Mehmet Kucukoner

A clinical, radiographic and laboratory evaluation of prognostic factors in 363 patients with malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) has a poor prognosis. Objectives: Only few studies in literature investigated the presence of pleural fluid and radiographic findings for the prognosis of MPM. Methods: We retrospectively investigated the hospital charts of 363 MPM patients who were diagnosed from January 1989 to March 2010. Survival time was calculated by the Kaplan-Meier method. Pretreatment clinical, laboratory and radiographic features of each patient at the time of diagnosis were obtained from patients’ charts. Results: The mean age of 363 patients (217 men, 146 women) was 50.6 ± 11.2 years (range 19–85) and the mean survival time was 11.7 ± 8.6 months (range 1–53). Histological types of MPM were epithelial (71.2%), mixed (15.9%) and sarcomatous type (4.9%). The frequency of disease stages were 31.4% for stage 1, 24.2% for stage 2, 28.6% for stage 3 and 15.8% for stage 4. The most frequent symptoms were dyspnea (82.1%), chest pain (68.3%) and weight loss (58.9%). Results of univariate and multivariate analyses revealed that a Karnofsky performance score ≤60, a pleural fluid glucose level ≤40 mg/dl, a C-reactive protein level >50 mg/l, a serum lactate dehydrogenase level >500 U/l, the presence of pleural fluid, pleural thickening >1 cm and a platelet count of >420 × 103/µl were found to be associated with poor prognosis in MPM. Conclusions: Our data suggest that low pleural fluid glucose and high C-reactive protein, the presence of pleural fluid and pleural thickening were associated with poor MPM prognosis. Further prospective studies are needed to highlight prognostic factors more clearly.

Is diabetes mellitus a negative prognostic factor for the treatment of advanced non-small-cell lung cancer?

BACKGROUND It has been demonstrated that there are a lot of different prognostic factors which are worthy of consideration whereas diabetes mellitus (DM) has not been clearly or consistently identified as a prognostic value in advanced non-small cell lung cancer (NSCLC). The aim of this study was to investigate the prognostic significance of the characteristics of patients in advanced NSCLC. Specifically, we investigated the impact of DM for progression-free survival (PFS) and overall survival (OS) in patients receiving first-line platinum-based doublets chemotherapy. METHODS We retrospectively reviewed 442 patients with advanced NSCLC. DM 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 The results of univariate analysis for OS were identified as having prognostic significance: performance status (p<0.001), stage (p<0.001), DM (p<0.001), liver metastasis (p=0.02) and brain metastasis (p<0.001). Stage, diabetes mellitus, and liver metastasis were identified as having prognostic significance for PFS. Multivariate analysis showed that poor performance status, presence of DM and advanced stage were considered independent negative prognostic factors for OS (p 0.001, p<0.001 and p<0.001 respectively). Furthermore, DM and stage were considered independent negative prognostic factors for PFS (p 0.005 and p 0.001 respectively). CONCLUSION In conclusion, DM at the time of diagnosis was associated with the negative prognostic importance for PFS and OS in the advanced stage patients who were receiving first-line platinum-based doublets chemotherapy. In addition poor performance status and advanced stage were identified as negative prognostic factors.

Prognostic factors and treatment outcomes in 93 patients with uterine sarcoma from 4 centers in Turkey.

INTRODUCTION Uterine sarcomas are a group of heterogenous and rare malignancies of the female genital tract and there is a lack of consensus on prognostic factors and optimal treatment. OBJECTIVE AND METHODOLOGY To perform a retrospective evaluation of clinicopathological characteristics, prognostic factors and treatment outcomes of 93 patients with uterine sarcomas who were diagnosed and treated at 4 different centers from November 2000 to October 2010. RESULTS Of the 93 patients, 58.0% had leiomyosarcomas, 26.9% malignant mixed Mullerian tumors, 9.7% endometrial stromal sarcomas, and 5.4% other histological types. According to the last International Federation of Gynecology and Obstetrics (FIGO) staging, 43.0% were stage I, 20.4% were stage II, 22.6% were stage III and 14.0 % were stage IV. Median relapse free survival (RFS) was 20 months (95% confidence interval (CI), 12.4-27.6 months), RFS after 1, 2, 5 years were 66.6%, 44.1%, 16.5% respectively. Median overall survival (OS) was 56 months (95% CI, 22.5-89.5 months), and OS after 1, 2, 5 years was 84.7%, 78%, 49.4% respectively. Multivariate analysis showed that age≥60 years and high grade tumor were significantly associated with poor OS and RFS; patients administered adjuvant treatment with sequential chemotherapy and radiotherapy had longer RFS time. Among patients with leiomyosarcoma, in addition to age and grade, adjuvant treatment with sequential chemotherapy and radiotherapy after surgery had significant effects on OS. CONCLUSION Uterine sarcomas have poor progrosis even at early stages. Prognostic factors affecting OS were found to be age and grade.

Childhood, adolescents, and young adults (≤25 y) colorectal cancer: study of Anatolian Society of Medical Oncology.

Purpose: To evaluate the clinicopathologic characteristics and treatment outcomes of young patients with colorectal cancer (CRC). Methods: Between May 2003 and June 2010, 76 patients were found eligible for this retrospective study. Age, sex, presenting symptoms, patients with acute presentation, family history, presence of polyps, histologic features, localization and stage of the tumor, treatment outcomes, time and site of recurrence, sites of metastasis, and survival outcomes were recorded from the patient files. Results: Seventy-six patients (55.3% male) with a median age of 23 years were evaluated. Patients were evaluated in 2 groups as follows: child-adolescent (0 to 19 y, n=20) and young adult (20 to 25 y, n=56). Sex and symptoms (abdominal pain and rectal bleeding) were significantly differed between the groups and acute presentation was close to statistical significance. Overall survival significantly increased in patients undergoing curative surgery (P<0.001). Other parameters affecting the survival was stage of disease (P=0.004). Response to palliative chemotherapy in metastatic patients (P=0.042) and postoperative adjuvant chemotherapy had a statistically significant survival advantage (P=0.028). Conclusions: Diagnosis of CRC should not be excluded solely on the basis of age. CRC features in young-adult patients are more similar to adults compared with that of child-adolescent patients according to the symptoms and presentation. In patients with CRC in this age group, curative surgery, adjuvant chemotherapy, and palliative chemotherapy provide survival advantage.

Biological Subtypes and Survival Outcomes in Breast Cancer Patients with Brain Metastases (Study of the Anatolian Society of Medical Oncology)

Background: The aim of this study is to determine the relationship between the survival outcomes and biological subtype in breast cancer patients with brain metastases. Methods: We retrospectively evaluated clinical data from 422 breast cancer patients with brain metastases between 2001 and 2011 from referral centers in Turkey. The study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression. Results: Systemic treatment prolonged median overall survival (OS) after brain metastases in the entire group (14 vs. 3.2 months, p < 0.001). It also prolonged median OS after brain metastases in the triple negative (7.5 vs. 1.6 months, p = 0.010) and luminal A (14.3 vs. 7.1 months, p = 0.003) subgroups. The median OS for untreated patients, chemotherapy and/or hormonal therapy receiving patients, and chemotherapy and/or hormonal therapy plus targeted therapy receivers was 2, 5.8, and 17.7 months, respectively (p < 0.001), in the HER2-overexpressing subgroup. In the luminal B subgroup, it was 3.7, 5.3, and 15.4 months, respectively (p = 0.003). Conclusions: The use of systemic therapy improves OS after brain metastases in all biological subgroups. Targeted therapies also improve OS after brain metastases in HER2-positive patients. The combined use of targeted therapies and lapatinib are superior to single use and trastuzumab, respectively, in these patients.

Oral Etoposide for Platinum-Resistant and Recurrent Epithelial Ovarian Cancer: a Study by the Anatolian Society of Medical Oncology

BACKGROUND The aim of this study was to evaluate the efficacy and toxicity of long-term, low-dose oral etoposide as an advanced treatment option in patients with platinum resistant epithelial ovarian cancer. MATERIALS AND METHODS For the purposes of this study, 51 patients with histologically-confirmed, recurrent or metastatic platinum-resistant epithelial ovarian cancer (EOC) treated at six different centers between January 2006 and January 2011 were retrospectively evaluated. Patients were treated with oral etoposide (50 mg/day for a cycle of 14 days, repeated every 21 days). RESULTS Among the 51 platinum-resistant patients, 17.6% demonstrated a partial response and 25.5% a stable response. The median progression-free survival (PFS) was 3.9 months (95% CI, 2.1-5.7), while the median overall survival was 16.4 months (11.8-20.9). No significant relationship was observed between the pre-treatment CA 125 levels, post-treatment CA-125 levels and the treatment response rates (p=0.21). Among the 51 patients who were evaluated in terms of toxicity, grade 1 or 4 hematologic toxicity was observed in 19 (37.3%); and grade 1-4 gastrointestinal toxicity occurred in 15 patients (29.4%). CONCLUSIONS Chronic low-dose oral etoposide treatment is generally effective and well-tolerated in platinum-resistant ovarian cancer patients.

Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected liver metastases from colorectal cancer.

Background: We aimed to investigate the impact of adjuvant systemic therapy with modern chemotherapy combinations on survival outcomes in patients with resected liver-confined metastases from colorectal carcinomas, and whether addition of bevacizumab (BEV) provides further benefit. Methods: A total of 229 consecutive patients who underwent resection for liver-confined colorectal liver metastases were retrospectively analyzed. Results: Of 229 patients, 204 who received chemotherapy with fluoropyrimidine-based (n = 27), irinotecan-based (n = 84) and oxaliplatin-based (n = 93) combinations were analyzed. Among these, 87 patients received BEV while 117 did not (NoBEV). With a median follow-up of 27 months after metastasectomy, the median recurrence-free survival (RFS) and overall survival (OS) were 17 and 53 months, respectively. OS rates at 3 and 5 years were 71% and 40%, respectively. No significant differences were found in the median RFS (p = 0.744) and OS (p = 0.440) among different chemotherapy regimens. The median RFS (p = 0.375) and OS (p = 0.251) were similar in BEV and NoBEV arms. In multivariate analysis, having 4 liver metastases was the only negative independent factor on both RFS and OS, while positive surgical margin was another negative independent factor for RFS. Conclusion: Chemotherapy type and addition of BEV have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal liver metastases.

Prognostic Factors in First-Line Chemotherapy Treated Metastatic Gastric Cancer Patients: A Retrospective Study

BACKGROUND The majority of patients with gastric cancer in developing countries present with advanced disease. Systemic chemotherapy therefore has limited impact on overall survival. Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyze prognostic factors for survival in advanced gastric cancer patients undergoing first-line palliative chemotherapy. METHODS We retrospectively reviewed 107 locally advanced or metastatic gastric cancer patients who were treated with docetaxel and cisplatin plus fluorouracil (DCF) as first-line treatment between June 2007 and August 2011. Twenty-eight potential prognostic variables were chosen for univariate and multivariate analyses. RESULTS Among the 28 variables of univariate analysis, nine variables were identified to have prognostic significance: performance status, histology, location of primary tumor, lung metastasis, peritoneum metastasis, ascites, hemoglobin, albumin, weight loss and bone metastasis. Multivariate analysis by Cox proportional hazard model, including nine prognostic significance factors evident in univariate analysis, revealed weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level to be independent variables. CONCLUSION Performance status, weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level were identified as important prognostic factors in advanced gastric cancer patients. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.

Relationship between Serum Soluble Vascular Adhesion Protein-1 Level and Gastric Cancer Prognosis

Background: Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion in a sialic acid-dependent manner. The prognostic importance of VAP-1 was determined in various human cancers. The aim of this study was to determine the relationship between VAP-1 and prognosis of gastric cancer. Materials and Methods: Serum of operable and metastatic gastric cancer patients was collected before treatment (surgery, radiotherapy, and/or chemotherapy). VAP-1 levels were measured by enzyme-linked immunosorbent assay. Results: A total of 86 gastric cancer patients (32 female, 54 male) were included in the study. Curative surgical treatment was performed in 54 (62.8%) patients. The mean serum VAP-1 level was 324.4 pg/ml and significantly higher in operable gastric cancer patients compared to metastatic gastric cancer patients (383.1 ± 173.5 vs. 225.2 ± 113.9 pg/ml; p < 0.001). When a cut-off value for VAP-1 of 218.8 pg/ml was determined by receiver operating characteristic (ROC) curves for presence of metastasis, sensitivity and specificity were 81.5 and 65.6%, respectively. Patients with decreased VAP-1 levels had a significantly poorer prognosis compared to patients with increased serum VAP-1 levels (median survival 8.2 vs. 23.5 months; p < 0.001). Multivariate analysis showed that VAP-1 is an independent prognostic factor of gastric cancer (odds ratio 2.3, 95% confidence interval 1.1-4.9; p = 0.032). Conclusion: A low serum VAP-1 level may be an indicator of poor prognosis in gastric cancer. This study demonstrated that low serum VAP-1 levels are associated with poor prognosis in gastric cancer patients.

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.