Senem Karabulut

Age is a prognostic factor affecting survival in lung cancer patients

Despite all efforts at management, prognosis of advanced lung cancer is extremely poor, with a median survival time of ~1 year. The number of cancer patients aged >70 years is significantly increased among the cancer patient population. The aim of this study was to investigate the clinical importance of age in lung cancer. Data from 110 patients with histologically confirmed lung cancer, who were treated and followed up in the Institute of Oncology, University of Istanbul, were recorded from medical charts. There were 100 (91%) males with a median age of 59 years (range, 35–88 years). The majority of patients had non-small cell lung cancer (NSCLC; 84%) and metastatic stage (56%). The rate of positive response to chemotherapy was lower in elderly patients (P=0.01) and the incidence of anemia was higher compared with that in younger patients (P=0.02). The majority of mortalities occurred in elderly patients (P=0.01). The median survival time of elderly patients was significantly lower compared with that of younger patients (37.8 vs. 57 weeks; P=0.009). The 1-year survival rates in younger and elderly patients were 67.3 and 42.5%, respectively. In multivariate analysis, elderly patients also had significantly poorer survival (P=0.023). In the group of elderly patients, analyses revealed that significant prognostic factors, including stage of disease and serum lactate dehydrogenase (LDH) levels, were associated with survival. Elderly patients diagnosed with small cell lung cancer had a poorer outcome compared with those with NSCLC (P=0.009), and older patients with elevated serum LDH levels had a shorter survival time compared with those with normal levels (P=0.042). In conclusion, age is one of the major prognostic factors affecting survival in lung cancer patients; therefore, patients should be managed according to age in clinical practice.

Does Beta-blocker Therapy Improve the Survival of Patients with Metastatic Non-small Cell Lung Cancer?

AIM To determine whether beta-blockers (BBs) improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS The medical charts of 107 patients with metastatic NSCLC were retrospectively assessed. Thirty-five patients (BB group) using BBs during chemotherapy (CT) were compared with 72 controls [control=(C) group] who did not use BBs following the diagnosis of NSCLC. The histological tumor subtype, performance status (ECOG), age, gender, smoking status, comorbidities, other medications and chemotherapeutics that were received in any line of treatment were recorded. We compared the overall survival (OS) of the patients in the BB and C groups. RESULTS The mean age of the patients was 61 years (range 42-81 years) and all patients were administered CT. The BB group was more likely to have HT and IHD and was more likely to use RAS blockers (p<0.01 for all) compared with the C group, as expected. The mean follow-up time was 17.8 months (range 1-102 months) for the entire group. The most commonly prescribed BB agent was metoprolol (80% of cases). At the time of the analysis, 74 (69%) of all patients had died. In the univariate analysis the median overall survival (OS) was 19.25 (±2.87) months (95%CI: 13.62-24.88) in the BB group and 13.20 (±2.37) months (95%CI: 8.55-17.85) in the C group (p=0.017). However, the benefit of BBs on survival disappeared in the multivariate analysis. CONCLUSIONS The use of BBs during CT may be associated with an improved OS for patients with metastatic NSCLC.

Circulating annexin A2 as a biomarker in gastric cancer patients: Correlation with clinical variables

Annexin A2 (ANXA2) plays an important role in the pathogenesis of multiple malignancies and its expression strongly also affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of ANXA2 in patients with gastric cancer. A total of 63 patients with a pathologically confirmed diagnosis of gastric cancer were enrolled into this study. Serum ANXA2 concentrations were determined by the solid-phase sandwich ELISA method. Age- and sex-matched 30 healthy controls were included in the analysis. The median age at diagnosis was 62years, range 28 to 82years. The baseline serum ANXA2 levels of the gastric cancer patients were a significantly higher than those in the control group (P<0.001). The known clinical variables including age of patient, gender, site of lesion, histology, histological grade, stage of disease, and serum levels of LDH, carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19.9 were not found to be correlated with serum ANXA2 concentrations (P>0.05). However, the chemotherapy-unresponsive patients had higher serum ANXA2 levels compared with chemotherapy-responsive ones (P=0.04). Conversely, serum ANXA2 concentration was found no prognostic role on survival (P=0.53). In conclusion, serum levels of ANXA2 may have a good diagnostic and predictive marker for response to chemotherapy in patients with gastric cancer and have not associated with prognosis.

Clinical significance of serum interleukin-18 (IL-18) levels in patients with gastric cancer.

An inappropriate production of interleukin-18 (IL-18) contributes to the pathogenesis of malignancies and may influence the clinical outcome of patients. The objective of this study was to determine the clinical significance of the serum levels of IL-18 in patients with gastric cancer. A total of 63 patients with a pathologically confirmed diagnosis of gastric cancer were enrolled into this study. Serum IL-18 concentrations were determined by the solid-phase sandwich Elisa method. Age- and sex-matched 30 healthy controls were included in the analysis. The median age at diagnosis was 62 years, range 28 to 82 years. The baseline serum IL-18 levels of the gastric cancer patients were a significantly higher than those in the control group (median values 1436.4 vs. 638.4 pg/mL, respectively, P<0.001). The known clinical variables including age of patient, gender, site of lesion, histology, histological grade, stage of disease, and serum tumor markers such as LDH, CEA, and CA 19.9 were not found to be correlated with serum IL-18 concentrations (P>0.05). Moreover, no correlation was found between serum IL-18 level and response to chemotherapy (P=0.34). Serum IL-18 concentration was also found no prognostic role on survival (P=0.21). In conclusion, serum levels of IL-18 may have a good diagnostic marker in patients with gastric cancer. However, its predictive and prognostic values were not determined.

Clinical significance of serum epidermal growth factor receptor (EGFR) levels in patients with breast cancer.

Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of multiple malignancies and its expression strongly also affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of EGFR in breast cancer (BC) patients. A total of 96 patients with a pathologically confirmed diagnosis of BC were enrolled into this study. Serum EGFR levels were determined by the solid-phase sandwich ELISA method. Age and sex matched 30 healthy controls were included in the analysis. Median age of diagnosis was 48years old (range: 29-80). Thirty-seven (39%) consisted of metastatic disease. The baseline serum EGFR levels were significantly higher than in the healthy control group (p<0.001). The serum EGFR concentrations were also significantly higher only in patients with ER-negative and triple-negative tumor (p=0.05 and p=0.04, respectively). The other known clinical variables, including grade of histology, stage of disease, serum CA 15.3 levels, and response to chemotherapy were not found to be correlated with serum EGFR concentrations (p>0.05). Likewise, serum EGFR levels were found to play no prognostic role for survival (p=0.35). In conclusion, while serum EGFR levels were elevated in BC patients, EGFR level has no predictive and prognostic value in these patients.

D-dimer and international normalized ratio (INR) are correlated with tumor markers and disease stage in colorectal cancer patients

BACKGROUND The aim of this study is to evaluate the correlation of coagulation tests with various clinicopathological variables and tumor markers among colorectal cancer (CRC) patients. MATERIALS AND METHODS Ninety-four CRC patients were included for evaluation of clinicopathological factors, coagulation assays and tumor marker levels. RESULTS Metastatic disease was related with elevated INR (p= 0.03). Stage III patients had higher D-dimer values compared with stage II patients (p= 0.03). Correlation of tumor markers indicated a tendency towards elevated D-dimer levels for CEA values higher than median (p= 0.01). High CA 19-9 levels were also associated with higher INR (p= 0.007). Elderly age, distant metastasis, high CEA, CA-19-9 and LDH levels were associated with poorer overall-survival. CEA level was the only independent prognostic factor in multivariate analysis. CONCLUSIONS Coagulation assays can be utilized as predictors of disease extent in CRC. Elevated D-dimer and INR values may indicate higher disease stage. Correlation of D-dimer levels with CEA supports their value for assessing tumor burden.

Clinical significance of serum omentin-1 levels in patients with pancreatic adenocarcinoma.

Background Omentin is related with metabolic syndrome and obesity. Pancreatic adenocarcinoma (PA) is a lethal and obesity-linked malignancy. This study was conducted to investigate the serum levels of omentin in patients with PA and the relationship with tumor progression and known prognostic parameters. Material and methods Serum samples were obtained from thirty-three patients on first admission before any treatment. Age, sex and body mass index (BMI) matched 30 healthy controls were included in the analysis. Both serum omentin levels were measured using enzyme-linked immunosorbent assay (ELISA). Results The median age at diagnosis was 59 years (32–84 years). Twenty (61%) patients were men and the remaining were women. The most common metastatic site was liver in 23 patients with metastasis (n = 19, 83%). Thirty-nine percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx–responsive. Median overall survival of the whole group was 41.3 ± 8.3 weeks [95% confidence interval (CI) = 25–58 weeks]. The baseline serum omentin levels were significantly higher in patients with PA than in the control group (p < 0.001). Serum omentin levels were significantly higher in patients with larger pathologic tumor size compared with smaller size (p = 0.03). Conversely, serum omentin concentration was found to have no prognostic role on survival (p = 0.54). Conclusion Serum levels of omentin may have a good diagnostic role in patients with PA.

Clinical significance of serum fibronectin and vitronectin levels in melanoma patients.

Fibronectin and vitronectin are the important components of the extracellular matrix proteins. The aim of this study was to determine the clinical significance of these protein serum levels in patients with melanoma. A total of 60 patients with a pathologically confirmed diagnosis of melanoma were enrolled in this study. Serum fibronectin and vitronectin concentrations were determined using the solid-phase sandwich ELISA method. Thirty age-matched and sex-matched healthy controls were included in the analysis. The baseline serum fibronectin and vitronectin levels were significantly higher in patients with melanoma than those in the healthy control group (P<0.001 and P=0.04, respectively). However, known clinical variables including age of the patient, sex, site of lesion, histology, stage of disease, serum lactate dehydrogenase levels, and response to chemotherapy were not found to be correlated with either serum fibronectin or vitronectin concentrations (P>0.05). Moreover, neither serum fibronectin nor vitronectin levels played a prognostic role in outcome in melanoma patients (P=0.47 and 0.24, respectively). In conclusion, serum levels of both fibronectin and vitronectin may be diagnostic markers in melanoma patients. However, their predictive and prognostic values were not determined.

Clinical significance of serum M30 and M65 levels in metastatic pancreatic adenocarcinoma

M30 and M65 are relatively new assays that detect different circulating forms of the epithelial cell structural protein cytokeratin 18. This study was conducted to investigate the serum levels of M30 and M65 in patients with metastatic pancreatic adenocarcinoma (MPA) and the relationship with tumor progression and known prognostic parameters. Twenty-six patients with MPA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum M30 and M65 levels were determined using enzyme-linked immunosorbent assay. The median age at diagnosis was 59 years, range 32–80 years; 14 patients were men. All patients had metastatic stage, and most (n = 21, 81 %) had hepatic metastasis. The baseline levels of both serum M30 and serum M65 were significantly higher in patients with MPA than those in the control group (p < 0.001, for both assays). Serum M65 level was only significantly higher in the patients with elevated serum LDH levels than in others with normal serum LDH levels (p = 0.03). For serum M30 levels, no correlation was found. The significant relationship was found between the serum levels of M30 and M65 (rs = 0. 926, n = 26, p < 0.001, Spearman’s correlation). The median survival for all patients was 31.7 ± 2.2 weeks (95 % CI = 27.31–36.08). Although only the serum LDH level was found to be a significant prognostic factor (p = 0.01), neither serum M30 nor serum M65 had significant effect on survival (p = 0.28 and p = 0.15, respectively). In conclusion, although both serum levels of M30 and M65 assays were found to be of diagnostic value, no predictive and prognostic values were determined in MPA patients.

Clinical significance of serum claudin-1 and claudin-7 levels in patients with colorectal cancer.

The present study aimed to investigate the serum levels and clinical relevance of claudin (CLDN) 1 and CLDN7 in patients with colorectal cancer (CRC). A total of 140 patients with a pathologically confirmed diagnosis of CRC were enrolled in this study. The serum levels of CLDN1 and CLDN7 were determined using the solid-phase sandwich ELISA method. A total of 40 healthy age- and gender-matched controls were included in the analysis. The median age of the patients was 60 years (range, 24–84 years). The localization of the tumor in the majority of the patients was the colon (n=81, 58%). Of the 55 metastatic patients who received palliative chemotheraphy, 31% were chemotherapy-responsive. The baseline median serum CLDN1 and CLDN7 levels were significantly lower in non-metastatic and metastatic patients compared with those in healthy controls (CLND1, P=0.008 and 0.002; and CLND7, P=0.002 and 0.002, respectively). Moreover, known clinical variables, including poor performance status and high carcinoembryonic antigen (CEA) levels were found to be associated with lower serum CLDN1 concentrations for all patients (P=0.03 and P=0.03, respectively). High T stage and high CEA levels were found to be correlated with lower serum CLDN7 concentrations for all patients (P=0.04 and 0.03, respectively). A correlation was identified between CLDN1 and CLDN7 levels in non-metastatic and metastatic CRC patients (both P-values <0.001). Our study results did not reveal any statistical significance for serum CLDN1 or CLND7 concentrations regarding progression-free and overall survival rate. Therefore, reduced serum levels of CLDN1 and CLND7 may be useful markers in the differential diagnosis of CRC.