Ghrelin prevents tumour- and cisplatin-induced muscle wasting: characterization of multiple mechanisms involved. Chen Ji-An,Splenser Andres,Guillory Bobby,Luo Jiaohua,Mendiratta Meenal,Belinova Blaga,Halder Tripti,Zhang Guohua,Li Yi-Ping,Garcia Jose M Journal of cachexia, sarcopenia and muscle BACKGROUND:Cachexia and muscle atrophy are common consequences of cancer and chemotherapy administration. The novel hormone ghrelin has been proposed as a treatment for this condition. Increases in food intake and direct effects on muscle proteolysis and protein synthesis are likely to mediate these effects, but the pathways leading to these events are not well understood. METHODS:We characterized molecular pathways involved in muscle atrophy induced by Lewis lung carcinoma (LLC) tumour implantation in c57/bl6 adult male mice and by administration of the chemotherapeutic agent cisplatin in mice and in C2C12 myotubes. The effects of exogenous ghrelin administration and its mechanisms of action were examined in these settings. RESULTS:Tumour implantation and cisplatin induced muscle atrophy by activating pro-inflammatory cytokines, p38-C/EBP-β, and myostatin, and by down-regulating Akt, myoD, and myogenin, leading to activation of ubiquitin-proteasome-mediated proteolysis and muscle weakness. Tumour implantation also increased mortality. In vitro, cisplatin up-regulated myostatin and atrogin-1 by activating C/EBP-β and FoxO1/3. Ghrelin prevented these changes in vivo and in vitro, significantly increasing muscle mass (P < 0.05 for LLC and P < 0.01 for cisplatin models) and grip strength (P = 0.038 for LLC and P = 0.001 for cisplatin models) and improving survival (P = 0.021 for LLC model). CONCLUSION:Ghrelin prevents muscle atrophy by down-regulating inflammation, p38/C/EBP-β/myostatin, and activating Akt, myogenin, and myoD. These changes appear, at least in part, to target muscle cells directly. Ghrelin administration in this setting is associated with improved muscle strength and survival. 10.1002/jcsm.12023
    Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling. Chen Xiangzheng,Wu Yangping,Yang Tinghan,Wei Mingtian,Wang Yuxi,Deng Xiangbing,Shen Congcong,Li Wenting,Zhang Hang,Xu Weiyong,Gou Lantu,Zeng Yong,Zhang Yonghui,Wang Ziqiang,Yang Jinliang Journal of cachexia, sarcopenia and muscle BACKGROUND:Cachexia has a devastating impact on survival and quality of life for many cancer patients and contributes to nearly one-third of all cancer deaths; also, it is associated with poor responses to chemotherapy and survival. A better understanding of the underlying mechanisms of cancer-associated cachexia (CAC), coupled with effective therapeutic approaches, will improve management of progressive functional impairment in cancer patients. Salidroside, a phenylpropanoid glycoside in Rhodiola rosea L, has been reported to possess potential anti-fatigue, anti-ageing, and anti-Alzheimer's disease properties. It is widely consumed as a nutritional supplement, but its effects on CAC and the possible mechanism remain a mystery. METHODS:In the murine models of cachexia induced by CT-26 and Lewis lung carcinoma (LLC) tumour, respectively, main features of CAC were determined after treatment of salidroside or chemotherapy. In vitro experiments were performed using murine C2C12 myotubes, which were treated by tumour necrosis factor-α. Levels of several critical muscle-related signal proteins such as mammalian target of rapamycin (mTOR), p-mTOR, and myosin heavy chain (MyHC) were examined using western blot both in vitro and in vivo. RESULTS:In the present study, we showed the exciting effect of salidroside on the treatment of CAC. In CT-26 and LLC models, respectively, salidroside treatment could effectively preserve the tumour-free body weight, decrease loss of adipose and gastrocnemius muscles, alleviate tumour burden, and prolong their survival time. Additionally, in combined chemotherapy, salidroside could synergistically enhance the anti-tumour activity of cisplatin, especially decreased or eliminated chemotherapy-induced cachexia. Further analysis demonstrated that salidroside could significantly increase expression of mTOR, p-mTOR, and MyHC in gastrocnemius muscle. Also, results in vitro showed that salidroside could not only obviously increase mTOR, p-mTOR, and MyHC expression in C2C12 myotubes but also effectively rescue their down-regulation induced by tumour necrosis factor-α. CONCLUSIONS:In the current study, the exciting effect of salidroside on CAC suggested that salidroside supplementation might be a promising approach for a multi-targeted therapy for the treatment of CAC. 10.1002/jcsm.12054
    Clinical outcomes related to muscle mass in humans with cancer and catabolic illnesses. Baracos Vickie,Kazemi-Bajestani Seyyed Mohammad Reza The international journal of biochemistry & cell biology It is generally accepted that excessive loss of skeletal muscle mass is detrimental. Depletion of muscle mass is associated with poor prognosis in diabetes, trauma, sepsis, lung disease, renal failure and heart failure. In this review we discuss the emergence of muscle mass measurement using diagnostic imaging and the relationship between muscle mass and clinical outcome. The pursuit of specific biochemical targets for reversal of muscle wasting, has spawned a host of investigator initiated research on muscle wasting as well as investigational new drug programs in pharmaceutical companies. Research on therapeutics targeting muscle is to a large extent done in animal models, with relatively few investigations done using human muscle or reporting upon muscle mass or muscle-related outcomes in humans. Since ∼1990, a quantitative approach, as opposed to a purely functional approach, to muscle atrophy and hypertrophy has become accessible with the advent of image-based assessments (dual energy X-ray absorptiometry, computed tomography and magnetic resonance imaging). These methods have high specificity and precision. In conclusion, current imaging techniques allow us to quantify the degree of muscularity of different individuals, to relate muscle mass to disease-specific outcomes, to define sarcopenia [severe muscle depletion] in quantitative terms, to detect the prevalence and rates of catabolic loss of muscle, the behavior of specific individual muscles and to define the efficacy of different therapies developed for the treatment of muscle wasting. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. 10.1016/j.biocel.2013.06.016
    Enobosarm (GTx-024, S-22): a potential treatment for cachexia. Srinath Reshmi,Dobs Adrian Future oncology (London, England) Muscle loss and wasting occurs with aging and in multiple disease states including cancer, heart failure, chronic obstructive pulmonary disease, end-stage liver disease, end-stage renal disease and HIV. Cachexia is defined as a multifactorial syndrome that is associated with anorexia, weight loss and increased catabolism, with increased morbidity and mortality. Currently no therapy is approved for the treatment or prevention of cachexia. Different treatment options have been suggested but many have proven to be ineffective or associated with adverse events. Nonsteroidal selective androgen receptor modulators (SARMs) are a new class of anabolic agents that bind the androgen receptor and exhibit tissue selectivity. Enobosarm (GTx-024, S-22) is a recently developed SARM, developed by GTx, Inc. (TN, USA), which has been tested in Phase I, II and III trials with promising results in terms of improving lean body mass and measurements of physical function and power. Enobosarm has received fast track designation by the US FDA and results from the Phase III trials POWER1 and POWER2 will help determine approval for use in the prevention and treatment of muscle wasting in patients with non-small-cell lung cancer. This article provides an introduction to enobosarm as a new therapeutic strategy for the prevention and treatment of cachexia. A review of the literature was performed using search terms 'cachexia', 'sarcopenia', 'SARM', 'enobosarm' and 'GTx-024' in September 2013 using multiple databases as well as online resources. 10.2217/fon.13.273
    The influence of different muscle mass measurements on the diagnosis of cancer cachexia. Blauwhoff-Buskermolen Susanne,Langius Jacqueline A E,Becker Annemarie,Verheul Henk M W,de van der Schueren Marian A E Journal of cachexia, sarcopenia and muscle BACKGROUND:Progressive loss of muscle mass is a major characteristic of cancer cachexia. Consensus definitions for cachexia provide different options to measure muscle mass. This study describes the effect of different methods to determine muscle mass on the diagnosis of cancer cachexia. In addition, the association of cachexia with other features of cachexia, quality of life, and survival was explored. METHODS:Prior to chemotherapy, cachexia was assessed by weight loss, body mass index, and muscle mass measurements, the latter by mid-upper arm muscle area (MUAMA), computed tomography (CT) scans, and bio-electrical impedance analysis (BIA). In addition, appetite, inflammation, muscle strength, fatigue, quality of life, and survival were measured, and associations with cachexia were explored. RESULTS:Included were 241 patients with advanced cancer of the lung (36%), colon/rectum (31%), prostate (18%), or breast (15%). Mean age was 64 ± 10 years; 54% was male. Prevalence of low muscle mass was as follows: 13% with MUAMA, 59% with CT, and 93% with BIA. In turn, the prevalence of cachexia was 37, 43, and 48%, whereby weight loss >5% was the most prominent component of being defined cachectic. Irrespective of type of muscle measurement, patients with cachexia presented more often with anorexia, inflammation, low muscle strength, and fatigue and had lower quality of life. Patients with cachexia had worse overall survival compared with patients without cachexia: HRs 2.00 (1.42-2.83) with MUAMA, 1.64 (1.15-2.34) with CT, and 1.50 (1.05-2.14) with BIA. CONCLUSIONS:Although the prevalence of low muscle mass in patients with cancer depended largely on the type of muscle measurement, this had little influence on the diagnosis of cancer cachexia (as the majority of patients was already defined cachectic based on weight loss). New studies are warranted to further elucidate the additional role of muscle measurements in the diagnosis of cachexia and the association with clinical outcomes. 10.1002/jcsm.12200
    Rapid atrophy of cardiac left ventricular mass in patients with non-small cell carcinoma of the lung. Kazemi-Bajestani Seyyed Mohammad Reza,Becher Harald,Butts Charles,Basappa Naveen S,Smylie Michael,Joy Anil Abraham,Sangha Randeep,Gallivan Andrea,Kavsak Peter,Chu Quincy,Baracos Vickie E Journal of cachexia, sarcopenia and muscle BACKGROUND:Cancer is a systemic catabolic condition affecting skeletal muscle and fat. We aimed to determine whether cardiac atrophy occurs in this condition and assess its association with cardiac function, symptoms, and clinical outcomes. METHODS:Treatment naïve metastatic non-small cell lung cancer patients (n = 50) were assessed prior to and 4 months after commencement of carboplatin-based palliative chemotherapy. Methods included echocardiography for left ventricular mass (LVM) and LV function [LV ejection fraction, global longitudinal strain (GLS), diastolic function], computed tomography to quantify skeletal muscle and total adipose tissue, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), validated questionnaires for dyspnoea and fatigue, plasma biomarkers, tumour response to therapy, and overall survival. RESULTS:During 112 ± 6 days, the median change in LVM was -8.9% [95% confidence interval (95% CI) -10.8 to -4.8, P < 0.001]. Quartiles of LVM loss were -20.1%, -12.9%, -4.8%, and +5.5%. Losses of muscle, adipose tissue, and LVM were frequently concurrent; LVM loss > median value was associated with loss of skeletal muscle [odds ratio (OR) = 4.5, 95% CI: 1.4-14.8, P=0.01] and loss of total adipose tissue (OR = 10.0, 95% CI: 2.7-36.7, P < 0.001). LVM loss was associated with decreased GLS (OR = 6.6, 95% CI: 1.9-22.7, P=0.003) but not with LV ejection fraction or diastolic function. In the population overall, plasma levels of C-reactive protein (P=0.008), high sensitivity troponin T (hs-TnT) (P=0.03), and galectin-3 (P=0.02) increased over time, while N-terminal pro B-type natriuretic peptide and hs-cTnI did not change over time. C-reactive protein was the only biomarker associated with LVM loss but at the univariate level only. Independent predictors of LVM loss were prior weight loss (adjusted OR = 10.2, 95% CI: 2.2-46.9, P=0.003) and tumour progression (adjusted OR = 14.6, 95% CI: 1.4-153.9, P=0.02). LVM loss was associated with exacerbations of fatigue (OR = 6.6, 95% CI: 1.9-22.7, P=0.003), dyspnoea (OR = 9.3, 95% CI: 2.4-35.8, P<0.001), and deterioration of performance status (OR = 4.8, 95% CI: 1.3-18.3,P=0.02). Patients with concurrent loss of LVM, skeletal muscle, and fat were more likely to deteriorate in all three symptom domains and to have reduced survival (P=0.05). CONCLUSIONS:Intense LVM atrophy is associated with non-small cell lung cancer-induced cachexia. Loss of LVM was associated with emerging alterations of GLS, indicating subtle changes in left ventricular function. Longer term studies are needed to assess the full scope of cardiac atrophy and its impact. LVM atrophy arises in conjunction with losses of fat and skeletal muscle and is temporally associated with meaningful declines in performance status, worsening of fatigue, and dyspnoea, as well as poorer tumour response and decreased survival. The specific contribution of LVM atrophy to these outcomes requires further study. 10.1002/jcsm.12451
    Muscle mass as a target to reduce fatigue in patients with advanced cancer. Neefjes Elisabeth C W,van den Hurk Renske M,Blauwhoff-Buskermolen Susanne,van der Vorst Maurice J D L,Becker-Commissaris Annemarie,de van der Schueren Marian A E,Buffart Laurien M,Verheul Henk M W Journal of cachexia, sarcopenia and muscle BACKGROUND:Cancer-related fatigue (CRF) reduces quality of life and the activity level of patients with cancer. Cancer related fatigue can be reduced by exercise interventions that may concurrently increase muscle mass. We hypothesized that low muscle mass is directly related to higher CRF. METHODS:A total of 233 patients with advanced cancer starting palliative chemotherapy for lung, colorectal, breast, or prostate cancer were studied. The skeletal muscle index (SMI) was calculated as the patient's muscle mass on level L3 or T4 of a computed tomography scan, adjusted for height. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-fatigue questionnaire (cut-off for fatigue <34). Multiple linear regression analyses were conducted to study the association between SMI and CRF adjusting for relevant confounders. RESULTS:In this group of patients with advanced cancer, the median fatigue score was 36 (interquartile range 26-44). A higher SMI on level L3 was significantly associated with less CRF for men (B 0.447, P 0.004) but not for women (B - 0.401, P 0.090). No association between SMI on level T4 and the Functional Assessment of Chronic Illness Therapy-fatigue score was found (n = 82). CONCLUSIONS:The association between SMI and CRF may lead to the suggestion that male patients may be able to reduce fatigue by exercise interventions aiming at an increased muscle mass. In women with advanced cancer, CRF is more influenced by other causes, because it is not significantly related to muscle mass. To further reduce CRF in both men and women with cancer, multifactorial assessments need to be performed in order to develop effective treatment strategies. 10.1002/jcsm.12199
    ESPEN guidelines on nutrition in cancer patients. Arends Jann,Bachmann Patrick,Baracos Vickie,Barthelemy Nicole,Bertz Hartmut,Bozzetti Federico,Fearon Ken,Hütterer Elisabeth,Isenring Elizabeth,Kaasa Stein,Krznaric Zeljko,Laird Barry,Larsson Maria,Laviano Alessandro,Mühlebach Stefan,Muscaritoli Maurizio,Oldervoll Line,Ravasco Paula,Solheim Tora,Strasser Florian,de van der Schueren Marian,Preiser Jean-Charles Clinical nutrition (Edinburgh, Scotland) Cancers are among the leading causes of morbidity and mortality worldwide, and the number of new cases is expected to rise significantly over the next decades. At the same time, all types of cancer treatment, such as surgery, radiation therapy, and pharmacological therapies are improving in sophistication, precision and in the power to target specific characteristics of individual cancers. Thus, while many cancers may still not be cured they may be converted to chronic diseases. All of these treatments, however, are impeded or precluded by the frequent development of malnutrition and metabolic derangements in cancer patients, induced by the tumor or by its treatment. These evidence-based guidelines were developed to translate current best evidence and expert opinion into recommendations for multi-disciplinary teams responsible for identification, prevention, and treatment of reversible elements of malnutrition in adult cancer patients. The guidelines were commissioned and financially supported by ESPEN and by the European Partnership for Action Against Cancer (EPAAC), an EU level initiative. Members of the guideline group were selected by ESPEN to include a range of professions and fields of expertise. We searched for meta-analyses, systematic reviews and comparative studies based on clinical questions according to the PICO format. The evidence was evaluated and merged to develop clinical recommendations using the GRADE method. Due to the deficits in the available evidence, relevant still open questions were listed and should be addressed by future studies. Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. They may be driven by inadequate food intake, decreased physical activity and catabolic metabolic derangements. To screen for, prevent, assess in detail, monitor and treat malnutrition standard operating procedures, responsibilities and a quality control process should be established at each institution involved in treating cancer patients. All cancer patients should be screened regularly for the risk or the presence of malnutrition. In all patients - with the exception of end of life care - energy and substrate requirements should be met by offering in a step-wise manner nutritional interventions from counseling to parenteral nutrition. However, benefits and risks of nutritional interventions have to be balanced with special consideration in patients with advanced disease. Nutritional care should always be accompanied by exercise training. To counter malnutrition in patients with advanced cancer there are few pharmacological agents and pharmaconutrients with only limited effects. Cancer survivors should engage in regular physical activity and adopt a prudent diet. 10.1016/j.clnu.2016.07.015
    PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic implications. Barreiro Esther,Gea Joaquim Biological chemistry Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia. Genetic inhibition of PARP activity attenuated the deleterious effects seen on depleted muscles in mouse models of oncologic cachexia. In the present minireview the mechanisms whereby PARP activity inhibition may improve muscle mass and performance in models of cancer-induced cachexia are discussed. Specifically, the beneficial effects of inhibition of PARP activity on attenuation of increased oxidative stress, protein catabolism, poor muscle anabolism and mitochondrial content and epigenetic modulation of muscle phenotype are reviewed in this article. Finally, the potential therapeutic strategies of pharmacological PARP activity inhibition for the treatment of cancer-induced cachexia are also being described in this review. 10.1515/hsz-2017-0158
    A systematic review on the role of vitamins, minerals, proteins, and other supplements for the treatment of cachexia in cancer: a European Palliative Care Research Centre cachexia project. Mochamat ,Cuhls Henning,Marinova Milka,Kaasa Stein,Stieber Christiane,Conrad Rupert,Radbruch Lukas,Mücke Martin Journal of cachexia, sarcopenia and muscle We provide a systematic review to support the European Palliative Care Research Collaboration development of clinical guidelines for cancer patients suffering from cachexia. CENTRAL, MEDLINE, PsycINFO, ClinicalTrials.gov, and a selection of cancer journals have been searched up until 15 April 2016. The systematic literature research yielded 4214 publications with 21 of these included in the final evaluation. Regarding minerals, our search identified only one study examining the use of magnesium with no effect on weight loss. As far as vitamins are concerned, vitamin E in combination with omega-3 fatty acids displayed an effect on survival in a single study, vitamin D showed improvement of muscle weakness in prostate cancer patients, and vitamin C supplementation led to an improvement of various quality of life aspects in a sample with a variety of cancer diagnoses. For proteins, a combination therapy of β-hydroxy-β-methylbutyrate (HMB), arginine, and glutamine showed an increase in lean body mass after 4 weeks in a study of advanced solid tumour patients, whereas the same combination did not show a benefit on lean body mass in a large sample of advanced lung and other cancer patients after 8 weeks. L-carnitine led to an increase of body mass index and an increase in overall survival in advanced pancreatic cancer patients. Adverse effects of food supplementation were rare and showed mild intensity. There is not enough solid evidence for the use of minerals, vitamins, proteins, or other supplements in cancer. No serious adverse effects have been reported with dietary supplementation. 10.1002/jcsm.12127
    Comorbidities of chronic obstructive pulmonary disease. Corsonello Andrea,Antonelli Incalzi Raffaele,Pistelli Riccardo,Pedone Claudio,Bustacchini Silvia,Lattanzio Fabrizia Current opinion in pulmonary medicine PURPOSE OF REVIEW:Defining the nature of the association between chronic obstructive pulmonary disease (COPD) and other chronic conditions is of primary importance to improve the health status of COPD patients through the optimal care of comorbidities. We aimed at providing a reasoned guide to understand, recognize and treat comorbidity of COPD with the perspective of shifting from comorbidity to multimorbidity. RECENT FINDINGS:Select comorbidities, such as atherosclerotic disease, depression, chronic kidney disease, cognitive impairment, obstructive sleep apnea syndrome, lung cancer, osteoporosis, diabetes, heart failure, sarcopenia, aortic aneurysm, arrhythmias and pulmonary embolism are highly prevalent among older COPD patients. Several concerns may affect the management of older COPD patients with comorbidity (e.g. the use of β-blockers in patients with COPD and cardiovascular diseases or concerns about the cardiovascular safety of inhaled COPD drugs). SUMMARY:Evidence suggests that systemic inflammation may be the link between COPD and comorbidities, but this issue is still debated. Whatever the mechanism underlying comorbidities in COPD may be, it has an important clinical, prognostic and therapeutic impact. Nevertheless, clinical practice guidelines do not take into account comorbidities in their recommendations. Additionally, clinical trials investigating COPD treatment in the context of multimorbidity and considering geriatric outcomes are also distinctly lacking. 10.1097/01.mcp.0000410744.75216.d0
    Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Prado Carla M M,Lieffers Jessica R,McCargar Linda J,Reiman Tony,Sawyer Michael B,Martin Lisa,Baracos Vickie E The Lancet. Oncology BACKGROUND:Emerging evidence on body composition suggests that sarcopenic obesity (obesity with depleted muscle mass) might be predictive of morbidity and mortality in non-malignant disease and also of toxicity to chemotherapy. We aimed to assess the prevalence and clinical implications of sarcopenic obesity in patients with cancer. METHODS:Between Jan 13, 2004, and Jan 19, 2007, 2115 patients with solid tumours of the respiratory or gastrointestinal tract from a cancer treatment centre serving northern Alberta, Canada, were identified. Available lumbar CT images of the obese patients were analysed for total skeletal muscle cross-sectional area; these values were also used to estimate total body fat-free mass (FFM). FINDINGS:Of the 2115 patients initially identified, 325 (15%) were classified as obese (body-mass index [BMI] > or =30). Of these obese patients, 250 had CT images that met the criteria for analysis. The remaining 75 patients were recorded as without assessable scans. Obese patients had a wide range of muscle mass. Sex-specific cut-offs that defined a significant association between low muscle mass with mortality were ascertained by optimum stratification analysis: 38 (15%) of 250 patients who had assessable CT images that met the criteria for analysis were below these cut-offs and were classified as having sarcopenia. Sarcopenic obesity was associated with poorer functional status compared with obese patients who did not have sarcopenia (p=0.009), and was an independent predictor of survival (hazard ratio [HR] 4.2 [95% CI 2.4-7.2], p<0.0001). Estimated FFM showed a poor association with body-surface area (r(2)=0.37). Assuming that FFM represents the volume of distribution of many cytotoxic chemotherapy drugs, we estimated that individual variation in FFM could account for up to three-times variation in effective volume of distribution for chemotherapy administered per unit body-surface area, in this population. INTERPRETATION:This study provides evidence of the great variability of body composition in patients with cancer and links body composition, especially sarcopenic obesity, to clinical implications such as functional status, survival, and potentially, chemotherapy toxicity. 10.1016/S1470-2045(08)70153-0
    Handgrip strength predicts survival and is associated with markers of clinical and functional outcomes in advanced cancer patients. Kilgour R D,Vigano A,Trutschnigg B,Lucar E,Borod M,Morais J A Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:Handgrip strength (HGS) has been shown to predict survival and is associated with changes in body composition, nutritional status, inflammation, and functional ability in several chronic disease conditions. Whether similar relationships exist between HGS and clinical outcomes in patients with advanced cancer are currently unknown. We evaluated the association between HGS and survival as well as several key markers of body composition (e.g., sarcopenia), subjective performance measures (e.g., quality of life), and muscle strength (e.g., isokinetic torque of the quadriceps) in patients with advanced forms of non-small cell lung and gastrointestinal cancers. METHODS:A consecutive cohort of 203 patients with advanced cancer was enrolled and categorized into three HGS percentiles (e.g., ≥50th, 25th, and ≤10th) according to published normative values. Multivariate regression analyses were used to test for independent associations between HGS and survival, sarcopenia, quality of life (QoL), and lower extremity muscle strength as well as key biological markers (e.g., hemoglobin, albumin, and C-reactive protein) while controlling for age, gender, cancer diagnosis, treatment (chemotherapy/radiotherapy), medications, and time from diagnosis to assessment. RESULTS:When compared to HGS ≥50th, patients in the HGS ≤10th percentile had lower BMI (B, -2.5 kg/m(2); 95% CI, -4.5 to -0.45), shorter survival (hazard ratio, 3.2; 2.0-5.1), lower hemoglobin (-19.70 g/L; -27.28 to -12.13) and albumin (-4.99 g/L; -7.85 to -2.13), greater occurrence of sarcopenia (odds ratio, 9.53; 1.95-46.55), lower isokinetic torque of the quadriceps at both 60°/s (-30.6 Nm; -57.9 to -3.3) and 120°/s (-25.1 Nm; -46.4 to -3.7), lower QoL (-1.6 on McGill Quality of Life Questionnaire scale; -2.5 to -0.6), higher levels of fatigue (18.8 on Brief Fatigue Inventory scale; 4.7 -32.9), poorer performance status (0.75 on Eastern Cooperative Oncology Group Performance Status scale; 0.34-1.15), lower fat mass (-7.4 kg; -14.4 to -0.5), and lower lean body mass (-6.5 kg; -10.3 to -2.8). CONCLUSIONS:HGS is independently associated with survival and important biological, functional, and quality of life characteristics in advanced cancer patients. Patients presenting with very low percentiles with respect to their handgrip assessment may require timely referral to supportive and/or palliative care services. 10.1007/s00520-013-1894-4
    Sarcopenia Is a Condition With Increasing Importance in Medical Oncology. Cintosun Umit,Altun Battal,Tasci Ilker The oncologist 10.1634/theoncologist.2015-0431
    Cancer-Associated Malnutrition and CT-Defined Sarcopenia and Myosteatosis Are Endemic in Overweight and Obese Patients. Martin Lisa,Gioulbasanis Ioannis,Senesse Pierre,Baracos Vickie E JPEN. Journal of parenteral and enteral nutrition BACKGROUND:Overweight/obese patients' large fat mass can mask the loss of skeletal muscle, which is associated with mortality in the oncology setting. We investigated the prevalence of computed tomography (CT)-defined sarcopenia and myosteatosis across different levels of nutrition risk assessed by the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF). We also evaluated whether the PG-SGA SF, sarcopenia, and myosteatosis were prognostic of overall survival. METHODS:This was a prospective, observational study. Consecutive patients with body mass index ≥25.0 kg/m with newly diagnosed head and neck cancer (any stage) or lung and gastrointestinal tract cancer (locally recurrent or metastatic) were screened at presentation to oncology clinics. Nutrition risk was assigned based on PG-SGA SF triage recommendations. Based on CT, patients were classified with sarcopenia and/or myosteatosis using published cutoffs. Survival analyses were conducted. RESULTS:Patients (n=1157) were 63.6 ± 11.4 years, 64% male, and 61% had stage IV disease. Sarcopenia and myosteatosis were prevalent across PG-SGA SF nutrition risk categories (scores 0-1 [no risk; 36% sarcopenic; 44% myosteatotic], scores 2-3 [37%; 37%], scores 4-8 [40%; 41%], and scores ≥9 [high risk; 50%; 49%]). In multivariable survival analysis, PG-SGA SF scores ≥9 (hazard ratio [HR] 2.08, 95% confidence interval [CI] 1.66-2.60, P<0.001), sarcopenia (HR 1.25, 95% CI 1.06-1.46, P=0.006), and myosteatosis (HR 1.25, 95% CI 1.07-1.46, P<0.001) independently predicted reduced survival. CONCLUSION:CT-defined sarcopenia and myosteatosis are prevalent across different levels of nutrition risk in overweight/obese patients with cancer. Assessment of skeletal muscle using CT adds prognostic value to the PG-SGA SF. 10.1002/jpen.1597
    Associations between severe co-morbidity and muscle measures in advanced non-small cell lung cancer patients. Grønberg Bjørn H,Valan Christine Damgaard,Halvorsen Tarje,Sjøblom Bjørg,Jordhøy Marit S Journal of cachexia, sarcopenia and muscle BACKGROUND:Studies show that low skeletal muscle index (SMI) and low skeletal muscle density (SMD) are negative prognostic factors and associated with more toxicity from systemic therapy in cancer patients. However, muscle depletion can be caused by a range of diseases, and many cancer patients have significant co-morbidity. The aim of this study was to investigate whether there were associations between co-morbidity and muscle measures in patients with advanced non-small cell lung cancer. METHODS:Patients in a Phase III trial comparing two chemotherapy regimens in advanced non-small cell lung cancer were analysed (n = 436). Co-morbidity was assessed using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), which rates co-morbidity from 0 to 4 on 14 different organ scales. Severe co-morbidity was defined as having any grades 3 and 4 CIRS-G score. Muscle measures were assessed from baseline computed tomography slides at the L3 level using the SliceOMatic software. RESULTS:Complete data were available for 263 patients (60%). Median age was 66, 57.0% were men, 78.7% had performance status 0-1, 25.9% Stage IIIB, 11.4% appetite loss, 92.4% were current/former smokers, 22.8% were underweight, 43.7% had normal weight, 26.6% were overweight, and 6.8% obese. The median total CIRS-G score was 7 (range: 0-16), and 48.2% had severe co-morbidity. Mean SMI was 44.7 cm /m (range: 27-71), and the mean SMD was 37.3 Hounsfield units (HU) (range: 16-60). When comparing patients with and without severe co-morbidity, there were no significant differences in median SMI (44.5 vs. 44.1 cm /m ; 0.70), but patients with severe co-morbidity had a significantly lower median SMD (36 HU vs. 39 HU; 0.001), mainly due to a significant difference in SMD between those with severe heart disease and those without (32.5 vs. 37.9 HU; 0.002). Linear regression analyses confirmed the association between severe co-morbidity and SMD both in the simple analysis (0.001) and the multiple analysis (0.037) adjusting for baseline characteristics. Stage of disease, gender, and body mass index (BMI) were significantly associated with SMI in both the simple and multiple analyses. Age and BMI were significantly associated with SMD in the simple analysis; and age, gender, and BMI were significantly associated in the multiple analysis. CONCLUSIONS:There were no significant differences in SMI between patients with and patients without severe co-morbidity, but patients with severe co-morbidity had lower SMD than other patients, mainly due to severe heart disease. Co-morbidity might be a confounder in studies of the clinical role of SMD in cancer patients. 10.1002/jcsm.12469
    [Managing nutritional support in thoracic oncology]. Antoun S,Besse B,Planchard D,Raynard B Revue des maladies respiratoires INTRODUCTION:Cancer treatments are based on specific anticancer chemotherapy. However, there is increasing interest in general aspects of care, which are increasingly evidence based. STATE OF THE ART:The importance of muscle mass is becoming increasingly evident. Its role is not only limited to the maintenance of physical performance and quality of life. In oncology, recent studies have shown a close link between sarcopenia (low muscle mass) and mortality as well as between sarcopenia and chemotherapy toxicity. To treat malnutrition and the lack of energy intake, nutritional support is considered, whether through the prescription of oral nutritional supplements, enteral nutrition or even parenteral nutrition. Scientific arguments are often absent and few studies have been carried out in patients with lung cancer. PERSPECTIVES:There are many experimental arguments and a few clinical trials that support using omega 3 fatty acids to modulate inflammatory reaction and to reduce its consequences on muscular proteolysis. The benefit of regular physical activity has already been proven in chronic respiratory disease and its use in association with nutritional support must be recommended in oncologic care. CONCLUSION:Given the increasing recognition of the role of muscle mass in cancer, the purpose of any nutritional support must be focused on increasing muscle anabolism and decreasing proteolysis. 10.1016/j.rmr.2013.02.004
    Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm, a Selective Androgen Receptor Modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER Trials). Crawford Jeffrey,Prado Carla M M,Johnston Mary Ann,Gralla Richard J,Taylor Ryan P,Hancock Michael L,Dalton James T Current oncology reports Muscle wasting in cancer is a common and often occult condition that can occur prior to overt signs of weight loss and before a clinical diagnosis of cachexia can be made. Muscle wasting in cancer is an important and independent predictor of progressive functional impairment, decreased quality of life, and increased mortality. Although several therapeutic agents are currently in development for the treatment of muscle wasting or cachexia in cancer, the majority of these agents do not directly inhibit muscle loss. Selective androgen receptor modulators (SARMs) have the potential to increase lean body mass (LBM) and hence muscle mass, without the untoward side effects seen with traditional anabolic agents. Enobosarm, a nonsteroidal SARM, is an agent in clinical development for prevention and treatment of muscle wasting in patients with cancer (POWER 1 and 2 trials). The POWER trials are two identically designed randomized, double-blind, placebo-controlled, multicenter, and multinational phase 3 trials to assess the efficacy of enobosarm for the prevention and treatment of muscle wasting in subjects initiating first-line chemotherapy for non-small-cell lung cancer (NSCLC). To assess enobosarm's effect on both prevention and treatment of muscle wasting, no minimum weight loss is required. These pivotal trials have pioneered the methodological and regulatory fields exploring a therapeutic agent for cancer-associated muscle wasting, a process hereby described. In each POWER trial, subjects will receive placebo (n = 150) or enobosarm 3 mg (n = 150) orally once daily for 147 days. Physical function, assessed as stair climb power (SCP), and LBM, assessed by dual-energy X-ray absorptiometry (DXA), are the co-primary efficacy endpoints in both trials assessed at day 84. Based on extensive feedback from the US Food and Drug Administration (FDA), the co-primary endpoints will be analyzed as a responder analysis. To be considered a physical function responder, a subject must have ≥10 % improvement in physical function compared to baseline. To meet the definition of response on LBM, a subject must have demonstrated no loss of LBM compared with baseline. Secondary endpoints include durability of response assessed at day 147 in those responding at day 84. A combined overall survival analysis for both studies is considered a key secondary safety endpoint. The POWER trials design was established with extensive clinical input and collaboration with regulatory agencies. The efficacy endpoints are a result of this feedback and discussion of the threshold for clinical benefit in patients at risk for muscle wasting. Full results from these studies will soon be published and will further guide the development of future anabolic trials. Clinical Trial ID: NCT01355484. https://clinicaltrials.gov/ct2/show/NCT01355484 , NCT01355497. https://clinicaltrials.gov/ct2/show/NCT01355497?term=g300505&rank=1 . 10.1007/s11912-016-0522-0
    Loss of skeletal muscle mass during neoadjuvant treatments correlates with worse prognosis in esophageal cancer: a retrospective cohort study. Järvinen Tommi,Ilonen Ilkka,Kauppi Juha,Salo Jarmo,Räsänen Jari World journal of surgical oncology BACKGROUND:Nutritional deficits, cachexia, and sarcopenia are extremely common in esophageal cancer. The aim of this article was to assess the effect of loss of skeletal muscle mass during neoadjuvant treatment on the prognosis of esophageal cancer patients. METHODS:Esophageal cancer patients (N = 115) undergoing neoadjuvant therapy and surgery between 2010 and 2014 were identified from our surgery database and retrospectively analyzed. Computed tomography imaging of the total cross-sectional muscle tissue measured at the third lumbar level defined the skeletal muscle index, which defined sarcopenia (SMI < 52.4 cm2/m2 for men and < 38.5 cm2/m2 for women). Images were collected before and after neoadjuvant treatments. RESULTS:Sarcopenia in preoperative imaging was prevalent in 92 patients (80%). Median overall survival was 900 days (interquartile range 334-1447) with no difference between sarcopenic (median = 900) and non-sarcopenic (median = 914) groups (p = 0.872). Complication rates did not differ (26.1% vs 32.6%, p = 0.725). A 2.98% decrease in skeletal muscle index during neoadjuvant treatment correlated with poor 2-year survival (log-rank p = 0.04). CONCLUSION:Loss of skeletal muscle tissue during neoadjuvant treatment correlates with worse overall survival. 10.1186/s12957-018-1327-4
    A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer. Solheim Tora S,Laird Barry J A,Balstad Trude Rakel,Stene Guro B,Bye Asta,Johns Neil,Pettersen Caroline H,Fallon Marie,Fayers Peter,Fearon Kenneth,Kaasa Stein Journal of cachexia, sarcopenia and muscle BACKGROUND:Cancer cachexia is a syndrome of weight loss (including muscle and fat), anorexia, and decreased physical function. It has been suggested that the optimal treatment for cachexia should be a multimodal intervention. The primary aim of this study was to examine the feasibility and safety of a multimodal intervention (n-3 polyunsaturated fatty acid nutritional supplements, exercise, and anti-inflammatory medication: celecoxib) for cancer cachexia in patients with incurable lung or pancreatic cancer, undergoing chemotherapy. METHODS:Patients receiving two cycles of standard chemotherapy were randomized to either the multimodal cachexia intervention or standard care. Primary outcome measures were feasibility assessed by recruitment, attrition, and compliance with intervention (>50% of components in >50% of patients). Key secondary outcomes were change in weight, muscle mass, physical activity, safety, and survival. RESULTS:Three hundred and ninety-nine were screened resulting in 46 patients recruited (11.5%). Twenty five patients were randomized to the treatment and 21 as controls. Forty-one completed the study (attrition rate 11%). Compliance to the individual components of the intervention was 76% for celecoxib, 60% for exercise, and 48% for nutritional supplements. As expected from the sample size, there was no statistically significant effect on physical activity or muscle mass. There were no intervention-related Serious Adverse Events and survival was similar between the groups. CONCLUSIONS:A multimodal cachexia intervention is feasible and safe in patients with incurable lung or pancreatic cancer; however, compliance to nutritional supplements was suboptimal. A phase III study is now underway to assess fully the effect of the intervention. 10.1002/jcsm.12201
    Skeletal muscle depletion is associated with reduced plasma (n-3) fatty acids in non-small cell lung cancer patients. Murphy Rachel A,Mourtzakis Marina,Chu Quincy S,Reiman Tony,Mazurak Vera C The Journal of nutrition Upwards of 50% of newly diagnosed advanced lung cancer patients have severe muscle wasting (sarcopenia). Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in advanced cancer has been shown to attenuate lean tissue wasting. However, the relationship between muscle mass and plasma (n-3) fatty acids in the absence of supplementation is unclear. We aimed to determine how plasma phospholipid (n-3) fatty acids relate to sarcopenia and change in muscle mass in non-small cell lung cancer patients receiving chemotherapy. Computed tomography images were used to measure muscle mass. Patients were classified as sarcopenic or nonsarcopenic based on sex-specific cutpoints. Change in muscle mass during chemotherapy (2.5 mo) was calculated and patients were divided into quartiles based on the rate of muscle loss or gain. Patients with sarcopenia had lower plasma EPA (16.7 +/- 2.1 micromol/L vs. 31.6 +/- 4.4 micromol/L; P = 0.001), DHA (36.6 +/- 4.0 micromol/L vs. 55.3 +/- 4.0 micromol/L; P = 0.003), and Sigma(n-3) fatty acids (63.6 +/- 5.6 micromol/L vs. 95.0 +/- 7.7 micromol/L; P = 0.002) than nonsarcopenic patients. Patients with maximal muscle loss (mean - 3.5 kg) had lower plasma EPA (12.2 +/- 3.3 micromol/L vs. 35.0 +/- 7.1 micromol/L; P = 0.03), DHA (26.9 +/- 8.7 micromol/L vs. 59.6 +/- 5.3 micromol/L; P = 0.01), and Sigma(n-3) fatty acids (57.8 +/- 13.5 micromol/L vs. 104.6 +/- 11.1 micromol/L; P = 0.005) compared with patients who were gaining muscle (mean +1 kg). Plasma (n-3) fatty acids are depleted in cancer patients with sarcopenia, which may contribute to accelerated rates of muscle loss. 10.3945/jn.110.123521
    The Role of Malnutrition and Muscle Wasting in Advanced Lung Cancer. Jain Rishi,Coss Chris,Whooley Peter,Phelps Mitch,Owen Dwight H Current oncology reports PURPOSE OF REVIEW:Malnutrition, cancer cachexia, and sarcopenia often co-occur in patients with advanced cancer and are associated with poorer response to chemotherapy and reduced survival. Here, we evaluate the current literature regarding the role of nutrition and these associated conditions in patients with advanced lung cancer. RECENT FINDINGS:While rates of malnutrition are high, nutritional intervention studies have generally been limited by small sample sizes. Novel strategies such as home-based meal delivery may have promise. While no therapy is approved for cancer cachexia, ghrelin agonists and other targeted therapies have yielded promising data in clinical trials. Recent data also suggest that obesity may improve immunotherapy responsiveness. Malnutrition and associated muscle wasting are clearly negative prognostic markers in advanced lung cancer. Patients with malnutrition should be urgently referred for dietary counseling and guidelines for nutritional support should be followed. Optimal treatment of these syndromes will likely include nutrition and anti-cachexia interventions used in combination. 10.1007/s11912-020-00916-9
    Muscle mass and association to quality of life in non-small cell lung cancer patients. Bye Asta,Sjøblom Bjørg,Wentzel-Larsen Tore,Grønberg Bjørn H,Baracos Vickie E,Hjermstad Marianne J,Aass Nina,Bremnes Roy M,Fløtten Øystein,Jordhøy Marit Journal of cachexia, sarcopenia and muscle BACKGROUND:Cancer wasting is characterized by muscle loss and may contribute to fatigue and poor quality of life (QoL). Our aim was to investigate associations between skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) and selected QoL outcomes in advanced non-small cell lung cancer (NSCLC) at diagnosis. METHODS:Baseline data from patients with stage IIIB/IV NSCLC and performance status 0-2 enrolled in three randomized trials of first-line chemotherapy (n = 1305) were analysed. Associations between SMI (cm /m ) and SMD (Hounsfield units) based on computed tomography-images at the third lumbar level and self-reported physical function (PF), role function (RF), global QoL, fatigue, and dyspnoea were investigated by linear regression using flexible non-linear modelling. RESULTS:Complete data were available for 734 patients, mean age 65 years. Mean SMI was 47.7 cm /m in men (n = 420) and 39.6 cm /m in women (n = 314). Low SMI values were non-linearly associated with low PF and RF (men P = 0.016/0.020, women P = 0.004/0.012) and with low global QoL (P = 0.001) in men. Low SMI was significantly associated with high fatigue (P = 0.002) and more pain (P = 0.015), in both genders, but not with dyspnoea. All regression analyses showed poorer physical outcomes below an SMI breakpoint of about 42-45 cm /m for men and 37-40 cm /m for women. In both genders, poor PF and more dyspnoea were significantly associated with low SMD. CONCLUSIONS:Low muscle mass in NSCLC negatively affects the patients' PF, RF, and global QoL, possibly more so in men than in women. However, muscle mass must be below a threshold value before this effect can be detected. 10.1002/jcsm.12206
    Nab-paclitaxel in older patients with non-small cell lung cancer who have developed disease progression after platinum-based doublet chemotherapy. Weiss Jared M,Pennell Nathan,Deal Allison M,Morgensztern Daniel,Bradford Daniel S,Crane Jeffrey,West Howard Jack,Lee Carrie,Pecot Chad,Stevenson James P,Irvin William,Socinski Mark,Stinchcombe Tom,Villaruz Liza C,Muss Hyman B Cancer BACKGROUND:The selection of later-line treatment for older patients with AJCC (version 7) stage IV non-small cell lung cancer (NSCLC) remains controversial. Nanoparticle albumin-bound (nab)-paclitaxel is approved with carboplatin for the first-line treatment of patients with NSCLC and subgroup analysis of phase 3 data has suggested superior survival in older patients. METHODS:The authors conducted a phase 2 study of nab-paclitaxel in 42 patients aged ≥70 years who had been treated previously with a platinum doublet regimen; patients also could have received a PD-1 inhibitor. The primary endpoint of the current study was grade 3 to 5 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). In addition to response rate, progression-free survival (PFS), and overall survival (OS), geriatric assessments also were performed before and during treatment, associations between baseline sarcopenia and outcomes were explored, and changes in T lymphocyte p16 before and during treatment were measured. The authors also performed a retrospective subgroup analysis of 19 older patients who were treated with nab-paclitaxel as part of a larger, randomized, phase 2 study; data were not combined. RESULTS:The rate of grade 3 to 5 toxicities was 33.7%. The most common grade 3 to 5 toxicities were decreased white blood cell count (11.9%), neutropenia (9.5%), and fatigue (11.9%). The response rate was 34.2% (2.6% complete response rate and 31.6% partial response rate). The median PFS was 5.2 months and the median OS was 9.3 months. Adverse prognostic factors were common: 42% of patients were frail and 39% of patients were prefrail, whereas 21% had an Eastern Cooperative Oncology Group performance status of 2 and 27% were sarcopenic. Only frailty was found to be predictive of inferior survival. A subgroup analysis of 19 older patients treated with nab-paclitaxel alone in a prior trial demonstrated a response rate of 15.8%, a PFS of 4.2 months, and an OS of 13.6 months. CONCLUSIONS:Fit and prefrail older patients with stage IV NSCLC should be considered for treatment with nab-paclitaxel after disease progression with doublet chemotherapy. 10.1002/cncr.32573
    Prevalence and predictive value of pre-therapeutic sarcopenia in cancer patients: A systematic review. Pamoukdjian Frédéric,Bouillet Thierry,Lévy Vincent,Soussan Michael,Zelek Laurent,Paillaud Elena Clinical nutrition (Edinburgh, Scotland) BACKGROUND & AIMS:To assess the prevalence of sarcopenia before cancer treatment and its predictive value during the treatment. METHODS:We searched MEDLINE via PubMed for articles published from 2008 to 2016 that reported prospective observational or interventional studies of the prevalence of pre-therapeutic sarcopenia and its consequences in adults with cancer who were 18 years or older. Two independent reviewers selected articles based on titles and/or abstracts before a complete review. Sarcopenia had to be measured before cancer treatment. Methods recommended by consensuses (CT scan, MRI, dual X-ray absorptiometry or bio-impedancemetry) to assess sarcopenia were considered. Characteristics of the studies included the prevalence of pre-therapeutic sarcopenia and the prognostic value for outcomes during the cancer treatment. RESULTS:We selected 35 articles involving 6894 participants (in/out patients, clinical trials). The mean age ranged from 53 to 69.6 years. Pre-therapeutic sarcopenia was found in 38.6% of patients [95% CI 37.4-39.8]. Oesophageal and small-cell lung cancers showed the highest prevalence of pre-therapeutic sarcopenia. Pre-therapeutic sarcopenia was significantly and independently associated with post-operative complications, chemotherapy-induced toxicity and poor survival in cancer patients. CONCLUSIONS:Pre-therapeutic sarcopenia is highly prevalent in cancer patients and has severe consequences for outcomes of cancer patients. 10.1016/j.clnu.2017.07.010
    Overall survival of pseudomyxoma peritonei and peritoneal mesothelioma patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy can be predicted by computed tomography quantified sarcopenia. Galan Alexandre,Rousset Pascal,Mercier Frederic,Képénékian Vahan,Valette Pierre-Jean,Glehen Olivier,Passot Guillaume European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology BACKGROUND:Malnutrition is associated with increased postoperative morbidity in abdominal surgery. This study aimed to determine if sarcopenia and/or abdominal fat composition could predict postoperative outcomes for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for pseudomyxoma peritonei (PMP) and peritoneal mesothelioma (PM). METHODS:All patients who underwent a complete CRS-HIPEC for PMP and PM, between January 2009 and September 2017, were retrospectively studied. Preoperative computed tomography (CT) was used to measure the cross-sectional surface of skeletal muscle mass and adipose tissue (visceral and subcutaneous), at the level of the third lumbar vertebrae, to assess for sarcopenia and abdominal fat composition. RESULTS:Among 115 patients, 82 were treated for PMP and 33 for PM. 64 patients (55.7%) were sarcopenic on the preoperative imagery. Major postoperative complications occurred in 63 patients (54.8%), without observable difference between sarcopenic and non-sarcopenic patients (56.2% vs. 52.9%; p = 0.723). The median overall survival (OS) was 73.3 for the patients with a normal muscle mass and 57.2 months for the sarcopenic patients (p = 0.05). CONCLUSION:CT measured sarcopenia is an independent predictive factor for overall survival in patients treated for PMP and PM with CRS-HIPEC, but cannot predict postoperative morbidity. 10.1016/j.ejso.2018.07.060
    Skeletal Muscle Mass Change During Chemotherapy: A Systematic Review and Meta-analysis. Jang Min Kyeong,Park Chang,Hong Susan,Li Hongjin,Rhee Esther,Doorenbos Ardith Z Anticancer research BACKGROUND/AIM:Skeletal muscle mass loss is an emerging concern in oncology. Our systematic review and meta-analysis identified the mean difference in skeletal muscle index pre- to post-chemotherapy and synthesized potential key factors. MATERIALS AND METHODS:We searched primary original research published through October 2019 in four databases: MEDLINE via PubMed, Scopus, CINAHL, and Embase. RESULTS:Fifteen studies were included, 60% published in the past 2 years (2018-2019). Advanced non-small cell lung cancer was the most frequently reported cancer, and overall survival the most often identified key related factor. Mean difference in skeletal muscle index during chemotherapy was 2.72 (95%CI=1.77-3.67, p=0.00), with muscle loss in males (4.52, 95%CI=3.34-5.71, p=0.00) about 1.6 times higher than that in females (2.86, 95%CI=0.81-4.92, p=0.01). CONCLUSION:Oncologists should recognize sex-specific differences in skeletal muscle mass loss during chemotherapy and consider adjusting treatment accordingly. 10.21873/anticanres.14210
    Lower Pectoralis Muscle Area Is Associated with a Worse Overall Survival in Non-Small Cell Lung Cancer. Kinsey C Matthew,San José Estépar Raul,van der Velden Jos,Cole Bernard F,Christiani David C,Washko George R Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology BACKGROUND:Muscle wasting is a component of the diagnosis of cancer cachexia and has been associated with poor prognosis. However, recommended tools to measure sarcopenia are limited by poor sensitivity or the need to perform additional scans. We hypothesized that pectoralis muscle area (PMA) measured objectively on chest CT scan may be associated with overall survival (OS) in non-small cell lung cancer (NSCLC). METHODS:We evaluated 252 cases from a prospectively enrolling lung cancer cohort. Eligible cases had CT scans performed prior to the initiation of surgery, radiation, or chemotherapy. PMA was measured in a semi-automated fashion while blinded to characteristics of the tumor, lung, and patient outcomes. RESULTS:Men had a significantly greater PMA than women (37.59 vs. 26.19 cm, P < 0.0001). In univariate analysis, PMA was associated with age and body mass index (BMI). A Cox proportional hazards model was constructed to account for confounders associated with survival. Lower pectoralis area (per cm) at diagnosis was associated with an increased hazard of death of 2% (HR, 0.98; confidence interval, 0.96-0.99; P = 0.044) while adjusting for age, sex, smoking, chronic bronchitis, emphysema, histology, stage, chemotherapy, radiation, surgery, BMI, and ECOG performance status. CONCLUSIONS:Lower PMA measured from chest CT scans obtained at the time of diagnosis of NSCLC is associated with a worse OS. IMPACT:PMA may be a valuable CT biomarker for sarcopenia-associated lung cancer survival. Cancer Epidemiol Biomarkers Prev; 26(1); 38-43. ©2016 AACR SEE ALL THE ARTICLES IN THIS CEBP FOCUS SECTION, "THE OBESITY PARADOX IN CANCER EVIDENCE AND NEW DIRECTIONS". 10.1158/1055-9965.EPI-15-1067
    Clinical impact of skeletal muscle area in patients with non-small cell lung cancer treated with anti-PD-1 inhibitors. Takada Kazuki,Yoneshima Yasuto,Tanaka Kentaro,Okamoto Isamu,Shimokawa Mototsugu,Wakasu Sho,Takamori Shinkichi,Toyokawa Gouji,Oba Taro,Osoegawa Atsushi,Tagawa Tetsuzo,Oda Yoshinao,Nakanishi Yoichi,Mori Masaki Journal of cancer research and clinical oncology PURPOSE:The aim of this study was to elucidate the clinical impact of skeletal muscle area (SMA) in patients with non-small cell lung cancer (NSCLC) treated with anti-programmed cell death-1 (PD-1) inhibitors. METHODS:Univariate and multivariate analyses were performed on data of 103 patients with advanced or recurrent NSCLC treated with anti-PD-1 inhibitors. The SMA was measured at the level of the third lumbar vertebral (L3) on computed tomography images using OsiriX software (32-bit, version 5.8; OsiriX, Geneva, Switzerland). The L3 muscle index (cm/m) was defined as the SMA (cm) at the L3 level divided by the height (m) squared. RESULTS:L3 muscle index was an independent predictor of both progression-free (P = 0.0399) and overall survival (P = 0.0155). Moreover, the disease control rate was significantly lower in the L3 muscle index group (49.0% [25/51]) than in the L3 muscle index group (73.1% [38/52]; P = 0.0117). However, there was no significant difference between the response rates of the L3 muscle index group (21.6% [11/51]) and L3 muscle index group (32.7% [17/52]; P = 0.2031). CONCLUSIONS:L3 muscle index is an independent predictor of worse outcomes in NSCLC patients treated with anti-PD-1 inhibitors. 10.1007/s00432-020-03146-5
    The safety of afatinib for the treatment of non-small cell lung cancer. Barron Feliciano,de la Torre-Vallejo Martha,Luna-Palencia Rosa Luz,Cardona Andres F,Arrieta Oscar Expert opinion on drug safety INTRODUCTION:Lung cancer tumors present EGFR mutations associated with an increased response rate to tyrosine kinase inhibitors (TKIs). Afatinib acts as an irreversible pan-ErbB-TKI. Areas covered: This review summarizes the results of clinical trials in NSCLC regarding its safety and efficacy. Expert opinion: Afatinib in 40 mg doses is highly effective in patients with NSCLC and EGFR mutations, improving progression-free survival and disease-related symptoms compared to chemotherapy. Additionally, afatinib has a better response rate and shows a small benefit in progression free survival compared to first-generation TKIs, and patients with exon 19 deletion could represent a subgroup with better prognosis and overall survival. Diarrhea, mucositis and rash are frequent adverse events induced by afatinib, these can impair quality of life and sometimes afatinib discontinuation is necessary. Management of adverse events, including early antidiarrheal treatment and prophylactic or early antibiotic management can reduce the gastrointestinal and cutaneous adverse events, respectively. Different risk factors, including malnourishment, sarcopenia, and low body surface might be associated with a higher toxicity risk, and these groups of patients could begin treatment with a low dose of afatinib followed by a close evaluation on tolerability and toxicity in order to slowly increase the dosage of afatinib. 10.1080/14740338.2016.1236910
    Feasibility of early multimodal interventions for elderly patients with advanced pancreatic and non-small-cell lung cancer. Naito Tateaki,Mitsunaga Shuichi,Miura Satoru,Tatematsu Noriatsu,Inano Toshimi,Mouri Takako,Tsuji Tetsuya,Higashiguchi Takashi,Inui Akio,Okayama Taro,Yamaguchi Teiko,Morikawa Ayumu,Mori Naoharu,Takahashi Toshiaki,Strasser Florian,Omae Katsuhiro,Mori Keita,Takayama Koichi Journal of cachexia, sarcopenia and muscle BACKGROUND:Combinations of exercise and nutritional interventions might improve the functional prognosis for cachectic cancer patients. However, high attrition and poor compliance with interventions limit their efficacy. We aimed to test the feasibility of the early induction of new multimodal interventions specific for elderly patients with advanced cancer Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) programme. METHODS:This was a multicentre prospective single-arm study. We recruited 30 of 46 screened patients aged ≥70 years scheduled to receive first-line chemotherapy for newly diagnosed, advanced pancreatic, or non-small-cell lung cancer. Physical activity was measured using pedometers/accelerometer (Lifecorder , Suzuken Co., Ltd., Japan). An 8 week educational intervention comprised three exercise and three nutritional sessions. The exercise interventions combined home-based low-intensity resistance training and counselling to promote physical activity. Nutritional interventions included standard nutritional counselling and instruction on how to manage symptoms that interfere with patient's appetite and oral intake. Supplements rich in branched-chain amino acids (Inner Power , Otsuka Pharmaceutical Co., Ltd., Japan) were provided. The primary endpoint of the study was feasibility, which was defined as the proportion of patients attending ≥4 of six sessions. Secondary endpoints included compliance and safety. RESULTS:The median patient age was 75 years (range, 70-84). Twelve patients (40%) were cachectic at baseline. Twenty-nine patients attended ≥4 of the six planned sessions (96.7%, 95% confidence interval, 83.3 to 99.4). One patient dropped out due to deteriorating health status. The median proportion of days of compliance with supplement consumption and exercise performance were 99% and 91%, respectively. Adverse events possibly related to the NEXTAC programme were observed in five patients and included muscle pain (Grade 1 in two patients), arthralgia (Grade 1 in one patient), dyspnoea on exertion (Grade 1 in one patient), and plantar aponeurositis (Grade 1 in one patient). CONCLUSIONS:The early induction of multimodal interventions showed excellent compliance and safety in elderly patients with newly diagnosed pancreatic and non-small-cell lung cancer receiving concurrent chemotherapy. We are now conducting a randomized phase II study to measure the impact of these interventions on functional prognosis. 10.1002/jcsm.12351
    Skeletal muscle mass predicts the outcome of nivolumab treatment for non-small cell lung cancer. Tsukagoshi Mariko,Yokobori Takehiko,Yajima Toshiki,Maeno Toshitaka,Shimizu Kimihiro,Mogi Akira,Araki Kenichiro,Harimoto Norifumi,Shirabe Ken,Kaira Kyoichi Medicine Nivolumab, a monoclonal antibody targeting programmed cell death-1, significantly prolongs survival for patients with advanced non-small-cell lung cancer (NSCLC). However, little is known about the value of predictive biomarkers. Hence, we investigated the impact of skeletal muscle (SM) mass loss on clinical outcomes in NSCLC patients undergoing nivolumab treatment. Thirty patients with histologically confirmed NSCLC treated with nivolumab were included in this study. Computed tomography was used to determine SM loss based on the SM index (SMI). The SMI is the cross-sectional area of the bilateral psoas muscles at the third lumbar vertebra, divided by height squared. The cut-off values were defined as 6.36 cm/m for men and 3.92 cm/m for women. Among the 30 patients, 13 (43%) had SM loss. There was no significant association between SM loss and immune-related adverse events. The SM loss group had undergone significantly more prior chemotherapy cycles (P = .04). SM loss was significantly associated with fewer nivolumab cycles (P = .01). No patients in the SM loss group achieved a partial response. Patients with SM loss had a significantly shorter progression-free survival period (P = .008) and median overall survival than those with normal SM mass (10 vs 25 months, respectively, P = .03). SM loss was an independent prognostic factor of poor survival. In conclusion, SM loss may be a predictive factor of poor outcomes in NSCLS patients undergoing nivolumab therapy. 10.1097/MD.0000000000019059
    Association of sarcopenia and observed physical performance with attainment of multidisciplinary team planned treatment in non-small cell lung cancer: an observational study protocol. Collins Jemima T,Noble Simon,Chester John,Davies Helen E,Evans William D,Lester Jason,Parry Diane,Pettit Rebecca J,Byrne Anthony BMC cancer BACKGROUND:Non-small cell lung cancer (NSCLC) frequently presents in advanced stages. A significant proportion of those with reportedly good ECOG performance status (PS) fail to receive planned multidisciplinary team (MDT) treatment, often for functional reasons, but an objective decline in physical performance is not well described. Sarcopenia, or loss of muscle mass, is an integral part of cancer cachexia. However, changes in both muscle mass and physical performance may predate clinically overt cachexia, and may be present even with normal body mass index. Physical fitness for treatment is currently subjectively assessed by means of the PS score, which may be inadequate in predicting tolerance to treatment. This study aims to evaluate whether measuring physical performance and muscle mass at baseline in NSCLC patients, in addition to PS score, is able to predict commencement and successful completion of MDT-planned treatment. METHODS/DESIGN:This is a prospective, single-centre exploratory study of NSCLC patients attending a Rapid Access Lung Cancer clinic. Baseline data collected are (methods in brackets): physical performance (Short Physical Performance Battery), muscle mass (bioelectrical impedance ± dual energy x-ray absorptiometry), patient and physician-assessed PS (ECOG and Karnofsky), nutritional status and presence of cachexia. Longitudinal data consists of receipt and completion of MDT treatment plan. The primary outcome measure is commencement of MDT-planned treatment, and important secondary outcomes include successful completion of treatment, length of stay in surgical patients, and risk of chemotherapy- and radiotherapy-related side effects. DISCUSSION:A more comprehensive assessment of phenotype, particularly with regards to physical performance and muscle mass, will provide additional discriminatory information of patients' fitness for treatment. If positive, this study has the potential to identify targets for early intervention in those who are at risk of deterioration. This will subsequently enable optimisation of performance of patients with NSCLC, in anticipation of systemic treatment. 10.1186/s12885-015-1565-6
    Prognostic impact of cancer cachexia in patients with advanced non-small cell lung cancer. Kimura Madoka,Naito Tateaki,Kenmotsu Hirotsugu,Taira Tetsuhiko,Wakuda Kazushige,Oyakawa Takuya,Hisamatsu Yasushi,Tokito Takaaki,Imai Hisao,Akamatsu Hiroaki,Ono Akira,Kaira Kyoichi,Murakami Haruyasu,Endo Masahiro,Mori Keita,Takahashi Toshiaki,Yamamoto Nobuyuki Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:Cancer cachexia (CC) is commonly seen in advanced lung cancer patients and associated with poor prognosis. However, little is known about CC that develops during chemotherapy. We evaluated the prognostic impact of CC and skeletal muscle wasting that develops during the course of chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. METHODS:The clinical data of 134 newly diagnosed NSCLC patients were retrospectively reviewed. CC was defined as a body weight loss >5 or >2 % in patients with a body mass index of <20 kg/m(2). CC was assessed at baseline (T1) and 3 months (T2), 6 months (T3), and 12 months (T4) after chemotherapy initiation. Skeletal muscle mass was assessed using the lumber skeletal muscle index (LSMI). RESULTS:The proportion of patients with CC at T1, T2, T3, and T4 was 45.6, 46.1, 25.5, and 26.0 %, respectively. The frequency of grade 3 chemotherapy-induced anorexia was higher in patients with CC than those without CC at T2 (15.4 vs. 0.0 %, P = 0.0044). At all time points, patients with CC had shorter survival times than those without CC. Patients with low LSMIs (men, <41 cm(2)/m(2); women, <38 cm(2)/m(2)) tended to have poor prognosis. Adjusted Cox proportional hazard ratios and corresponding confidence intervals for CC at T1, T2, T3, and T4 were 2.53 (1.33-4.88), 1.97 (1.27-3.06), 3.86 (2.14-6.81), and 1.62 (0.80-3.16), respectively. CONCLUSION:CC presence and decreased skeletal muscle mass are associated with poor prognosis in advanced NSCLC patients receiving chemotherapy. 10.1007/s00520-014-2534-3
    Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non-small cell lung cancer patients: A "hypothesis-generator" preliminary report. Cortellini Alessio,Verna Lucilla,Porzio Giampiero,Bozzetti Federico,Palumbo Pierpaolo,Masciocchi Carlo,Cannita Katia,Parisi Alessandro,Brocco Davide,Tinari Nicola,Ficorella Corrado Thoracic cancer Sarcopenia represents one of the hallmarks of all chronic disease, including non-small cell lung cancer (NSCLC). A computed tomography scan is an easy modality to estimate the skeletal muscle mass through cross-sectional image analysis at the level of the third lumbar vertebra (L3). Baseline skeletal muscle mass (SMM) was evaluated using gender-specific cutoffs for skeletal muscle index in NSCLC patients administered immunotherapy with nivolumab to evaluate its possible correlations with clinical outcomes. From April 2015 to August 2018, 23 stage IV NSCLC patients were eligible for image analysis. Nine patients (39.1%) had low SMM. Among patients with baseline low and non-low SMM, median progression free survival was 3.1 and 3.8 months, respectively (P = 0.0560), while median overall survival was 4.1 and 13 months, respectively (P = 0.2866). This hypothesis-generating preliminary report offers the opportunity to speculate about the negative influence of sarcopenia on immune response. In our opinion, nutritional status could affect the clinical outcomes of immunotherapy, even if we cannot make definitive conclusions here. Further studies on the topic are required. 10.1111/1759-7714.12965
    Skeletal muscle radiodensity is prognostic for survival in patients with advanced non-small cell lung cancer. Sjøblom Bjørg,Grønberg Bjørn H,Wentzel-Larsen Tore,Baracos Vickie E,Hjermstad Marianne J,Aass Nina,Bremnes Roy M,Fløtten Øystein,Bye Asta,Jordhøy Marit Clinical nutrition (Edinburgh, Scotland) BACKGROUND & AIMS:Recent research indicates that severe muscular depletion (sarcopenia) is frequent in cancer patients and linked to cachexia and poor survival. Our aim was to investigate if measures of skeletal muscle hold prognostic information in advanced non-small cell lung cancer (NSCLC). METHODS:We included NSCLC patients with disease stage IIIB/IV, performance status 0-2, enrolled in three randomised trials of first-line chemotherapy (n = 1305). Computed tomography (CT) images obtained before start of treatment were used for body composition analyses at the level of the third lumbar vertebra (L3). Skeletal muscle mass was assessed by measures of the cross sectional muscle area, from which the skeletal muscle index (SMI) was obtained. Skeletal muscle radiodensity (SMD) was measured as the mean Hounsfield unit (HU) of the measured muscle area. A high level of mean HU indicates a high SMD. RESULTS:Complete data were available for 734 patients, mean age 65 years. Both skeletal muscle index (SMI) and muscle radiodensity (SMD) varied largely. Mean SMI and SMD were 47.7 cm/m and 37.4 HU in men (n = 420), 39.6 cm/m and 37.0 HU in women (n = 314). Multivariable Cox regression analyses, adjusted for established prognostic factors, showed that SMD was independently prognostic for survival (Hazard ratio (HR) 0.98, 95% CI 0.97-0.99, p = 0.001), whereas SMI was not (HR 0.99, 95% CI 0.98-1.01, p = 0.329). CONCLUSION:Low SMD is associated with poorer survival in advanced NSCLC. Further research is warranted to establish whether muscle measures should be integrated into routine practice to improve prognostic accuracy. 10.1016/j.clnu.2016.03.010
    Utility of creatinine/cystatin C ratio as a predictive marker for adverse effects of chemotherapy in lung cancer: A retrospective study. Suzuki Kensuke,Furuse Hideaki,Tsuda Takeshi,Masaki Yasuaki,Okazawa Seisuke,Kambara Kenta,Inomata Minehiko,Miwa Toshiro,Matsui Shoko,Kashii Tatsuhiko,Taniguchi Hirokazu,Hayashi Ryuji,Tobe Kazuyuki The Journal of international medical research OBJECTIVE:To determine whether the creatinine/cystatin C (Cr/CysC) ratio, which is influenced by muscle mass, can be used as a predictive marker of the adverse effects of chemotherapy. METHODS:This single-centre, retrospective, observational study assessed patients with lung cancer. Serum Cr and CysC levels were measured once within 1 month prior the commencement of chemotherapy. RESULTS:A total of 25 patients with lung cancer were enrolled in the study: 22 received first-line therapy; three received second-line therapy. A significant difference was noted regarding the Cr/CysC ratios between patients with nonsmall-cell lung cancer (NSCLC) and those with small-cell lung cancer (0.78 versus 0.92, respectively). A significant difference was also noted in the Cr/CysC ratios of patients with NSCLC with toxicity grades <3 and ≥3 (0.84 versus 0.70, respectively). Similar findings were observed in patients with NSCLC who received platinum-based combination therapy (toxicity grade < 3, 0.85; toxicity grade ≥3, 0.69). CONCLUSION:The Cr/CysC ratio could serve as a useful predictive marker for chemotherapy-related adverse effects in patients with NSCLC. 10.1177/0300060515579116
    Skeletal muscle depletion during chemotherapy has a large impact on physical function in elderly Japanese patients with advanced non-small-cell lung cancer. Naito Tateaki,Okayama Taro,Aoyama Takashi,Ohashi Takuya,Masuda Yoshiyuki,Kimura Madoka,Shiozaki Hitomi,Murakami Haruyasu,Kenmotsu Hirotsugu,Taira Tetsuhiko,Ono Akira,Wakuda Kazushige,Imai Hisao,Oyakawa Takuya,Ishii Takeshi,Omori Shota,Nakashima Kazuhisa,Endo Masahiro,Omae Katsuhiro,Mori Keita,Yamamoto Nobuyuki,Tanuma Akira,Takahashi Toshiaki BMC cancer BACKGROUND:Elderly patient with advanced cancer is one of the most vulnerable populations. Skeletal muscle depletion during chemotherapy may have substantial impact on their physical function. However, there is little information about a direct relationship between quantity of muscle and physical function. We sought to explore the quantitative association between skeletal muscle depletion, and muscle strength and walking capacity in elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS:Thirty patients aged ≥70 years with advanced NSCLC (stage III-IV) scheduled to initiate first-line chemotherapy were prospectively enrolled between January 2013 and November 2014. Lumbar skeletal muscle index (LSMI, cm/m), incremental shuttle walking distance (ISWD, m), and hand-grip strength (HGS, kg) were assessed at baseline, and 6 ± 2 weeks (T2) and 12 ± 4 weeks (T3) after study enrollment. Associations were analyzed using linear regression. RESULTS:Altogether, 11 women and 19 men with a median age of 74 (range, 70-82) years were included in the study; 24 received cytotoxic chemotherapy and 6, gefitinib. Mean ± standard deviation of LSMI, ISWD and HGS were 41.2 ± 7.8 cm/m, 326.0 ± 127.9 m, and 29.3 ± 8.5 kg, respectively. LSMI and ISWD significantly declined from baseline to T2 and T3. HGS significantly declined from baseline to T2 and T3 only in men. Change in LSMI was significantly associated with change in HGS (β = 0.3 ± 0.1, p = 0.0127) and ISWD (β = 8.8 ± 2.4, p = 0.0005). CONCLUSIONS:Skeletal muscle depletion accompanied with physical functional decline started in the early phase of the chemotherapy in elderly patients with advanced NSCLC. Our results suggest that there may be a need for early supportive care in these patients to prevent functional decline during chemotherapy. TRIAL REGISTRATION:Trial registration number: UMIN000009768 Name of registry: UMIN (University hospital Medical Information Network). URL of registry: Date of registration: 14 January 2013. Date of enrolment of the first participant to the trial: 23 January 2013. 10.1186/s12885-017-3562-4
    Prognostic Impact of CT-Quantified Muscle and Fat Distribution before and after First-Line-Chemotherapy in Lung Cancer Patients. Nattenmüller Johanna,Wochner Raoul,Muley Thomas,Steins Martin,Hummler Simone,Teucher Birgit,Wiskemann Joachim,Kauczor Hans-Ulrich,Wielpütz Mark Oliver,Heussel Claus Peter PloS one INTRODUCTION:Cachexia and sarcopenia are associated with poor outcome and increased chemotherapy-induced toxicity in lung cancer patients. However, the complex interplay of obesity, sarcopenia and cachexia, and its impact on survival in the context of first-line-chemotherapy is not yet understood. METHODS:In 200 consecutively recruited lung cancer patients (70 female, mean age 62y; mean BMI 25 kg/m2; median follow-up 15.97 months) with routine staging-CT before and after chemotherapy (CTX, mean interval: 4.3 months), densitometric quantification of total (TFA), visceral (VFA), and subcutaneous-fat-area (SFA), inter-muscular-fat-area (IMFA), muscle-density (MD), muscle-area (MA) and skeletal-muscle-index (SMI) was performed retrospectively to evaluate changes under chemotherapy and the impact on survival. RESULTS:We observed increases in TFA, VFA, SFA, VFA/SFA, and IMFA (p<0.05-0.001), while there were decreases in MA, MD and BMI (p<0.05-0.001) after chemotherapy. High pre-therapeutic VFA/SFA was a predictive factor for poor survival (HR = 1.272; p = 0.008), high pre-therapeutic MD for improved survival (HR = 0.93; p<0.05). Decrease in BMI (HR = 1.303; p<0.001), weight (HR = 1.067; p<0.001) and SMI (HR = 1.063; p<0.001) after chemotherapy were associated with poor survival. Patients with ≥4 CTX-cycles showed increased survival (17.6 vs. 9.1months), less muscle depletion (SMIdifference: p<0.05) and no BMI loss (BMIdifference: p<0.001). CONCLUSIONS:After chemotherapy, patients exhibited sarcopenia with decreased muscle and increased adipose tissue compartments, which was not adequately mirrored by BMI and weight loss but by imaging. Particularly sarcopenic patients received less CTX-cycles and had poorer survival. As loss of BMI, weight and muscle were associated with poor survival, early detection (via imaging) and prevention (via physical exercise and nutrition) of sarcopenia may potentially improve outcome and reduce chemotherapy-induced toxicity. 10.1371/journal.pone.0169136
    Predictors of Physical and Functional Loss in Advanced-Stage Lung Cancer Patients Receiving Platinum Chemotherapy. Kinsey Emily,Ajazi Elizabeth,Wang Xiaofei,Johnston Mary Ann Mayzie,Crawford Jeffrey Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer INTRODUCTION:Muscle wasting has detrimental effects, including increased mortality. Identifying patients at risk can guide treatment efforts. METHODS:POWER 1 and 2 were randomized, double-blind, placebo-controlled, multinational phase III trials that studied 600 patients with lung cancer at the start of chemotherapy; the studies' aim was to assess the efficacy of enobosarm on prevention and treatment of muscle loss. We performed a secondary analysis restricted to the control group, using a cumulative logit model for ordinal outcome to determine which baseline characteristics predicted physical and functional loss during chemotherapy. RESULTS:In all, 53% of patients had loss of lean body mass and 49% had loss of stair climb power (SCP) at day 84 of treatment. Of the 322 patients who received placebo, 232 with observable outcome and baseline covariates were included for lean body mass analysis and 236 for SCP analysis. More advanced disease predicted a higher probability of greater physical loss (OR = 1.96; 95% confidence interval [CI]: 1.14-3.36). Three factors predicted higher probability of SCP loss: taxane chemotherapy (OR = 1.73; 95% CI: 1.06-2.83), tobacco use before chemotherapy (OR = 2.15, 95% CI: 1.10-4.18), and SCP at baseline (OR = 1.01, 95% CI: 1.004-1.015). Higher body mass index was a protective factor for functional loss (OR = 0.85; 95% CI: 0.73-0.98). A higher Eastern Cooperative Oncology Group Performance Status trended toward being predictive of greater probability of both physical loss (0.767) and functional loss (0.070), but the results were not statistically significant. CONCLUSIONS:Approximately 50% of patients with advanced lung cancer who were undergoing chemotherapy had ongoing loss of muscle mass and muscle function. Advanced stage predicted physical loss. Tobacco use and taxane chemotherapy predicted functional loss. Body mass index was a protective factor for functional loss. We identified predictors of physical and functional loss that could be used as therapeutic targets or to guide treatment efforts. 10.1016/j.jtho.2018.05.029
    Sarcopenia and inflammation are independent predictors of survival in male patients newly diagnosed with small cell lung cancer. Go Se-Il,Park Mi Jung,Song Haa-Na,Kang Myoung Hee,Park Hee Jung,Jeon Kyung Nyeo,Kim Seok-Hyun,Kim Moon Jin,Kang Jung-Hun,Lee Gyeong-Won Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:Sarcopenia is suggested to be associated with cancer-related inflammation. We assessed the clinical outcome of small cell lung cancer (SCLC) patients according to sarcopenia and the neutrophil-to-lymphocyte ratio (NLR). METHODS:A total of 117 male SCLC patients treated with first-line chemo- or chemoradiotherapy were assessed based on a retrospective chart review. The mass of the pectoralis muscle was measured by computed tomography and normalized to height. Patients with the lowest quartile of muscle mass were considered to have sarcopenia. Patients were classified into four groups according to their sarcopenia and NLR statuses: sarcopenia/high NLR, sarcopenia/low NLR, non-sarcopenia/high NLR, and non-sarcopenia/low NLR. RESULTS:Sarcopenic patients had lower progression-free survival (PFS) than did non-sarcopenic patients (median 6.0 vs. 7.5 months, p = 0.009), but the difference in overall survival (OS) was not statistically significant (median 10.5 vs. 13.5 months, p = 0.052). However, the OS of sarcopenic patients with high NLR was significantly lower than that in all other groups (median 3.2 vs. 16.0 vs. 12.5 vs. 13.7 months, respectively, p < 0.001), as was PFS (median 3.2 vs. 7.7 vs. 7.6 vs. 7.1 months, respectively, p < 0.001). On multivariate analysis, sarcopenia with high NLR was an independent prognostic factor for shorter PFS and OS. Early discontinuation of treatment (20.0 vs. 10.3 %) and treatment-related mortality (50.0 vs. 8.4 %) occurred more frequently in these patients than in the other groups (p < 0.001). CONCLUSIONS:In SCLC, sarcopenic male patients with high NLR have a poor prognosis and do not tolerate standard treatment. Intensive supportive care is needed in these patients. 10.1007/s00520-015-2997-x
    Early Skeletal Muscle Loss in Non-Small Cell Lung Cancer Patients Receiving Chemoradiation and Relationship to Survival. Kiss Nicole,Beraldo Julian,Everitt Sarah Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:Sarcopenia is associated with reduced survival in cancer. Currently, data on sarcopenia at presentation and muscle loss throughout treatment are unknown in patients receiving chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC). This study evaluated skeletal muscle changes in NSCLC patients receiving CRT and relationship with survival. METHODS:Secondary analysis of 41 patients with NSCLC treated with CRT assessed for skeletal muscle area and muscle density by computed tomography pre-treatment and 3 months post-treatment. Images at week 4 of treatment were available for 32 (78%) patients. Linear mixed models were applied to determine changes in skeletal muscle over time and related to overall survival using Kaplan-Meier plots. RESULTS:Muscle area and muscle density decreased significantly by week 4 of CRT (- 6.6 cm, 95% CI - 9.7 to - 3.1, p < 0.001; - 1.3 HU, 95% CI - 1.9 to - 0.64, p < 0.001, respectively), with minimal change between week 4 of CRT and 3 months post-CRT follow-up (- 0.2 cm, 95% CI - 3.6-3.1, p = 0.91; - 0.27, 95% CI - 0.91-0.36, p = 0.36, respectively). Sarcopenia was present in 25 (61%) and sarcopenic obesity in 6 (14%) of patients prior to CRT, but not associated with poorer survival. Median survival was shorter in patients with low muscle density prior to treatment although not statistically significant (25 months + 8.3 vs 53 months + 13.0, log-rank p = 0.17). CONCLUSION:Significant loss of muscle area and muscle density occurs in NSCLC patients early during CRT. A high proportion of patients are sarcopenic prior to CRT; however, this was not significantly associated with poorer survival. 10.1007/s00520-018-4563-9
    Single-institution study of correlations between skeletal muscle mass, its density, and clinical outcomes in non-small cell lung cancer patients treated with first-line chemotherapy. Cortellini Alessio,Palumbo Pierpaolo,Porzio Giampiero,Verna Lucilla,Giordano Aldo V,Masciocchi Carlo,Parisi Alessandro,Cannita Katia,Ficorella Corrado,Bozzetti Federico Thoracic cancer BACKGROUND:Sarcopenia and muscle tissue degradation are hallmarks of the majority of chronic diseases, including non-small cell lung cancer (NSCLC). A computed tomography scan could be an easy modality to estimate the skeletal muscle mass through cross-sectional image analysis at the level of the third lumbar vertebra. METHODS:Baseline skeletal muscle mass (SMM) was evaluated through the skeletal muscle index (SMI), together with skeletal muscle radiodensity (SMD), in NSCLC patients undergoing first-line chemotherapy to evaluate correlations with safety and clinical outcomes. When SMIs at different time points were available, further comparison was made between patients with worse and improved SMIs. RESULTS:Among 81 stage IV NSCLC patients, 28 had low SMM and 23 had low SMD. There were no significant differences in univariate analysis of progression-free survival (PFS) between patients with baseline low and non-low SMM (P = 0.06388) or between patients with low and non-low SMD (P = 0.9126). Baseline low SMM, however, proved a significant predictor of shorter PFS in multivariate analysis (hazard ratio 0.54, 95% confidence interval 0.31-0.93; P = 0.0278), but not low SMD. There were no differences in overall survival (OS) between patients with baseline low and non-low SMM or low and non-low SMD. No differences in PFS and OS between evaluable patients with worse or improved SMI were found. A significant difference in hematological toxicities between patients with baseline low and non-low SMM (P = 0.0358) was observed. CONCLUSIONS:Low SMM is predictive of shorter PFS, while consecutive changes in muscular mass do not seem to be a predictor of PFS or OS. The role of muscle radiodensity remains a matter of debate. 10.1111/1759-7714.12870
    Does sarcopenia affect outcome in patients with non-small-cell lung cancer harboring EGFR mutations? Rossi Sabrina,Di Noia Vincenzo,Tonetti Laura,Strippoli Antonia,Basso Michele,Schinzari Giovanni,Cassano Alessandra,Leone Antonio,Barone Carlo,D'Argento Ettore Future oncology (London, England) AIM:To evaluate gefitinib outcomes in EGFR-mutated non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations, according to their sarcopenia status. PATIENTS & METHODS:We retrospectively evaluated 33 patients with advanced NSCLC and EGFR mutations (exon 19 or 21), dividing them into sarcopenic patients, with low skeletal muscle index ≤39 cm/m for women and ≤55 cm/m for men, and nonsarcopenic patients. RESULTS:Sarcopenia does not affect response to gefitinib treatment in EGFR mutated NSCLC patients, even if it is a bad prognostic indicator for overall survival (p = 0.035). CONCLUSION:Early recognition of sarcopenia is beneficial for prevention of cancer cachexia and detection of patients at potential risk of serious adverse events. Gefitinib dosage should be reduced and modulated in sarcopenic patients. 10.2217/fon-2017-0499
    The value of physical performance measurements alongside assessment of sarcopenia in predicting receipt and completion of planned treatment in non-small cell lung cancer: an observational exploratory study. Collins Jemima T,Noble Simon,Chester John,Davies Helen E,Evans William D,Farewell Daniel,Lester Jason F,Parry Diane,Pettit Rebecca,Byrne Anthony Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer INTRODUCTION:The presence of muscle mass depletion is associated with poor outcomes and survival in cancer. Alongside muscle mass, assessment of muscle strength or physical performance is essential for the diagnosis of sarcopenia. Non-small cell lung cancer (NSCLC) is a prevalent form of cancer with high mortality, and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) is commonly used to assess patients' suitability for treatment. However, a significant proportion of patients with good PS are unable to complete multidisciplinary team (MDT)-planned treatment. Little is known about the ability of objective measurements of physical performance in predicting patients' ability to complete MDT-planned treatment and outcomes in NSCLC. OBJECTIVES:We sought to establish whether physical performance, utilising the short physical performance battery (SPPB), alongside muscle mass measurements, was able to predict receipt and completion of MDT-planned treatment, with a focus on chemotherapy in NSCLC. MATERIALS AND METHODS:Participants with NSCLC treated through a single lung cancer MDT and ECOG PS 0-2 were recruited and the following assessed: body composition [bioelectrical impedance (BIA) and whole body dual-energy X-ray absorptiometry (DXA) in a subset], physical performance (SPPB), PS and nutritional status. We recorded receipt and completion of chemotherapy, as well as any adverse effects, hospitalisations, and treatment delays. RESULTS:We included a total of 62 participants with NSCLC, and in 26 of these, the MDT-planned treatment was chemotherapy. Participants with earlier stage disease and weight loss of <10% were more likely to complete MDT-planned treatment (p < 0.001 and p < 0.05). Patients with a higher total SPPB score were more likely to complete more cycles of chemotherapy as well as the full course. Quicker gait speeds and sit-to-stand times were associated with completion of three or more cycles of chemotherapy (all p < 0.05). For every unit increase in SPPB score, there was a 28.2% decrease in adverse events, hospitalisations and delays of chemotherapy (incidence rate ratio 0.718, p = 0.001), whilst ECOG PS showed no correlation with these outcomes. CONCLUSION:Assessing physical performance by SPPB is quick and simple to do in clinical settings and may give better indication of likely chemotherapy treatment course completion than muscle mass alone and ECOG PS. In turn, this may identify specific targets for early functional intervention and impact on MDT decision-making and prudent use of resources. 10.1007/s00520-017-3821-6
    Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer. Stene Guro B,Helbostad Jorunn L,Amundsen Tore,Sørhaug Sveinung,Hjelde Harald,Kaasa Stein,Grønberg Bjørn H Acta oncologica (Stockholm, Sweden) BACKGROUND:Sarcopenia is a defining feature of cancer cachexia associated with physical decline, poor quality of life and poor prognosis. Thus, maintaining muscle mass is an important aim of cachexia treatment. Many patients at risk for developing cachexia or with cachexia experience side effects of chemotherapy that might aggravate the development of cachexia. However, achieving tumor control might reverse the catabolic processes causing cachexia. There is limited knowledge about muscle mass changes during chemotherapy or whether changes in muscle mass are associated with response to chemotherapy. PATIENTS AND METHODS:In this pilot study, patients with advanced non-small cell lung cancer (NSCLC) receiving three courses of palliative chemotherapy were analyzed. Muscle mass was measured as skeletal muscle cross sectional area (SMCA) at the level of the third lumbar vertebrae using CT images taken before and after chemotherapy. RESULTS:In total 35 patients, 48% women, mean age 67 years (range 56-86), participated; 83% had stage IV disease and 71% were sarcopenic at baseline. Mean reduction in SMCA from pre- to post-chemotherapy was 4.6 cm2 (CI 95% -7.3--1.9; p<0.002), corresponding to a 1.4 kg loss of whole body muscle mass. Sixteen patients remained stable or gained SMCA. Of these, 14 (56%) responded to chemotherapy, while two progressed (p=0.071). Maintaining or gaining SMCA resulted in longer median overall survival (loss: 5.8 months, stable/gain: 10.7 months; p=0.073). Stage of disease (p=0.003), treatment regimen (p=0.023), response to chemotherapy (p=0.007) and SMCA change (p=0.040), but not sarcopenia at baseline, were significant prognostic factors in the multivariate survival analyses. CONCLUSION:Almost half of the patients had stable or increased muscle mass during chemotherapy without receiving any cachexia treatment. Nearly all of these patients responded to the chemotherapy. Increase in muscle mass, but not sarcopenia at baseline, was a significant prognostic factor. 10.3109/0284186X.2014.953259
    Differences in skeletal muscle loss caused by cytotoxic chemotherapy and molecular targeted therapy in patients with advanced non-small cell lung cancer. Kakinuma Kazutaka,Tsuruoka Hazime,Morikawa Kei,Furuya Naoki,Inoue Takeo,Miyazawa Teruomi,Mineshita Masamichi Thoracic cancer BACKGROUND:Recent studies have revealed a reduction in the skeletal muscle area in patients with advanced non-small cell lung cancer (NSCLC) after chemotherapy. EGFR and ALK tyrosine kinase inhibitor (TKI)-based therapies are less cytotoxic than chemotherapy, but differences in skeletal muscle mass between patients receiving EGFR and ALK TKI therapies and patients receiving cytotoxic chemotherapy have not yet been reported. METHODS:Data of pathologically proven NSCLC patients were reviewed, and chest computed tomography and/or positron emission tomography-computed tomography images obtained from January 2012 to December 2014 were selected. Patients were divided into two groups: cytotoxic chemotherapy (CG) and molecular targeted (MG). Muscle mass was measured with a single cross-sectional area of the muscle at the third lumber vertebra (L3MA). To estimate skeletal muscle changes during chemotherapy, we defined the following L3 skeletal muscle index (L3SMI) ratio: post L3SMI/pre L3SMI. Differences in the SMI ratio between the groups were evaluated using the Wilcoxon signed-rank test. RESULTS:Sixty-five patients were included in this study: 44 patients received cytotoxic chemotherapy and 21 received molecular targeted therapy (EGFR and ALK TKI). The loss of L3MA in the CG was higher than in the MG (P = 0.03). In the CG, the L3SMI ratio defined to evaluate skeletal muscle mass changes was significantly lower than in the MG (P = 0.0188). CONCLUSION:Our results suggest that skeletal muscle loss during first-line therapy was significantly different between patients receiving cytotoxic chemotherapy and those receiving TKIs. Specifically, skeletal muscle loss was lower in patients receiving TKIs than in patients receiving cytotoxic chemotherapy. 10.1111/1759-7714.12545
    Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer-chemotherapy toxicity and prognostic value. Srdic Drazena,Plestina Sanja,Sverko-Peternac Ana,Nikolac Nora,Simundic Ana-Maria,Samarzija Miroslav Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer. The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical markers (CRP, IL-6, protein, and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment. METHODS:Between December 2013 and April 2015, the prospective cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases "Jordanovac," was evaluated. Anthropometric measurements and biochemical data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross-sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively. RESULTS:One hundred patients with advanced lung cancer were recruited: 67 were male and median age was 64 years. The median time to disease progression was 187 days. The prevalence of cachexia and sarcopenia in study cohort was 69 and 47 %, respectively. CRP, IL-6, and albumin concentration in cachectic compared to non-cachectic patients demonstrated statistically significant difference (p = 0.020, p = 0.040, p = 0.003). Cachexia and sarcopenia were not found to be predictors of chemotoxicity nor was time to tumor progression. On the contrary, albumin concentration with established cutoff point of 37.5 g/L was clearly proved as the predictive factor of both chemotoxicity (OR (95 % CI) = 0.85; p < 0.001) and survival (HR (95 % CI) = 0.55). CONCLUSIONS:Albumin level has been shown to be more important predictive marker of chemotherapy toxicity and survival than cachexia and sarcopenia are. This approach in clinical settings can be used to guide the choice of oncologic treatment. 10.1007/s00520-016-3287-y