Predictive Value of Skeletal Muscle Mass in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Patients Treated With Immune Checkpoint Inhibitors.

BACKGROUND: Reduced muscle mass has been associated with increased treatment complications in several tumor types. We evaluated the impact of skeletal muscle index (SMI) on prognosis and immune-related adverse events (IrAEs) in a cohort of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoints inhibitors (ICI). METHODS: A single-institutional, retrospective study was performed including 61 consecutive patients of R/M HNSCC diagnosed between July 2015 and December 2018. SMI was quantified using a CT scan at L3 to evaluate body composition. Median baseline SMI was used to dichotomize patients in low and high SMI. Kaplan-Meier estimations were used to detect overall survival (OS) and progression-free survival (PFS). Toxicity was recorded using Common Terminology Criteria for Adverse Event v4.3. RESULTS: Patients were 52 men (85.2%) with mean of age 57.7 years (SD 9.62), mainly oral cavity (n = 21; 34.4%). Low SMI was an independent factor for OS in the univariate (HR, 2.06; 95% CI, 1.14-3.73, p = 0.017) and multivariate Cox analyses (HR, 2.99; 95% CI, 1.29-6.94; p = 0.011). PFS was also reduced in patients with low SMI (PFS HR, 1.84; 95% CI, 1.08-3.12; p = 0.025). IrAEs occurred in 29 (47.5%) patients. There was no association between low SMI and IrAEs at any grade (OR, 0.56; 95% CI, 0.20-1.54; p = 0.261). However, grades 3 to 4 IrAEs were developed in seven patients of whom three had low SMI. CONCLUSIONS: Low SMI before ICI treatment in R/M HNSCC patients had a negative impact on OS and PFS. Further prospective research is needed to confirm the role of body composition as a predictive biomarker in ICI treatment.

3D patient-specific finite element models of the proximal femur based on DXA towards the classification of fracture and non-fracture cases.

Osteoporotic bone fractures reduce quality of life and drastically increase mortality. Minimally irradiating imaging techniques such as dual-energy X-ray absorptiometry (DXA) allow assessment of bone loss through the use of bone mineral density (BMD) as descriptor. Yet, the accuracy of fracture risk predictions remains limited. Recently, DXA-based 3D modelling algorithms were proposed to analyse the geometry and BMD spatial distribution of the proximal femur. This study hypothesizes that such approaches can benefit from finite element (FE)-based biomechanical analyses to improve fracture risk prediction. One hundred and eleven subjects were included in this study and stratified in two groups: (a) 62 fracture cases, and (b) 49 non-fracture controls. Side fall was simulated using a static peak load that depended on patient mass and height. Local mechanical fields were calculated based on relationships between tissue stiffness and BMD. The area under the curve (AUC) of the receiver operating characteristic method evaluated the ability of calculated biomechanical descriptors to discriminate fracture and control cases. The results showed that the major principal stress was better discriminator (AUC > 0.80) than the volumetric BMD (AUC ≤ 0.70). High discrimination capacity was achieved when the analysis was performed by bone type, zone of fracture and gender/sex (AUC of 0.91 for women, trabecular bone and trochanter area), and outcomes suggested that the trabecular bone is critical for fracture discrimination. In conclusion, 3D FE models derived from DXA scans might significantly improve the prediction of hip fracture risk; providing a new insight for clinicians to use FE simulations in clinical practice for osteoporosis management.

Validation of the FRAX predictive model for major osteoporotic fracture in a historical cohort of Spanish women.

FRAX is a fracture risk assessment tool to estimate the 10-yr probability of a major osteoporotic fracture or a hip fracture. The aim of the study was to assess the predictive ability of FRAX for major osteoporotic fracture in a cohort of Spanish women. The study was based on a retrospective cohort of women aged 40-90 yr. Patients were followed from their first bone densitometry to the first major osteoporotic fracture event (forearm, proximal humerus, clinical spine, or hip fracture) or for 10 yr whichever comes first. A total of 1231 women were included. Bone mineral density data and self-reported data on risk factors for fracture were obtained. The predictive ability of FRAX was assessed by analyzing calibration and discrimination, with the calculation of observed-to-expected (O/E) fracture ratios and the receiver operating characteristic (ROC) curve, respectively. A total of 222 women (18.1%) reported at least 1 fracture after the first assessment. The incidence of fracture was 14 (95% confidence interval [CI]: 10-17), 19 (95% CI: 15-23), 28 (95% CI: 21-36), and 67 (95% CI: 8-125) cases per 1000 woman-years in women aged <55, 55-64, 65-74, and ≥75 yr, respectively. The O/E ratio was 3.9 (95% CI: 3.4-4.5; p<0.0001). The area under the ROC curve was 61% (95% CI: 57-65%). FRAX underestimated the risk of major osteoporotic fracture in this cohort of Spanish women, particularly in those with a low risk of fracture according to the clinical factors used in the FRAX tool. Our findings highlight the need for validation studies of FRAX in Spain.

Factores de riesgo de fracturas por fragilidad en una cohorte de mujeres españolas / Risk factors for fragility fractures in a cohort of Spanish women

Introducción Las fracturas por fragilidad constituyen un problema de salud pública. El objetivo fue analizar la asociación de los principales factores de riesgo de osteoporosis con la fracturas por fragilidad en una cohorte de mujeres con indicación de densitometría ósea. Métodos Cohorte retrospectiva con seguimiento hasta una fractura por fragilidad, de una población de mujeres de 40 a 90 años de edad con una primera visita para realizarse una densitometría entre enero de 1992 y febrero de 2008. Se calcularon la tasa de incidencia de fracturas por 1000 mujeres-año de seguimiento y la hazard ratio (HR) de fractura mediante un modelo de regresión de Cox. Resultados Se estudiaron 49.735 mujeres con una edad media de 57,8 años (desviación estándar: 8,5). De ellas, 3631 mujeres (7,1%) declararon al menos una fractura por fragilidad en las visitas posteriores a la basal. Los factores de riesgo con una mayor HR ajustada fueron la edad ≥75 años respecto a < 55 años (HR: 3,8; intervalo de confianza del 95% [IC95%]: 3,3-4,4) y tener un resultado de la densitometría valorable como osteoporosis respecto a normal (HR: 2; IC95%: 1,8-2,2). Los antecedentes de fracturas de húmero, cadera o vertebral tuvieron una HR ajustada de 1,2 (IC95%: 1,1-1,3).Conclusiones Los principales factores de riesgo de fracturas por fragilidad fueron la edad avanzada, el resultado de la densitometría y los antecedentes de fractura, aunque un 74% de las fracturas se produjeron con una densidad mineral ósea normal u osteopenia. Otros factores significativos fueron la artritis reumatoide y haber estado en tratamiento prolongado con corticosteroides(AU)

Introduction Fragility fractures are an important public health issue. The aim of this study was to analyze the association of the main osteoporotic risk factors related to fragility fracture in a cohort of women with an indication of bone densitometry (BD).Methods A retrospective cohort was followed-up until a fragile fracture occurred, in a population of women aged 40 to 90 years with a first visit for BD between January 1992 and February 2008. We calculated the incidence rate of fracture per 1000 women-years of follow-up, and the hazard ratio (HR) of fragile fracture using a Cox regression model. Results A total of 49,735 women were studied. The average age of participants was 57.8 years (SD: 8.5). Of these, 3631 women (7.1%) reported a new fragility fracture in post-baseline visits. Risk factors with higher adjusted HR were age ≥ 75 years compared with age < 55 years (HR: 3.8; 95% CI: 3.3-4.4) and having a BC result evaluated as osteoporosis compared to normal (HR: 2.0; 95% CI: 1.8-2.2). A personal history of humerus, hip or vertebral fractures had an adjusted HR of 1.2 (95% CI: 1.1-1.3).Conclusions The main risk factors for fragility fracture were advanced age, BD result and a personal history of fracture, although 74% of fractures were detected with a bone mineral density classified as normal or osteopenia. Other relevant factors were rheumatoid arthritis or having received prolonged corticosteroid therapy (AU)

[Risk factors for fragility fractures in a cohort of Spanish women]. / Factores de riesgo de fracturas por fragilidad en una cohorte de mujeres españolas.

INTRODUCTION: Fragility fractures are an important public health issue. The aim of this study was to analyze the association of the main osteoporotic risk factors related to fragility fracture in a cohort of women with an indication of bone densitometry (BD). METHODS: A retrospective cohort was followed-up until a fragile fracture occurred, in a population of women aged 40 to 90 years with a first visit for BD between January 1992 and February 2008. We calculated the incidence rate of fracture per 1000 women-years of follow-up, and the hazard ratio (HR) of fragile fracture using a Cox regression model. RESULTS: A total of 49,735 women were studied. The average age of participants was 57.8 years (SD: 8.5). Of these, 3631 women (7.1%) reported a new fragility fracture in post-baseline visits. Risk factors with higher adjusted HR were age ≥ 75 years compared with age < 55 years (HR: 3.8; 95% CI: 3.3-4.4) and having a BC result evaluated as osteoporosis compared to normal (HR: 2.0; 95% CI: 1.8-2.2). A personal history of humerus, hip or vertebral fractures had an adjusted HR of 1.2 (95% CI: 1.1-1.3). CONCLUSIONS: The main risk factors for fragility fracture were advanced age, BD result and a personal history of fracture, although 74% of fractures were detected with a bone mineral density classified as normal or osteopenia. Other relevant factors were rheumatoid arthritis or having received prolonged corticosteroid therapy.

The search for a new marker of renal function in older patients with chronic kidney disease stages 3-4: usefulness of cystatin C-based equations.

BACKGROUND/AIM: Cystatin C (Cys C) is an endogenous marker of glomerular filtration rate (GFR) unaffected by body composition. The aim of the present study was to assess the utility of Cys C-based GFR prediction equations (Hoek, Larsson and Stevens) and creatinine (modification of diet in renal disease-isotope dilution mass spectrometry--MDRD-IDMS, and Cockcroft-Gault--CG) compared with 51Cr-EDTA. METHODS: This study was carried out in 40 Caucasian older patients with advanced age (> or = 60) and chronic kidney disease stages 3-4. To assess the utility of prediction equations in relation to body composition, we measured lean mass (LM) with densitometry (DXA). Pearson's, Bland-Altman and Lin's coefficient (Rc) were used to study accuracy and precision. RESULTS: 51Cr-EDTA was 36.9 +/- 9.2 ml/min/1.73 m2 (22-60). Cys C levels were 2.2 +/- 0.8 mg/l (r = 0.085; p = 0.662 LM) and creatinine 2.8 +/- 1.1 mg/dl (r = 0.427; p = 0.021 LM). The most accurate equations were the Hoek, Larsson and Stevens formulae, with a bias of -0.2 (Rc 0.48), -2.9 (Rc 0.44) and 2.6 ml/min/1.73 m2 (Rc 0.58). The biases obtained with MDRD-IDMS and CG were -14.6 (Rc 0.35) and -12.5 (Rc 0.40). All correlations among biases obtained with creatinine-based formulae and LM were negative and statistically significant (p < 0.05). CONCLUSIONS: The results show superiority of Cys C-based GFR formulae over the MDRD-IDMS and CG equations. This significant underestimation obtained with conventional prediction equations was directly related to the influence of LM.