Comparison of SKIP expression in malignant pleural mesotheliomas with Ki-67 proliferation index and prognostic parameters.

We aimed to determine the presence of SKI-interacting protein (SKIP) expression in malignant pleural mesothelioma (MPM) and its effect on prognosis by investigating SKIP correlation with the Ki-67 proliferation index and prognostic parameters. Pathological preparations of the patients diagnosed with MPM between 2006 and 2012 were evaluated. Immunohistochemical analyses were performed to evaluate the expression of SKIP and the Ki-67 proliferation index. Correlations between SKIP expression, clinicopathological factors and survival were investigated. Survival data were calculated using the Kaplan-Meier method, and Cox regression analysis was used to evaluate the prognostic value of the variables. In total, 52 patients were evaluated in the study; 36 of them were male and 16 were female. The mean age of the patients was 62.3 ±12.2 years. The median overall survival period was 8.5 months. Factors negatively affecting general survival in the univariate analysis included high SKIP expression, Ki-67 proliferative index over 30%, presence of non-epithelioid type MPM and stage III-IV disease (p < 0.05). Cox regression analysis revealed that high SKIP expression, high Ki-67 proliferative index and presence of non-epithelioid type MPM are independent factors that affect the survival rate. Higher SKIP expression is associated with poor prognosis in MPM.

Prognostic factors influencing survival in 35 patients with malignant peritoneal mesothelioma.

Malignant mesothelioma is a rare but highly lethal form of cancer that affects the serosal membranes. Malignant peritoneal mesothelioma (MPM) is the second most common form of malignant mesothelioma (pleural mesothelioma is the most common). The aim of this study was to evaluate prognostic factors influencing the survival of patients with MPM. A retrospective analysis was performed on 35 patients who were admitted to our hospital between March 2005 and July 2013. The patients' demographic and clinical data, laboratory results, radiological signs, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and treatment outcomes were evaluated. The mean age of the 35 patients was 59.0±14.4 years, the mean survival time was 16.2±12.9 months, and the majority of the histopathological types of MPM were epithelial (68.6%). 82.9% of the patients had been exposed to asbestos, and the mean duration of exposure was 28.3±14.5 years. The most frequent symptoms were abdominal distention/pain, weight loss, dyspnea, and chest pain. The mean interval between the onset of symptoms and the diagnosis was 4.6±3.3 months. Platinum-based combination chemotherapy in combination with supportive care was used in the treatment of 68.6% of the patients, while supportive treatment alone was used in the others. Our results revealed that patients who were >60 years old (p=0.019), who were exposed to asbestos >20 years (p=0.033), who had an ECOG PS of 3 (p=0.000) were more likely to have a poor MPM prognosis.In conclusion, increased age, duration of environmental asbestos exposure and ECOG PS are important factors that influence the prognosis of MPM patients.

Prognostic analysis of patients with operable gastric cancer and tolerability to adjuvant radio-chemo-therapy.

The aim of this study is to evaluate the tolerability and toxicity of adjuvant chemoradiotherapy (CRT) and to analyze the prognosis in patients with operable gastric cancer. The retrospective analysis included 723 patients with operable gastric cancer; stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. The patients' age, sex, tumor localization, Lauren classification, grade and stage of the disease, type of dissection, the toxicity and tolerability status and survival rate were analyzed. All patients were divided into two groups as tolerable group to adjuvant CRT and intolerable group to adjuvant CRT .Among the patient, 73.9% had stage III-IVM0 disease; 61.0% had the intestinal type of gastric cancer, 51.1% had the distal type, and 61.4% had undergone D2 dissections. The number of patients who completed the entire course of the adjuvant CRT was 545 (75.4%).The median follow-up period was 20.8 months (range: 1.5-107 months). Overall Survival (OS) rates were 80% and 52%, while the relapse free survival (RFS) rates were 75% and 48% at 1 and 3 years, respectively.In the univariate analysis of the groups based on the the age defined as <65 or ≥ 65 (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), disease stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), presence or absence of toxicity (p=0.062 / p=0.077) and tolerability of the therapy (p=0.002 / p=0.001). In the cox regression analysis, tumor stage (Hazard Ratio (HR): 0.332; 95% confidence interval (CI): 0.195-0.566; p<0.001), and tolerability (HR: 0.516; 95% CI: 0.305-0.872; p=0.014), were found to be related with the OS. Tumor stage (HR: 0.318; 95% CI: 0.190-0.533; p=<0.001) and tolerability (HR: 0.604; 95% CI: 0.367-0.995; p=0.048) were observed to be statistically significant in terms of the RFS.We have observed that whether a patient can or cannot tolerate adjuvant CRT due to its toxicity is an independent prognostic factor besides the known prognostic factors like tumor stage and Lauren classification. We are of the opinion that the treatment of patients who cannot tolerate adjuvant CRT should be replaced with less toxic adjuvant therapies.

Effects of treatment regimens on survival in patients with malignant pleural mesothelioma.

BACKGROUND AND OBJECTIVE: In this study, we aimed to investigate the factors affecting the survival of patients with malignant pleural mesothelioma (MPM) according to their treatment regimens, including best supportive care (BSC), chemotherapy, surgical group and multimodality (MM) therapy. PATIENTS: A retrospective analysis was performed on clinical data and treatment outcomes of 400 patients registered in our hospital with MPM between January 1989 and April 2010. RESULTS: Mean age (p < 0.001), presence of asbestos exposure (p = 0.0014), presence of smoking history (p < 0.001), Karnofsky performance status (p < 0.001), histological subtype (p = 0.034) and stage (p < 0.001) variables were found to be significantly different among the four treatment regimens. Mean survival time of all patients was 12.32 months. Mean survival time 10.5 months for the BSC group, 15.7 for the surgical group, 16.02 for the chemotherapy group, and 26.55 for the MM group. There were significant differences in mean survival time among the four treatment regimens. In addition, a significant difference was found in survival time between the two chemotherapy groups (p = 0.032). Mean survival time for cisplatin + gemcitabine was found to be 14.49 months and for cisplatin + pemetrexed, 18.34 months. CONCLUSIONS: The MM group had better survival rates than the other groups. The new chemotherapy combination, cisplatin + pemetrexed, can be helpful in improving survival time.      

Docetaxel and Cisplatin Plus Fluorouracil compared with Modified Docetaxel, Cisplatin, and 5-Fluorouracil as first-line therapy for advanced gastric cancer: a retrospective analysis of single institution.

Gastric cancer is the second most common among cancer-related deaths in the world. Systemic chemotherapy for patients with gastric cancer has limited impact on overall survival. We performed a retrospective analysis of the efficacy and side effects of Docetaxel and Cisplatin Plus Fluorouracil (DCF) versus Modified-Dose Docetaxel, Cisplatin, and 5-Fluorouracil (mDCF) in the metastatic gastric cancer with first-line chemotherapy treated patients. Retrospectively were reviewed 107 locally advanced or metastatic gastric cancer patients who were treated DCF or mDCF as first-line treatment from June 2007 to August 2011 in Dicle University Hospital, Department of Medical Oncology.The DCF protocol included 75 mg/m2 docetaxel and cisplatin on day 1 and 750 mg/m2/day 5-FU infusion for 5 days, repeated every 3 weeks. The mDCF protocol included 60 mg/m² docetaxel and cisplatin on day 1 and 600 mg/m² 5-Fluorouracil continuous infusion per day on days 1-5, every 3 weeks.Patients were treated using DCF arm 85 (M: 56, F: 29), the mDCF arm 22 (M: 13, F: 9) After treatment toxicities were: Grade III-IV neutropenia (48.2% vs 13.6% p=0.003), anemia (21.2% vs 4.5% p=0.06), nausea (44.7% vs 13.6% p=0.008) and vomiting (31.8% vs 4.5%, p=0.01) was higher in the DCF arm. Other toxicities profile was similar in both groups (p>0.05). The rate of response was similar in both arm. Among patients with the DCF and mDCF arm rate complete response (10.3% vs 6.7%, p>0.05), partial response (35.3% vs 40.0%, p>0.05), stable disease (32.4% vs 33.3%, p>0.05), progressive disease (22.1% vs 20.0%, p>0.05) and overall response (45.6% vs 46.7%, p>0.05) did not have a statistically difference (p>0.05). Progression-free survival (PFS) and overall survival (OS) were more favorable in the DCF arm than mDCF arm, but the difference was not significant statistically (9.9 vs 8.6, 7.4 vs 6.5 p>0.05)In conclusion, the response rate, median PFS and median OS are similar in both arms, while the mDCF regimen are more favorable than the DCF for toxicity profile regimen in advanced gastric cancer patients who were undergoing first-line palliative treatment. Therefore, a prospective and larger clinical trials are needed.

Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study.

The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.

Prognostic factors in elderly patients with advanced non-small cell lung cancer treated with first-line cisplatin-based chemotherapy: a retrospective analysis of single institution.

PURPOSE: Non-small cell lung cancer (NSCLC) makes up 80-85% of all lung cancers cases. Lung cancer in older individuals is frequently undertreated. Patients eligible for cisplatin- based chemotherapy should be selected carefully. The aim of this retrospective single-center study was to evaluate prognostic factors for overall survival (OS) in elderly (≥65 years) patients with advanced NSCLC who received first-line cisplatin-based chemotherapy. METHODS: We retrospectively reviewed 110 elderly patients with locally advanced or metastatic NSCLC who had been administered cisplatin-based first-line chemotherapy between December 2004 and November 2011. Seventeen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. RESULTS: Among the 17 variables of univariate analysis, 4 were identified to have prognostic significance for OS: comorbidities (p<0.001), Eastern Cooperative Oncology Group (ECOG) performance status (PS) (p=0.02), first-line chemotherapy cycles (p<0.001) and serum albumin level (p=0.04). Multivariate analysis showed that only ECOG PS (p=0.01) was independent prognostic factor for OS. CONCLUSION: PS was important prognostic factor in elderly patients with advanced NSCLC. The findings of this study may facilitate pretreatment prediction of OS and therefore can be used for selecting the most appropriate treatment for elderly patients.

Prognostic value of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with advanced non-small cell lung cancer: single center experience.

PURPOSE: The purpose of this retrospective single-center study was to evaluate the prognostic implication on overall survival (OS) of the F-18 FDG PET scan in locally advanced or metastatic non small cell lung cancer (NSCLC) patients. METHODS: We retrospectively reviewed 120 locally advanced or metastatic NSCLC patients (December 2004-November 2011) treated/followed at the Dicle University, School of Medicine, Department of Medical Oncology. SUVmax and other potential prognostic variables (n=18) were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors for OS. RESULTS: Among 18 variables of univariate analysis, 6 were identified to bear prognostic significance: sex (p=0.01), performance status (PS) (p =0.03), stage (p=0.04), bone metastases (p=0.002), serum albumin (p=0.01) and blood glucose level (p=0.03). Multivariate analysis showed that PS, bone metastases and serum albumin level were independent prognostic factors for OS (p=0.01, p=0.004, p=0.003, respectively). CONCLUSION: PS, serum albumin levels and bone metastases were independent prognostic factors, while FDG uptake of the primary lesion was not associated with prognosis of OS in locally advanced or metastatic NSCLC patients.

Contribution of low-molecular weight heparin addition to concomitant chemoradiotherapy in the treatment of glioblastoma multiforme.

PURPOSE: Glioblastoma multiforme (GBM) is the most common brain tumor in adults and has a very aggressive course. Median survival is as short as 2 years with standard treatment (chemoradiotherapy followed by adjuvant temozolomide). The purpose of this study was to determine the contribution of low molecular weight heparin (LMWH) addition to concomitant chemoradiotherapy in the treatment of GBM. METHODS: All patients with newly diagnosed GBM between March 2004-May 2009 were evaluated. After surgical intervention (total, subtotal resection or only biopsy) all of them were treated with concomitant chemoradiotherapy (2 Gy daily, 5 days a week, 30 fractions, total tumor dose 60 Gy; and 75 mg/m² temozolomide, 7 days a week), followed by adjuvant temozolomide (6 cycles, 150-200 mg/m², 5 days every 28 days), with or without LMWH (4000 IU/day, 7 days a week, concomitant with radiotherapy) because of risk of thrombosis. The primary endpoint was the determination of progression-free survival (PFS) and overall survival (OS); secondary endpoints were 1- and 2-year OS survival. RESULTS: 30 patients (13 patients in the group non receiving LMWH (LMWH-) and 17 patients in the group receiving LMWH (LMWH+)) were included in the study. Median age was 54 years (range 24-75). Median PFS was 57 and 38 weeks in LMWH+ and LMWH- groups, respectively (p=0.068). Median OS was 69 and 44 weeks (p=0.095), 1-year OS survival 84.6 and 41.2% (p=0.016), and 2-year OS survival 38.5 and 5.9% in LMWH+ and LMWH-, respectively (p=0.061). No significant difference was noted between the two groups for grade 3-4 toxicity (p>0.05). CONCLUSION: Better PFS, OS and 2-year OS survival were obtained in present study with the addition of LMWH to concomitant chemoradiation for GBM but without statistical significance. One-year OS survival was statistically significant favoring the LMWH group. The addition of LMWH did not increase temozolomide toxicity.

Prognostic factors in patients with advanced pancreatic cancer treated with gemcitabine alone or gemcitabine plus cisplatin: retrospective analysis of a multicenter study.

PURPOSE: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyse prognostic factors for OS in advanced pancreatic cancer patients treated with first-line palliative chemotherapy with gemcitabine alone or gemcitabine plus cisplatin. METHODS: We retrospectively reviewed 343 locally advanced or metastatic pancreatic cancer patients who were treated with gemcitabine or gemcitabine plus cisplatin as first-line chemotherapy between December 2000 and June 2011. Fifteen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. Univariate and multivariate statistical methods were used to determine prognostic factors. RESULTS: Among the 15 variables of univariate analysis, 6 were identified to have prognostic significance: stage (p<0.001), cholestasis (p=0.02), weight loss, prior pancreatectomy, serum CEA level (p<0.001) and serum CA19-9 level (p>0.001). In addition, age, chemotherapy and liver metastasis were of borderline significance (p=0.06). Multivariate analysis (Cox proportional hazard model) included the 6 significant prognostic factors of univariate analysis and showed that stage was independent prognostic factor for OS, as were weight loss, and serum CEA level. CONCLUSION: Stage, weight loss, and serum CEA level were identified as important prognostic factors for OS in advanced pancreatic cancer patients. These findings may also facilitate pretreatment prediction of OS and can be used for selecting patients for treatment.

Is (18)F-FDG-PET/CT prognostic factor for survival in patients with small cell lung cancer? Single center experience.

BACKGROUND: Although a number of studies in patients with a variety of malignant tumors have shown that metabolic activity on fluorine-18 deoxyglucose positron emission tomography computed tomography ((18)F-FDG-PET/CT) is correlated with survival, there are few studies about the impact of (18)F-FDG-PET/CT for survival in small cell lung cancer (SCLC) patients. There is still some ambiguity as to whether FDG PET in patients with SCLC will ensure prognostic knowledge for survival. We performed a retrospective analysis of prognostic implication of (18)F-FDG-PET/CT in patients with SCLC. METHODS: We retrospectively reviewed 54 patients with histologically or cytologically proven SCLC who had undergone pre-treatment (18)F-FDG-PET/CT scanning between September 2007 and November 2011 in the Dicle University, School of Medicine, Department of Medical Oncology. SUVmax and other potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. RESULT: Among the eleven variables of univariate analysis, three variables were identified as having prognostic significance: Performance status (p < 0.001), stage (p = 0.02) and diabetes mellitus (p = 0.05). Multivariate analysis showed that performance status and stage were considered independent prognostic factors for survival (p < 0.001 and p = 0.002 respectively). CONCLUSION: In conclusion, performance status and stage were identified as important prognostic factors, while (18)F-FDG-PET/CT uptake of the primary lesions was not associated with prognostic importance for survival in patients with SCLC.

Phase II study of lapatinib in combination with vinorelbine in patients with HER2 positive recurrent or metastatic breast cancer: a multicentric Turkish Oncology Group (TOG) trial.

BACKGROUND: The aim of this explorative phase II study was to evaluate the activity and safety of lapatinib in combination with intravenous vinorelbine in women with HER2 positive metastatic or recurrent breast cancer. METHODS: Twenty-nine patients were enrolled. The primary objectives were response and clinical benefit (CB) rates, secondary objectives were toxicity, response duration and progression free survival. Patients received 1250 mg oral lapatinib continuously once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS: Although 25 patients were evaluable for response, according to intend to treat analysis of 28 patients; 14% had confirmed partial response (PR) and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3 extra-hematologic toxicities. CONCLUSION: The results of this trial provide evidence to further investigate the potential of this combination for patients unsuitable for trastuzumab or who become refractory to trastuzumab.