Evaluation of the efficacy and safety of nivolumab in the second- or later-line treatment of patients with locally advanced/metastatic non-small cell lung cancer in Türkiye: a retrospective multicenter non-interventional registry study.

OBJECTIVE: To evaluate the efficacy and safety of nivolumab in the second-line (2L) or later-line (LL) treatment of patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) in real-life setting in Türkiye. METHODS: This study was designed as a national, multi-center, retrospective study. The study population was evaluated in two groups for the line of nivolumab therapy: those receiving nivolumab in the 2L (Group 2L) and third-line (3L) or LL (Group 3L/LL). Efficacy was evaluated based on one-year overall survival (OS) and progression-free survival (PFS). Safety was evaluated based on treatment-related adverse events (AEs) and nivolumab discontinuation rate. RESULTS: Of 244 patients, 52.9% were in Group 2L and 47.1% were in Group 3L/LL. Demographic and clinical characteristics did not differ between the groups. In Group 2L and Group 3L/LL, one-year OS and PFS rates were 60.8% and 61.4% (p = 0.592) and 31.2% and 21.3% (p = 0.078), respectively. The objective response rate (ORR) was 34.7% in Group 2L and 27.3% in Group 3L/LL (p = 0.262). The percentage of patients reporting at least one AE in Groups 2L and 3L/LL was 34.9% and 43.5%, respectively (p = 0.169). Fatigue was the most common (16.4%) treatment-related AE in each group. The groups were comparable regarding the AE frequency. Nivolumab was discontinued in 61 patients in Group 2L and 53 patients in Group 3L/LL, with the most common reason being disease progression (57.4% and 66.0%, respectively). CONCLUSION: Nivolumab is safe and effective in the 2L or 3L/LL treatment of locally advanced/metastatic NSCLC and associated with acceptable AEs in real-life setting.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (around 85% of all lung cancers). Patients with NSCLC are usually diagnosed at advanced or metastatic stages. When cancer cells spread to other areas from where they first formed, it is called metastatic cancer. Surgery may not be a treatment option for such patients. Currently, immunotherapeutic agents are used in the treatment of NSCLC. Nivolumab is one of the approved immunotherapeutic agents in the treatment of patients with metastatic NSCLC, who have failed after receiving chemotherapy. Our study explored the efficacy and safety of nivolumab in real-life setting in Türkiye. Nivolumab effectiveness was evaluated by overall survival (OS) and progression-free survival (PFS) rates. OS indicates the proportion of patients who are still alive at a given time after diagnosis or treatment initiation. PFS refers to "the length of time during and after cancer treatment that a person lives with the disease but does not get worse." In the present study, one-year OS for 244 patients who received nivolumab was 61.1% and one-year PFS was 26.4%. Nivolumab safety was evaluated based on the frequency of adverse events observed during nivolumab therapy. Of the patients 38.9% had at least one side effect, with fatigue being the most common (16.4%). Our results support the earlier studies and showed that nivolumab was a safe and effective agent and is associated with acceptable side effects.

Cisplatin plus paclitaxel and bevacizumab versus carboplatin plus paclitaxel and bevacizumab for the first-line treatment of metastatic or recurrent cervical cancer.

OBJECTIVE: Cisplatin-paclitaxel and bevacizumab is a frequently used treatment regimen for metastatic or recurrent cervical cancer, and carboplatin-paclitaxel and bevacizumab are also among the recommended regimens. In this study we aimed to evaluate the efficacy of these two regimens for the treatment of metastatic or recurrent cervical cancer. METHODS: Patients with metastatic or recurrent cervical cancer treated with cisplatin-paclitaxel and bevacizumab or carboplatin-paclitaxel and bevacizumab were retrospectively evaluated in this study. The clinical and demographic characteristics of patients in each group were evaluated. Median overall survival, progression-free survival, and response rates between the two groups were compared. RESULTS: A total of 250 patients were included. Overall, the numbers of patients with recurrent disease and metastatic disease were 159 and 91, respectively. The most common histologic subtype was squamous cell carcinoma (83.2%). The median duration of follow-up was 13.6 (range 0.5-86) months. The median progression-free survival was 10.5 (95% CI 9.0 to 11.8) months in the cisplatin-paclitaxel and bevacizumab group (group 1), and 10.8 (95% CI 8.6 to 13.0) months in the carboplatin-paclitaxel and bevacizumab group (group 2) (HR 1.20; 95% CI 0.88 to 1.63; p=0.25). The median overall survival was 19.1 (95% CI 13.0 to 25.1) months in group 1 and 18.3 (95% CI 15.3 to 21.3) months in group 2 (HR 1.28; 95% CI 0.91 to 1.80; p=0.15). CONCLUSIONS: There is no survival difference between cisplatin or carboplatin combined with paclitaxel and bevacizumab in metastatic or recurrent cervical cancer.

Isolated Superior Mesenteric Vein Tumor Thrombus in a Patient with Gastric Cancer.

Tumor thrombus in the portal vein can rarely originate from gastric cancer via hematogenous spread, with only few case reports published in the literature. Isolated superior mesenteric vein tumor thrombus in gastric cancer has not been previously reported. A 61-year-old male patient who had undergone distal gastrectomy and gastroenterostomy for gastric ulcer 20 years ago was diagnosed with an obstructive tumor originating from the gastroenterostomy anastomosis site on upper gastrointestinal endoscopy that was performed for complaints of fatigue, oral feeding problems, and anemia. The PET-CT imaging revealed a hypermetabolic mass in the gastroenterostomy region along with hypermetabolic suspected tumor thrombus in the superior mesenteric vein (SMV). A suspected tumor thrombus with contrast enhancement that completely obstructed the SMV was detected on triphasic abdominal computed tomography. Decision for surgery was made due to gastric tumor obstruction. Firstly, lesions suspected with tumor thrombus were extirpated from the SMV and sent to frozen section. Then, it was completely recanalized. A locally advanced tumor originating from the gastroenterostomy anastomosis site that totally obliterated the lumen was observed on surgical exploration. After proving tumor thrombus by frozen, near-total gastrectomy was performed for palliative purposes. Histopathologic examination of the specimen showed gastric invasive adenocarcinoma and tumor thrombi in the SMV (T4N2M1). The patient received adjuvant chemotherapy, and he is at his 22nd-month follow-up with extensive hepatic metastases and intra-abdominal disease. It should be kept in mind that gastric cancer may lead to portal vein tumor thrombus or that it may rarely be associated with an isolated SMV tumor thrombus, both of which are associated with poor prognosis.

Primary splenic angiosarcoma diagnosed after splenectomy for spontaneous rupture.

Primary splenic angiosarcoma is a rare abnormality and has a bad prognosis. It has unknown pathogenesis. This abnormality is usually presented by splenic rupture. Surgery is the most promising treatm Surgery is the most accepted and accurate method for diagnosis and treatment. Surgery before rupture increases the life expectancy. A 65-year-old woman who presented to the emergency room with abdominal pain, abdominal distension, and anemia was found to have a splenic mass and massive ascites. After getting a hemorrhagic sample from the abdomen, the patient was operated with splenic rupture prediagnosis. The spleen material was reported as splenic angiosarcoma. The staging 18F-FDG-Positron Emission Tomography-Computed Tomography did not show any metastasis. Five months later, paclitaxel treatment was initiated upon liver and bone metastasis, and the treatment still continues. Splenic angiosarcoma has a place among splenic parenchymal lesions. The splenectomy material names the diagnosis. Pathologic examination of splenectomy material is revealed certain diagnosis.

Serum levels of HMGB1 have a diagnostic role in metastatic renal cell cancer.

RCC constitutes approximately 90% of all renal malignancies and 2-3% of all malignant tumours in adults. In spite of the improvement in radiologic methods, nearly 30% of the early metastatic RCC patients are incidentally diagnosed. HMGB1 is an extracellular signalling molecule that plays a role both in inflammation and carcinogenesis. Patients who were followed in Medical Oncology Departments of Denizli Government Hospital and Antalya Education and Research Hospital with a histopathological diagnosis of RCC between years 2010-2012 were enrolled in this study. HMGB1 levels were also assessed in a manually performed quantitative sandwich-enzyme-linked immunosorbent assay (ELISA) assay kit. In our study, we showed that the serum level of HMGB1, whether 149.9 pg/ml or not is important in differential diagnosis between patient and control group.

Use of cryoablation beyond the prostate.

UNLABELLED: Cryoablation has been used for many years as a surgical ablation technique in the prostate and kidney. However, since the introduction of high-intensity focused ultrasound (HIFU) and robotic surgery for prostate tumours, its popularity in the urologic community has declined. In the early 2000s, innovations in cryoablation technology allowed the use of thinner probes, which were suitable for percutaneous application. As a result, radiologists began using cryoablation, first in the liver, and then in other organs or tissues such as the kidney, lung, breast, pancreas, bone, and soft tissue. In most of these locations, cryoablation has great potential given its inherent advantages, including the use of local anaesthesia, little or no pain during and after the procedure, real-time monitoring of the ablation area on US, CT or MRI, the potential for ablation of large tumours with multiple probes, and the ability to change the shape of the ablation in non-spherical tumours. Yet despite these advantages, the use of percutaneous cryoablation among radiologists appears to be far lower than that of heat-based ablation techniques. The aim of this article is to outline specific aspects of cryoablation and to illustrate its potential clinical applications with case presentations. KEY POINTS: • Recent advances have made cryoablation suitable for percutaneous use by radiologists with image guidance. • Cryoablation has distinct advantages over heat-based ablation techniques. • Cryoablation is becoming increasingly popular for lung, breast, kidney, bone, and soft tissue tumours.

Metronomic oral chemotherapy with old agents in patients with heavily treated metastatic breast cancer.

BACKGROUND: We aimed to assess the efficacy of a metronomic regimen with cyclophosphamide and etoposide in heavily treated patients with metastatic breast cancer (MBC). MATERIALS AND METHODS: A total of 77 patients with MBC used continuous oral cyclophosphamide 50 mg/day and oral etoposide given as 2 × 50 mg/day for 2 days per week, were analyzed retrospectively from Akdeniz University and Selcuk University. The patients with MBC are predominantly refractory to antracyclines, taxanes, and antimetabolites. RESULTS: The patients were treated and followed between May 2005 and June 2014. The median progression-free and overall survival (PFS and OS) were 7.03 (5.06-8.99) and 32.5 (22.5-42.4) months, respectively. No prognostic factor was found for OS. CONCLUSIONS: Metronomic treatment regimen with cyclophosphamide and etoposide is a novel and effective strategy in heavily pretreated MBC patients. This regimen can be used in early or late steps as independently from prognostic factors. Moreover, it has very low toxicity and is cheap. Impressive survival data and low cost may make this regimen a highly preferable option.

Prognostic factors in clinical stage T4N2 locally advanced non-small cell lung cancer.

PURPOSE: Relatively few studies have focused on T4N2 (stage IIIB) locally advanced non-small cell lung cancer (NSCLC). In this study, we tried to identify prognostic factors for patients with clinical stage T4N2 NSCLC. METHODS: We retrospectively identified 223 patients, of which 168 met the inclusion criteria. Patients treated with curative intent using concurrent chemoradiotherapy (CRT) with or without adjuvant chemotherapy, or concurrent CRT after induction chemotherapy, were included in this study. Relevant patient, treatment, and disease factors were evaluated for their prognostic significance in both univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: The median progression-free survival (PFS) was 13 months (95% confidence interval [CI], 10.6-15.4). The median overall survival (OS) was 20 months (95% CI, 16.8-23.1), and 71, 40.3 and 28.2% of the patients survived for 1, 2 and 3 years after diagnosis, respectively. Multivariate analysis showed Eastern Cooperative Oncology Group (ECOG) performance status (PS) was independent predictor of PFS (hazard ratio [HR], 0.24; 95% CI, 0.13-0.43; p=0.001), and OS [HR, 0.48; 95% CI, 0.26-0.87; p=0.015). Absence of multifocal T4 tumors was also associated with a significantly longer OS (HR, 046; 95% CI, 0.31-0.7; p=0.001). There was no statistically significant difference in OS and PFS between treatment modalities. CONCLUSION: PFS and OS were significantly shorter in patients with poor ECOG PS. OS was also significantly shorter in patients with multifocal T4 tumors. There were no differences between the two therapeutic approaches with respect to outcome.

Prolonged progression-free survival with maintenance metronomic oral cyclophosphamide and etoposide treatment in macroscopic residual disease or recurrent/advanced stage ovarian cancer.

PURPOSE: In ovarian cancer permanent remission may be provided with optimal cytoreductive surgery and adjuvant chemotherapy. However survival is short in patients with residual macroscopic disease after surgery or recurrent ovarian cancer. Applicable maintenance therapies with low toxicity are required to prolong progression-free survival (PFS) for patients with no curative treatment options. In this study, we investigated the effect of maintenance metronomic oral cyclophosphamide and etoposide (CE) in ovarian cancer patients with post operative residual or recurrent disease. METHODS: Forty five patients that received metronomic oral CE (cyclophosphamide 50 mg/daily and etoposide 50 mg for 1-5 days, every 21 days) as maintenance therapy for residual disease due to incomplete surgical resection or recurrent advanced-stage ovarian cancer were evaluated. The time between the beginning of oral CE and disease progression was also evaluated. RESULTS: The mean patient age was 58 years, the vast majority had serous adenocarcinoma (78%) and received a mean of 2 (range 1-4) lines of various intravenous regimens for postoperative residual or recurrent disease. Mean duration of oral CE was 11.3 months (range 2.9-29). Median PFS was 10.3 months (range 7.9-12.8). Only 5 patients discontinued treatment due to intolerance and grade 3-4 toxicity was recorded in 3 patients (7%). CONCLUSION: Maintenance metronomic oral CE treatment was found effective, minimally toxic and sustainable in patients with macroscopic residual or recurrent advanced-stage ovarian cancer. However, randomized and placebo-controlled well designed studies are required.

Blood eosinophil and platelet levels, proteomics patterns of trail and CXCL8 correlated with survival in bevacizumab treated metastatic colon cancers.

STrail (soluble TNF-related apoptosis-inducing-ligand) has also been observed where the cytotoxic effects of antiangiogenic agents are increased in clinical phase II and III studies when these agents are combined with TRAIL related therapies. Recent studies have shown that CXCL8 and its receptors are significantly up-regulated in CRC and act as regulators of proliferation, angiogenesis, and metastasis. sTRAIL, CXCL8, CEA, together with complete blood count parameters (hemoglobine, platelet, eosinophil, basophil, neutrophil, lymphocyte) were recorded in the beginning and every three months afterwards for a period of 4 years. The study population comprised 21 of the 42 patients with metastatic colorectal cancer (MCRC), undergoing 18 FDG-PET/CT scanning prior to treatment. Progression free survival was 262 days and overall survival was 1148 days. Overall survival was higher in patients whose Karnofsky Performance scores were above 86% (p = 0.003). Progression free survival was higher in patients whose blood eosinophil counts at 0, 6, and 9 months were higher than the mean levels of corresponding values (p-values are 0.016, 0.032, and 0.001, respectively). Another significant positive correlation was found between the platelet levels at 9 months and progression free survival (p = 0.019). There were significant changes (p < 0.05) prior to treatment and three months later for sTRAIL (p = 0.0060) and CXCL8 (p = 0.00001), based on the Wilcoxon matched pairs signed rank test. Generally, sTRAIL values increased during therapy, while a decrease was observed for CXCL8 without any significant differences for other variables.

Level of TNF-related apoptosis-inducing-ligand and CXCL8 correlated with 2-[18F]Fluoro-2-deoxy-D-glucose uptake in anti-VEGF treated colon cancers.

BACKGROUND: The changes and correlations of TRAIL (TNF-related apoptosis-inducing-ligand) and CXCL8 (IL8) prior to treatment and three months following therapy as well as the corresponding Positron emission tomography (PET/CT) (SUV(max): standardized uptake maximum values) results were evaluated. MATERIAL AND METHODS: The measurements were taken before and after treatment for comparison purposes. The study population comprised 29 patients with Metastatic Colorectal cancer (MCRC), undergoing PET/CT scanning prior to treatment. RESULTS: There were significant changes prior to treatment and three months later for sTRAIL (p=0.0080) and CXCL8 (p=0.0001)values. Generally, sTRAIL values were increasing during therapy, while a decrease was observed for CXCL8. Correlation analysis was applied to the data and revealed significant correlations for the SUV(max) in the primary tumor prior to treatment and CXCL8 prior to therapy (p=0.0303). Furthermore, significant correlations were observed for the SUV(max) and sTRAIL (p=0.0237) as well as CXCL8 (p=0.0002) three months after treatment initiation. CXCL8 prior to treatment was also correlated with the SUV three months after onset of treatment (p=0.0072). A significant correlation was noted for one combination of two variables, the SUV(max) in the metastases and CXCL8 prior to treatment (p=0.0175). These results are supported when we group the SUV(max) in the metastases following treatment into two groups with SUV(max) <5 and SUV(max) >5. CONCLUSIONS: This study provides evidence that proteomics patterns of sTRAIL and CXCL8 predict tumor response und survival in MCRC patients treated with bevacizumab and within a high concordance of FDG-PET/CT findings.

Increased serum S-TRAIL level in newly diagnosed stage-IV lung adenocarcinoma but not squamous cell carcinoma is correlated with age and smoking.

BACKGROUND: Lung cancer is the leading cause of cancer mortality in the world. Many factors can protect against or facilitate its development. A TNF family member TRAIL, has a complex physiological role beyond that of merely activating the apoptotic pathway in cancer cells. Vitamin D is converted to its active form locally in the lung, and is also thought to play an important role in lung health. Our goal was to investigate the possible clinical significance of serum sTRAIL and 1,25-dihydroxyvitamin D(3) levels in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Totals of 18 consecutive adenocarcinoma and 22 squamous cell carcinoma patients with stage-IV non-small cell lung cancer referred to our institute were included in this study. There were 12 men and 6 women, with ages ranging from 38 to 97 (mean 60.5) years with adenocarcinoma, and 20 men and 2 women, with ages ranging from 46 to 80 (mean 65) years with squamous cell carcinoma. Serum levels of sTRAIL and 1,25-dihydroxyvitamin D(3) were measured in all samples at the time of diagnosis. RESULTS: sTRAIL levels in NSCLC patients were higher than in the control group. Although there was no correlation between patient survival and sTRAIL levels, the highest sTRAIL levels were correlated with age and cigarette smoking in the adenocarcinoma patients. sTRAIL level in healthy individuals were correlated with serum 1,25-dihydroxyvitamin D(3). CONCLUSIONS: Serum sTRAIL concentrations were increased in NSCLC patients, and correlated with age and smoking history, but not with overall survival.

Isolated and solitary splenic metastasis detected by positron emission tomography in a patient with malignant melanoma: case report and review of the literature.

Splenic metastasis from malignant melanoma is an extremely rare occurrence and is most often reported during autopsy. As in other solid tumors, splenic metastasis is usually part of multiple organ metastases in melanoma and is rarely an isolated or solitary mass. As the use of positron emission tomography /computed tomography and imaging techniques become more common, splenic metastases are seen more often than before. Even though it is a commonly known fact that positron emission tomography/computed tomography is no help during primary staging and patient relations in malignant melanoma, several studies and meta-analyses have proven that it is more specific, sensitive and accurate to identify metastases than raditional methods. Therefore, using techniques with high specificity and accuracy rates such as positron emission tomography/computed tomography in the diagnosis of splenic metastasis in patients with malignant melanoma will increase the survival rate with an earlier splenectomy. We report the case of a 35-year-old male patient with cutaneous malignant melanoma whose splenic metastasis was detected with positron emission tomography/computed tomography. This article describes, with reference to the literature, a malignant melanoma case, which presented with splenomegaly and solitary mass lesion and was diagnosed as metastasis by splenectomy after positron emission tomography/computed tomography.

Erratum to "IL8 and serum soluble TRAIL levels following anti-VEGF monoclonal antibody treatment in patients with metastatic colon cancer" [Clin. Lab. 2012; 58:501-505].

BACKGROUND: Colorectal cancer is the third most common human cancer and the third leading cause of cancer related death. BevacizumAb is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF) for the treatment of metastatic cancers. Our goal was to evaluate the possibility of using serum sTRAIL and IL8 as markers of treatment efficacy and prognosis in patients with metastatic colon cancer. METHODS: The study was conducted in Denizli between November 10, 2009 and September 20, 2010. 25 patients (6 female, 19 male) with metastatic colon cancer whose mean age was 58.7 years, were selected and included in the study. All patients received therapy with BevacizumAb. All patients were followed in the Oncology Clinic of Denizli State Hospital and were evaluated by clinical status. sTRAIL and IL8 levels were measured by ELISA in the sera of 25 BevacizumAb treated metastatic colon cancer patients and 20 healthy age-gender matched controls. Measurements were taken before and after treatment. RESULTS: The serum sTRAIL concentrations in patients before therapy were similar to those of healthy age-gender matched controls, namely 1.23 +/- 0.06 ng/mL and 1.21 +/- 0.04 ng/mL, respectively. After BevacizumAb treatment, sTRAIL ratios were increased significantly in 11 of 25 patients. 14 patients showed progressive disease with median overall survival of only 8.1 +/- 0.4 months. These 14 patients were the same ones who showed no increase in sTRAIL levels after BevacizumAb treatment. We explored evidence for a correlation between sTRAIL levels and overall survival rates and observed that elevated sTRAIL levels after the BevacizumAb treatment were significantly associated with increased median overall survival up to 22.6 months. Serum IL8 levels were decreased in all patients who received BevacizumAb therapy. CONCLUSIONS: In BevacizumAb therapy, serum IL8 levels were decreased in all patients, and thus, changes in such levels were not correlated with disease outcome. Our data suggest measurement of changes in sTRAIL following BevacizumAb treatment may have prognostic value in metastatic colon cancer patients.

MDR1 single nucleotide polymorphism C3435T in Turkish patients with non-small-cell lung cancer.

We assessed whether single nucleotide polymorphisms (SNPs) in MDR1 gene C3435T predicted the outcome of platinum-based chemotherapies and survival in our non small cell lung cancer (NSCLC) patients. A total of 79 non-small cell lung cancer patients were enrolled to study. We determined the MDR1 C3435T single nucleotide gene polymorphisms. Median age was 60years: 91.7% male, 8.9% female. We found that CC, CT, TT genotype and T, C allele frequencies in lung cancer patients as 24.1%, 62%, 13.9% and 44.3%, 55.7%, respectively. Patients with CT genotype had a higher response rate (11.4%) than the other genotypes. However, this difference is not statistically significant (p=0.743). Cox regression analysis for overall survival showed that ECOG PS status 0 (HR PS 1 vs. 0, 5.68 p=0.002; HR of PS 2 vs. 0 is 21.579, p=0.001; HR of PS 3 vs. 0 is 35.35, p=0.001), stage ≤II (HR of stage III vs. I+II is 17.77; p=0.016, HR of stage IV vs. I+II is 26.97, p=0.006), and albumin level ≥3g/dl (HR of albumin <3g/dl vs. ≥3g/dl is 2.46, p=0.044) were the most important prognostic factors (also, time to progression was related to these factors). There was no significant association between the genotypes and clinicopathologic parameters; however, good performance status, early stage and ≥3g/dl albumin level were found to be the most important prognostic factors for overall survival and progression-free survival.

IL8 and serum soluble TRAIL levels following anti-VEGF monoclonal antibody treatment in patients with metastatic colon cancer.

BACKGROUND: Colorectal cancer is the third most common human cancer and the third leading cause of cancer related death. BevacizumAb is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF) for the treatment of metastatic cancers. Our goal was to evaluate the possibility of using serum sTRAIL and IL8 as markers of treatment efficacy and prognosis in patients with metastatic colon cancer. METHODS: The study was conducted in Denizli between November 10, 2009 and September 20, 2010. 25 patients (6 female, 19 male) with metastatic colon cancer whose mean age was 58.7 years, were selected and included in the study. All patients received therapy with BevacizumAb. All patients were followed in the Oncology Clinic of Denizli State Hospital and were evaluated by clinical status, sTRAIL and IL8 levels were measured by ELISA in the sera of 25 BevacizumAb treated metastatic colon cancer patients and 20 healthy age-gender matched controls. Measurements were taken before and after treatment. RESULTS: The serum sTRAIL concentrations in patients before therapy were similar to those of healthy age-gender matched controls, namely 1.23 +/- 0.06 ng/mL and 1.21 +/- 0.04 ng/mL, respectively. After BevacizumAb treatment, sTRAIL ratios were increased significantly in 11 of 25 patients. 14 patients showed progressive disease with median overall survival of only 8.1 +/- 0.4 months. These 14 patients were the same ones who showed no increase in sTRAIL levels after BevacizumAb treatment. We explored evidence for a correlation between sTRAIL levels and overall survival rates and observed that elevated sTRAIL levels after the BevacizumAb treatment were significantly associated with increased median overall survival up to 22.6 months. Serum IL8 levels were decreased in all patients who received BevacizumAb therapy. CONCLUSIONS: In BevacizumAb therapy, serum IL8 levels were decreased in all patients, and thus, changes in such levels were not correlated with disease outcome. Our data suggest measurement of changes in sTRAIL following BevacizumAb treatment may have prognostic value in metastatic colon cancer patients.

Systemic levels of ceruloplasmin oxidase activity in allergic asthma and allergic rhinitis.

CONTEXT: The role of ceruloplasmin oxidase activity (COA) involving the interaction of oxidant and antioxidant balance in allergic diseases is still unknown. OBJECTIVE: Our study was designed to examine the changes in COAs in severe persistent asthma-allergic rhinitis, new diagnosed allergic asthma-allergic rhinitis and allergic rhinitis patients. METHODS: The study included 20 age- and sex-matched healthy individuals as control (Group I); Group II included 15 newly diagnosed allergic asthma-allergic rhinitis; Group III included 15 patients with severe persistent asthma-allergic rhinitis and in the fourth group there were 20 patients with allergic rhinitis. Group III was divided in two groups, severe persistent asthma-allergic rhinitis who were pre-(III-A) and post-treated (III-B) with omalizumab. Group IV was divided to two groups, pretreatment (IV-A) and posttreatment (IV-B) with specific subcutaneous immunotherapy modalities. All the posttreatment measurements were 12 months after the therapy. All the patients were assessed by the skin prick test, high sensitive C-reactive protein (hs-CRP) and COA. RESULTS: There were significant differences between Group I and Groups III-A, III-B, IV-A and IV-B; Group II and Groups III-A, III-B, IV-A and IV-B; Group III-A and Groups III-B, IV-A and IV-B; Group III-A and Groups IV-A and IV-B; and Group IV-A and IV-B. Interestingly, there was a correlation between the hs-CRP and COA levels in Group III-A. CONCLUSIONS: Our data suggest that hs-CRP and COA levels might be an indicator of an inflammation and important in revelation of patients with allergy related diseases, especially of asthma patients.

Total antioxidant capacity, hydrogen peroxide, malondialdehyde and total nitric oxide concentrations in patients with severe persistent allergic asthma: its relation to omalizumab treatment.

BACKGROUND: Asthma is a chronic inflammatory disease and omalizumab is indicated for moderate-to-severe persistent asthma. The results of many studies have shown that oxidative stress is involved in asthma pathogenesis. However, there is no data available to evaluate the alterations in total antioxidant capacity, hydrogen peroxide, malondialdehyde, and total nitric oxide concentrations. OBJECTIVES: The objective was to determine whether treatment with omalizumab in severe allergic asthma influences systemic levels of oxidative stress markers. METHODS: The first group of 14 patients included 6 male and 8 female subjects with severe persistent asthma, having a mean age of 42.4 years. The second group included 14 newly diagnosed allergic asthma patients with a mean age of 43.8 years. All patients were followed in the Immunology and Allergy Clinic of the Antalya Education and Training Hospital and were evaluated by clinical status. A third group of 14 age-sex matched healthy controls were also included. Serum samples were collected and stored at -70 degrees C until use for the determination of total antioxidant capacity, hydrogen peroxide, malondialdehyde, and total nitric oxide concentrations. Serum IgE levels, ANA (antinuclear antibody), RF (rheumatoid factor), hepatitis markers, C3, C4, and eosinophil levels were evaluated in all patients. All assays were carried out in duplicate. RESULTS: The mean IgE levels were as follow: Group I: 459.785 IU/mL; Group II: 124.8 IU/mL, and Group III: 39.88 IU/mL. Total antioxidant capacity levels of Group IB, group II, and group III were lower than the IA group. Total antioxidant capacity levels of groups II and III were higher than in group IB. Hydrogen peroxide concentrations in group IB were lower than in group IA, while concentrations in group II were higher than in group IB. The malondialdehyde concentration of group IB was lower than in all other groups. The malondialdehyde concentration of group III was higher than all other groups. The malondialdehyde concentration of group II was lower than in group III. The total nitric oxide level of group IB was lower than all other groups. The total nitric oxide level of group III was higher than all other groups, while that of group II was higher than for both groups IA/IB. CONCLUSIONS: To monitor the omalizumab treatment efficacy in severe allergic asthma patients, total antioxidant capacity, hydrogen peroxide, malondialdehyde, and total nitric oxide concentrations might be new markers.

Increased serum sTRAIL levels were correlated with survival in bevacizumab-treated metastatic colon cancer.

BACKGROUND: Colorectal cancer is the third most common cancer and the third leading cause of cancer-related death. Bevacizumab is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF) for the treatment of metastatic cancer. The parameters of RECIST (Response Evaluation Criteria for Solid Tumors) are not adequate to detect important treatment effects and response. Our goal was to evaluate the possibility of using sTRAIL (serum-soluble TNF-related apoptosis-inducing ligand) and VEGF as markers of treatment efficacy and prognosis in patients with metastatic colon cancer. METHODS: sTRAIL and VEGF levels were measured by ELISA in the sera of 16 bevacizumab-treated metastatic colon cancer patients and 10 presumably healthy age-matched controls. The measurements were taken before and after treatment for comparison purposes. RESULTS: Elevated levels of sTRAIL were found in seven out of 16 patients after bevacizumab treatment. Although these patients had a median survival time of 20.6 months, the remaining bevacizumab-treated patients who did not show an increase in sTRAIL had a median survival time of 9.4 months. As expected, serum VEGF levels were decreased in all patients who received bevacizumab therapy and showed no correlation between serum VEGF levels and patient survival (data not shown). CONCLUSIONS: Serum sTRAIL levels might be a useful predictor of prognosis in metastatic colon cancer, in the early evaluation stages following bevacizumab treatment.

Serum-soluble TRAIL levels in patients with severe persistent allergic asthma: its relation to omalizumab treatment.

BACKGROUND: In this study we compare the Omalizumab treatment modality in the dynamics of cell apoptosis regulating molecules in both severe persistent asthma patients who had no other any allergic disease, newly diagnosed patients with allergic asthma, and healthy volunteers. MATERIAL/METHODS: Severe persistent allergic asthma patients were subjected to measurement of serum soluble TRAIL (TNF-related apoptosis-inducing ligand) levels during the active disease phase and the stable phase which occurred 4 months after Omalizumab treatment. Serum sTRAIL concentrations were measured by a solid phase sandwich enzyme-linked immunosorbent assay. Concentration levels were compared with those of age- and sex-matched newly diagnosed patients with allergic asthma, and healthy controls. All assays were carried out in duplicate. Total serum IgE levels, antinuclear antibody (ANA), rheumatoid factor (RF), hepatitis markers, C3, C4 and eosinophil levels were evaluated in all patients. RESULTS: ANA, RF, hepatitis markers were negative in all patients. Complement 3 and 4 levels were normal in all patients. Prick tests in all patients were detected in mite and grass allergy. These results correlated with specific IgE. There were no differences between the healthy controls, newly diagnosed allergic asthma patients, and non-treated severe persistent allergic asthma patients during the active phase. Interestingly, the levels in variances of the patients who had the effective omalizumab treatment were significantly lower than the healthy controls, while the mean values were not statistically significant. CONCLUSIONS: Our study gives a different perspective on severe persistent allergic asthma and omalizumab treatment efficacy at the cell apoptosis-linked step by the serum sTRAIL levels.