The role of inflammation, iron, and nutritional status in cancer-related anemia: results of a large, prospective, observational study

Abstract

ABSTRACTfore, essential to analyze all these factors that cause anemia, particularly before beginning any form of therapy that may worsen anemia.The aim of this work was to document the prevalence of anemia in a large cohort of patients with solid tumors before any exposure to antineoplastic treatment, and to assess the possible correlation between Hb levels and the commonly used indices of inflammation, malnutrition, and metabolic stress. We hypothesized that inflammation and malnutrition are independent predictors of the development and severity of anemia and that a better knowledge of CRA may enable its more adequate treatment. MethodsThis study was a prospective, observational trial performed in accordance with the Helsinki declaration after approval by the Local Institutional Ethics Committee. Between May 2011 and January 2014, 888 consecutive patients with histologically confirmed solid cancer at different sites referred to the Departments of Obstetrics and Gynecology, Sirai Hospital, Carbonia, Medical Oncology at "N.S. Bonaria" Hospital, San Gavino, "Nuova Casa di Cura", Decimomannu, and "A. Businco" Hospital, Cagliari, Italy, were enrolled. Table 1 reports the participants' clinical characteristics. Patients were assessed at diagnosis before receiving any cancer treatment. Exclusion criteria were: evidence of infections, chronic inflammatory disease, active bleeding, hemolysis, renal insufficiency, or hypothyroidism; known history of hematologic disorders (including hemoglobinopathies), family history of thalassemia or hemocromatosis; treatment with EPO, i.v. iron or blood transfusion in the preceding 12 weeks; current iron, vitamin B12 or folate supplementation.Anemia was defined according to our laboratory populationbased normal ranges as Hb <13.0 g/dL for males and <12.0 g/dL for females. Karnofsky PS was categorized into four prognostic classes. 17 Blood samples were obtained at 8 a.m. after overnight fasting since serum hepcidin and iron levels show similar circadian changes. In accordance with Ganz et al., 18 the 8 a.m. fasting hepcidin concentrations were more consistent than those at other times of the day. After centrifugation of the blood samples, serum was stored at -80°C until analysis.In all patients Hb levels and parameters of chronic inflammation [CRP, fibrinogen, IL-6, IL-1β, tumor necrosis factor-α (TNFα)], iron metabolism (iron, ferritin, transferrin, hepcidin), EPO, nutritional status (albumin, leptin, cholesterol, HDL, LDL, triglycerides) and oxidative stress [ROS, glutathione peroxidase (GPx), superoxide dismutase (SOD)] were measured. The formula for expected EPO was: 2.5 x (140-Hb g/L). 19 Since leptin is highly dependent on body mass index (BMI), the leptin/BMI ratio was reported. The modified Glasgow prognostic score (mGPS) was calculated as follows: 2, both elevated CRP (≥10 mg/L) and low albumin (<3.5 g/dL); 1, elevated CRP only; 0, normal CRP (<10 mg/L). 20 Laboratory assaysRoutine analyses of Hb, CRP, fibrinogen, serum iron, transferrin, ferritin, triglycerides, cholesterol...

Establishment and characterization of a novel murine model of pancreatic cancer cachexia

“…One possible contributing mechanism of fatigue and cardiovascular strain in cancer cachexia is that chronic inflammation can result in anaemia of chronic disease via liver and bone marrow signalling 29, 30. Consistent with a systemic inflammatory state, KPC tumour burden results in a marked neutrophil‐dominant leukocytosis ( P  < 0.001) with increases in other innate immune cells including monocytes ( P  < 0.01) and eosinophils ( P  < 0.01) (Supporting Information, Figure 4A).…”

Regulation of Iron Metabolism by Hepcidin under Conditions of Inflammation

“…Furthermore, recent work demonstrated that hepcidin is elevated in breast cancer patients and that diminished tumor expression of ferroportin promotes breast cancer growth (86,87). Finally, patients with the most advanced cancers have the lowest RBC hemoglobin concentration, and hemoglobin measurements are conversely correlated with inflammatory markers and hepcidin (88). This research indicates that efficacious treatment of CKD, and a number of distinct malignancies, requires not only directed therapy toward each disease, but also appropriate management of patient iron status.…”

The usefulness of routinely used malnutrition screening tools in predicting anemia in lung cancer patients

“…Cancer-related anemia is closely linked to systemic inflammation and malnutrition. 28 This explains the lower TIBC and iron concentration in group 2 compared to the remaining participants. Hypoferremia, often observed in cancer patients, is induced by impaired reutilization of iron.…”

“…Moreover, the association between them has been investigated by several authors. [27][28][29] However, to the best of our knowledge, there has been no study concerning the relationship between nutritional status evaluated by simple, routinely used anthropometric parameters and the MNA test, and parameters related to red blood cells and iron status in lung cancer patients. Moreover, the study evaluated the relationship between anemia and inflammation using Glasgow Prognostic Score in this condition.…”