Mini Nutritional Assessment (MNA) and biochemical markers of cachexia in metastatic lung cancer patients: interrelations and associations with prognosis.

PURPOSE: Lung cancer patients frequently present with weight loss in the context of the cachexia syndrome. Despite its high clinical significance, definite diagnostic criteria of cachexia are lacking. Nutritional screening questionnaires, like the Mini Nutritional Assessment (MNA), have been proposed for the timely diagnosis of the syndrome. The aim of this study was to evaluate the correlation of MNA with laboratory markers of inflammation/cachexia in patients with metastatic lung cancer. The prognostic value of the measured parameters was also examined. PATIENTS AND METHODS: Patients with metastatic lung cancer referred for systemic therapy were eligible. Baseline clinical characteristics were recorded and nutritional status was assessed using MNA. Blood samples were also collected and the following parameters were measured: hemoglobin (Hb), albumin (Alb), C-reactive protein (CRP), ghrelin, adiponectin, leptin and insulin growth factor I (IGF-I). RESULTS: Totally, 115 patients (101 males) [median age 66 years (range 32-86)] were evaluated. According to MNA score, 27 (23.5%) patients were well nourished, 59 (51.3%) were at nutritional risk and 29 (25.2%) were already malnourished at diagnosis. MNA correlated with the following parameters: Hb (p=0.001), albumin (p<0.001), CRP (p=0.002), adiponectin (p=0.037) and leptin (p=0.008). After a median follow up of 38.2 months, multivariate analysis revealed that age (p=0.008), number of metastatic sites (p<0.001), MNA (p=0.044) and leptin (p=0.004) independently correlated with overall survival. CONCLUSIONS: Based on the MNA, the majority of patients were either malnourished or at nutritional risk. MNA correlated with laboratory parameters related to inflammation/cachexia and was independently associated with survival.

Assessment of highly angiogenic and disseminated in the peripheral blood disease in breast cancer patients predicts for resistance to adjuvant chemotherapy and early relapse.

The assessment of tumor molecular features in combination with the detection of occult malignant cells may provide important clinical information, beyond the standard staging of breast cancer. Using a nested RT-PCR technique, we assessed prospectively the presence of cytokeratin-19 (CK19) mRNA positive cells in the blood of 100 operated patients with breast cancer before the initiation of adjuvant chemotherapy and local radiotherapy. Tissue samples were prospectively collected and analyzed for estrogen (ER) and progesterone (PgR) receptor, c-erbB-2 overexpression, mutant-p53 and bcl-2 protein accumulation, proliferation index and microvessel density (MVD). CK-19 mRNA-positive cells were detected in the peripheral blood of 33% of patients. Simultaneous display of high intratumoral MVD and of CK-19 mRNA-positive cells, which characterized highly angiogenic and disseminated in the peripheral blood (HAD) disease was noted in 25% of patients. Detection of CK-19 positive cells was significantly associated with increased MVD (p = 0.002). In univariate analysis (median follow-up 30 months) CK19 mRNA detection and MVD were the most significant factors related to a short relapse-free survival (RFS), (p < 0.0001). In multivariate analysis, CK19 positivity, high MVD and c-erbB-2 overexpression were the only significant and independent variables associated with relapse (p = 0.0005, 0.03 and 0.04, respectively). Patients with HAD had an expected relapse rate close to 70% vs. <5% in the remaining patients irrespectively of the used chemotherapy regimen. The simultaneous presence of high MVD and CK19-positive cells in the blood of patients with early breast is linked with poor prognosis, which cannot be improved with standard chemotherapy regimens.