Refractory Cachexia Research Articles

The Role of a Cachexia Grading System in Patients with Non-Small Cell Lung Cancer Treated with Immunotherapy: Implications for Survival

Objective The association between cancer-induced weight-loss (CIWL) and poor clinical outcomes in patients treated with immunotherapy is scarcely understood. We evaluated the use of a cachexia-grading system in IO-treated non-small cell lung cancer (NSCLC) patients in order to predict clinical outcomes. Materials 300 patients with NSCLC, who received immunotherapy during any line of therapy, were included. All patients were graded according to a previously validated cachexia scale, which takes into consideration body mass index (BMI) and weight loss, stratifying patients into five risk categories (0 [pre-cachexia] − 4 [refractory cachexia]). Primary endpoint was overall survival (OS). Results Ninety-one (30.3%) patients were classified in the low risk category, 176 (58.6%) were classified in the intermediate risk category and 33 (11%) were in the high risk category. Patients classified as low-risk had a significantly longer OS compared with those with intermediate or high risk (22.4 mo, [95%CI: 16.6–NR] vs. 17.1 [95%CI: 13.5–22.4] vs. 8.0 [3.9–18.4]; p < 0.001). In the multivariate analysis, after adjusting for age, hemoglobin and ORR, hazard of death increased as per the cachexia risk scale (Hazard ratio: 1.62 [1.22–2.16]; p = 0.001). Conclusion Cachexia is independently associated with worse OS in NSCLC patients who receive immunotherapy, highlighting the role for nutritional assessment.

Determining the prevalence and severity of cancer cachexia in advanced non-small cell lung cancer and its relationship with chemotherapy outcomes

PurposeCancer cachexia (CC) is a syndrome characterised by an ongoing loss of skeletal muscle mass associated with reduced tolerance to treatment. This study explored the prevalence and severity of CC in advanced non-small cell lung cancer (NSCLC) patients and determined its relationship with chemotherapy outcomes.MethodsCC was classified into a four-stage model: no cachexia, pre-cachexia (PC), cachexia and refractory cachexia (RC) with categorisation determined from biochemical and body composition and performance assessment. Associations between the stage of cachexia and chemotherapy outcomes including radiological response, the number of chemotherapy cycles completed and the number of cycles delayed or dose reduced were explored.ResultsTwenty-four patients were included with 4 (18%) classified as having no cachexia, 4 (18%) PC, 3 (14%) cachexia (13.6%), and 11 (50%) RC. No association was observed between the stage of cachexia and the radiological response to chemotherapy number of cycles delayed or the number of cycle’s dose reduced; however, there was an association with the number of cycles completed (p = 0.030). An association between C-reactive protein (CRP) and the number of chemotherapy cycles completed (p = 0.044) and the number of dose reductions (p = 0.044) was also identified.ConclusionsLimited conclusions can be drawn given the small sample size. However, the majority of patients presented with some degree of cachexia at diagnosis. A relationship was identified between the increasing severity of cachexia and a lower number of chemotherapy cycles completed, as well as between CRP and the number of chemotherapy cycles completed and the number of dose reductions required, and therefore warrants further exploration in larger studies.

Difficulties and Related Factors of Care for Refractory Cachexia in Palliative Care Units

Difficulties and Related Factors of Care for Refractory Cachexia in Palliative Care Units

Clinical utility of the modified Glasgow Prognostic Score to classify cachexia in patients with advanced cancer in palliative care

It is a challenge in clinical practice to identify and classify cancer cachexia. Currently, it has been extensively discussed if the presence of alterations in inflammatory biomarkers implies the presence of cachexia. This study aimed to evaluate the clinical relevance of cachexia classification through modified Glasgow Prognostic Score (mGPS) in advanced cancer patients in palliative care. Observational prospective cohort study conducted at a Palliative Care Unit in Brazil. Cachexia classification was performed according to mGPS (based on albumin and C-reactive protein) in four different stages: no cachexia (NCa), undernourished (Un), pre cachexia (PCa), and refractory cachexia (RCa). Logistic regression models were used to test the association between cachexia stages and clinical, nutritional and functional domains. Kaplan-Meier curve and Cox multivariate model were used to analyze overall survival (OS). A total of 1166 patients were included in the study. According to the cachexia framework 37.5% were NCa, 32.3% Un, 3.9% PCa and 26.4% RCa. Significant differences were observed among cachexia stages for most of the outcome measures. This classification was able to predict mortality in 90 days [Un (HR, 1.55; 95% CI, 1.25; 1.93); PCa (HR, 2.00; 95% CI, 1.34; 2.98); RCa (HR, 2.45; 95% CI, 1.34; 2.98)]. Cachexia stages were associated with significant differences in poor clinical outcomes and were also capable of predicting OS. This framework based on simple and objective criteria can be used as part of the routine to characterize the presence and stages of cachexia in advanced cancer patients.

Ten years of Croatian national guidelines for use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome – Evaluation of awareness and implementation among Croatian oncologists

Cancer cachexia (CC) syndrome and anorexia-cachexia syndrome are common terms used to describe changes in metabolism with increased inflammatory activity and can progressively develop through various stages such as pre-cachexia; cachexia; and refractory cachexia. Therefore in year 2007 Croatian guidelines for use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome were published. Aim of this study was to assess the awareness and implementation of Croatian guidelines for use of eicosapentaenoic acid (EPA) and megestrol acetate (MA) into clinical practice among Croatian oncologists approximately 10 years after the publication, but also to point out the importance of adequate recognition and treatment of CC. Survey with questions was designed to assess the awareness and implementation of Croatian guidelines for use of EPA and MA into clinical practice and was distributed among all Croatian oncologists in secondary and tertiary hospital centers. Survey was conducted in January 2011 (40 months following release of the guidelines), February 2013 and June 2018, and were formed in a way of yes/no answers. Additional multiple choice questions that focus on the implementation of guidelines were added in June 2018. A total of 128 oncologists completed a questionnaire. There was no statistically significant difference in follow up period (2011-2018) of percentage of oncologists that are familiar with Croatian guidelines for use of EPA and MA in CC, percentage of oncologists in which Croatian national guidelines changed their approach in treating patients with CC syndrome and proportion of oncologists that are using MA, enteral nutrition formulas with EPA or their combination. Most of the oncologists 38% (N=44) are using>2.2g of EPA per day. Nutritional support is prescribed in 25-50% of patients by 42% (N=48) of oncologists and most of the oncologists (35%, N=41) start with nutritional support when a body mass loss is >5%. Oncologists mostly recommend patients to use nutritional support during 1 year or more (43%, N=49) or two months to 1 year (42%, N=48). Compliance of patients with malignant diseases for using nutritional support was mostly evaluated as medium (69%, N=60). Results have shown that majority of oncologists who filled the questionnaire believe that the Croatian national guidelines for use of EPA and MA in CC syndrome changed their approach in treating patients with CC, but also that there are several targeted issues that can be significantly improved. The awareness of and adherence to national guidelines was maintained at high level even 11 years after the guidelines were published.

Vancomycin Pharmacokinetics in Patients with Advanced Cancer Near End of Life.

The effect of cancer cachexia on the pharmacokinetics of vancomycin remains unclear. We investigated whether the pharmacokinetics of vancomycin and the risk of kidney injury are altered with the development of cancer cachexia. A retrospective analysis was conducted using therapeutic drug monitoring data obtained from 86 cancer patients who received vancomycin intravenously for infection. The patients were classified into four groups according to the stage of cachexia defined by international consensus-non-cachexia (n = 26), pre-cachexia (n = 10), cachexia (n = 21) and refractory cachexia (n = 29). Vancomycin pharmacokinetics were analyzed by a traditional one-compartment model and Bayesian method using plasma concentrations measured in these patients. Renal function and pharmacokinetic parameters were compared between the non-cachexia patients (n = 26) and total cancer cachexia patients (n = 60). No significant difference in estimated glomerular filtration rate was observed between the non-cachexia and the total cancer cachexia patients. In contrast, systemic clearance of vancomycin was significantly lower in the total cancer cachexia patients compared with the non-cachexia patients when analyzed by the traditional one-compartment model [median (range)-49.7 (9.8‒98.7) vs 70.2 (12.5‒211.8) mL/min, p < 0.01] and by the Bayesian method [45.6 (12.5-84.7) vs 63.3 (12.2-102.5) mL/min, p < 0.05]. None of the non-cachexia patients developed kidney injury, whereas 15% (9 of 60 patients) of the total cancer cachexia patients developed kidney injuries (p = 0.052). The present study revealed that cancer patients with cachexia may have reduced vancomycin clearance compared with those without cachexia. Cancer cachexia may be a risk factor of vancomycin-associated kidney injury, independent of renal function.

Patient-generated subjective global assessment predicts cachexia and death in patients with head, neck and abdominal cancer: A retrospective longitudinal study

Cancer is a complex disease, with poor prognosis when associated with malnutrition. This condition can lead to Cancer Cachexia (CC), a syndrome characterized by loss of muscle mass with or without fat loss, often associated with higher risk of death. Although there are recommended screening tools to assess nutritional status in cancer patients, such as Patient-Generated Subjective Global Assessment (PG-SGA), little is known about CC prediction. The aim was to investigate the association between nutritional status of patients with head, neck and abdominal cancer, assessed by PG-SGA at the day of hospitalization, with CC, hospitalization time and death. This is a retrospective longitudinal study, where we collected data of 97 patients about PG-SGA nutritional classification, anthropometry, gender, age, cachexia diagnosis and death. PG-SGA classification was strongly associated with all the anthropometric measures (p<0.0001). According to PG-SGA classification, 30.61% (n=15) of patients in group A developed pre-cachexia; 38.24% in group B developed CC (n=13); and 60% (n=9) in group C developed refractory cachexia (p<0.0001). Death rate was 24.49% (n=12), 54.55% (n=18) and 80% (n=12) in groups A, B and C, respectively (p<0.0001). PG-SGA had good sensibility (89.5%) and accuracy (72%) for CC, and also good specificity (75.51%) and accuracy (69%) for death. PG-SGA demonstrated a significative association with the variables measured and was able to predict CC and death. This, in addition to its simple applicability, suggests that PG-SGA can be a useful tool to screen cancer patients for CC establishment and death risk.

Staging of nutrition disorders in non-small-cell lung cancer patients: utility of skeletal muscle mass assessment.

BackgroundAn international consensus proposed in 2011 a definition and classification system for cachexia (CAX), mainly based on weight loss, sarcopenia [skeletal muscle mass (SMM) loss], inflammation, and anorexia. The aim of this study was to stage CAX in non‐small‐cell lung cancer (NSCLC) patients by using a classification based on the Fearon criteria and supported by quantifiable parameters.MethodsThis was a cross‐sectional and non‐interventional multicentre study. SMM was assessed by analysing L3 computed tomography‐scan images. Patients completed the anorexia/CAX subscale of the Functional Assessment of Anorexia/Cachexia Therapy, EORTC QLQ‐C30 quality of life (QoL) and International Physical Activity Questionnaire (IPAQ).ResultsPatients were recruited in 56 sites. The analysis population comprised 531 patients, and SMM was assessed in 312 patients. Male patients were 66.5%, with a mean (SD) age of 65.2 (10.0) years, 79.9% were PS 0–1, and the tumour stage was mainly IIIB‐IV (87.3%). Overall, 38.7% of patients had CAX, 33.8% pre‐CAX, and 0.9% refractory CAX. Molecular tumour profiles were significantly associated with the presence of CAX: 23.9% in EGFR, ALK, ROS1, BRAF, or HER2+ patients, 41.4% in K‐RAS+, and 43.2% in patients with no molecular abnormality (P = 0.003). The more advanced the CAX stage, the poorer the scores of functional items of the QoL (P < 0.001) and International Physical Activity Questionnaire (P < 0.001). Sarcopenia was present in 66.7% of CAX and 68.5% of pre‐CAX patients. Overall, 43.8% of pre‐CAX patients had only sarcopenia with limited weight loss (≤2%) and no anorexia.ConclusionsThis is the first study to show the distribution of CAX in a population of NSCLC patients and an association between molecular abnormality in NSCLC and CAX. The original Fearon classification for CAX stages was supported by the associated functional QoL scores and physical activity levels, resulting in a clinically relevant system for detection of early stages of CAX.

Potential role of immunological factors in early diagnosis of cancer cachexia in C26 tumor-bearing mice

Cachexia is a wasting syndrome associated with high mortality in cancer patients through inducing the failure of normal metabolism and reducing the efficacy of cancer treatment. Thus, it is critically important to diagnose cancer cachexia early. To provide background data for the diagnosis of cachexia, cancer cachectic factors were characterized in the present situation, including immunological cachectic changes during cachexia progression in a cancer cachexia mouse model. Major constitution of cachexia progression is known as the stages of pre-cachexia, cachexia, and refractory cachexia. In the pre-cachexia stage, the weights of immune-related organs, including the thymus and spleen were significantly. T cell populations in spleen were markedly reduced and cachectic cytokines consistently increased in a time-dependent manner. Immunosuppression by activation of cytotoxic T-lymphocyte-associated antigen 4 was induced earlier in CD4+ cells versus other T cell populations. Furthermore, monocyte chemoattractant protein 1 and interleukin-6 levels in the cachexia group were significantly increased at 3 days from C26 cell inoculation whereas significant carcass weight loss as a classical diagnostic marker occurred at 9 days from C26 cell inoculation. In conclusion, the initiation of cachectic immunological changes was observed prior to weight loss, during the pre-cachexia stage. Accordingly, these findings reveal that the monitoring of humoral and immunological factors may be more sensitive than weight loss for the initial diagnosis and treatment of cachexia.

Health-related quality of life across cancer cachexia stages.

Cancer cachexia (CC) is common in advanced cancer and is accompanied by negative effects on health-related quality of life (HRQOL). However, methods to identify the impact of CC on HRQOL are limited. Single questionnaire items may provide insight on the effect of CC on HRQOL. Specifically, the use of "feeling of wellbeing" (FWB) on the Edmonton Symptom Assessment System (ESAS) questionnaire and the Distress Thermometer (DT) have been explored. Assessing how these two surrogate measures of HRQOL are impacted among CC stages and what drives these negative effects may allow for focused treatments. Five-hundred and twelve patients referred to a Cancer Rehabilitation Program completed the ESAS, with the question on FWB and the DT at baseline. Patients were separated into CC stages: non-cachexia (NC), pre-cachexia (PC), cachexia (C), refractory cachexia (RC). A mixed model ANOVA with post hoc Tukey adjustment was used to compare means of FWB and distress among the CC stages. To understand what was driving the differences between CC stages, a robust regression model was created with either distress or FWB as the outcome measure, dependent on the other measures in ESAS, age and sex. Finally, the use of cannabinoids in treating appetite loss was examined, as it has a detrimental effect on FWB; 54 patients underwent cannabinoid treatment for appetite loss within a community-based, physician-lead, medical cannabis clinic. A t-test to assess changes in ESAS appetite score after 3 months of cannabinoid treatment was examined. RC patients had a significantly poorer sense of wellbeing than the other cachexia stages (RC: 6.07±0.33). Significant differences in distress were identified between RC patients and those with NC and C, but not with PC (RC: 4.87±0.38, NC: 3.35±0.26, PC: 4.11±0.30, C: 3.60±0.28). FWB was negatively affected by worsening appetite in all CC stages except NC (PC: 0.19±0.08, P=0.022; C: 0.26±0.06, P<0.001; RC: 0.23±0.08, P=0.007). ESAS score for lack of appetite significantly improved between baseline (5.07±3.21) and follow-up (3.56±3.15, P=0.003) after cannabinoid treatment, with no significant difference in weight (baseline: 70.7±14.6 kg, 3-month follow-up: 71.0±14.8 kg). Future research should validate both multidimensional and single-item tools to measure HRQOL in patients at different stages of CC. Improvement of HRQOL via appetite stimulation, may be achieved through a multidisciplinary approach, which includes cannabinoid therapy.

Measuring cachexia-diagnostic criteria.

Cancer cachexia is characterized by the loss of lean body mass with or without the loss of fat and is associated with increased susceptibility to treatment related toxicities, decreased quality of life, functional impairment, and increased cancer-related mortality. Uncontrolled symptoms which impair nutritional intake, metabolic derangements including elevated energy expenditure and increased catabolism, and chronic inflammation contribute to the development of cancer cachexia. Weight loss in cancer patients is not readily reversible by conventional nutritional support. The definition of cachexia and sarcopenia are evolving with time, as well as the assessment of weight loss in cancer patients. Clinicians should assess all cancer patients regardless of history of weight loss for risk for malnutrition at presentation and periodically throughout the trajectory of illness-pre-cachectic, cachexia, and refractory cachexia stage. For cancer patients with weight loss, assessments of BMI and percentage weight loss, symptoms which impact nutritional intake, quality of life, physical function, biological markers, energy expenditure, and body composition are ideally needed in order to measure cachexia and implement therapeutic interventions.

Body composition skeletal muscle analysis in cancer cachexia studies: Is there a place for 3T MRI analysis?

AbstractAimsCancer cachexia is a condition often seen in end stage Non‐Small Cell Lung Cancer (NSCLC) patients. Recent developments include the use of pharmaceutical agents and/or exercise to induce stability/hypertrophy of muscle volume. This requires accurate assessment of the change in both quantity and quality of the muscle during cancer cachexia clinical studies. Magnetic Resonance Imaging (MRI) is appropriately placed to address both of these factors. The present study aimed to investigate total quadriceps muscle volume change by 3T MRI within a cancer cachexia clinical study.Methods and resultsAuckland's Cancer Cachexia evaluating Resistance Training (ACCeRT) study is a randomised controlled feasibility study investigating eicosapentaenoic acid (EPA) and cyclo‐oxygenase‐2 (COX‐2) inhibitor (celecoxib) (Arm A) versus EPA, COX‐2 inhibitor (celecoxib), Progressive Resistance Training (PRT) plus essential amino acids (EAAs) high in leucine (Arm B) in NSCLC cachectic patients. All participants underwent 3T MRI scanning at baseline and at last or end of trial (EOT) visit. Analysis showed a mean total quadriceps muscle volume percentage change from baseline to EOT of +12.5% (Arm A), compared with −3% (Arm B). There was a difference in muscle volume between genders. Arm B participant data showed a percentage change of +4.2% within females (n=2) compared with −10.2% (n=2) within males at EOT visit. All EOT results suggests the use of EPA and celecoxib +/‐ PRT and EAAs could potentially preserve muscle volume loss during refractory cachexia.ConclusionsACCeRT is the first study to utilise 3T MRI total quadriceps muscle volume within a cancer cachexia study, along with the first in an end‐stage/refractory cachexia population. These results can be used for baseline/reference for future cancer cachexia studies targeting the anabolic muscle pathways in end‐stage/refractory cachexia patients.

Muscle protein anabolism in advanced cancer patients: response to protein and amino acids support, and to physical activity

In the field of oncology, it is well recognized that a decrease in mass, density, strength, or function of skeletal muscle is associated to increased treatment toxicities and postoperative complications, as well as poor progression-free survival and overall survival. The ability of amino acids to stimulate protein synthesis in cancer patients is reduced. Considering nutritional intervention, this anabolic resistance could be in a part counteracted by increasing protein or by giving specific amino acids. In particular, Leucine might counteract this anabolic resistance not only by increasing substrate availability, but also by directly modulating the anabolic signal pathway. Few studies showed the possibility of increasing muscle protein synthesis by specific nutriments and/or by increasing amino acids or protein administration. In addition, whereas many studies provide evidence of a benefit of adapted physical activity in advanced cancer patients, it is difficult to specify the most appropriate type of exercise, and the optimum rhythm and intensity. Moreover, the benefits of physical activities and of protein support seem greater when it is started at the precachexia stage rather than at the cachexia stage, and their benefits are limited or nonexistent at the stage of refractory cachexia. Future approaches should integrate the combination of several complementary treatments in order to prevent (or improve) cachexia and/or sarcopenia in cancer patients.

Development and validation of a clinically applicable score to classify cachexia stages in advanced cancer patients.

BackgroundCachexia is a multifactorial syndrome that is highly prevalent in advanced cancer patients and leads to progressive functional impairments. The classification of cachexia stages is essential for diagnosing and treating cachexia. However, there is a lack of simple tools with good discrimination for classifying cachexia stages. Therefore, our study aimed to develop a clinically applicable cachexia staging score (CSS) and validate its discrimination of clinical outcomes for different cachexia stages.MethodsAdvanced cancer patients were enrolled in our study. A CSS comprising the following five components was developed: weight loss, a simple questionnaire of sarcopenia (SARC‐F), Eastern Cooperative Oncology Group, appetite loss, and abnormal biochemistry. According to the CSS, patients were classified into non‐cachexia, pre‐cachexia, cachexia, and refractory cachexia stages, and clinical outcomes were compared among the four groups.ResultsOf the 297 participating patients, data from 259 patients were ultimately included. Based on the CSS, patients were classified into non‐cachexia (n = 69), pre‐cachexia (n = 68), cachexia (n = 103), and refractory cachexia (n = 19) stages. Patients with more severe cachexia stages had lower skeletal muscle indexes (P = 0.002 and P = 0.004 in male and female patients, respectively), higher prevalence of sarcopenia (P = 0.017 and P = 0.027 in male and female patients, respectively), more severe symptom burden (P < 0.001), poorer quality of life (P < 0.001 for all subscales except social well‐being), and shorter survival times (P < 0.001).ConclusionsThe CSS is a simple and clinically applicable tool with excellent discrimination for classifying cachexia stages. This score is extremely useful for the clinical treatment and prognosis of cachexia and for designing clinical trials.

Cachexia Stage, Patient-Generated Subjective Global Assessment, Phase Angle, and Handgrip Strength in Patients with Gastrointestinal Cancer

ABSTRACTThe aim of this study was to correlate patients with gastrointestinal cancer, classified according to different stages of cancer cachexia (SCC) as proposed by Fearon, with nutritional assessment tools such as PG-SGA, phase angle (PA), and handgrip strength. One hundred one patients with a mean age of 61.8 ± 12.8 yr, with 58.4% being men were included. 32.6% were malnourished according to the body mass index (BMI). A severe or moderate malnutrition had been diagnosed in 63.3% when assessed using the PG-SGA, 60.4% had decreased handgrip strength, and 57.4% had lower grades of PA. Among the patients in the study, 26% did not have cachexia, 11% had precachexia, 56% cachexia, and 8% refractory cachexia. The PG-SGA, PA, and handgrip strength were associated with cachexia (P ≤ 0.001). An increased risk of death was found in patients with cachexia [RR: 9.1; confidence interval (CI) 95%: 0.1–90.2, P = 0.039], refractory cachexia (RR: 69.4, CI 95%: 4.5–1073.8, P = 0.002), and increased serum C-reactive protein (CRP) levels (P < 0.001). In conclusion, most of the patients with digestive system cancer had cachexia or refractory cachexia in the first nutritional assessment. Nutritional risk, as determined by PG-SGA, was correlated with PA and handgrip strength. High CRP levels, cachexia, and refractory cachexia were prognostic factors for cancer patients.

Cancer-induced muscle wasting: latest findings in prevention and treatment.

Cancer cachexia is a severe and disabling clinical condition that frequently accompanies the development of many types of cancer. Muscle wasting is the hallmark of cancer cachexia and is associated with serious clinical consequences such as physical impairment, poor quality of life, reduced tolerance to treatments and shorter survival. Cancer cachexia may evolve through different stages of clinical relevance, namely pre-cachexia, cachexia and refractory cachexia. Given its detrimental clinical consequences, it appears mandatory to prevent and/or delay the progression of cancer cachexia to its refractory stage by implementing the early recognition and treatment of the nutritional and metabolic alterations occurring during cancer. Research on the molecular mechanisms underlying muscle wasting during cancer cachexia has expanded in the last few years, allowing the identification of several potential therapeutic targets and the development of many promising drugs. Several of these agents have already reached the clinical evaluation, but it is becoming increasingly evident that a single therapy may not be completely successful in the treatment of cancer-related muscle wasting, given its multifactorial and complex pathogenesis. This suggests that early and structured multimodal interventions (including targeted nutritional supplementation, physical exercise and pharmacological interventions) are necessary to prevent and/or treat the devastating consequences of this cancer comorbidity, and future research should focus on this approach.

Practical and theoretical implications of weight gain in advanced non-small cell lung cancer patients

Involuntary weight loss occurs frequently in individuals with many types of cancers and was shown to be associated with inferior survival almost 40 years ago (1). More recently, there is evidence that weight loss prior to initiation of systemic anti-cancer therapies is associated with increased treatment related side effects (2,3). The majority of these patients are suffering from the cancer anorexia cachexia syndrome. In 2011, a panel of cancer cachexia experts published a consensus statement which defined and classified cancer cachexia (4). This group pointed out that the predominant feature of this syndrome includes loss of skeletal muscle mass which cannot be reversed by conventional nutritional support and which may or may not be accompanied by loss of body fat. Their consensus for diagnostic criteria for cancer cachexia are weight loss greater than 5% in individuals with body mass index (BMI) of ≥20 during the preceding 6 months and 2% weight loss in individuals with BMI <20. They also defined stages of cachexia as pre cachexia (<5% weight loss), cachexia as defined above, and refractory cachexia which is usually associated with progressive cancer and poor performance status.

Differences in Symptom Burden Among Cancer Patients With Different Stages of Cachexia

ContextCancer patients with cachexia may suffer from significant burden of symptoms and it can severely impair patients' quality of life. However, only few studies have targeted the symptom burden in cancer cachexia patients, and whether the symptom burden differed in different cachexia stages is still unclear. ObjectivesThe aims of this study were to evaluate the symptom burden in cancer cachexia patients and to compare the severity and occurrence rates of symptoms among cancer patients with non-cachexia, pre-cachexia, cachexia, and refractory cachexia. MethodsAdvanced cancer patients (n = 306) were included in this cross-sectional study. Patients were divided into four groups, based on the cachexia stages of the international consensus. The M.D. Anderson Symptom Inventory added with eight more cachexia-specific symptoms were evaluated in our patients. Differences in symptom severity and occurrence rates among the four groups were compared using one-way ANOVA or Kruskal-Wallis test analyses. ResultsLack of appetite, disturbed sleep, fatigue, lack of energy, and distress were the symptoms with highest occurrence rates and severity scores in all four groups and were exacerbated by the severity of cachexia stages. After confounders were adjusted for, significant differences were seen in symptoms of pain, fatigue, disturbed sleep, remembering problems, lack of appetite, dry mouth, vomiting, numbness, feeling dizzy, early satiety, lack of energy, tastes/smell changes, and diarrhea. ConclusionThis study identified higher symptom burden in cancer patients with cachexia and it increased with the stages of cachexia, which emphasized the importance of screening in multiple co-occurring symptoms for cachexia patients.

P1.06-010 Analysis of the Incidence of Cancer Cachexia in Patients with Advanced Lung Cancer at Referral to a Dietitian

Lung cancer is the second most common cancer diagnosed in men and women in the UK with a very poor 5 year survival (10%). There is a lack of robust data on the stage of cachexia in which patients with lung cancer present. The severity of cachexia can influence overall outcomes and a patient’s quality of life. Refractory (irreversible) cachexia indicates a poor prognosis. We reviewed all patients diagnosed with metastatic primary lung cancer that were referred to the Macmillan Oncology Dietitians over a 4 year period at the Royal Surrey County Hospital. Reasons for referral commonly included: weight loss, glycemic control in diabetes, decreased oral intake and food texture modification. We compared self-reported usual body weight (UBW) to weight at referral. Patients were defined as cachectic if weight loss was >5% and refractory cachexia if survival was <90 days from dietitian review. 310 patients with incurable lung cancer were reviewed by the dietitian. Mean age was 68.8 (range 36-89). 42% were female, 58% were male. Mean weight loss was 10%. 76% of patients had lost >5% of usual body weight. Mean pre-cancer body mass index (BMI) was 26.9 (kg/m2), mean BMI at referral was 23.0 (kg/m2). Median survival of non-cachectic and cachectic cohorts were different (299 vs 188 days respectively, p=0.0078). 24% (73 patients) had refractory cachexia. Our study shows cachexia is very common (76%) in lung cancer and affects survival. A quarter of patients had refractory cachexia. BMI is an insensitive measure of weight loss. Early symptom control improves survival in lung cancer and this data suggests patients are routinely being referred too late to a dietitian. Cachexia in lung cancer is a significant clinical problem. Could upfront assessment of cachexia improve outcome in patients with advanced lung cancer? We propose to investigate this further.

Oncology Update: Anamorelin.

Background:Cancer cachexia is a catabolic syndrome associated with uncontrolled muscle breakdown. There may be associated fat loss. Occurring in high frequency in advanced cancer, it is an indicator of poor prognosis. Besides weight loss, patients experience a cluster of symptoms including anorexia, early satiety, and weakness. The 3 stages of cachexia include stages of precachexia, cachexia, and refractory cachexia. Refractory cachexia is associated with active catabolism or the presence of factors that make active management of weight loss no longer possible. Patients with refractory cachexia often receive glucocorticoids or megasterol acetate. Glucocorticoid effect is short and responses to megasterol are variable. Anamorelin is a new agent for cancer anorexia-cachexia, with trials completed in advanced lung cancer. Acting as an oral mimetic of ghrelin, it improves appetite and muscle mass. This article reviews the pharmacology, pharmacodynamics, and effect on cancer cachexia.Methods:A PubMed search was done using the Medical Subject Headings term anamorelin. Articles were selected to provide a pharmacologic characterization of anamorelin.Results:Anamorelin increases muscle mass in patients with advanced cancer in 2-phase 3 trials.Conclusions:Anamorelin improves anorexia-cachexia symptoms in patients with advanced non–small-cell lung cancer.