Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients.
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ABSTRACT: Background
Little is known on factors predicting sunitinib toxicity. Recently, the condition of low muscle mass, named sarcopenia, was identified as a significant predictor of toxicity in metastatic renal cell cancer (mRCC) patients treated with sorafenib. We investigated whether sarcopenia could predict early dose-limiting toxicities (DLTs) occurrence in mRCC patients treated with sunitinib.Methods
Consecutive mRCC patients treated with sunitinib were retrospectively reviewed. A DLT was defined as any toxicity leading to dose reduction or treatment discontinuation. Body composition was evaluated using CT scan obtained within 1 month before treatment initiation.Results
Among 61 patients eligible for analysis, 52.5% were sarcopenic and 32.8% had both sarcopenia and a body mass index (BMI)<25?kg?m(-2). Eighteen patients (29.5%) experienced a DLT during the first cycle. Sarcopenic patients with a BMI<25?kg?m(-2) experienced more DLTs (P=0.01; odds ratio=4.1; 95% CI: (1.3-13.3)), more cumulative grade 2 or 3 toxicities (P=0.008), more grade 3 toxicities (P=0.04) and more acute vascular toxicities (P=0.009).Conclusion
Patients with sarcopenia and a BMI<25?kg?m(-2) experienced significantly more DLTs during the first cycle of treatment.
SUBMITTER: Huillard O
PROVIDER: S-EPMC3619075 | biostudies-literature | 2013 Mar
REPOSITORIES: biostudies-literature
Publications
Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients.
Huillard O O Mir O O Peyromaure M M Tlemsani C C Giroux J J Boudou-Rouquette P P Ropert S S Delongchamps N Barry NB Zerbib M M Goldwasser F F
British journal of cancer 20130305 5
<h4>Background</h4>Little is known on factors predicting sunitinib toxicity. Recently, the condition of low muscle mass, named sarcopenia, was identified as a significant predictor of toxicity in metastatic renal cell cancer (mRCC) patients treated with sorafenib. We investigated whether sarcopenia could predict early dose-limiting toxicities (DLTs) occurrence in mRCC patients treated with sunitinib.<h4>Methods</h4>Consecutive mRCC patients treated with sunitinib were retrospectively reviewed. A ...[more]
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Project description:BACKGROUND: Sorafenib induces frequent dose limiting toxicities (DLT) in patients with advanced hepatocellular carcinoma (HCC). Sarcopenia has been associated with poor performance status and shortened survival in cancer patients. PATIENTS AND METHODS: The characteristics of Child Pugh A cirrhotic patients with HCC receiving sorafenib in our institution were retrospectively analyzed. Sorafenib plasma concentrations were determined at each visit. Toxicities were recorded during the first month of treatment, and sarcopenia was determined from baseline CT-scans. RESULTS: Forty patients (30 males) were included. Eleven (27.5%) were sarcopenic. Eighteen patients (45%) experienced a DLT during the first month of treatment. Sarcopenic patients experienced significantly more DLTs than non-sarcopenic patients did (82% versus 31%, p = 0.005). Grade 3 diarrhea was significantly more frequent in sarcopenic patients than in non-sarcopenic patients (45.5% versus 6.9%, p = 0.01), but not grade 3 hand foot syndrome reaction (9% versus 17.2%, p = 1). On day 28, median sorafenib AUC (n = 17) was significantly higher in sarcopenic patients (102.4 mg/l.h versus 53.7 mg/l.h, p = 0.013). CONCLUSIONS: Among cirrhotic Child Pugh A patients with advanced HCC, sarcopenia predicts sorafenib exposure and the occurrence of DLT within the first month of treatment.
| S-EPMC3364283 | biostudies-literature
Project description:BackgroundIncreasing evidence suggests that severe skeletal muscle index (SMI) loss (sarcopenia) is associated with poor overall survival in metastatic colorectal cancer patients, but its mechanisms are unknown. We recently found, using data of the randomized phase 3 CAIRO3 study, that SMI loss was related with shorter time to disease progression and overall survival during first-line maintenance treatment with capecitabine + bevacizumab (CAP-B) or observation and during more intensive capecitabine + oxaliplatin + bevacizumab (CAPOX-B) reintroduction treatment. As a potential risk factor for reduced survival, we explored whether sarcopenia and SMI loss were associated with dose-limiting toxicities (DLTs) during CAP-B and CAPOX-B.MethodsSarcopenia status and SMI loss were assessed by using consecutive computed tomography scans. DLTs were defined as any dose delay/reduction/discontinuation of systemic treatment because of reported CTCAE (version 3.0) toxicities at the start or during treatment. Poisson regression models were used to study whether sarcopenia and body mass index (BMI) at the start of treatment and SMI and BMI loss during treatment were associated with DLTs.ResultsOne hundred eighty-two patients (mean age 63.0 ± 8.8 years, 37% female) received CAP-B, and 232 patients (mean age 63.0 ± 9.0 years, 34% female) received CAPOX-B. At the start of CAP-B and CAPOX-B, 54% and 46% of patients were sarcopenic, respectively. Mean BMI was lower in sarcopenic patients, although patients were on average still overweight (sarcopenic vs. non-sarcopenic at the start of CAP-B 25.0 ± 3.9 vs. 26.7 ± 4.1 and CAPOX-B 25.8 ± 3.8 vs. 27.1 ± 3.8 kg/m2 ). Sarcopenia at the start of CAP-B was not associated with DLTs [relative risk 0.87 (95% confidence interval 0.64-1.19)], whereas patients with >2% SMI loss had a significantly higher risk of DLTs [1.29 (1.01-1.66)]. At the start of subsequent CAPOX-B, 25% of patients received a dose reduction, and the risk of dose reduction was significantly higher for patients with preceding SMI loss [1.78 (1.06-3.01)] or sarcopenia [1.75 (1.08-2.86)]. After the received dose reductions, sarcopenia or SMI loss was not significantly associated with a higher risk of DLTs during CAPOX-B [sarcopenia vs. non-sarcopenic: 0.86 (0.69-1.08) and SMI loss vs. stable/gain: 0.83 (0.65-1.07)]. In contrast, BMI (loss) at the start or during either treatment was not associated with an increased risk of DLTs.ConclusionsIn this large longitudinal study in metastatic colorectal cancer patients during palliative systemic treatment, sarcopenia and/or muscle loss was associated with an increased risk of DLTs. BMI was not associated with DLTs and could not detect sarcopenia or SMI loss. Prospective (randomized) studies should reveal whether normalizing chemotherapeutic doses to muscle mass or muscle mass preservation (by exercise and nutritional interventions) increases chemotherapeutic tolerance and improves survival.
| S-EPMC6711417 | biostudies-literature
Project description:BackgroundWarfarin inhibits vitamin K-dependent coagulation factors. Being fat-soluble, the availability of vitamin K may vary according to body fat. We hypothesized that body mass index (BMI), a proxy of body fat, may interact with vitamin K intake in determining a warfarin maintenance (WM) dose.MethodsPatients with data on vitamin K intake, potential confounders and WM dose (n = 172) were included in linear regression models to test whether BMI modifies the relation between vitamin K intake and WM dose.ResultsWarfarin loading dose correlated with the maintenance dose (r = 0.36, p < 0.0001) but was not significantly associated with WM dose in analyses adjusted for vitamin K epoxide reductase (VKORC1) and cytochrome P450 2C9 (CYP2C9) genotypes. In fully adjusted models, BMI was associated (p = 0.001) with WM dose but vitamin K was only marginally positively associated (p = 0.06) with WM dose. We found no interaction (p > 0.05) between BMI and vitamin K intake with regard to WM dose. Inclusion of vitamin K intake in the model only slightly improved the amount of variance (1.1%) explained by age, gender, BMI, race, physical activity, energy intake and VKORC1 and CYP2C9 genotypes.ConclusionOur data suggest that body fat does not affect the relation between vitamin K intake and WM dose.
| S-EPMC4038335 | biostudies-literature
Project description:The multitargeted tyrosine-kinase inhibitor sunitinib has emerged as one of the standards of care for good- and intermediate-risk metastatic renal cell carcinoma. Although generally associated with acceptable toxicity, sunitinib exhibits a novel and distinct toxicity profile that requires monitoring and management. Fatigue, diarrhea, anorexia, oral changes, hand-foot syndrome and other skin toxicity, thyroid dysfunction, myelotoxicity, and hypertension seem to be the most common and clinically relevant toxicities of sunitinib. Drug dosing and treatment duration are correlated with response to treatment and survival. Treatment recommendations for hypertension have been published but, currently, no standard guidelines exist for the management of noncardiovascular side effects. To discuss the optimal management of noncardiovascular side effects, an international, interdisciplinary panel of experts gathered in November 2009. Existing literature on incidence, severity, and underlying mechanisms of side effects as well as on potential treatment options were carefully reviewed and discussed. On the basis of these proceedings and the thorough review of the existing literature, recommendations were made for the monitoring, prevention, and treatment of the most common noncardiovascular side effects and are summarized in this review. The proactive assessment and consistent and timely management of sunitinib-related side effects are critical to ensure optimal treatment benefit by allowing appropriate drug dosing and prolonged treatment periods.
| S-EPMC3228204 | biostudies-literature
Project description:AimsThe definition of sarcopenia based on appendicular lean mass/height (2) (ALM/height (2) ) is often used, although it can underestimate the prevalence of sarcopenia in overweight/obese patients with heart failure. Therefore, new methods have been proposed to overcome this limitation. We aimed to evaluate the prevalence of sarcopenia by three methods and compare body composition in this population.Methods and resultsWe enrolled 168 male patients with heart failure (left ventricular ejection fraction <40%). Sixty-six patients (39.3%) were identified with sarcopenia by at least one method. The lower 20th percentile defined as the cut-off point for sarcopenia was 7.03 kg/m2 , -2.32 and 0.76 for Baumgartner's (20.8%), Newman's (21.4%), and Studenski's methods (21.4%), respectively. Patients with body mass index (BMI) <25 kg/m2 were more likely to be identified by Baumgartner's than Studenski's method (P < 0.001). However, in patients with BMI ≥ 25 kg/m2 , Studenski's and Newman's methods were more likely to detect sarcopenia than Baumgartner's method (both P < 0.005). Patients were further divided into three subgroups: (i) patients classified in all indexes (n = 8), (ii) patients classified in Baumgartner's (sarcopenic; n = 27), and (iii) patients classified in both Newman's and Studenski's methods (sarcopenic obesity; n = 31). Comparing body composition among groups, all sarcopenic groups presented lower total lean mass compared with non-sarcopenic patients, whereas sarcopenic obese patients had higher total lean mass than lean sarcopenic patients.ConclusionsOur results demonstrate that the prevalence of sarcopenia in overweight/obese patients is similar to lean sarcopenic patients when other methods are considered. In patients with higher BMI, Studenski's method seems to be more feasible to detect sarcopenia.
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Project description:PURPOSE:Obesity is an established risk factor for clear cell renal cell carcinoma (RCC); however, some reports suggest that RCC developing in obese patients may be more indolent. We investigated the clinical and biologic effect of body mass index (BMI) on treatment outcomes in patients with metastatic RCC. METHODS:The impact of BMI (high BMI: ? 25 kg/m2 v low BMI: < 25 kg/m2) on overall survival (OS) and treatment outcome with targeted therapy was investigated in 1,975 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and in an external validation cohort of 4,657 patients. Gene expression profiling focusing on fatty acid metabolism pathway, in The Cancer Genome Atlas data set, and immunohistochemistry staining for fatty acid synthase (FASN) were also investigated. Cox regression was undertaken to estimate the association of BMI with OS, adjusted for the IMDC prognostic factors. RESULTS:In the IMDC cohort, median OS was 25.6 months (95% CI, 23.2 to 28.6) in patients with high BMI versus 17.1 months (95% CI, 15.5 to 18.5) in patients with low BMI (adjusted hazard ratio, 0.84; 95% CI, 0.73 to 0.95). In the validation cohort, high BMI was associated with improved OS (adjusted hazard ratio, 0.83; 95% CI, 0.74 to 0.93; medians: 23.4 months [95% CI, 21.9 to 25.3 months] v 14.5 months [95% CI, 13.8 to 15.9 months], respectively). In The Cancer Genome Atlas data set (n = 61), FASN gene expression inversely correlated with BMI (P = .034), and OS was longer in the low FASN expression group (medians: 36.8 v 15.0 months; P = .002). FASN immunohistochemistry positivity was more frequently detected in IMDC poor (48%) and intermediate (34%) risk groups than in the favorable risk group (17%; P-trend = .015). CONCLUSION:High BMI is a prognostic factor for improved survival and progression-free survival in patients with metastatic RCC treated with targeted therapy. Underlying biology suggests a role for the FASN pathway.
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Project description:Background and purposePredicting the appropriate needle length to use in oblique interlaminar-approach fluoroscopy-guided lumbar punctures in patients with a large body mass index is difficult. Using the wrong needle length can lead to an increased radiation dose and patient discomfort. We hypothesized that body mass index could help determine the appropriate needle length to use in patients.Materials and methodsWe randomly selected patients who underwent oblique interlaminar-approach fluoroscopy-guided lumbar punctures and had cross-sectional imaging of the lumbar spine within 1 year of imaging (n = 50). The distance from the skin to the midlumbar spinal canal (skin-canal distance) at the level of the lumbar puncture was measured by using an oblique angle of 8.6°, which is an average of angles most often used to perform the procedure. A formula was devised using the skin-canal distance and body mass index to predict the appropriate needle length, subsequently confirmed in 45 patients.ResultsThe body mass index and skin-canal distance were significantly higher (P < .001) in patients who underwent fluoroscopy-guided lumbar puncture with 5- or 7-inch needles (n = 22) than in patients requiring 3.5-inch needles (n = 28). Using linear regression, we determined the formula to predict the needle length as Skin-Canal Distance (inches) = 0.077 × Body Mass Index + 0.88. We found a strong correlation (P < .001) between the predicted and actual skin canal distance in 45 patients, and our formula better predicted the skin-canal distance than others.ConclusionsWe designed a formula that uses body mass index to predict the appropriate needle length in oblique interlaminar-approach fluoroscopy-guided lumbar punctures and validated it by demonstrating a strong correlation between the predicted and actual skin-canal distance.
| S-EPMC7960139 | biostudies-literature
Project description:Bariatric surgery is the treatment for severe obesity, with proven efficacy in reducing weight. Weight loss associated with bariatric surgery is greatly associated with a significant reduction of skeletal muscle and bone mineral mass, which leads us to induce that after bariatric surgery, patients incur an increased risk of sarcopenia. Prophylactic programs that prevent sarcopenia in bariatric surgery patients seems to be one of the crucial points for the long-term surgical success of bariatric and metabolic surgery. This article presents a initial data set of skeletal muscle mass index, body composition and strength to determinate sarcopenia in bariatric patients. The data were collected in a Central Hospital and in the University. In total, is necessary to recruit 46 patients waiting for bariatric surgery, between 18 and 60 years, men, and woman, without contradiction for exercise. The patients are randomized in two groups, for exercise group and control group. The evaluation is made on five points of timeline, before the surgery, after the surgery, after de exercise program, six months, and twelve months after the exercise program.
| S-EPMC9852481 | biostudies-literature
Project description:Obesity is a risk factor for renal cell (or renal) cancer. The increasing prevalence of obesity may be contributing to the rising incidence of this cancer over the past several decades. The effects of early-age obesity and change in body mass index (BMI) on renal cancer have been studied less thoroughly, and the influence of race has never been formally investigated.Using data gathered as part of a large case-control study of renal cancer (1214 cases and 1234 controls), we investigated associations with BMI at several time points, as well as with height. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic regression modeling. Race- and sex-stratified analyses were conducted to evaluate subgroup differences.Obesity (BMI ? 30 kg/m) early in adulthood (OR = 1.6 [95% CI = 1.1 to 2.4]) and 5 years before diagnosis (1.6 [1.1 to 2.2]) was associated with renal cancer. The association with early-adult obesity was stronger among whites than blacks (test for interaction, P = 0.006), whereas the association with obesity near diagnosis was marginally stronger in women than men (test for interaction, P = 0.08). The strongest association with renal cancer was observed for obese whites both in early adulthood and before interview (2.6 [1.5 to 4.4]); this association was not present among blacks. Estimates of the annual excess rate of renal cancer (per 100,000 persons) attributed to both overweight and obesity (BMI > 25 kg/m) ranged from 9.9 among black men to 5.6 among white women.Obesity, both early and later in life, is associated with an increased risk of renal cancer. The association with early obesity seems to be stronger among whites than blacks.
| S-EPMC3466395 | biostudies-literature
Project description:ImportanceBody mass index (BMI) is used to diagnose obesity in adolescents worldwide, despite evidence that weight does not scale with height squared in adolescents. To account for this, health care providers diagnose obesity using BMI percentiles for each age (BMI z scores), but this does not ensure that BMI is accurate in adolescents.ObjectiveTo compare the accuracy of BMI vs other body fat indices of the form body mass divided by heightn in estimating body fat levels in adolescents.Design, setting, and participantsCross-sectional data from the 1999 to 2006 US National Health and Nutrition Examination Survey were analyzed between September 2015 and December 2016.Main outcomes and measuresDual-energy x-ray absorptiometry and anthropometric data were used to determine changes in body fat levels, body proportions, and the scaling relationships among body mass, height, and percent body fat. To assess the merits of each adiposity index, 3 criteria were used: stability with age, accuracy in estimating percent body fat, and accuracy in classifying adolescents as overweight vs normal weight.ResultsParticipants included 2285 non-Hispanic white participants aged 8 to 29 years. Percent body fat varied with both age and height during adolescence, invalidating the standard weight-to-height regression as the way of finding the optimal body fat index. Because the correct regression model (percent body fat is proportional to mass divided by heightn) suggested that percent body fat scales to height with an exponent closer to 3, we therefore focused on the tri-ponderal mass index (TMI; mass divided by height cubed) as an alternative to BMI z scores. For ages 8 to 17 years, TMI yielded greater stability with age and estimated percent body fat better than BMI (R2?=?0.64 vs 0.38 in boys and R2?=?0.72 vs 0.66 in girls). Moreover, TMI misclassified adolescents as overweight vs normal weight less often than BMI z scores (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 19.4%; 95% CI, 17.8%-20.0%; P?<?.001) and performed equally as well as updated BMI percentiles derived from the same data set (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 8.0%; 95% CI, 6.9%-9.1%; P?=?.62).Conclusions and relevanceThe tri-ponderal mass index estimates body fat levels more accurately than BMI in non-Hispanic white adolescents aged 8 to 17 years. Moreover, TMI diagnoses adolescents as overweight more accurately than BMI z scores and equally as well as updated BMI percentiles but is much simpler to use than either because it does not involve complicated percentiles. Taken together, it is worth considering replacing BMI z scores with TMI to estimate body fat levels in adolescents.
| S-EPMC5710345 | biostudies-literature