At 4° CP sampling, LT, MCSv, and LTMCS were found to be significantly correlated with VMAT dosimetric accuracy, expressed as Γ pass-rates. These parameters were found to be possible candidates for scoring plan complexity using threshold values. A finer CP separation (3°∕2°) led to a significant increase in dosimetric accuracy for plans with high leaf travel values, and to a decrease in correlation between LT and Γ passing rates. These results indicated that the influence of LT on VMAT dosimetric accuracy can be controlled by reducing CP separation. CP spacing for all plans requiring large leaf motion should not exceed 3°. The reported data were integrated to optimize our clinical workflow for plan creation, optimization, selection among rival plans, and patient-specific QA of VMAT treatments.

Fibrous Dysplasia / McCune Albright syndrome (FD/MAS) represents a wide spectrum of diseases due to somatic gain-of-function mutations of the GNAS gene. The mutation leads to overactivity in the target tissues and to a wide phenotype of clinical features that vary in severity and age of onset. The rarity of the disease and its variable presentation to multiple specialities often leads to misdiagnosis and inappropriate variability in investigations and treatments. To address this, our international consortium of clinicians, researchers, and patients’ advocates has developed pragmatic clinical guidelines for best clinical practice for the definition, diagnosis, staging, treatment and monitoring for FD/MAS to empower patients and support clinical teams in both general and specialised healthcare settings. With the lack of strong evidence to inform care, the guidelines were developed based on review of published literature, long-standing extensive experience of authors, input from other healthcare professionals involved in the care of FD/MAS patients and feedback from patients and patient groups across the globe. This has led to the formulation of a set of statements to inform healthcare professionals, patients, their families, carers and patient groups of the best practice of care. It is anticipated the implementation of these recommendations will lead to improvement in the care of patients with FD/MAS internationally. Electronic supplementary material The online version of this article (10.1186/s13023-019-1102-9) contains supplementary material, which is available to authorized users.

Stereotactic body radiotherapy was effective in disease eradication of limited nodal recurrences from prostate cancer, saving patients from, or at least postponing, systemic treatments.

Monte Carlo simulation was used to calculate correction factors for output factor (OF), percentage depth-dose (PDD), and off-axis ratio (OAR) measurements with the CyberKnife M6 System. These include the first such data for the InCise MLC. Simulated detectors include diodes, air-filled microchambers, a synthetic microdiamond detector, and point scintillator. Individual perturbation factors were also evaluated. OF corrections show similar trends to previous studies. With a 5 mm fixed collimator the diode correction to convert a measured OF to the corresponding point dose ratio varies between  -6.1% and  -3.5% for the diode models evaluated, while in a 7.6 mm  ×  7.7 mm MLC field these are  -4.5% to  -1.8%. The corresponding microchamber corrections are  +9.9% to  +10.7% and  +3.5% to  +4.0%. The microdiamond corrections have a maximum of  -1.4% for the 7.5 mm and 10 mm collimators. The scintillator corrections are <1% in all beams. Measured OF showed uncorrected inter-detector differences >15%, reducing to <3% after correction. PDD corrections at d > d were<2% for all detectors except IBA Razor where a maximum 4% correction was observed at 300 mm depth. OAR corrections were smaller inside the field than outside. At the beam edge microchamber OAR corrections were up to 15%, mainly caused by density perturbations, which blurs the measured penumbra. With larger beams and depths, PTW and IBA diode corrections outside the beam were up to 20% while the Edge detector needed smaller corrections although these did vary with orientation. These effects are most noticeable for large field size and depth, where they are dominated by fluence and stopping power perturbations. The microdiamond OAR corrections were <3% outside the beam. This paper provides OF corrections that can be used for commissioning new CyberKnife M6 Systems and retrospectively checking estimated corrections used previously. We recommend the PDD and OAR corrections are used to guide detector selection and inform the evaluation of results rather than to explicitly correct measurements.

No abstract

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

Patients with JIA have a low bone mass and, after a first increase due to therapy, do not reach a healthy condition over time despite our current more effective drugs. These patients have a high risk of osteoporosis in early adulthood. To reduce the risk and improve the bone mass, close monitoring of bone mineral density, better control of disease activity, physical activity, and intake of calcium and vitamin D are recommended. In patients with osteoporosis, therapeutic approaches including bisphosphonates should be considered.

No abstract