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 ...tumor-associated macrophage (TAM) polarization in advanced ovarian cancer patients. We carried out a prospective observational study that included 140 consecutive patients with advanced-stage high-grade 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.
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Cancer-related anemia (CRA) is a common sign occurring in more than 30% of cancer patients at diagnosis before the initiation of antineoplastic therapy. CRA has a relevant influence on survival, ...disease progression, treatment efficacy, and the patients' quality of life. It is more often detected in patients with advanced stage disease, where it represents a specific symptom of the neoplastic disease, as a consequence of chronic inflammation. In fact, CRA is characterized by biological and hematologic features that resemble those described in anemia associated to chronic inflammatory disease. Proinflammatory cytokine, mainly IL-6, which are released by both tumor and immune cells, play a pivotal action in CRA etiopathogenesis: they promote alterations in erythroid progenitor proliferation, erythropoietin (EPO) production, survival of circulating erythrocytes, iron balance, redox status, and energy metabolism, all of which can lead to anemia. The discovery of hepcidin allowed a greater knowledge of the relationships between immune cells, iron metabolism, and anemia in chronic inflammatory diseases. Additionally, chronic inflammation influences a compromised nutritional status, which in turn might induce or contribute to CRA. In the present review we examine the multifactorial pathogenesis of CRA discussing the main and novel mechanisms by which immune, nutritional, and metabolic components affect its onset and severity. Moreover, we analyze the status of the art and the perspective for the treatment of CRA. Notably, despite the high incidence and clinical relevance of CRA, controlled clinical studies testing the most appropriate treatment for CRA are scarce, and its management in clinical practice remains challenging. The present review may be useful to indicate the development of an effective approach based on a detailed assessment of all factors potentially involved in the pathogenesis of CRA. This mechanism-based approach is essential for clinicians to plan a safe, targeted, and successful therapy, thereby promoting a relevant amelioration of patients' quality of life.
Anemia in oncology patients is often considered a side effect of cancer therapy; however, it may occur before any antineoplastic treatment (cancer-related anemia). This study was aimed to evaluate ...the prevalence of cancer-related anemia in a large cohort of oncology patients and whether inflammation and malnutrition were predictive of its development and severity. The present study included 888 patients with cancer at different sites between May 2011 and January 2014. Patients were assessed at diagnosis before any cancer treatment. The prevalence of anemia according to the main clinical factors (tumor site, stage and performance status) was analyzed. In each patient markers of inflammation, iron metabolism, malnutrition and oxidative stress as well as the modified Glasgow prognostic score, a combined index of malnutrition and inflammation, were assessed and their role in predicting hemoglobin level was evaluated. The percentage of anemic patients was 63% with the lowest hemoglobin levels being found in the patients with most advanced cancer and compromised performance status. Hemoglobin concentration differed by tumor site and was lowest in patients with ovarian cancer. Hemoglobin concentration was inversely correlated with inflammatory markers, hepcidin, ferritin, erythropoietin and reactive oxygen species, and positively correlated with leptin, albumin, cholesterol and antioxidant enzymes. In multivariate analysis, stage, interleukin-6 and leptin were independent predictors of hemoglobin concentration. Furthermore, hemoglobin was inversely dependent on modified Glasgow Prognostic Score. In conclusion, cancer-related anemia is a multifactorial problem with immune, nutritional and metabolic components that affect its severity. Only a detailed assessment of the pathogenesis of cancer-related anemia may enable clinicians to provide safe and effective individualized treatment.
Endometrioid endometrial cancer is associated with increased BMI and obesity through multiple pathogenetic mechanisms involving hyperestrogenism, hyperinsulinemia, altered adipokine secretion, ...inflammation, and oxidative stress. In the present study, we aimed to investigate the correlation between BMI, leptin, the proinflammatory cytokines IL-6 and TNFα, reactive oxygen species (ROS), and the traditional prognostic factors T, G, N and M status among type I endometrioid and type II endometrial cancer patients. We enrolled 305 consecutive endometrial cancer patients prospectively. We found that BMI, leptin, and IL-6 significantly correlated with T status, N status, and M status among endometrioid type I endometrial cancer patients. Among type II endometrial cancer patients, BMI and leptin did not correlate with any of the prognostic parameters, whereas there was a positive correlation between IL-6 and the presence of distant metastases. In the multivariate regression analysis, BMI, leptin, and IL-6 were independent predictive variables of T, N, and M status in endometrioid type I endometrial cancer patients. Our study demonstrates that weight gain, adiposity-related adipokines, inflammation, and oxidative stress correlate with the prognostic factors of endometrioid endometrial cancer. Knowledge of the role of obesity-related biological pathways and mediators in the pathogenesis and prognosis of endometrioid endometrial malignancies may offer new perspectives on combined therapeutic strategies that have not been explored to date, both in the advanced disease and in the adjuvant setting.
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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.
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Abstract Objectives Myelofibrosis (MF) is characterized by shortened survival and a greatly compromised quality of life. Weight loss and cachexia seem to be the most important factors influencing ...survival in patients with MF. The aim of this study was to assess the efficacy of an integrated supportive therapy in improving cachexia and MF-related symptoms. Methods We reported on a case of a patient with MF who presented with weight loss and cachexia associated with severe anemia, fatigue, fever, and bone pain. The circulating levels of inflammatory, oxidative stress parameters, hepcidin, and erythropoietin were evaluated and were above normal ranges. The patient was treated with a multitargeted approach specifically developed for cachexia including oral l -carnitine, celecoxib, curcumin, lactoferrin, and subcutaneous recombinant human erythropoietin (EPO)-α. Results Surprisingly, after 1 y, cachexia features improved, all MF symptoms were in remission, and inflammatory and oxidative stress parameters, hepcidin, and EPO were reduced. Conclusions Because our protocol was targeted at inflammation and the metabolic state, its effectiveness may emphasize the role of inflammation in the pathogenesis of MF symptoms and demonstrates a need for the study of new integrated therapeutic strategies.
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Purpose: To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support, antioxidants,
and drugs, all given orally, in a population of advanced cancer patients with ...cancer-related anorexia/cachexia and oxidative
stress.
Patients and Methods: An open early-phase II study was designed according to the Simon two-stage design. The integrated treatment
consisted of diet with high polyphenols content (400 mg), antioxidant treatment (300 mg/d α-lipoic acid + 2.7 g/d carbocysteine
lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C), and pharmaconutritional support enriched with
2 cans per day ( n -3)-PUFA (eicosapentaenoic acid and docosahexaenoic acid), 500 mg/d medroxyprogesterone acetate, and 200 mg/d selective cyclooxygenase-2
inhibitor celecoxib. The treatment duration was 4 months. The following variables were evaluated: ( a ) clinical (Eastern Cooperative Oncology Group performance status); ( b ) nutritional lean body mass (LBM), appetite, and resting energy expenditure; ( c ) laboratory proinflammatory cytokines and leptin, reactive oxygen species (ROS) and antioxidant enzymes; ( d ) quality of life (European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D, and MFSI-SF).
Results: From July 2002 to January 2005, 44 patients were enrolled. Of these, 39 completed the treatment and were assessable.
Body weight increased significantly from baseline as did LBM and appetite. There was an important decrease of proinflammatory
cytokines interleukin-6 (IL-6) and tumor necrosis factor-α, and a negative relationship worthy of note was only found between
LBM and IL-6 changes. As for quality of life evaluation, there was a marked improvement in the European Organization for Research
and Treatment of Cancer QLQ-C30, Euro QL-5D VAS , and multidimensional fatigue symptom inventory-short form scores. At the end of the study, 22 of the 39 patients were “responders”
or “high responders.” The minimum required was 21; therefore, the treatment was effective and more importantly was shown to
be safe.
Conclusion: The efficacy and safety of the treatment have been shown by the study; therefore, a randomized phase III study
is warranted. (Cancer Epidemiol Biomarkers Prev 2006;15(5):1030–4)
Fatigue is a multidimensional symptom that is described in terms of perceived energy, mental capacity, and psychological status: it can impair daily functioning and lead to negative effects on ...quality of life. It is one of the most common side effects of chemotherapy and radiotherapy. In recent studies,
l-carnitine (LC) supplementation has been demonstrated to be able to improve fatigue symptoms in patients with cancer.
In the present study we tested the efficacy and safety of LC supplementation in a population of patients who had advanced cancer and developed fatigue, high blood levels of reactive oxygen species, or both. As outcome measures we evaluated fatigue and quality of life in relation to oxidative stress, nutritional status, and laboratory variables, mainly levels of reactive oxygen species, glutathione peroxidase, and proinflammatory cytokines. From March to July 2004, 12 patients who had advanced tumors (50% at stage IV) at different sites were enrolled (male-to-female ratio 2:10, mean age 60 y, range 42–73). Patients were only slightly anemic (hemoglobin 10.9 g/dL) and hemoglobin levels did not change after treatment. LC was administered orally at 6 g/d for 4 wk. All patients underwent antineoplastic treatment during LC supplementation.
Fatigue, as measured by the Multidimensional Fatigue Symptom Inventory—Short Form, decreased significantly, particularly for the General and Physical scales, and for quality of life in each subscale of quality of life in relation to oxidative stress. Nutritional variables (lean body mass and appetite) increased significantly after LC supplementation. Levels of reactive oxygen species decreased and glutathione peroxidase increased but not significantly. Proinflammatory cytokines did not change significantly.
Improvement of symptoms with respect to fatigue and quality of life in relation to oxidative stress may be explained mainly by an increase in lean body mass, which may be considered the most important nutritional or functional parameter in assessing the cachectic state of patients. In this view, fatigue with related symptoms can well be considered an important constituent of cancer-related anorexia cachexia syndrome.
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