Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer.

BACKGROUND: Patients with potentially curative oesophago-gastric cancer typically undergo neo-adjuvant chemotherapy prior to surgery. The majority of anti-cancer drugs have a narrow therapeutic index. The aim of this study was to determine if features of body composition, assessed using computed tomography (CT) scans, may be predictive of dose-limiting toxicity (DLT) in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. The influence of sarcopenia and DLT on overall survival was also evaluated. METHODS: 89 Patients having potentially curative oesophago-gastric cancer surgery were studied. Patients studied had histologically confirmed oesophago-gastric cancer with no evidence of distant metastasis on pre-operative staging. CT scan was performed in all cases at diagnosis. DLT was defined as toxicity leading to postponement of treatment, a drug dose reduction or definitive interruption of drug administration. RESULTS: DLT occurred in 37 out of 89 patients (41.6%) undergoing chemotherapy. Sarcopenia (odds ratio, 2.95; 95% confidence interval, 1.23-7.09; p = 0.015) was associated with DLT on multivariate analysis. Median overall survival for patients who were sarcopenic was 569 days (IQ range: 357-1230 days) vs. 1013 days (IQ range: 496-1318 days) for patients who were not sarcopenic (p = 0.04). There was no significant difference in overall survival in patients who experienced DLT compared with those that did not (p = 0.665). CONCLUSIONS: Sarcopenia is a significant predictor of DLT in oesophago-gastric cancer patients undergoing neo-adjuvant chemotherapy. These results raise the potential for use of assessment of skeletal muscle mass using CT scans to predict toxicity and individualize chemotherapy dosing.

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer.

BACKGROUND: Macrophage inhibitory cytokine-1(MIC-1) is a potential modulator of systemic inflammation and nutritional depletion, both of which are adverse prognostic factors in oesophago-gastric cancer (OGC). METHODS: Plasma MIC-1, systemic inflammation (defined as plasma C-reactive protein (CRP) of > or =10 mg l(-1) or modified Glasgow prognostic score (mGPS) of > or =1), and nutritional status were assessed in newly diagnosed OGC patients (n=293). Healthy volunteers (n=35) served as controls. RESULTS: MIC-1 was elevated in patients (median=1371 pg ml(-1); range 141-39 053) when compared with controls (median=377 pg ml(-1); range 141-3786; P<0.001). Patients with gastric tumours (median=1592 pg ml(-1); range 141-12 643) showed higher MIC-1 concentrations than patients with junctional (median=1337 pg ml(-1); range 383-39 053) and oesophageal tumours (median=1180 pg ml(-1); range 258-31 184; P=0.015). Patients showed a median weight loss of 6.4% (range 0.0-33.4%), and 42% of patients had an mGPS of > or =1 or plasma CRP of > or =10 mg l(-1) (median=9 mg l(-1); range 1-200). MIC-1 correlated positively with disease stage (r(2)=0.217; P<0.001), age (r(2)=0.332; P<0.001), CRP (r(2)=0.314; P<0.001), and mGPS (r(2)=0.336; P<0.001), and negatively with Karnofsky Performance Score (r(2)=-0.269; P<0.001). However, although MIC-1 correlated weakly with dietary intake (r(2)=0.157; P=0.031), it did not correlate with weight loss, BMI, or anthropometry. Patients with MIC-1 levels in the upper quartile showed reduced survival (median=204 days; 95% CI 157-251) when compared with patients with MIC-1 levels in the lower three quartiles (median=316 days; 95% CI 259-373; P=0.036), but MIC-1 was not an independent prognostic indicator. CONCLUSIONS: There is no independent link between plasma MIC-1 levels and depleted nutritional status or survival in OGC.

Biomarkers for cancer cachexia: is there also a genetic component to cachexia?

INTRODUCTION: Cancer cachexia is a severe debilitating disorder, which causes significant morbidity and mortality. In clinical practice, cachexia is often not treated until a late stage, when therapeutic options are limited. OBJECTIVE: It is therefore of great interest to analyse early biomarkers of this syndrome. CONCLUSION: In this review article, we summarise recent biomarkers found in various body compartments. We also explore the likelihood of a genetic predisposition to cachexia and focus on the potential role of single nucleotide polymorphisms in genes coding for pro- and anti-inflammatory cytokines, and 'atrogenes' associated with wasting in skeletal muscle.