Femurs Using Three Imaging Methods and Finite Element Models-The European Fracture Study (EFFECT).

Purpose To evaluate the performance of three imaging methods (radiography, dual-energy x-ray absorptiometry [DXA], and quantitative computed tomography [CT]) and that of a numerical analysis with finite element modeling (FEM) in the prediction of failure load of the proximal femur and to identify the best densitometric or geometric predictors of hip failure load. Materials and Methods Institutional review board approval was obtained. A total of 40 pairs of excised cadaver femurs (mean patient age at time of death, 82 years ± 12 [standard deviation]) were examined with (a) radiography to measure geometric parameters (lengths, angles, and cortical thicknesses), (b) DXA (reference standard) to determine areal bone mineral densities (BMDs), and (c) quantitative CT with dedicated three-dimensional analysis software to determine volumetric BMDs and geometric parameters (neck axis length, cortical thicknesses, volumes, and moments of inertia), and (d) quantitative CT-based FEM to calculate a numerical value of failure load. The 80 femurs were fractured via mechanical testing, with random assignment of one femur from each pair to the single-limb stance configuration (hereafter, stance configuration) and assignment of the paired femur to the sideways fall configuration (hereafter, side configuration). Descriptive statistics, univariate correlations, and stepwise regression models were obtained for each imaging method and for FEM to enable us to predict failure load in both configurations. Results Statistics reported are for stance and side configurations, respectively. For radiography, the strongest correlation with mechanical failure load was obtained by using a geometric parameter combined with a cortical thickness (r(2) = 0.66, P < .001; r(2) = 0.65, P < .001). For DXA, the strongest correlation with mechanical failure load was obtained by using total BMD (r(2) = 0.73, P < .001) and trochanteric BMD (r(2) = 0.80, P < .001). For quantitative CT, in both configurations, the best model combined volumetric BMD and a moment of inertia (r(2) = 0.78, P < .001; r(2) = 0.85, P < .001). FEM explained 87% (P < .001) and 83% (P < .001) of bone strength, respectively. By combining (a) radiography and DXA and (b) quantitative CT and DXA, correlations with mechanical failure load increased to 0.82 (P < .001) and 0.84 (P < .001), respectively, for radiography and DXA and to 0.80 (P < .001) and 0.86 (P < .001) , respectively, for quantitative CT and DXA. Conclusion Quantitative CT-based FEM was the best method with which to predict the experimental failure load; however, combining quantitative CT and DXA yielded a performance as good as that attained with FEM. The quantitative CT DXA combination may be easier to use in fracture prediction, provided standardized software is developed. These findings also highlight the major influence on femoral failure load, particularly in the trochanteric region, of a densitometric parameter combined with a geometric parameter. (©) RSNA, 2016 Online supplemental material is available for this article.

Opportunistic Identification of Vertebral Fractures.

Vertebral fractures are powerful predictors of future fracture, so, their identification is important to ensure that patients are commenced on appropriate bone protective or bone-enhancing therapy. Risk factors (e.g., low bone mineral density and increasing age) and symptoms (back pain, loss of height) may herald the presence of vertebral fractures, which are usually confirmed by performing spinal radiographs or, increasingly, using vertebral fracture assessment with dual-energy X-ray absorptiometry scanners. However, a large number (30% or more) of vertebral fractures are asymptomatic and do not come to clinical attention. There is, therefore, scope for opportunistic (fortuitous) identification of vertebral fractures from various imaging modalities (radiographs, computed tomography, magnetic resonance imaging, and radionuclide scans) performed for other clinical indications and which include the spine in the field of view, with midline sagittal reformatted images from computed tomography having the greatest potential for such opportunistic detection. Numerous studies confirm this potential for identification but consistently find underreporting of vertebral fractures. So, a valuable opportunity to improve the management of patients at increased risk of future fracture is being squandered. Educational training programs for all clinicians and constant reiteration, stressing the importance of the accurate and clear reporting of vertebral fractures ("you only see what you look for"), can improve the situation, and automated computer-aided diagnostic tools also show promise to solve the problem of this underreporting of vertebral fractures.

Bone Densitometry in Children.

Maximizing peak bone mass in childhood is relevant to optimizing bone health in later life, so the study of the skeleton in children in health and disease is important. Dual-energy X-ray absorptiometry (DXA) is the most widely used clinical tool for the assessment of bone status in children. Technological developments in DXA enable vertebral fracture assessment at much lower ionizing radiation doses than spinal radiographs. Quantitative computed tomography remains predominantly a research tool but has some advantages over DXA in not being size dependent. High-resolution peripheral computed tomography measures trabecular and cortical bone microstructure but is technically challenging, particularly in children, and not widely available, so it is unlikely to be used in clinical practice. Other quantitative techniques (quantitative magnetic resonance imaging, digital X-ray absorptiometry, quantitative ultrasound) have been applied in children but remain research applications, and they are only covered briefly in this review.

Idiopathic Juvenile Osteoporosis: Clinical Experience from a Single Centre and Screening of LRP5 and LRP6 Genes.

We report clinical findings, bone mineral density (BMD) and bone biopsy data in ten children with features of classic idiopathic juvenile osteoporosis (IJO). We also screened the patients for mutations in LRP5 and LRP6. We found low BMD in the lumbar spine, the hip and distal radius. In the spine and distal radius, the reduction in BMD was more marked in the trabecular compartment. Biopsy confirmed that the trabecular compartment is more severely involved with reduction in bone formation and increase in bone resorption. No mutations in LRP5 and LRP6 could be identified. IJO is likely to be a heterogeneous bone disorder, and next-generation genomic sequencing studies may help reveal causative genes.

Imaging of Ancient Egyptian Animal Mummies.

Human mummies have long been studied by using imaging as a primary investigative method. Mummified animal remains from ancient Egypt are less well researched, yet much can be learned about species diversity and the methods of preservation. Noninvasive imaging methods enable mummy bundles to remain intact, with no detrimental physical effects, thus ensuring protection of a valuable archaeological resource. This article is based on the research experience gathered during 13 years (2000-2012) with 152 animal mummies held in the collections of 17 museums in the United Kingdom. Conventional radiography, computed radiography, digital radiography, and computed tomography (CT) available in the clinical setting were used to assess the value of each imaging modality in the study of animal mummies and related material. Radiography proved to be an excellent research method that provided initial insight into the contents of the mummy bundle, and CT contributed additional useful detail in some cases. Paleoradiologic analyses enabled information on mummy bundle contents to be proved, including the nature of the skeletal remains and the methods of mummification. An optimum method involving radiography and CT is described.

Low heel ultrasound parameters predict mortality in men: results from the European Male Ageing Study (EMAS).

BACKGROUND: low bone mineral density measured by dual-energy x-ray absorptiometry is associated with increased mortality. The relationship between other skeletal phenotypes and mortality is unclear. The aim of this study was to determine the relationship between quantitative heel ultrasound parameters and mortality in a cohort of European men. METHODS: men aged 40-79 years were recruited for participation in a prospective study of male ageing: the European Male Ageing Study (EMAS). At baseline, subjects attended for quantitative ultrasound (QUS) of the heel (Hologic-SAHARA) and completed questionnaires on lifestyle factors and co-morbidities. Height and weight were measured. After a median of 4.3 years, subjects were invited to attend a follow-up assessment, and reasons for non-participation, including death, were recorded. The relationship between QUS parameters (broadband ultrasound attenuation [BUA] and speed of sound [SOS]) and mortality was assessed using Cox proportional hazards model. RESULTS: from a total of 3,244 men (mean age 59.8, standard deviation [SD] 10.8 years), 185 (5.7%) died during the follow-up period. After adjusting for age, centre, body mass index, physical activity, current smoking, number of co-morbidities and general health, each SD decrease in BUA was associated with a 20% higher risk of mortality (hazard ratio [HR] per SD = 1.2; 95% confidence interval [CI] = 1.0-1.4). Compared with those in higher quintiles (2nd-5th), those in the lowest quintile of BUA and SOS had a greater mortality risk (BUA: HR = 1.6; 95% CI = 1.1-2.3 and SOS: HR = 1.6; 95% CI = 1.2-2.2). CONCLUSION: lower heel ultrasound parameters are associated with increased mortality in European men.

Physical activity across adulthood in relation to fat and lean body mass in early old age: findings from the Medical Research Council National Survey of Health and Development, 1946-2010.

Fat and lean body mass have important implications for health and physical functioning in older age, and physical activity is purported to be an important modifiable determinant. However, our evidence-based understanding of its role is limited. We examined the associations of physical activity, assessed both by self-report (using data on leisure time physical activity (LTPA) collected on 4 occasions over a 28-year period) and objectively (using 5-day heart rate and movement monitoring), with fat and lean mass at ages 60-64 years in 1,162 British participants from the Medical Research Council National Survey of Health and Development in 1946-2010. Higher objectively assessed physical activity energy expenditure (PAEE) at ages 60-64 years was associated with lower fat mass and android (abdominal):gynoid (hip) fat ratio (mean differences in fat mass per 1-standard deviation increase in PAEE were -0.79 kg/m(1.2) in men (95% confidence interval: -1.08, -0.50) and -1.79 kg/m(1.2) (95% confidence interval: -2.15, -1.42) in women). After adjustment for fat mass, higher PAEE was associated with higher appendicular lean mass. Both light and moderate-to-vigorous intensities of activity were associated with fat mass, and the latter was associated with lean mass. More frequent LTPA across adulthood was associated with lower fat mass (in women only) and higher appendicular lean mass (in both sexes, after adjustment for fat mass). These results support the promotion of LTPA across adulthood, as well as both light and moderate-to-vigorous intensities of activity among older adults.

Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas.

BACKGROUND: Negative surgical margins are uncommon for spine sarcomas; hence, adjuvant radiotherapy (RT) may be recommended but tumor dose may be constrained by spinal cord, nerve, and viscera tolerance. METHODS: Prospective Phase II clinical trial incorporating high dose RT. Eligible patients had primary or locally recurrent thoracic, lumbar, and/or sacral spine/paraspinal chordomas or sarcomas. Treatment included pre- and/or post-operative photon/proton RT ± radical resection. RESULTS: Fifty patients (29 chordoma, 14 chondrosarcoma, 7 other) underwent gross total (n = 25) or subtotal (n = 12) resection or biopsy (n = 13). RT dose was ≤72.0 GyRBE in 25 patients and 76.6-77.4 GyRBE in 25 patients. With 7.3-year median follow-up, the 5 and 8-year actuarial local control (LC) rates were 94% and 85% for primary tumors and 81% and 74% for the entire group. Local recurrence was less common for primary tumors, 4/36 (11%) versus 7/14 (50%) for recurrent tumors, P = 0.002. The 8-year actuarial risk of grade 3-4 late RT morbidity was 13%. No myelopathies were seen. No late neurologic toxicities noted with radiation doses ≤72.0 GyRBE while three sacral neuropathies appeared after doses of 76.6-77.4 GyRBE. CONCLUSIONS: LC with this treatment is high in patients with primary tumors. Late morbidity appears to be acceptable.

Quantitative computer tomography in children and adolescents: the 2013 ISCD Pediatric Official Positions.

In 2007, International Society of Clinical Densitometry Pediatric Positions Task Forces reviewed the evidence for the clinical application of peripheral quantitative computed tomography (pQCT) in children and adolescents. At that time, numerous limitations regarding the clinical application of pQCT were identified, although its use as a research modality for investigation of bone strength was highlighted. The present report provides an updated review of evidence for the clinical application of pQCT, as well as additional reviews of whole body QCT scans of the central and peripheral skeletons, and high-resolution pQCT in children. Although these techniques remain in the domain of research, this report summarizes the recent literature and evidence of the clinical applicability and offers general recommendations regarding the use of these modalities in pediatric bone health assessment.

Body composition changes during breast cancer preventive treatment with anastrozole: Findings from the IBIS-II trial.

Background: Uptake to anastrozole for breast cancer prevention is low, partly due to women's concerns about side effects including gains in weight and specifically gains in body fat. Previous evidence does not link anastrozole with gains in weight, but there is a lack of data on any effects on body composition i.e. changes in fat and fat free mass. Here we assess association of anastrozole with body composition changes in a prospective sub-study from the second international breast intervention trial (IBIS-II). Methods: Participants had DXA scans at baseline and for five years of anastrozole/placebo and beyond (between March 2004 and September 2017. Primary outcomes were changes in body weight, body fat and fat free mass at 9-18 months. A linear model was used to estimate the size of a differential effect in these outcomes by randomised treatment allocation adjusted for baseline value and time since last scan, age, 10-year breast cancer risk, smoking and HRT status. Results: 203 postmenopausal women were recruited (n = 95 anastrozole, n = 108 placebo), mean age 58 years (SD = 5.4), BMI 28.0 kg/m2 (SD = 5.5). There was no evidence of a strong association between anastrozole or placebo and endpoints at 9-18 months; effect size (95 %CI) for anastrozole minus placebo for body weight (per/kg) -0.11 (-1.29-1.08); body fat 0.11 (-0.75-0.96) and fat free mass -0.30 (-0.79-0.19). Conclusions: There is unlikely to be a clinically significant change to body composition with anastrozole for breast cancer prevention.

Proton-Based Radiation Therapy for Skull Base Chondrosarcomas in Children and Adolescents: 40-Year Experience From the Massachusetts General Hospital.

PURPOSE: The literature on skull base chondrosarcoma (CHS) is scarce. We report outcomes for pediatric and young patients ≤22 years with base of skull CHSs treated with proton-based radiation therapy (PBRT). METHODS AND MATERIALS: We retrospectively reviewed all patients treated with PBRT between 1981 and 2023. Primary endpoints were overall survival (OS), chondrosarcoma-specific survival (CSS), progression-free survival (PFS), local control, and distal control. RESULTS: Eighty-four patients were identified. Median age at diagnosis was 19 years (range, 6-22). Most patients (n = 79, 94%) had conventional CHS, whereas 5 (6%) had mesenchymal CHS. Nine patients (11%) underwent gross total resection, 64 (76%) subtotal resection, and 11 patients (13%) underwent biopsy. Twenty-four (29%) patients progressed before radiation therapy. The median prescription dose was 70 Gy (relative biological equivalent) (range, 50-79.7). At a median follow-up of 18.0 years (IQR, 9.2-26.2) from diagnosis, 11 patients recurred (7 local, 4 distant). Six patients died of disease. Five patients died of other causes. Ten-year OS, CSS, and PFS rates for all patients were 93.3%, 94.7%, and 88%, respectively. Twenty-year OS, CSS, and PFS rates for conventional CHS (n = 79) were 93.1%, 97.1%, and 89.2%, respectively. Mesenchymal histology was significantly associated with worse OS and PFS. Preradiation therapy tumor progression portended worse OS and CSS. Eight patients (9.9 %) experienced a late toxicity grade 3 or greater. CONCLUSIONS: This is the largest cohort of pediatric base of skull CHSs in literature to date. High-dose PBRT after surgical resection achieves excellent disease control with minimal toxicity.

Predictors of Advance Care Planning Engagement Among Muslim Americans.

Advance care planning (ACP) enables people to discuss their physical, psychological, social, and spiritual needs before nearing death. Most literature examining the determinants of ACP engagement is limited and does not include minority faith communities in the United States, including Muslim communities. The purpose of this cross-sectional correlational study was to examine ACP engagement determinants among Muslims in the United States. Using the Social Ecological Model, we conceptualized the determinants of ACP engagement into intrapersonal, interpersonal, and community factors. The study self-administered questionnaires were distributed using convenience and snowball techniques. Multiple linear regression was used to predict ACP engagement. The total sample was 148 Muslim adults. The age range was 18 to 79 years. Among all tested factors, being Asian American, knowing a deceased person who had received aggressive or minimal medical treatments near death, being born in the United States, having knowledge and awareness about ACP, and being accepting of the American culture were the determinants of ACP engagement. Engagement in ACP is a multifactorial behavior. Several intrapersonal and interpersonal factors, but none of the community factors, were associated with ACP engagement among Muslim adults. Future ACP interventions targeted toward Muslim Americans should be planned with an understanding of the multifactorial nature of ACP engagement.