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Body composition, defined as the proportions and distribution of lean and fat tissues in the human body, is an emergent theme in clinical oncology. Severe muscle depletion (sarcopenia) is most easily overlooked in obese patients; the advent of secondary analysis of oncologic images provides a precise and specific assessment of sarcopenia. Here, we review the definitions, prevalence and clinical implications of sarcopenic obesity (SO) in medical and surgical oncology. Reported prevalence of SO varies due to the heterogeneity in the definitions and the variability in the cut points used to define low muscle mass and high fat mass. Prevalence of SO in advanced solid tumor patient populations average 9% (range 2.3%-14.6%) overall, and one in four (24.7%, range 5.9%-39.2%) patients with body mass index ≥30 kg/m2 are sarcopenic. SO is independently associated with higher mortality and higher rate of complications in systemic and surgical cancer treatment, across multiple cancer sites and treatment plans. These associations remain unexplained, however, it has been hypothesized that patients with sarcopenia are generally unfit and unable to tolerate stress. Another proposed mechanism relates to increased exposure to antineoplastic therapy, i.e. a large fat mass would be expected to inflate drug dose in BSA-based treatments, causing an increased rate of dose-limiting toxicity. Pharmacokinetic data are needed to confirm or refute this hypothesis. Old age, deconditioning, cancer progression, acute or chronic nonmalignant disease and drug side-effects are suggested causes of muscle loss, and it is unknown the degree to which this can be reversed. Sarcopenia can be readily detected before start of cancer treatment, however, clinical management protocols for SO patients require development. Studies of cancer treatment dose-modulation are in progress. [ABSTRACT FROM AUTHOR]

Background: Advances in the treatment of metastatic colorectal cancer (mCRC) in the last decade have significantly improved survival; however, simple biomarkers to predict response or toxicity have not been identified, which are applicable to all community oncology settings worldwide. The use of inflammatory markers based on differential white-cell counts, such as the neutrophil/lymphocyte ratio (NLR), may be simple and readily available biomarkers.Methods: Clinical information and baseline laboratory parameters were available for 349 patients, from two independent cohorts, with unresectable mCRC receiving first-line palliative chemotherapy. Associations between baseline prognostic variables, including inflammatory markers such as the NLR and tumour response, progression and survival were investigated.Results: In the training cohort, combination-agent chemotherapy (P=0.001) and NLR ≤ 5 (P=0.003) were associated with improved clinical benefit. The ECOG performance status 1 (P=0.002), NLR>5 (P=0.01), hypoalbuminaemia (P=0.03) and single-agent chemotherapy (P<0.0001) were associated with increased risk of progression. The ECOG performance status ≥ 1 (P=0.004) and NLR>5 (P=0.002) predicted worse overall survival (OS). The NLR was confirmed to independently predict OS in the validation cohort (P<0.0001). Normalisation of the NLR after one cycle of chemotherapy in a subset of patients resulted in improved progression-free survival (P=0.012).Conclusion: These results have highlighted NLR as a potentially useful clinical biomarker of systemic inflammatory response in predicting clinically meaningful outcomes in two independent cohorts. Results of this study have also confirmed the importance of a chronic systemic inflammatory response influencing clinical outcomes in patients with mCRC. [ABSTRACT FROM AUTHOR]

Infectious complications are a major cause of morbidity and mortality from dose-intensive cancer chemotherapy. In spite of the importance of intestinal bacteria translocation in these infections, information about the effect of high-dose chemotherapy on gut mucosal immunity is minimal. We studied prophylactic ciprofloxacin (Cipro) treatment on irinotecan (CPT-11) toxicity and host immunity in rats bearing Ward colon tumour. Cipro abolished chemotherapy-related mortality, which was 45% in animals that were not treated with Cipro. Although Cipro reduced body weight loss and muscle wasting, it was unable to prevent severe late-onset diarrhoea. Seven days after CPT-11, splenocytes were unable to proliferate (stimulation index=0.10+/-0.02) and produce proliferative and inflammatory cytokines (i.e., Interleukin (IL)-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) IL-1beta, IL-6) on mitogen stimulation in vitro (P<0.05 vs controls), whereas mesenteric lymph node (MLN) cells showed a hyper-proliferative response and a hyper-production of pro-inflammatory cytokines on mitogen stimulation. This suggests compartmentalised effects by CPT-11 chemotherapy on systemic and intestinal immunity. Cipro normalised the hyper-responsiveness of MLN cells, and in the spleen, it partially restored the proliferative response and normalised depressed production of IL-1beta and IL-6. Taken together, Cipro prevented infectious challenges associated with immune hypo-responsiveness in systemic immune compartments, and it may also alleviate excessive pro-inflammatory responses mediating local gut injury. [ABSTRACT FROM AUTHOR]

Overweight /obese cancer patients face significant risk of malnutrition and they should not be spared from regular nutritional screening/assessment. Malnourishment, in this particular cohort, is additionally associated with adverse survival.Background Obesity is causally related with tumor development, and thus, many cancer patients are overweight or obese at diagnosis. Whether these patients need regular nutritional assessment is not known. In the present study, we evaluated the utility of Mini Nutritional Assessment (MNA), a nutritional screening/assessment questionnaire, in overweight or obese patients with metastatic tumors. Patients and methods Overweight or obese patients referred for initiation of systemic therapy in three cancer centers were eligible. Basic demographics and clinical data were recorded. MNA was completed at baseline and patients were divided into three groups: A (well nourished), B (at risk), and C (malnourished). Survival data were subsequently collected. The prevalence of malnutrition and prognostic significance were evaluated. Results In total, 1469 patients with metastatic primaries were identified. Of them, 594 (41.9%) were overweight or obese and included in the analysis. According to MNA, almost 50% were at risk and around 12% were already malnourished at presentation. A significant difference in overall survival was found between groups [group A 17.8 (15.5–20.1) months, group B 8.2 (7.3–9.3) months, and group C 6.4 (3.2–9.6) months, P < 0.001]. Moreover, MNA was the only independent predictor of survival. Conclusions Our findings support that a significant percentage of overweight or obese cancer patients may be at nutritional risk and this is moreover related with adverse prognosis. An MNA score could be used for the identification of this risk. [ABSTRACT FROM PUBLISHER]

A cancer cachexia classification into stages is warranted in order to guide treatment decisions and clinical trial inclusion. Weight loss and BMI clearly discriminate between non-cachectic and cachectic patients both with regards to all the domains (Intake, Catabolism and Function) and survival. The precachexia stage might be better defined by additional factors in order to be discriminative.Background Weight loss limits cancer therapy, quality of life and survival. Common diagnostic criteria and a framework for a classification system for cancer cachexia were recently agreed upon by international consensus. Specific assessment domains (stores, intake, catabolism and function) were proposed. The aim of this study is to validate this diagnostic criteria (two groups: model 1) and examine a four-group (model 2) classification system regarding these domains as well as survival. Patients and methods Data from an international patient sample with advanced cancer (N = 1070) were analysed. In model 1, the diagnostic criteria for cancer cachexia [weight loss/body mass index (BMI)] were used. Model 2 classified patients into four groups 0-III, according to weight loss/BMI as a framework for cachexia stages. The cachexia domains, survival and sociodemographic/medical variables were compared across models. Results Eight hundred and sixty-one patients were included. Model 1 consisted of 399 cachectic and 462 non-cachectic patients. Cachectic patients had significantly higher levels of inflammation, lower nutritional intake and performance status and shorter survival. In model 2, differences were not consistent; appetite loss did not differ between group III and IV, and performance status not between group 0 and I. Survival was shorter in group II and III compared with other groups. By adding other cachexia domains to the model, survival differences were demonstrated. Conclusion The diagnostic criteria based on weight loss and BMI distinguish between cachectic and non-cachectic patients concerning all domains (intake, catabolism and function) and is associated with survival. In order to guide cachexia treatment a four-group classification model needs additional domains to discriminate between cachexia stages. [ABSTRACT FROM AUTHOR]