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...

The identification of prognostic and predictive markers is crucial for choosing the most appropriate management method for ovarian cancer patients. We aimed to assess the prognostic role of tumorassociated macrophage (TAM) polarization in advanced ovarian cancer patients. We carried out a prospective observational study that included 140 consecutive patients with advanced-stage highgrade serous ovarian cancer as well as patients with other histotypes of ovarian cancer and patients with ovarian metastasis from other sites between June 2013 and December 2018. Patients were enrolled at the time of laparoscopic surgery before receiving any antineoplastic treatment. We found that patients with high-grade serous papillary ovarian cancers had a prevalence of M1 TAMs, a higher M1/M2 ratio, and a longer overall survival (OS) and progression-free survival (PFS) than other patients. Regression analysis confirmed that there was a significant positive association between the M1/M2 ratio and an improved OS, PFS and platinum-free interval (PFI), both in the entire population and in patients stratified according to tumor type and initial surgery. Kaplan-Meier analysis was performed after the patients were divided into 2 groups according to the median M1/M2 ratio and revealed that patients with a high M1/M2 ratio had a higher OS, PFS and PFI than those with a low M1/M2 ratio. In conclusion, the prognostic and predictive role of TAM polarization in the tumor microenvironment could be of great clinical relevance and may allow the early identification of patients who are likely to respond to therapy. Further studies in a larger prospective sample are warranted.www.nature.com/scientificreports www.nature.com/scientificreports/ linear relationship (β coefficient = 0.504, 95% CI 0.493-10.334, p = 0.033) was found between the platinum-free interval and M1/M2 ratio (Fig. 2).The median value for the M1/M2 ratio was 1.4. Then, we analyzed the difference in OS and PFS by Kaplan-Meier curve analysis and log-rank analysis between patients with an M1/M2 ratio ≥ 1.4 and those with an M1/M2 ratio < 1.4. We found that patients with an M1/M2 ratio ≥ 1.4 had a significantly longer OS (34 months versus 18 months, HR 2.7483, 95% CI: 1.1667-6.4736; p = 0.0207), PFS (24 months versus 9 months, HR 2.1285, 95% CI: 1.0461-4.3309; p = 0.0371) and PFI (12 months versus 6 months, HR 3.3959, 95% CI 1.2471-9.2469; p = 0.0168) ( Fig. 3). Scientific RepoRtS |(2020) 10:6096 | https://doi.

Since chronic inflammation is associated with ovarian cancer growth and progression, some clinical studies have assessed the association between the pre-treatment neutrophil-to-lymphocyte ratio (NLR) and the prognosis of ovarian cancer. The purpose of this study was to assess the dynamic behavior of the NLR during the course of neoadjuvant chemotherapy (NACT) in patients with high grade serous (HGS) advanced epithelial ovarian cancer and assess its correlation with clinical response, progression free survival (PFS) and changes in other inflammatory indexes. We performed a prospective observational study on 161 patients who underwent NACT at the Department of Gynecologic Oncology, ARNAS G. Brotzu, Cagliari, between 2009 and 2019. NLR was evaluated before starting and after three cycles of NACT. Based on response after three cycles of NACT, patients were divided into two groups: responsive and non-responsive. The primary endpoint was to assess the predictive role of NLR by comparing the responsive and non-responsive patients at baseline and after three cycles of NACT. Secondary endpoints were (a) to correlate NLR with other inflammation markers (CRP, fibrinogen, ferritin, IL-6), albumin, and modified Glasgow Prognostic Score (mGPS) with NLR at baseline and after NACT; (b) to assess the association between NLR and PFS. We found that the NLR value at baseline was not associated with response to NACT, while a decrease in NLR after three cycles was correlated with a better response to NACT. Also, values of CRP, IL-6, ferritin, and mGPS after three cycles of NACT (but not at baseline) were significantly associated with clinical response. Moreover, we found that patients with a low NLR value after 3 cycles of NACT, but not at baseline, had a significantly higher PFS than patients with high NLR after 3 cycles of NACT. In conclusion, NLR change during treatment could serve as a predictive marker of response to NACT in patients with HGS advanced ovarian cancer. This allows for the early identification of non-responsive patients who will need treatment remodeling.

189 Background: Cancer progression is characterized by specific energy metabolism alterations and by symptoms including fatigue, anorexia, nausea, depression, which results in cachexia syndrome and compromised quality of life (QL). This condition is often associated to anemia (cancer-related anemia, CRA), which negatively impacts patient QL and disease outcome. Methods: Adult advanced cancer patients with cachexia (i.e., weight loss > 5% in the previous 6 months) and CRA were randomly assigned (1:1 by computer generated list) to receive 3 months of a combined approach consisting of celecoxib (200 mg/day), L-carnitine (2 g/day), curcumin (Meriva) (4 g/day) and lactoferrin (200 mg/day) or placebo. The rationale for selecting these agents was: L-carnitine for modulating cell energy metabolism; celecoxib for counteracting inflammation, which is a key feature of cachexia; curcumin for its antiinflammatory and antioxidant action, without disregarding its action on the NF-kB and JAK-STAT pathway and the related synthesis of proinflammatory cytokines; lactoferrin for its ability to regulate iron metabolism in anemic cancer patients. Primary endpoints were improvement of lean body mass (LBM), appetite, fatigue and anemia. Additionally, we assessed the impact of treatment on the main metabolic/inflammatory and iron metabolism parameters: C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, leptin, reactive oxygen species (ROS), glutathione peroxidase, serum iron, ferritin, hepcidin and erythropoietin (EPO). Results: From January 2013 to March 2014, 66 patients have been enrolled. The combination arm was more effective than placebo arm in improving body weight, LBM, appetite, fatigue, and anemia. Among secondary parameters IL-6, TNF-α, CRP, ROS, ferritin, hepcidin and EPO decreased, while leptin increased significantly in the combination arm. No significant changes were observed in the placebo arm. Conclusions: To date a standard effective treatment of cancer cachexia is lacking. Our combined multitargeted approach was able to improve the nutritional and immunometabolic alterations of cachexia, ameliorate patient QL and correct CRA.

These data confirm the thyroid inhibitory effect of sunitinib, in keeping with the key role of kinases in controlling thyroid function and growth. However, the novel appearance of TPOAb in a subgroup of patients with more severe hypothyroidism and longer survival indicates that sunitinib may also trigger/exacerbate thyroid autoimmunity contributing to thyroid failure. The development of TPOAb was associated with a longer PFS.