Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer.

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group.

INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.

Does nutritional status affect treatment tolerability, chemotherapy response and survival in metastatic gastric cancer patients? Results of a prospective multicenter study in Turkey.

BACKGROUND: The possible impact of malnutrition on the efficacy and tolerability of modern chemotherapy for metastatic gastic adenocarcinoma (mGC) patients is unclear. With this study, we aimed to represent the possible impact of malnutrition on the efficacy and tolerability of chemotherapy, and also on the overall survival of mGC patients. METHODS: In this prospective multicenter study, we collected demographic, oncological and nutritional data of our mGC patients. The nutritional status of patients were assessed with the Nutritional Risk Index (NRI), Body Mass Index (BMI) and weight loss percentage within 21-day period, between the chemotherapy cycles. All of these parameters along with toxicity assessment were evaluated after each courses of chemotherapy in order to determine inter-treatment weight loss. NRIs were calculated with a formula as follows; [1.519 × serum albumin level(g/L) + 41.7 × current weight/basic weight]. Patients were classified as having 'no malnutrition' (NRI > 97.5), 'moderate malnutrition' (97.5 ≥ NRI ≥ 83.5) or 'severe malnutrition' (NRI < 83.5). Drug-induced toxicities and treatment responses were evaluated via National Cancer Institute CTCAE version 4.0 and RECIST Criteria 1.1, respectively. RESULTS: One hundred and sixteen mGC patients were enrolled into the study. Median age was 60 years with range 32-83. Primary location of the tumor was antrum in 40% of the patients and of which 24% had undergone primary tumor resection. Ninety-eight percent of the patients had WHO performance status 0 or 1. Malnutrition was diagnosed in 67% of the patients and was severe in 31% of them. All patients received chemotherapy as first-line setting. Severe malnutrition was not associated with chemotherapy responses (p = 0.57). Moderate/severe malnutrition was associated with more cytopenia, nausea/vomiting, diarrhea, neuropathy, (p < 0.05 for all parameters). Moderate/severe malnutrition is associated with worser non-hematological toxicities (p = 0.038). Forty-one percent of patients died during the follow up period (Median: 138 days, range: 21-378). Malnutritional level was associated with significantly reduced overall survival. Severe malnutrition was associated with shorter median overall survival (74 days (95% CI, 20.7-111.0) vs. 237 (95% CI, 148.4-325.6) in none/moderate groups, p = 0.007). CONCLUSIONS: In mGC patients, moderate/severe malnutrition is associated with worse non-hematological toxicities. Severe malnutrition is also associated with reduced overall survival.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Does nutritional status affect treatment tolarability, response and survival in metastatic colorectal cancer patients? Results of a prospective multicenter study.

BACKGROUND: The efficacy and tolerability of modern cytotoxic chemotherapy regimens used in malnourished metastatic colorectal cancer (mCRC) patients is uncertain. The aim of this study was to investigate the effect of malnutrition on efficacy and tolerability of cytotoxic chemotherapy and overall survival in mCRC patients. METHODS: In this multicenter study, demographic, oncologic and nutritional data were collected prospectively from mCRC patients. Nutritional status of the patients were evaluated on the basis of NRI (Nutritional Risk Assessment), BMI (Body Mass Index) and WL (Weight Loss) before the first chemotherapy, after the first and second chemotherapy during 2 cycles of chemotherapy every 15 days. To determine the inter-treatment weight loss toxicity assessment was included to theese parameters after each chemotherapy. NRI calculation was performed as [1.51xserum albumin level (g/L)+41.7xcurrent weight/basic weight]. NRIs were examined in 3 categories as 'no malnutrition' (NRI >97.5), 'moderate malnutrition' (97.5 ≥NRI ≥83.5) or 'severe malnutrition' (NRI <83.5). Response to treatment and drug-induced toxicities were assessed based on Criteria in Solid Tumors (RECIST) 1.1 and National Cancer Institute CTCAE version 4.0 respectively. RESULTS: One-hundred and thirty-seven mCRC patients were prospectively included. Median age was 48 (range 18-83). Primary location was colon in 66% of patients and 84% of their primary source was left colon. Malnutrition was detected in 39% of the cases. Response rate to treatment was twenty four percent. While there was no significant relationship between chemotherapy response and moderate/severe malnutrition (p = 0.24), moderate/severe malnutrition was associated with multipl site of metastases, WHO PS (World Health Organization Performance Status) of 1, over the median value of CEA/CA 19-9 (carcinoembryonic antigen/carbohydate antigen 19-9) levels (p = 0.003, p = 0.03, p < 0.001, and p = 0.02; respectively). Hypoalbuminemia and moderate/severe malnutrition were associated with all types of toxicity (p < 0.001 and p < 0.001). Moderate/severe malnutrition was associated with thrombocytopenia, and diarrhea following chemotherapy predominately, (p = 0.02 and p = 0.04; respectively). In moderate/severe malnutrition group median overall survival was prominently shorter than those with no malnutrition [6.6 moths (95%CI, 5.6-7.6) vs 11.9 moths (95% CI, 11.1-12.7) respectively, p < 0.001]. CONCLUSIONS: Our study showed that moderate/severe malnutrition in mCRC patients was associated with decreased overall survival and increased chemotherapy toxicity.

Circulating interleukin-18 (IL-18) is a predictor of response to gemcitabine based chemotherapy in patients with pancreatic adenocarcinoma.

BACKGROUND: This study was conducted to investigate the serum levels of interleukin-18 (IL-18) in patients with pancreatic adenocarcinoma (PA) and the relationship with tumor progression and known prognostic parameters. METHODS: Thirty-three patients with PA were studied. Serum samples were obtained on first admission before any treatment. Serum IL-18 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched 30 healthy controls were included in the analysis. RESULTS: The median age at diagnosis was 59 years, range 32-84 years; 20 (61%) patients were men and the remaining were women. The median follow-up time was 26.0 weeks (range: 1.0-184.0 weeks). The median overall survival of the whole group was 41.3 ± 8.3 weeks [95% confidence interval (CI) = 25-58 weeks]. The baseline serum IL-18 levels were significantly higher in patients with PA than in the control group (p < 0.001). Serum IL-18 levels were significantly higher in the patients with high erythrocyte sedimentation rate (ESR) and lactate dehydrogenase (LDH) (p = 0.01 and p = 0.05). Moreover, the chemotherapy-(CTx) unresponsive patients had higher serum IL-18 levels compared to CTx-responsive (p = 0.04) subjects. Conversely, serum IL-18 concentration was found to have no prognostic role on survival (p = 0.45). CONCLUSION: Serum levels of IL-18 can be a good diagnostic and predictive marker; especially for predicting the response to gemcitabine based CTx in patients with PA but it has no prognostic role.

Neoadjuvant sequential chemoradiotherapy versus radiotherapy alone for treatment of high-risk extremity soft tissue sarcoma: a single-institution experience.

AIM OF THE STUDY: Patients with large and high-grade extremity soft-tissue sarcoma are at significant risk for distant metastasis and sarcoma-related death. There is no randomized trial comparing chemoradiotherapy to radiotherapy in the neoadjuvant setting for high risk extremity soft-tissue sarcoma. The aim of this study is to evaluate the outcomes of patients treated with two different modalities (neoadjuvant sequential chemoradiotherapy vs. radiotherapy alone) in a single center. MATERIAL AND METHODS: Data of 67 patients were analyzed retrospectively. Thirty-four patients received neoadjuvant sequential chemoradiotherapy (2-3 cycles of doxorubicin (75 mg/m2) and ifosfamide (6 g/m2) followed by radiotherapy of 28 Grays (Gy) administered as 8 fractions of 35 Gy) and 33 patients received radiotherapy alone. R0 resection rates and 3-year survival estimates were evaluated. RESULTS: Median follow-up time was 37 months. The estimated 3-year overall and disease-free survival rates for the whole patient group were 79% (95% CI: 67.0-86.4) and 57.9% (95% CI: 46.3-69.0), respectively. The most common side effects were nausea and leucopenia. Three-year overall, disease-free, local recurrence-free and distant recurrence-free survival rates did not differ significantly. All patients except one underwent wide excision or compartmental resection. R0 resection rate for the whole patient group was 92.5% (n = 62). Sites of progression were similar across both treatment arms. CONCLUSIONS: Preoperative hypofractionated radiotherapy alone or sequentially with chemotherapy result in high rates of limb salvage and acceptable toxicity. Our study results did not show a statistically significant treatment effect regarding survival and patterns of failure.

Clinical significance of serum interleukin-17 levels in colorectal cancer patients.

PURPOSE: The proinflammatory cytokine, interleukin-17 (IL-17) plays a potent role in T-cell mediated angiogenesis and promotes tumorigenicity. The objective of this study was to determine the clinical outcomes of colorectal cancer (CRC) patients in relation to serum IL-17 levels. METHODS: Ninety-six CRC patients were enrolled in this study. Pre-treatment serum IL-17 levels were determined by enzyme- linked immunosorbent assay (ELISA). Thirty age - and sex-matched healthy controls were included in the analysis. RESULTS: The median patient age was 60 years (range: 24-84) and the most frequent localization was colon (N=59;61%). Median follow-up time was 14 months, 27 patients (28%) experienced disease progression, and 20 of the remaining patients (20%) died. The estimated and 1-year progression-free survival (PFS) and 2-year overall survival (OS) rates for the whole patient group were 26.9% (95% confidence interval [CI]=9.9-44.0) and 71% (95% CI=56.0- 85.0), respectively. The number of patients who received neoadjuvant treatment was 25. Of the patients who received palliative treatment, 11 had oxaliplatin whereas 18 and 7 had irinotecan and FU/capecitabine, chemotherapy (CTx). Twenty-four and nine of the patients who received targeted therapy had bevacizumab and cetuximab, respectively. Thirty-three percent of 36 metastatic patients who received palliative CTx were CTx-responsive. The baseline median serum IL-17 levels were significantly lower in patients with CRC than in the healthy control group (p=0.01). Moreover, known clinical variables including older age, poor grade and low albumin levels were found to be correlated with high serum IL-17 concentrations (p=0.02, p=0.02, and p=0.04, respectively). No statistically significant serum IL- 17 concentrations were noted regarding PFS and OS. CONCLUSION: Serum levels of IL-17 may be diagnostic marker in CRC patients. However, no predictive and prognostic values were determined.

Serum leptin levels may have diagnostic and predictive roles in patients with pancreatic adenocarcinoma treated with gemcitabine-based chemotherapy.

PURPOSE: Leptin is a highly pleiotropic adipokine. Pancreatic adenocarcinoma (PA) and leptin relationship is important. Our aim was to investigate the serum levels of leptin in patients with PA, the relationship of leptin with tumor progression and known prognostic parameters and its diagnostic, predictive and prognostic role. METHODS: Thirty-three patients with PA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum leptin levels were determined using enzyme-linked immunosorbent assay (ELISA). Age, sex, and body mass index (BMI) matched to 20 healthy controls were included in the analysis. RESULTS: The median patient age at diagnosis was 59 years (range 32-84) and 20 (61%) patients were men. The tumor was located in the head of pancreas in 21 (63%) patients. The most common metastatic site was liver in 23 patients with metastasis (N=19; 83%). The median follow-up time was 26.0 weeks (range 1.0-184.0). At the end of the observation period, 32 patients (97%) had died. The baseline serum leptin levels were significantly higher in patients with PA than in the control group (p=0.02). Thirty-nine percent of 23 metastatic patients who received palliative gemcitabine-based chemotherapy (gCTx) were gCTx-responsive. Serum leptin levels were significantly higher in the gCTx-unresponsive patients compared with gCTx -responsive (median 5.32 vs 1.16 ng/mL, p=0.004). Conversely, serum leptin concentration was found to have no prognostic role on survival (p=0.20). CONCLUSION: Serum leptin levels may be a good diagnostic and predictive tool on the response to gCTx in PA patients.

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.

Serum transforming growth factor-beta1 levels may have predictive and prognostic roles in patients with gastric cancer.

Transforming growth factor-beta1 (TGF-beta1) plays an important role in the pathogenesis of multiple malignancies, and also, its expression strongly affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of TGF-beta1 in gastric cancer patients. A total of 63 patients with a pathologically confirmed diagnosis of gastric cancer were enrolled into this study. Serum TGF-beta1 concentrations were determined by the solid-phase sandwich ELISA method. Thirty healthy age- and sex-matched controls were included in the analysis. The median age at diagnosis was 62 years, range 28 to 82 years. There was no significant difference in baseline serum TGF-beta1 levels between gastric cancer patients and the healthy control group (p = 0.08). The known clinical variables including age of patient, gender, site of lesion, histology, histological grade, stage of disease, and serum levels of lactate dehydrogenase (LDH), CEA, and carbohydrate antigen (CA) 19.9 were not found to be correlated with serum TGF-beta1 concentrations (p > 0.05). However, the chemotherapy-responsive patients had higher serum TGF-beta1 levels compared with chemotherapy-unresponsive ones (median values 330.50 v 49.54 pg/mL, respectively, p = 0.01). Moreover, patients with elevated serum TGF-beta1 concentrations had significantly favorable overall survival compared with those with lower levels (median 71.1 v 39.9 weeks, respectively, p = 0.04). In conclusion, serum levels of TGF-beta1 may have predictive and prognostic roles in patients with gastric cancer.

Combination of capecitabine and phenytoin may cause phenytoin intoxication: a case report.

Capecitabine is an oral antineoplastic agent, and phenytoin is an anticonvulsant drug with a narrow therapeutic index. Although the interaction between capecitabine and phenytoin is rare, it may be potentially fatal. This interaction is thought to be at the level of CYP2C9 isoenzyme system in the liver. Here, we present a patient with metastatic breast cancer who developed phenytoin intoxication when using capecitabine and phenytoin together. Closely monitoring plasma phenytoin levels is essential if capecitabine is used with phenytoin concurrently.

Serum levels of vascular cell adhesion molecule-1 (VCAM-1) may have diagnostic, predictive, and prognostic roles in patients with lung cancer treated with platinum-based chemotherapy.

Cellular adhesion molecules might be good markers in some types of malignant tumors and provide useful information in diagnosis and prognosis. The objective of this study was to determine the clinical significance of the serum levels of vascular cell adhesion molecule-1 (VCAM-1) in lung cancer patients treated with platinum-based chemotherapy. One hundred and thirty lung cancer patients were enrolled into this study. Serum VCAM-1 levels were determined by the solid-phase sandwich ELISA method. Age- and sex-matched 34 healthy controls were included in the analysis. Median age was 58 years old, range 35 to 80 years. The majority of the patients had non-small cell lung cancer (NSCLC) (83.8 %) and stage IV disease (60.8 %). The patients' baseline serum VCAM-1 levels were significantly higher than those in the healthy control group (p = 0.02). Male patients had higher serum VCAM-1 level compared with female patients (p = 0.04). The stage of disease and tumor histology were not correlated with serum VCAM-1 assay (p > 0.05). Elevated serum VCAM-1 levels were associated with chemotherapy unresponsive patients compared with responsive patients (p = 0.02). The patients with elevated serum VCAM-1 levels had lower survival rates than the ones with lower levels (1-year survival rate 57.6 vs 69.7 %, respectively, p = 0.04). In conclusion, serum VCAM-1 concentrations may have diagnostic, predictive, and prognostic role in lung cancer patients treated with platinum-based chemotherapy.

Serum transforming growth factor-beta 1 (TGF-ß1) levels have diagnostic, predictive, and possible prognostic roles in patients with melanoma.

Transforming growth factor-beta 1 (TGF-ß1) plays an important role in the pathogenesis of multiple malignancies, and its expression also strongly affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of TGF-ß1 in melanoma patients. A total of 60 patients with a pathologically confirmed diagnosis of melanoma were enrolled into this study. Serum TGF-ß1 concentrations were determined by the solid-phase sandwich ELISA method. Thirty age- and sex-matched healthy controls were included in the analysis. The median age at diagnosis was 53.5 years (range 16 to 88 years). The baseline serum TGF-ß1 levels of the melanoma patients were significantly higher than those in the control group (median values 171.85 vs. 19.95 pg/mL, respectively; p < 0.001). The known clinical variables including age of patient, gender, site of lesion, histology, stage of disease, and serum LDH levels were not found to be correlated with serum TGF-ß1 concentrations (p > 0.05). However, the chemotherapy-responsive patients had higher serum TGF-ß1 levels compared with chemotherapy-unresponsive ones (p = 0.05). Additionally, serum TGF-ß1 concentration was a trend to have a prognostic role on survival (p = 0.07). Patients with elevated serum TGF-ß1 concentrations had close to significantly favorable overall survival compared to those with lower levels (median 30.1 vs. 20.9 months, respectively). In conclusion, serum levels of TGF-ß1 have diagnostic, predictive, and possible prognostic roles in melanoma patients.

Clinical significance of serum epithelial cell adhesion molecule (EPCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in patients with epithelial ovarian cancer.

Cellular adhesion molecules might be good markers in some types of malignant tumors, useful information in diagnosis and prognosis. The objective of this study was to evaluate the serum levels of epithelial cell adhesion molecule (EPCAM) and vascular cell adhesion molecule-1 (VCAM-1) in epithelial ovarian cancer (EOC) patients. Fifty patients were enrolled into the study. Serum EPCAM and VCAM-1 levels were determined by the solid-phase sandwich ELISA method. Age- and sex-matched 30 healthy controls were included in the analysis. The median age of the patients was 56.5 years, range 22 to 83 years. Majority of the patients had advanced disease (stages III-IV) (90%). The baseline serum EPCAM levels of the EOC patients were significantly higher than in those in the control group (p = 0.03). However, there was no significant difference in the serum VCAM-1 level between EOC patients and controls (p = 0.24). Metastatic patients had higher serum VCAM-1 levels compared with the non-metastatic patients (p = 0.03). Moreover, no other clinical variables including response to chemotherapy were found to be correlated with both serum assays (p > 0.05). No correlation was found between serum EPCAM and VCAM-1 levels in EOC patients (r(s) = 0.105, p = 0.362). Neither serum EPCAM level nor serum VCAM-1 level had significant adverse effect on survival. In conclusion, the higher baseline serum levels of VCAM-1 were associated with metastatic disease, and serum EPCAM level was found to be a diagnostic marker in EOC patients. However, both serum assays had no prognostic roles on outcome.

Clinical significance of serum transforming growth factor-beta 1 (TGF-ß1) levels in patients with epithelial ovarian cancer.

Transforming growth factor-beta 1 (TGF-ß1) plays an important role in the pathogenesis of multiple malignancies, and its expression also strongly affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of TGF-ß1 in epithelial ovarian cancer (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum TGF-ß1 concentrations were determined by the solid-phase sandwich ELISA method. Thirty age- and sex-matched healthy controls were included in the analysis. Median age of patients was 56.5 years old (range 22 to 83 years). Majority of the patients had advanced disease (FIGO stage III-IV; 90%). There was no significant difference in baseline serum TGF-ß1 levels between EOC patients and the controls (p = 0.39). A trend to significant relationship was found between the serum levels of TGF-ß1 and stage of disease (p = 0.06). The elevated serum TGF-ß1 level was associated with metastatic disease. The other known clinical variables including histology, grade of histology, debulking surgery, and serum CA 125 levels were not found to be correlated with serum TGF-ß1 concentrations (p > 0.05). Only the chemotherapy-unresponsive patients had higher serum TGF-ß1 levels compared with responsive ones (p = 0.02). Serum TGF-ß1 concentration was found to have no prognostic role for both progression-free and overall survivals (p = 0.42 and p = 0.09, respectively). In conclusion, although the serum level of TGF-ß1 has no diagnostic and prognostic role, it is associated with sensitivity to standard chemotherapy in EOC patients.

Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) in patients with epithelial ovarian cancer.

Insulin-like growth factor-1 (IGF-1) and its primary binding protein IGFBP-3 play an important role in cellular proliferation, differentiation, and apoptosis in many tumors, including ovarian cancer. The objective of this study was to determine the clinical significance of the serum levels of IGF-1 and IGFBP-3 in epithelial ovarian cancer (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum IGF-1 and IGFBP-3 levels were determined by the solid-phase sandwich ELISA method. Twenty age- and sex-matched healthy controls were included in the analysis. Median age of patients was 56.5 years old (range 22 to 83 years). Majority of the patients had advanced disease (FIGO stage III-IV; 90%). No significant difference was observed in baseline serum IGF-1 and IGFBP-3 levels between EOC patients and healthy controls (p = 0.99 and p = 0.80, respectively). The young patients had higher serum IGF-1 and IGFBP-3 concentrations (p = 0.04 and p = 0.02, respectively). Patients with normal CA-125 levels had higher serum IGFBP-3 concentrations compared with those with higher CA-125 levels (p = 0.008). However, no other clinical variables including histology, tumor grade, stage of disease, and response to chemotherapy were found to be correlated with serum IGF assays (p > 0.05). A trend to significant relationship was found between the serum levels of IGF-1 and IGFBP-3 (r(s) = 0.212, p = 0.07). The patients with elevated serum IGF-1 levels had favorable progression-free and overall survivals than those with lower levels (p = 0.04 and p = 0.03, respectively). However, serum IGFBP-3 concentrations were found to have no prognostic role for both survivals (p = 0.12 and p = 0.26, respectively). In conclusion, elevated serum level of IGF-1 is associated with favorable progression-free and overall survivals in EOC patients.

Serum levels of macrophage migration-inhibitory factor (MIF) have diagnostic, predictive and prognostic roles in epithelial ovarian cancer patients.

Macrophage migration-inhibitory factor (MIF) plays an important role in the pathogenesis of multiple malignancies, and its expression strongly also affects outcomes of cancer patients. The objective of this study was to determine the clinical significance of serum levels of MIF in epithelial ovarian cancer (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum MIF concentrations were determined using the solid-phase sandwich ELISA method. Age- and sex-matched 30 healthy controls were included in the analysis. Median age of patients was 56.5 years old, range 22 to 83 years. Majority of the patients had an advanced disease (International Federation of Gynecologists and Obstetricians (FIGO) stages III and IV) (90%). Baseline serum MIF levels were significantly higher than those in the healthy control group (p = 0.005). No known clinical variables including histology, grade of histology, stage of disease, debulking surgery, and serum CA 125 levels were found to be correlated with serum MIF levels (p > 0.05). Only those chemotherapy-unresponsive patients had higher serum MIF levels compared with responsive ones (p = 0.02). Patients with elevated serum MIF concentrations had significantly unfavorable overall survival compared to those with lower levels (p = 0.01). However, a serum MIF level was found to play no prognostic role for progression-free survival (p = 0.09). In conclusion, serum levels of MIF have diagnostic, predictive, and prognostic roles in EOC patients.

Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with breast cancer.

Insulin-like growth factor-1 (IGF-1) and its primary binding protein-3 (IGFBP-3) play an important role in cellular proliferation, differentiation and apoptosis in many tumors, including breast cancer (BC). The objective of this study was to determine the clinical significance of the serum levels of IGF-1 and IGFBP-3 in BC patients. A total of 96 patients with a pathologically confirmed diagnosis of BC were enrolled into this study. Serum IGF-1 and IGFBP-3 levels were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) methods. Age- and sex-matched 30 healthy controls were included in the analysis. The median age of diagnosis was 48 years (range: 29-80). Thirty-seven (39 %) consisted of metastatic disease. No significant difference in baseline serum was found in both IGF-1 and IGFBP-3 levels between BC patients and healthy controls (p = 0.92 and p = 0.26, respectively). None of the prognostic parameters analyzed was correlated significantly with the serum assay concentrations. Likewise, no correlations were also found between these serum concentrations and response to chemotherapy. No significant correlation was found between serum IGF-1 and IGFBP-3 levels in BC patients (r s = 0.048, p = 0.66).The patients with elevated serum IGF-1 levels had favorable in survival than those with lower levels (p = 0.05). However, serum IGFBP-3 concentrations were found no prognostic role for outcome (p = 0.35). In conclusion, elevated serum IGF-1 level is afavorable prognostic factor for overall survival in BC patients.