High bone mass and cam morphology are independently related to hip osteoarthritis: findings from the High Bone Mass cohort.

BACKGROUND: High bone mass (HBM, BMD Z-score ≥ + 3.2) and cam morphology (bulging of lateral femoral head) are associated with greater odds of prevalent radiographic hip osteoarthritis (rHOA). As cam morphology is itself a manifestation of increased bone deposition around the femoral head, it is conceivable that cam morphology may mediate the relationship between HBM and rHOA. We therefore aimed to determine if individuals with HBM have increased odds of prevalent cam morphology. In addition, we investigated whether the relationship between cam and prevalent and incident osteoarthritis was preserved in a HBM population. METHODS: In the HBM study, a UK based cohort of adults with unexplained HBM and their relatives and spouses (controls), we determined the presence of cam morphology using semi-automatic methods of alpha angle derivation from pelvic radiographs. Associations between HBM status and presence of cam morphology, and between cam morphology and presence of rHOA (or its subphenotypes: osteophytes, joint space narrowing, cysts, and subchondral sclerosis) were determined using multivariable logistic regression, adjusting for age, sex, height, weight, and adolescent physical activity levels. The association between cam at baseline and incidence of rHOA after an average of 8 years was determined. Generalised estimating equations accounted for individual-level clustering. RESULTS: The study included 352 individuals, of whom 235 (66.7%) were female and 234 (66.5%) had HBM. Included individuals contributed 694 hips, of which 143 had a cam deformity (20.6%). There was no evidence of an association between HBM and cam morphology (OR = 0.97 [95% CI: 0.63-1.51], p = 0.90) but a strong relationship was observed between cam morphology and rHOA (OR = 3.96 [2.63-5.98], p = 5.46 × 10-11) and rHOA subphenotypes joint space narrowing (OR = 3.70 [2.48-5.54], p = 1.76 × 10-10), subchondral sclerosis (OR = 3.28 [1.60-6.60], p = 9.57 × 10-4) and osteophytes (OR = 3.01 [1.87-4.87], p = 6.37 × 10-6). Cam morphology was not associated with incident osteoarthritis (OR = 0.76 [0.16-3.49], p = 0.72). CONCLUSIONS: The relationship between cam morphology and rHOA seen in other studies is preserved in a HBM population. This study suggests that the risk of OA conferred by high BMD and by cam morphology are mediated via distinct pathways.

Socio-economic inequalities in fragility fracture incidence: a systematic review and meta-analysis of 61 observational studies.

Individuals with low socio-economic status (SES) have a more than 25% higher risk of fragility fractures than individuals with high SES. Body mass index and lifestyle appear to mediate the effect of SES on fracture risk. Strategies to prevent fractures should aim to reduce unhealthy behaviours through tackling structural inequalities. INTRODUCTION: This systematic review and meta-analysis aimed to evaluate the impact of socio-economic status (SES) on fragility fracture risk. METHODS: Medline, Embase, and CINAHL databases were searched from inception to 28 April 2021 for studies reporting an association between SES and fragility fracture risk among individuals aged ≥50 years. Risk ratios (RR) were combined in meta-analyses using random restricted maximum likelihood models, for individual-based (education, income, occupation, cohabitation) and area-based (Index of Multiple Deprivation, area income) SES measures. RESULTS: A total of 61 studies from 26 different countries including more than 19 million individuals were included. Individual-based low SES was associated with an increased risk of fragility fracture (RR 1.27 [95% CI 1.12, 1.44]), whilst no clear association was seen when area-based measures were used (RR 1.08 [0.91, 1.30]). The strength of associations was influenced by the type and number of covariates included in statistical models: RR 2.69 [1.60, 4.53] for individual-based studies adjusting for age, sex and BMI, compared with RR 1.06 [0.92, 1.22] when also adjusted for health behaviours (smoking, alcohol, and physical activity). Overall, the quality of the evidence was moderate. CONCLUSION: Our results show that low SES, measured at the individual level, is a risk factor for fragility fracture. Low BMI and unhealthy behaviours are important mediators of the effect of SES on fracture risk. Strategies to prevent fractures and reduce unhealthy behaviours should aim to tackle structural inequalities in society thereby reducing health inequalities in fragility fracture incidence.

Osteoarthritis: Insights Offered by the Study of Bone Mass Genetics.

PURPOSE OF REVIEW: This paper reviews how bone genetics has contributed to our understanding of the pathogenesis of osteoarthritis. As well as identifying specific genetic mechanisms involved in osteoporosis which also contribute to osteoarthritis, we review whether bone mineral density (BMD) plays a causal role in OA development. RECENT FINDINGS: We examined whether those genetically predisposed to elevated BMD are at increased risk of developing OA, using our high bone mass (HBM) cohort. HBM individuals were found to have a greater prevalence of OA compared with family controls and greater development of radiographic features of OA over 8 years, with predominantly osteophytic OA. Initial Mendelian randomisation analysis provided additional support for a causal effect of increased BMD on increased OA risk. In contrast, more recent investigation estimates this relationship to be bi-directional. However, both these findings could be explained instead by shared biological pathways. Pathways which contribute to BMD appear to play an important role in OA development, likely reflecting shared common mechanisms as opposed to a causal effect of raised BMD on OA. Studies in HBM individuals suggest this reflects an important role of mechanisms involved in bone formation in OA development; however further work is required to establish whether the same applies to more common forms of OA within the general population.

Individuals with high bone mass have increased progression of radiographic and clinical features of knee osteoarthritis.

OBJECTIVE: High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. DESIGN: A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score≥+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering. RESULTS: 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean (SD) age was 58 (12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR = 1.55 [0.56.4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45 [0.01.0.89] and 0.15 [0.01.0.29], respectively). HBM individuals had higher WOMAC knee pain scores (ß = 7.42 [1.17.13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation. CONCLUSIONS: HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.

Correction to: Lean mass and lower limb muscle function in relation to hip strength, geometry and fracture risk indices in community-dwelling older women.

The original version of this article, published on 14 December 2018, unfortunately contained a mistake.

Lean mass and lower limb muscle function in relation to hip strength, geometry and fracture risk indices in community-dwelling older women.

In a population-based sample of British women aged over 70 years old, lean mass and peak lower limb muscle force were both independently associated with hip strength and fracture risk indices, thereby suggesting a potential benefit of promoting leg muscle strengthening exercise for the prevention of hip fractures in postmenopausal women. INTRODUCTION: To investigate cross-sectional associations of lean mass and physical performance, including lower limb muscle function, with hip strength, geometry and fracture risk indices (FRIs) in postmenopausal women. METHODS: Data were from the Cohort of Skeletal Health in Bristol and Avon. Total hip (TH) and femoral neck (FN) bone mineral density (BMD), hip geometry and total body lean mass (TBLM) were assessed by dual x-ray absorptiometry (DXA). Finite element analysis of hip DXA was used to derive FN, intertrochanteric and subtrochanteric FRIs. Grip strength, gait speed and chair rise time were measured objectively. Lower limb peak muscle force and muscle power were assessed by jumping mechanography. RESULTS: In total, 241 women were included (age = 76.4; SD = 2.6 years). After adjustment for age, height, weight/fat mass and comorbidities, TBLM was positively associated with hip BMD (ßTH BMD = 0.36, P ≤ 0.001; ßFN BMD = 0.26, P = 0.01) and cross-section moment of inertia (0.24, P ≤ 0.001) and inversely associated with FN FRI (- 0.21, P = 0.03) and intertrochanteric FRI (- 0.11, P = 0.05) (estimates represent SD difference in bone measures per SD difference in TBLM). Lower limb peak muscle force was positively associated with hip BMD (ßTH BMD = 0.28, P ≤ 0.001; ßFN BMD = 0.23, P = 0.008) and inversely associated with FN FRI (- 0.17, P = 0.04) and subtrochanteric FRI (- 0.18, P = 0.04). Associations of grip strength, gait speed, chair rise time and peak muscle power with hip parameters were close to the null. CONCLUSIONS: Lean mass and lower limb peak muscle force were associated with hip BMD and geometrical FRIs in postmenopausal women. Leg muscle strengthening exercises may therefore help prevent hip fractures in older women.

Dexamethasone-related adrenal insufficiency in patients with brain and skull base tumours.

PURPOSE: This study aimed to evaluate the prevalence of glucocorticoid-induced adrenal insufficiency in a cohort of patients with brain and skull base tumours and to identify factors which may predict its occurrence. METHODS: Patients with brain or skull base tumours attending for a short synacthen test (SST) (adrenocorticotropin hormone (ACTH) stimulation test) at a single institution over a 3-year period were retrospectively identified. Baseline demographics and dexamethasone exposure were examined. Only patients with dexamethasone exposure were included in the final analysis looking at the primary end point of SST failure. Fisher's exact test, Student's t test, Mann-Whitney test and the Kendall's tau-b test were used to evaluate the influence of age, gender, diagnosis and mean pituitary radiation dose on the primary endpoint. Receiver operating characteristic (ROC) curves were generated to explore the impact of duration and total exposure to dexamethasone on likelihood of SST failure. RESULTS: Thirty-one of 51 patients with previous dexamethasone exposure failed their first SST (61%). No significant relationship was demonstrated between age, gender, diagnosis or mean pituitary radiation dose and SST failure. Duration of and total exposure to dexamethasone were significantly associated with SST failure (p = 0.001 and p = 0.007, respectively). ROC curves generated values of 78 days and 171 mg days to give a sensitivity of 94 and 97%, respectively, to detect SST failure. CONCLUSIONS: Duration of dexamethasone use and total exposure predict for adrenal insufficiency in patients with brain and skull base tumours. Values derived from this study may be useful to identify patients at higher risk of adrenal suppression who require empirical hydrocortisone pending formal testing of the hypothalamic-pituitary-adrenal axis.

Habitual levels of higher, but not medium or low, impact physical activity are positively related to lower limb bone strength in older women: findings from a population-based study using accelerometers to classify impact magnitude.

This study assessed the effect of accelerometry-measured higher impacts resulting from habitual weight-bearing activity on lower limb bone strength in older women. Despite higher impacts being experienced rarely in this population-based cohort, positive associations were observed between higher vertical impacts and lower limb bone size and strength. INTRODUCTION: We investigated whether the benefit of habitual weight-bearing physical activity (PA) for lower limb bone strength in older women is explained by exposure to higher impacts, as previously suggested by observations in younger individuals. METHODS: Four hundred and eight women from the Cohort for Skeletal Health in Bristol and Avon (COSHIBA), mean 76.8 years, wore tri-axial accelerometers at the waist for a mean of 5.4 days. Y-axis peaks were categorised, using previously identified cutoffs, as low (0.5-1.0 g), medium (1.0-1.5 g), and higher (≥1.5 g) impacts. Mid and distal peripheral quantitative computed tomography scans of the tibia and radius were performed, as were hip and lumbar spine Dual X-ray Absorptiometry (DXA) scans. Regressions between (log transformed) number of low, medium and high impacts, and bone outcomes were adjusted for artefact error grade, age, height, fat and lean mass and impacts in other bands. RESULTS: Eight thousand eight hundred and nine (4047, 16,882) low impacts were observed during the measurement week, 345 (99, 764) medium impacts and 42 (17, 106) higher impacts (median with 25th and 75th quartiles). Higher vertical impacts were positively associated with lower limb bone strength as reflected by cross-sectional moment of inertia (CSMI) of the tibia [0.042 (0.012, 0.072) p = 0.01] and hip [0.067 (0.001, 0.133) p = 0.045] (beta coefficients show standard deviations change per doubling in impacts, with 95 % confidence interval). Higher impacts were positively associated with tibial periosteal circumference (PC) [0.015 (0.003, 0.027) p = 0.02], but unrelated to hip BMD. Equivalent positive associations were not seen for low or medium impacts. CONCLUSIONS: Despite their rarity, habitual levels of higher impacts were positively associated with lower limb bone size and strength, whereas equivalent relationships were not seen for low or medium impacts.

A novel accelerometer-based method to describe day-to-day exposure to potentially osteogenic vertical impacts in older adults: findings from a multi-cohort study.

This observational study assessed vertical impacts experienced in older adults as part of their day-to-day physical activity using accelerometry and questionnaire data. Population-based older adults experienced very limited high-impact activity. The accelerometry method utilised appeared to be valid based on comparisons between different cohorts and with self-reported activity. INTRODUCTION: We aimed to validate a novel method for evaluating day-to-day higher impact weight-bearing physical activity (PA) in older adults, thought to be important in protecting against osteoporosis, by comparing results between four cohorts varying in age and activity levels, and with self-reported PA levels. METHODS: Participants were from three population-based cohorts, MRC National Survey of Health and Development (NSHD), Hertfordshire Cohort Study (HCS) and Cohort for Skeletal Health in Bristol and Avon (COSHIBA), and the Master Athlete Cohort (MAC). Y-axis peaks (reflecting the vertical when an individual is upright) from a triaxial accelerometer (sampling frequency 50 Hz, range 0-16 g) worn at the waist for 7 days were classified as low (0.5-1.0 g), medium (1.0-1.5 g) or higher (≥1.5 g) impacts. RESULTS: There were a median of 90, 41 and 39 higher impacts/week in NSHD (age 69.5), COSHIBA (age 76.8) and HCS (age 78.5) participants, respectively (total n = 1512). In contrast, MAC participants (age 68.5) had a median of 14,322 higher impacts/week. In the three population cohorts combined, based on comparison of beta coefficients, moderate-high-impact activities as assessed by PA questionnaire were suggestive of stronger association with higher impacts from accelerometers (0.25 [0.17, 0.34]), compared with medium (0.18 [0.09, 0.27]) and low impacts (0.13 [0.07,0.19]) (beta coefficient, with 95 % CI). Likewise in MAC, reported moderate-high-impact activities showed a stronger association with higher impacts (0.26 [0.14, 0.37]), compared with medium (0.14 [0.05, 0.22]) and low impacts (0.03 [-0.02, 0.08]). CONCLUSIONS: Our new accelerometer method appears to provide valid measures of higher vertical impacts in older adults. Results obtained from the three population-based cohorts indicate that older adults generally experience very limited higher impact weight-bearing PA.

Feasibility and acceptability of using jumping mechanography to detect early components of sarcopenia in community-dwelling older women.

OBJECTIVE: To determine the feasibility and acceptability of using peak power and force, measured by jumping mechanography (JM), to detect early age-related features of sarcopenia in older women. METHODS: Community-dwelling women aged 71-87 years were recruited into this cross-sectional study. Physical function tests comprised the short physical performance battery (SPPB), grip strength and, if SPPB score≥6, JM. JM measured peak weight-adjusted power and force from two-footed jumps and one-legged hops respectively. Questionnaires assessed acceptability. RESULTS: 463 women were recruited; 37(8%) with SPPB⟨6 were ineligible for JM. Of 426 remaining, 359(84%) were able to perform ≥1 valid two-footed jump, 300(70%) completed ≥1 valid one-legged hop. No adverse events occurred. Only 14% reported discomfort. Discomfort related to JM performance, with inverse associations with both power and force (p⟨0.01). Peak power and force respectively explained 8% and 10% of variance in SPPB score (13% combined); only peak power explained additional variance in grip strength (17%). CONCLUSIONS: Peak power and force explained a significant, but limited, proportion of variance in SPPB and grip strength. JM represents a safe and acceptable clinical tool for evaluating lower-limb muscle power and force in older women, detecting distinct components of muscle function, and possibly sarcopenia, compared to those evaluated by more established measures.

The epidemiology of tick infestation in dog breeds in the UK.

OBJECTIVES: The purpose of this study is to report the prevalence and risk factors for tick infestation in dogs in the UK based on anonymised electronic patient records. MATERIALS AND METHODS: Clinical records of dogs under veterinary care in 2016 at clinics participating in the VetCompass Programme were followed over a 5-year period to identify cases of tick infestation. Risk factor analysis used multivariable logistic regression modelling. RESULTS: The study included 905,553 dogs. From a random sample, 1903 tick infestation cases were identified. The estimated 5-year (2014 to 2018) period prevalence was 2.03% (95% confidence interval: 2.00 to 2.06). Sixteen breeds showed increased odds compared with non-designer-crossbreed dogs. Breeds with the highest odds included Cairn terrier (odds ratio 2.86, 95% confidence interval 1.64 to 4.98), standard poodle (odds ratio 2.80, 95% confidence interval 1.25 to 6.29) and Goldendoodle (odds ratio 2.63, 95% confidence interval 1.17 to 5.91). Six breeds showed reduced odds, with lowest odds shown by Staffordshire bull terrier (odds ratio 0.35, 95% confidence interval 0.25 to 0.50), Rottweiler (odds ratio 0.35, 95% confidence interval 0.15 to 0.85) and Chihuahua (odds ratio 0.38, 95% confidence interval 0.26 to 0.55). Males had 1.24 (95% confidence interval 1.13 to 1.36) times the odds of females. Compared with non-designer-crossbred dogs, designer-crossbreed dogs had increased odds (odds ratio 1.81, 95% confidence interval 1.52 to 2.15). Compared with breeds with short coats, breeds with medium length coats (odds ratio 2.20, 95% confidence interval 1.96 to 2.48) showed increased odds. Breeds with V-shaped drop and pendulous ear carriage had higher odds compared with breeds with erect ear carriage. CLINICAL SIGNIFICANCE: These findings provide an evidence base for veterinary professionals to raise awareness of tick infestation as a preventable disorder in dogs in the UK and to support more effective prevention and therapeutic protocols based on targeted approaches.

Evidence-based decision-making in a climate of political expediency: insights from local government.

AIMS: Local authorities in England are responsible for public health and health promotion. This article sought to explore how research and decision-making co-exist in a local authority in England. METHODS: An Embedded Researcher was based within the local authority and used qualitative methodology to address the research aim. Interviews and focus groups were employed to ascertain a range of stakeholder views in the local authority. All transcripts were coded on NVivo 12 by the Embedded Researcher and two members of the research team cross-checked a sample for coding accuracy. Data were analysed using framework analysis. RESULTS: The data suggest several barriers to using research to inform decision-making in health promotion and public health. The study shows that research is valued in local authorities, but not always privileged - this is due to cultural factors and practical political reasons which often means that decisions need to be made expediently. Participants outlined a juxtaposition between academic credibility; timeliness to complete the research and the financial cost associated with it; against the independence and credibility that independent academics could bring. CONCLUSION: Policy formulation and delivery is an integral aspect of health promotion and critical to achieving improved population health and reductions in health inequalities. However, there exists tensions between gathering research evidence and making research-informed decisions. The article concludes by advocating the use of Embedded Researchers to fully understand how research is gathered and used to support public health and health promotion policymaking.

A randomised trial of weekend and evening breast screening appointments.

BACKGROUND: There is a need to research interventions that improve access to and convenience of breast cancer screening services. METHODS: We conducted a randomised trial comparing invitations to out-of-hours appointments with standard office hour appointments. Women who were to be invited for routine breast screening were randomised (3 : 1 : 1 : 1) to one of these screening invitations: standard office hour appointment, office hour appointment with the option to change to an out-of-hours appointment, weekday evening appointment, or weekend appointment. RESULTS: A total of 9410 women were invited to an office hour, 3519 to an office hour with the option to change, 3271 to a weekday evening, and 3162 to a weekend appointment. The offer of an initial out-of-hours appointment was associated with a non-significant decrease in attendance rates (73.7% vs 74.1%). The highest attendance was observed in the group offered an initial office hour appointment with the option to change to out-of-hours (76.1% vs 73.3% for standard office hour, P=0.001), with 7% of invitees exercising the option to change. CONCLUSION: The optimum strategy for improving attendance at breast screening is to offer a traditional office hour appointment and including in the letter of invitation an option to change to an evening or weekend appointment if wished.

Machine learning outperforms clinical experts in classification of hip fractures.

Hip fractures are a major cause of morbidity and mortality in the elderly, and incur high health and social care costs. Given projected population ageing, the number of incident hip fractures is predicted to increase globally. As fracture classification strongly determines the chosen surgical treatment, differences in fracture classification influence patient outcomes and treatment costs. We aimed to create a machine learning method for identifying and classifying hip fractures, and to compare its performance to experienced human observers. We used 3659 hip radiographs, classified by at least two expert clinicians. The machine learning method was able to classify hip fractures with 19% greater accuracy than humans, achieving overall accuracy of 92%.

Improvement in Dysphagia Outcomes Following Clinical Target Volume Reduction in the De-ESCALaTE Study.

AIMS: The De-ESCALaTE study showed an overall survival advantage for the administration of synchronous cisplatin chemotherapy with radiotherapy in low-risk oropharyngeal cancer when compared with synchronous cetuximab. During the trial, a radiotherapy quality assurance protocol amendment permitted centres to swap from the original radiotherapy contouring protocol (incorporating the whole oropharynx into the high-dose clinical target volume (CTV); anatomical protocol) to a protocol that incorporated the gross tumour volume with a 10 mm margin into the CTV (volumetric protocol). The purpose of this study was to examine both toxicity and tumour control related to this protocol amendment. MATERIALS AND METHODS: Overall survival and recurrence at 2 years were used to compare tumour control in the two contouring cohorts. For toxicity, the cohorts were compared by both the number of severe (grades 3-5) and all grades acute and late toxicities. In addition, quality of life and swallowing were compared using EORTC-C30 and MD Anderson Dysphagia Inventory, respectively. RESULTS: Of 327 patients included in this study, 185 were contoured according to the anatomical protocol and 142 by the volumetric protocol. The two cohorts were well balanced, with the exception of significantly more patients in the anatomical cohort undergoing prophylactic feeding tube insertion (P < 0.001). With a minimum of 2 years of follow-up there was no significant difference in overall survival or recurrence between the two contouring protocols. Similarly, there was no significant difference in the rate of reported severe or all grades acute or late toxicity and no sustained significant difference in quality of life. However, there was a significant difference in favour of volumetric contouring in several domains of the MD Anderson Dysphagia Inventory questionnaire at 1 year, which persisted to 2 years in the dysphagia functional (P = 0.002), dysphagia physical (P = 0.009) and dysphagia overall function (P = 0.008) domains. CONCLUSION: In the context of the unplanned post-hoc analysis of a randomised trial, measurable improvement in long-term dysphagia has been shown following a reduction in the CTV. Further reductions in the CTV should be subject to similar scrutiny within the confines of a prospective study.

Autosomal dominant epidermodysplasia verruciformis lacking a known EVER1 or EVER2 mutation.

Epidermodysplasia verruciformis is a rare genodermatosis characterized by abnormal susceptibility to infection with specific human papillomavirus serotypes. Epidermodysplasia verruciformis is a genetically heterogeneous disease, and autosomal recessive and X-linked inheritance patterns have been reported. Nonsense mutations in the genes EVER1 and EVER2 have been identified in over 75% of cases. We present epidermodysplasia verruciformis in a father and a son with typical histologic and clinical findings that occur in the absence of mutations in EVER1 or EVER2. Epidermodysplasia verruciformis in this father/son pair in a nonconsanguinous pedigree is consistent with autosomal dominant inheritance. This is the first report of autosomal dominant transmission of epidermodysplasia verruciformis, providing further evidence of the genetic heterogeneity of epidermodysplasia verruciformis.

Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using Multiparametric Magnetic Resonance Imaging and a Review of the Literature.

AIMS: Following stereotactic radiosurgery (SRS), brain metastases initially increase in size in up to a third of cases, suggesting treatment failure. Current imaging using structural magnetic resonance imaging (MRI) cannot differentiate between tumour recurrence and SRS-induced changes, creating difficulties with patient management. Combining multiparametric MRI techniques, which assess tissue physiological and metabolic information, has shown promise in answering this clinical question. MATERIALS AND METHODS: Multiparametric MRI techniques, including spectroscopy, diffusion and perfusion imaging, were used for the differentiation of radiation-related changes and tumour recurrence after SRS for intracranial metastases in six cases. All patients presented with enlargement of the treated lesion, an increase in perilesional brain oedema and aggravation or appearance of neurological signs and symptoms from 7 to 29 weeks after primary treatment. RESULTS: Multiparametric imaging helped to differentiate features of tumour progression (n = 4) from radiation-related changes (n = 2). A low apparent diffusion coefficient (ADC) <1000 × 10-6 mm2/s, high relative cerebral blood volume (rCBV) ratio > 2.1, high choline:creatine (Cho:Cr) ratio > 1.8 suggested tumour recurrence. A high ADC > 1000 × 10-6 mm2/s, low rCBV ratio < 2.1, Cho:Cr ratio < 1.8 suggested SRS-induced radiation changes. Multiparametric MRI diagnosis was confirmed by histology or radiological and clinical follow-up. CONCLUSION: Multiparametric MRI was helpful in the early identification of radiation-related changes and tumour recurrence and may be useful for monitoring treatment changes in intracranial neoplasms after SRS treatment.

Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck.

BACKGROUND: Radiation dermatitis occurs to some degree in most patients receiving radiotherapy, with or without chemotherapy. Patients with squamous cell carcinoma of the head and neck (SCCHN) who receive radiotherapy in combination with epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab, may develop a characteristic acne-like rash in addition to dermatitis. DESIGN: An advisory board of 11 experienced radiation oncologists, medical oncologists and dermatologists discussed the management options for skin reactions in patients receiving EGFR inhibitors and radiotherapy for SCCHN. Skin toxicity was categorised according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (version 3) grading. RESULTS: Both general and grade-specific approaches for the management of dermatitis in this patient group are presented. It was concluded that where EGFR inhibitor-related acne-like rash and dermatitis coexist within irradiated fields, management should be based on the grade of dermatitis: for grade 1 (or no dermatitis), treatment recommendations for EGFR-related acne-like rash outside irradiated fields should be followed; for grades 2 and above, treatment recommendations for dermatitis were proposed. CONCLUSIONS: This paper presents comprehensive consensus guidelines for the treatment of dermatitis in patients with SCCHN receiving EGFR inhibitors in combination with radiotherapy.

Chemoradiotherapy for rectal cancer: an updated analysis of factors affecting pathological response.

AIMS: With the aim of improving locoregional control, the use of preoperative chemoradiotherapy (CRT) for rectal cancer has increased. A pathological complete response (pCR) is often used as a surrogate marker for the efficacy of different CRT schedules. By analysing factors affecting pCR, this analysis aims to guide the development of future trials. MATERIALS AND METHODS: Searches of Medline, EMBASE and the electronic American Society of Clinical Oncology abstract databases were carried out to identify prospective phase II and phase III trials using preoperative CRT to treat rectal cancer. Trials were eligible for inclusion if they defined: the CRT drugs, the radiation dose and the pCR rate. Phase I patients were excluded from the analysis. A multivariate analysis examined the effect of the above variables on the pCR rate and in addition the use of neoadjuvant chemotherapy, the type of publication (peer reviewed vs abstract), the year of publication and whether the cancers were stated to be inoperable, fixed or threatening the circumferential resection margin were included. The method of analysis used was weighted linear modelling of the pCR rate. RESULTS: Sixty-four phase II and seven phase III trials were identified including a total of 4732 patients. Statistically significant factors associated with pCR were the use of two drugs, the method of fluoropyrimidine administration (with continuous intravenous 5-fluorouracil being the most effective) and a higher radiotherapy dose. Although the use of two drugs was associated with a higher rate of pCR, no single schedule seemed to be more effective. None of the other factors analysed significantly influenced pCR. CONCLUSIONS: A higher rate of pCR is seen in studies using two drugs, infusional 5-fluorouracil and a radiotherapy dose of 45 Gy and above.