Masses In Cancer Patients Research Articles

The Obesity Paradox in Cancer: How Important Is Muscle?

Although higher body mass index (BMI) increases the incidence of many cancers, BMI can also exhibit a null or U-shaped relationship with survival among patients with existing disease; this association of higher BMI with improved survival is termed the obesity paradox. This review discusses possible explanations for the obesity paradox, the prevalence and consequences of low muscle mass in cancer patients, and future research directions. It is unlikely that methodological biases, such as reverse causality or confounding, fully explain the obesity paradox. Rather, up to a point, higher BMI may truly be associated with longer survival in cancer patients. This is due, in part, to the limitations of BMI, which scales weight to height without delineating adipose tissue distribution or distinguishing between adipose and muscle tissue. Thus, cancer patients with higher BMIs often have higher levels of protective muscle. We assert that more precise measures of body composition are required to clarify the relationship of body size to cancer outcomes, inform clinical decision-making, and help tailor lifestyle interventions.

Lean body mass, muscle fibre size and muscle function in cancer patients during chemotherapy and 10 weeks exercise

AbstractBackgroundChemotherapy can reduce muscle mass in cancer patients but the potential of exercise to ameliorate this is understudied, particularly at the myocellular level. The primary purpose was to investigate changes in lean body mass (LBM) and secondly single fibre cross‐sectional area (CSA) in cancer patients during chemotherapy and in combination with 10 weeks of exercise.MethodsIn a single‐arm trial, patients adhered to chemotherapy for at least 4 weeks (control period) before 10 weeks of exercise adjunct to chemotherapy (exercise period). LBM (Dual Energy X‐ray Absorptiometry) and single fibre CSA (muscle biopsies) were assessed at baseline, pre‐ and post‐exercise. Muscle strength, functional performance and aerobic capacity were also assessed.ResultsTen patients were included, however only six patients completed the protocol. LBM changed over time (p=0.013), but no significant changes were observed between specific time points. Numerically, LBM decreased by 0.3 kg (p=0.41, 95% CI: ‐1.1;0.5) from 41.3–41.0kg, during the control period and increased by 0.7 kg (p=0.16, 95% CI: ‐0.6;2.0) from 40.4–41.1 kg during exercise. Muscle fibre CSA did not change significantly over time (p=0.13), but decreased numerically in the control period by 703 μm2 (p=0.20, 95% CI: ‐1877; 470) and increased by 846 μm2 (trend, p=0.08, 95% CI: ‐162; 1854) following exercise. Muscle strength and functional performance were unchanged during the control period but improved post‐exercise.ConclusionsDespite non‐significant changes in muscle mass (due to small sample size), this study adds novel information on LBM and myocellular changes in cancer patients during chemotherapy and concurrent exercise.

The Prevalence and Prognostic Value of Low Muscle Mass in Cancer Patients: A Review of the Literature

An increasing number of studies underline the clinical value of low muscle mass as a prognostic factor for adverse outcomes in cancer patients. However, studies show large heterogeneity because of the lack of a standardized approach to measure muscle mass and the lack of reference populations. As a result, the interpretation of data and further progress are severely hampered, hindering the implementation of muscle measurement in oncological care. This review summarizes the methods of diagnosing low muscle mass in cancer patients, the difference between underlying syndromes such as sarcopenia and cachexia, and the association with clinical outcomes described so far.

The relationship of Beck depression inventory with vitamin D levels and visceral fat mass in cancer patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The Level of Serum Cholesterol is Negatively Associated with Lean Body Mass in Korean non-Diabetic Cancer Patients

Due to poor nutrition and abnormal energy metabolism, cancer patients typically experience the loss of muscle mass. Although the diabetic conditions or dyslipidemia have been reported as a causal link of cancer but the consequence of such conditions in relation to gain or loss of skeletal muscle mass in cancer patients has not been well documented. The purpose of this study was to investigate the relationship of lean body mass and systemic parameters related to lipid metabolism in non-diabetic cancer patients using data from the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2011. As results the level of serum total cholesterol (total-C) was negatively associated with both total lean body mass and appendicular lean body mass in cancer patients after adjustment for sex, physical activity, energy intake and comorbidity. The associations between consumption of dietary factors (energy, carbohydrate, protein and fat) and lean body mass were disappeared after adjusting comorbidities of cancer patients. Multivariate-adjusted linear regression analysis by quartiles of serum total-C showed that higher quartile group of total-C had significantly lower percent of lean body mass than reference group in cancer patients. The data indicate that serum lipid status can be the potential estimate of loss of skeletal muscle mass in cancer patients and be referenced in nutrition care of cancer patients under the onset of cachexia or parenteral/enteral nutrition. This data need to be confirmed with large pool of subjects and should be specified by stage of cancer or the site of cancer in future studies.

Voluntary exercise prevents cisplatin-induced muscle wasting during chemotherapy in mice.

Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P<0.001), lean body mass (20.6%, P = 0.001), as well as anorexia, impaired muscle strength (22.5% decrease, P<0.001) and decreased glucose tolerance. In addition, cisplatin impaired Akt-signalling, induced genes related to protein degradation and inflammation, and reduced muscle glycogen content. Voluntary wheel running during treatment attenuated body weight loss by 50% (P<0.001), maintained lean body mass (P<0.001) and muscle strength (P<0.001), reversed anorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may preserve muscle mass in cancer patients receiving cisplatin treatment, potentially improving physical capacity, quality of life and overall survival.

Effects of the ghrelin receptor agonist anamorelin on lean body mass in cancer patients with cachexia; results from a Phase II randomized, double blind, multicenter study

Background Cancer anorexia-cachexia is a frequent, debilitating and life-threatening condition in which altered metabolism and reduced food intake contribute to weight loss (mainly due to lean body mass [LBM] loss), which cannot be reverted by conventional nutritional support. Safe/effective treatments for cancer cachexia remain an unmet need. The hunger hormone ghrelin has been shown to activate key pathways in the regulation of body composition. Anamorelin (ANAM) is a novel, selective, oral ghrelin receptor agonist with appetiteenhancing and anabolic activity. Anamorelin is currently being investigated in phase III studies for the treatment of anorexia-cachexia in advanced non-small cell lung cancer (also known as the ROMANA program). Material and Methods Eighty-two patients with advanced cancer, ECOG performance score ≤ 2 and weight loss 5% within prior 6 months were treated with placebo (n=36) or 50mg anamorelin (n=38) once daily for 12 weeks. Body composition by DXA, handgrip strength (HGS) and Quality of Life (QoL; ASAS scale) were assessed at baseline, 4, 8 and 12 weeks. Solid tumors represented prevalent malignancy (>93%) with no difference in cancer types between treatment groups. Results Treatment with anamorelin for 12 weeks significantly increased total body mass (TBM) and LBM. Increases in LBM and TBM in anamorelin-treated patients were strongly correlated (r 2 =0.7249, p< 0.0001). Anamorelin treatment improvements in HGS and QoL were previously presented [1]. Anamorelin was well tolerated, and types and prevalence of AEs were similar between treatment arms.

Impact of denosumab on bone mass in cancer patients

Cancer therapy-induced bone loss (CTIBL) is a form of secondary osteoporosis associated with systemic chemotherapy and hormonal ablation therapy. The monitoring and treatment of CTIBL is an important component of comprehensive cancer care, especially for patients with curable disease and long life expectancies. Whereas oral bisphosphonates remain the most commonly used therapeutic option for CTIBL, additional treatment options may be required for patients who do not respond adequately or are intolerant to bisphosphonates, have renal insufficiency, or are receiving treatment with nephrotoxic medications. For these patients, denosumab, a monoclonal antibody targeting the receptor activator of nuclear factor-κB ligand (RANKL), offers an effective and well-tolerated alternative. Several recent randomized trials have examined the use of denosumab as treatment for CTIBL associated with hormone ablation therapy for breast and prostate cancer. Recent data suggest a possible role for RANKL inhibitors in both chemoprevention and the prevention of cancer recurrence through direct effects on breast tissue and breast cancer stem cells. The outcomes of several international Phase III clinical trials currently underway will help clarify the role of denosumab in patients undergoing cancer therapy.

1588P - Anamorelin's Effects on Appendicular Lean Body Mass in Cancer Patients with Cachexia; Results from A Phase II Randomized, Double Blind, Multicenter Study

ABSTRACT Background Cancer cachexia is associated with increased morbidity and poor survival, and is characterized by decreased muscle strength and overall lean body mass including in the extremities (appendicular LBM or aLBM). As most lean tissue in the extremities is striated muscle, aLBM is a good surrogate for muscle mass. Anamorelin is an investigational orally active ghrelin receptor agonist with orexigenic and anabolic activity. We present here a Phase II study post-hoc analysis on a subset of patients who were assessed for aLBM. Methods A Phase II trial enrolled patients with advanced cancer, performance score ≤ 2 and weight loss ≥5% within 6 months from enrollment. Patients were randomized to treatment with placebo (PL) or 50mg anamorelin (ANA) once daily for 12 weeks. Eighty-two patients were assessed for total LBM by DXA, handgrip strength (HGS) and Quality of Life (QoL; ASAS scale) at baseline, 4, 8 and 12 weeks. For 72 subjects (N = 38, ANA; N = 34, PL), data was also available for aLBM. Solid tumors represented prevalent malignancy (>93%) with no difference in cancer types between treatment groups Results Analysis of aLBM indicated that PL-treated patients lost aLBM in the arms during the whole 12 weeks, while aLBM in the legs was more stable. In ANA-treated patients, aLBM increased significantly in the arms and in the legs. At week 12, the percentage change from baseline of aLBM in arms + legs showed a statistically significant increase in ANA vs PL groups (5.8% and 1.5%, respectively; p Conclusion Decreased LBM and HGS are poor prognostic factors in cancer cachexia patients. This study demonstrates that 50mg ANA treatment for 12 weeks significantly increased aLBM and HGS. Together with the orexigenic activity of ANA, these results support the use of ANA in treating cancer cachexia/anorexia and the evaluation of higher ANA doses. Disclosure J.M. Garcia: I receive research support from Helsinn, Y. Yan: I am an Helsinn employee E. Duus: I am an Helsinn employee, J. Friend: I am an Helsinn employee.

Cytokine gene polymorphisms and susceptibility to cachexia

Cachexia is a progressive deterioration of body habitus associated with chronic diseases. The finding that only a proportion of patients with chronic disease develop cachexia has prompted studies looking for genetic polymorphisms that may underlie differential susceptibility. The aim of this review is to explore how inflammation and gene polymorphisms influence susceptibility to cachexia. There has been evidence that certain cytokine gene polymorphisms are associated with cachexia. However, only the IL10 -1082 G allele, which is associated with an increased risk of developing cachexia has been replicated in more than one study. Variation in genes outwith inflammation pathways (e.g. genes involved in protein metabolism) is also likely to contribute the susceptibility of developing cachexia. The insertion/deletion angiotensin converting enzyme (ACE) gene polymorphism has recently been linked with lower lean body mass in cancer patients with cachexia. Although there is an increasing body of evidence of genetic susceptibility to cachexia, most studies so far have only focussed on a small number of polymorphisms and have small sample sizes. Large-scale candidate gene studies or genome-wide association studies are required to further elucidate the link between genotype and cachexia.

Incidental Non-Secreting Adrenal Masses in Cancer Patients: Intra-Individual Comparison of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography with Computed Tomography and Shift Magnetic Resonance Imaging

The ability of integrated (18)F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to distinguish between benign and malignant incidental non-secreting adrenal masses was evaluated in cancer patients. Results were compared with those of CT and shift magnetic resonance imaging (MRI). A total of 1832 cancer patients who had undergone FDG PET/CT scans were retrospectively evaluated. Visual interpretation, tumour maximum standardized uptake value (SUV(max)), liver SUV(max) and tumour/liver SUV(max) ratios were correlated with the findings of CT, shift MRI and final diagnosis (based on biopsy or clinical/radiological follow-up). A total of 109 adrenal masses were found: 49 were malignant and 60 were benign on final diagnosis. A tumour/liver SUV(max) ratio threshold of 1.0 was more accurate in differentiating the tumour type than tumour SUV(max) or visual interpretation alone. Diagnostic accuracy of CT and shift MRI (92 - 97%) was similar to that for FDG PET/CT (94 - 97%). In conclusion, FDG PET/CT accurately characterizes adrenal tumours, with excellent sensitivity and specificity. Use of 1.0 as the threshold for the tumour/liver SUV(max) ratio seems to be promising for distinguishing benign from malignant adrenal masses in cancer patients.

Ostarine increases lean body mass and improves physical performance in healthy elderly subjects: Implications for cancer cachexia patients

9119 Background: Cancer cachexia results in selective loss of skeletal muscle resulting in weakness, reduced physical activity and a lower quality of life. Cancer cachexia also diminishes response to chemotherapy and survival. Anabolic steroids appear to increase weight and muscle mass in cancer patients, but have the potential for masculinization in women and prostate stimulation in men. A new class of non-steroidal selective androgen receptor modulators (SARMs) is being developed for use in cancer cachexia. SARMs are designed to have predominately anabolic activity in muscle and bone with minimal androgenic effects in most other tissues. We conducted a randomized phase II proof of concept study of ostarine, the first-in-class SARM, in healthy postmenopausal women and elderly men prior to intitiating a phase II study in cancer patients. Methods: Sixty elderly men (mean age 66 years) and 60 postmenopausal women (mean age 63 years) were randomly assigned to ostarine 0.1, 0.3, 1 mg, 3 mg or placebo for three months. The primary end point was change from baseline to three months in total lean body mass (LBM) measured by dual energy x-ray absorptiometry (DXA). The key secondary end point was a stair climb functional performance test that measured speed and power exerted. Evaluations included laboratory safety assessments and additional assessments of androgenic activity including PSA, sebum production and luteinizing hormone. Results: Ostarine treatment resulted in a dose dependent increase in total LBM, with an increase of 1.4 kg compared to placebo (p&lt;0.001) at the 3 mg dose. Increased LBM translated to an improvement in the stair climb test in both speed (+15.5% ± 12.9 faster time, p=0.006) and power (+25.5% ± 20.3 watts, p=0.005). There were no serious adverse events reported. There were no significant changes in PSA, sebum production or luteinizing hormone. Conclusions: Ostarine improves LBM and physical performance in healthy older men and women. Ostarine had no unwanted androgenic side effects. A phase II study is planned to evaluate the safety and efficacy of ostarine in patients with cancer cachexia. No significant financial relationships to disclose.

Evaluation of an adrenal mass in a patient with progressive prostate cancer reveals pheochromocytoma

Adrenal masses in cancer patients pose diagnostic problems. We report the case of a 59 years old male with a history of prostate cancer who presented to us with serially rising prostate specific antigen. On imaging studies he had bone lesions and in addition had a 1.7 cm left adrenal mass. Since metastasis to the adrenal gland has rarely been reported in prostate cancer, and since the radiological criteria in our case favored malignancy, we proceeded with hormonal evaluation and fine needle aspiration biopsy of the adrenal mass which proved it to be pheochromocytoma. This was followed by an uneventful adrenalectomy.

Cysteine and glutathione in catabolic conditions and immunological dysfunction.

The conspicuous increase in the plasma cysteine disulphide/thiol ratio in elderly persons and cancer patients indicates a shift of the plasma redox state. The most important redox buffers in skeletal muscle tissue and blood plasma, i.e. glutathione and albumin, respectively, are significantly decreased in different models of cachexia. Treatment with N-acetyl cysteine, i.e. a thiol-containing antioxidant, was found to increase the plasma albumin level and to ameliorate the loss of body cell mass in cancer patients and healthy individuals. The treatment of HIV infection with N-acetyl cysteine, in contrast, serves mainly as a tool to ameliorate the physiological and immunological consequences of the virus-induced cysteine deficiency.

Does an increased adreno-cortical activity explain loss of lean body mass in cancer patients : [formula omitted], C. Drott & K. Lundholm.Departments of Surgery II & I, Sahlgrenska Hospital, Gothenburg, Sweden

Does an increased adreno-cortical activity explain loss of lean body mass in cancer patients : [formula omitted], C. Drott & K. Lundholm.Departments of Surgery II & I, Sahlgrenska Hospital, Gothenburg, Sweden