Relationship between angiotensin-converting enzyme gene polymorphism and body composition, functional performance, and blood biomarkers in advanced cancer patients.

PURPOSE: Nutritional and functional outcome measures have been shown to vary in patients with chronic diseases according to the polymorphic alleles of angiotensin-converting enzyme (ACE), but little is known about the associations between ACE gene polymorphism (ACEGP) and the components of body composition, strength, and selected blood markers in advanced cancer patients (ACP). EXPERIMENTAL DESIGN: Data were collected from an inception cohort of 172 newly diagnosed ACP with gastrointestinal and non-small cell lung cancer. ACEGP status was defined by the presence of one of the following three combinations of alleles: insertion/insertion, insertion/deletion, and deletion/deletion. Body composition measurements using Dual-energy X-ray Absorptiometry comprised of the following: total fat mass, percent body fat, lean body mass, and appendicular lean mass. Body mass index; handgrip force by Jamar dynamometry; subjective recording of nutrition and performance status as per patient-generated subjective global assessment; cell blood count and differential, serum albumin, ACE, and C-reactive protein were also recorded. RESULTS: Multiple regression analysis, controlling for gender, age, diagnosis, treatments (radio/chemo), survival, and medication use (ACE inhibitors, anti-inflammatories, statins) revealed the following significant (P

Use of prediction equations to determine the accuracy of whole-body fat and fat-free mass and appendicular skeletal muscle mass measurements from a single abdominal image using computed tomography in advanced cancer patients.

Measurements of body composition using dual-energy X-ray absorptiometry (DXA) and single abdominal images from computed tomography (CT) in advanced cancer patients (ACP) have important diagnostic and prognostic value. The question arises as to whether CT scans can serve as surrogates for DXA in terms of whole-body fat-free mass (FFM), whole-body fat mass (FM), and appendicular skeletal muscle (ASM) mass. Predictive equations to estimate body composition for ACP from CT images have been proposed (Mourtzakis et al. 2008; Appl. Physiol. Nutr. Metabol. 33(5): 997-1006); however, these equations have yet to be validated in an independent cohort of ACP. Thus, this study evaluated the accuracy of these equations in estimating FFM, FM, and ASM mass using CT images at the level of the third lumbar vertebrae and compared these values with DXA measurements. FFM, FM, and ASM mass were estimated from the prediction equations proposed by Mourtzakis and colleagues (2008) using single abdominal CT images from 43 ACP and were compared with whole-body DXA scans using Spearman correlations and Bland-Altman analyses. Despite a moderate to high correlation between the actual (DXA) and predicted (CT) values for FM (rho = 0.93; p ≤ 0.001), FFM (rho = 0.78; p ≤ 0.001), and ASM mass (rho = 0.70; p ≤ 0.001), Bland-Altman analyses revealed large range-of-agreement differences between the 2 methods (29.39 kg for FFM, 15.47 kg for FM, and 3.99 kg for ASM mass). Based on the magnitude of these differences, we concluded that prediction equations using single abdominal CT images have poor accuracy, cannot be considered as surrogates for DXA, and may have limited clinical utility.

The abridged patient-generated subjective global assessment is a useful tool for early detection and characterization of cancer cachexia.

Cancer cachexia (CC) is a syndrome characterized by wasting of lean body mass and fat, often driven by decreased food intake, hypermetabolism, and inflammation resulting in decreased lifespan and quality of life. Classification of cancer cachexia has improved, but few clinically relevant diagnostic tools exist for its early identification and characterization. The abridged Patient-Generated Subjective Global Assessment (aPG-SGA) is a modification of the original Patient-Generated Subjective Global Assessment, and consists of a four-part questionnaire that scores patients' weight history, food intake, appetite, and performance status. The purpose of this study was to determine whether the aPG-SGA is associated with both features and clinical sequelae of cancer cachexia. In this prospective cohort study, 207 advanced lung and gastrointestinal cancer patients completed the following tests: aPG-SGA, Edmonton Symptom Assessment System, handgrip strength, a complete blood count, albumin, apolipoprotein A and B, and C-reactive protein. Ninety-four participants with good performance status as assessed by the Eastern Cooperative Oncology Group Performance Status completed additional questionnaires and underwent body composition testing. Of these, 68 patients tested for quadriceps strength and completed a 3-day food recall. Multivariable regression models revealed that higher aPG-SGA scores (≥9 vs 0 to 1) are significantly associated (P<0.05) with the following: unfavorable biological markers of cancer cachexia, such as higher white blood cell counts (10.0 vs 6.7×10(9)/L; lower hemoglobin (115.6 vs 127.7 g/L), elevated C-reactive protein (42.7 vs 18.2 mg/L [406.7 vs 173.3 nmol/L]); decreased anthropometric and physical measures, such as body mass index (22.5 vs 27.1); fat mass (14.4 vs 26.0 kg), handgrip (24.7 vs 34.9 kg) and leg strength; an average 12% greater length of hospital stay; a dose reduction in chemotherapy; and increased mortality. Given its association with the main features of cancer cachexia and its ease of use, the aPG-SGA appears to be a useful tool for detecting and predicting outcomes of cancer cachexia. Additional research is required to determine what impact the aPG-SGA has on quality of care when used in the clinical setting.

Metabolic, nutritional and inflammatory characteristics in elderly women with advanced cancer.

OBJECTIVE: Few studies have focused on the metabolic profiling of patients with advanced cancer and the relationship with nutritional and inflammatory characteristics, which have important diagnostic, treatment and prognostic implications, particularly in the elderly. Our objective was to determine differences in energy expenditure during rest and activity, body composition, nutrition, and inflammatory markers between healthy elderly females and those with advanced cancer. MATERIALS AND METHODS: Twenty elderly (74.8±6.7years) females (9 with solid malignancies, 11 healthy) were evaluated for energy expenditure using indirect calorimetry at rest and throughout a 6-min walk test (6MWT). Body composition (dual-energy x-ray absorptiometry); nutritional intake (3-day 24-h food recall); and markers of nutrition and inflammation (complete blood count, albumin and C-reactive protein) were also measured. RESULTS: Compared to healthy controls, patients with cancer had similar energy expenditures, but significantly lower (p<0.05) respiratory quotients at rest. During the 6MWT, the group with cancer walked shorter distances at slower speeds (p<0.001), consumed less oxygen (p<0.05), and trended toward an increased oxygen cost while walking. The patients with cancer ingested fewer calories and presented with higher levels of inflammatory markers (p<0.05). No differences in body composition were observed. CONCLUSION: Early signs of cachexia (i.e. reduced caloric intake, inflammation and greater fat metabolism) may be present in older patients with cancer, along with poorer levels of functional capacity, compared to healthy controls. Timely recognition of these signs may allow therapeutic interventions to better prevent or delay nutritional and functional demise in elderly patients with cancer.

Is IL-6 the best pro-inflammatory biomarker of clinical outcomes of cancer cachexia?

BACKGROUND & AIMS: Despite the descriptive presence of cancer cachexia (CC) in clinical practice, the underlying mechanisms and diagnostic definition have not been clearly identified. Recent work, attempting to establish diagnostic and staging criteria for CC, has identified IL-6 as a biomarker. This study aimed to investigate the clinical relevance of plasma levels of four pro-inflammatory cytokines (IL-6, IL-1ß, IL-8 and TNF-α) in advanced cancer patients (ACP) to further establish their potential in the diagnostic definition of CC. METHODS: Blood was obtained from 83 ACP (47 male and 36 female, aged 34-85 years) and analyzed for white blood cells, lymphocytes, C-reactive protein, albumin and cytokines. Subjects completed questionnaires to establish weakness, loss of appetite, fatigue, quality of life and weight loss; completed tests to determine strength, body composition and sarcopenia; and consented to chart review to calculate survival and total days admitted to hospital. RESULTS: This study shows that, in ACP, IL-1ß is better associated with clinical features of the cachectic condition, such as weakness, loss of appetite, weight loss and sarcopenia, than IL-6. CONCLUSION: IL-6 may not best represent the clinical correlates of CC in ACP. Additional cytokines should be considered in the definition of this condition.

Cancer-related fatigue: the impact of skeletal muscle mass and strength in patients with advanced cancer.

BACKGROUND: Although exertional fatigue is directly and negatively related to skeletal muscle mass and strength, it is currently unknown if these variables are associated with cancer-related fatigue (CRF). Therefore, the purpose of this study was to determine if CRF is associated with measures of appendicular lean muscle mass and strength in advanced cancer patients (ACP). METHODS AND RESULTS: Eighty-four patients (48 men, 36 women aged 61.6 ± 13.2 year) newly diagnosed (≤6 months) with inoperable (Stages III-IV) gastrointestinal or non-small cell lung cancer participated in this study. All patients completed the Brief Fatigue Inventory (BFI). Handgrip (HGS) and quadriceps (QS) strength were assessed using isometric and isokinetic dynamometry, respectively. Skeletal muscle mass index (SMMI) was calculated from the appendicular lean mass measured via dual-energy X-ray absorptiometry divided by body height squared. Univariate analysis showed BFI to be significantly associated with body mass index, weight loss, anemia, hypoalbuminemia, activity level, pain, depression, and sarcopenia along with SMMI, HGS, and QS. HGS (r = -0.34; p = 0.018), QS (r = -0.39; p = 0.024), and SMMI (r = -0.60; p < 0.001) were negatively correlated with BFI total scores in men but not in women. When adjusted for sex, age, diagnosis, survival, along with the above characteristics, multivariate analyses showed that BFI scores were negatively associated with HGS (B = -0.90; 95% CI -1.5:-0.3), QS (-0.2; -0.3:-0.01), and SMMI (-7.5; -13.0:-2.0). There was a significant sex × SMMI interaction (10.8; 1.2:20.5), where BFI decreased with increasing SMMI in men, but did not change with SMMI in women. CONCLUSION: These results suggest that in ACP, CRF is related to muscle mass and strength, which may provide targets for future interventions.