Esma Turkmen

Clinicopathological characteristics and prognosis of patients according to recurrence time after curative resection for colorectal cancer.

PURPOSE To investigate clinicopathological features in patients with recurrent colorectal cancer within 1 year and more than 1 year after curative resection. MATERIALS AND METHODS We retrospectively evaluated 103 patients with disease recurrence before versus after 1 year of resection. Thirty-two patients (31%) were diagnosed with recurrence less than 1 year after curative resection for colorectal cancer (early recurrence) and 71 (69%) after more than 1 year (non-early recurrence). RESULTS The early recurrence group displayed a significantly lower overall survival rate for both colon cancer (p=0, 01) and rectal cancer (p<0.001). Inadequate lymph node dissection was a significant predictor for early relapse. There were no statistically significant differences in clinicopathological variables such as age, sex, primary tumor localization, stage, depth of invasion, lymphovascular invasion and perineural invasion between the early and non-early recurrence groups. However, a K-ras mutation subgroup was significantly associated with early recurrence (p<0.001). CONCLUSIONS Poor survival is associated with early recurrence for patients undergoing resection for non-metastatic colorectal cancer, as well as K-ras mutation.

Comparative Analysis of the Efficacy and Safety of Oxaliplatin Plus 5-Fluorouracil/Leucovorin (Modified FOLFOX6) with Advanced Gastric Cancer Patients having a Good or Poor Performance Status

BACKGROUND Combination chemotherapy of 5 fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin, mainly FOLFOX regimens, has shown considerable antitumor activity and a tolerable toxicity profile in gastric cancer. The goal of this study was to retrospectively compare the efficacy and toxicity of modified FOLFOX-6 (mFOLFOX6) regimen in advanced gastric cancer (AGC) patients with good and poor performance status (PS). MATERIALS AND METHODS AGC patients receiving the mFOLFOX6 regimen including oxaliplatin 85 mg/m2, bolus of 5-FU 400 mg/m2 and LV 400 mg/m2 on the first day, followed by 2400mg/m2 of 5- FU as a continious infusion over 46 hour for first-line treatment were eligible for the study. RESULTS A total 58 patients with a median age of 59.5 (32-81) were included. The median follow up of the study was 9.2 months. Thirty patients (51.7%) with an ECOG PS 0-1 were assigned to the good PS arm, while 28 patients (48.3%) with ECOG PS 2 were in the poor PS arm. Overall response rates were 36.6 and 28.8%, respectively (p=0.91). Median PFS was 6.7 and 6.3 months in good PS and poor PS arms (p=0.50) and median OS was 9.6 and 10.4 months (p=0.55). As compared with good PS arm, poor PS arm was associated with more grade 3-4 neutropenia and anemia. Dose reduction and dose delays were also significantly higher. CONCLUSIONS In this study, mFOLFOX6 was similarly effective in both arms. Although hematologic toxicity was significantly higher in patients with poor PS, it remained manageable. Our results suggest that this regimen may be an effective treatment option for AGC patients with poor PS.

Unknown primary adenocarcinomas: a single-center experience.

This study aimed to elucidate the clinical and prognostic characteristics of a homogeneous group of patients with cancer of unknown primary (CUP). Between 1999 and 2014, CUP was diagnosed in 159 (1.3%) of 11,742 cancer patients at Trakya University Hospital (Edirne, Turkey). Ninety-seven (61%) of the 159 patients were retrospectively reviewed. Among these, 61 (62.8%) patients with adenocarcinoma were included in this study. The most frequently predicted primary tumor site was the lung (37.7%), and 59% of the patients were smokers. There was a significant relationship between smoking and the lung as a potential primary cancer site (p = 0.042). The most frequent site of metastasis was the liver (60.7%). The median number of metastases per patient was two, but patients with liver metastases had a median of five metastases. The overall median survival time was 7 months. Median survival was significantly longer in patients with a predicted primary site than in patients without the predicted site (7 vs. 6 months, respectively; p = 0.038). When the patients with predicted ovarian and peritoneal tumors were excluded from the comparison, the statistical p value was still close to significant (p = 0.07). Multivariate analysis revealed that smoking, liver metastasis, serum alkaline phosphatase ≥92 U/L, and progression in response to chemotherapy were independent predictors of a poor prognosis. The present study identified several independent prognostic factors in patients with unknown primary adenocarcinomas who received chemotherapy. Smoking, the presence of liver metastasis, and response to chemotherapy were independent risk factors for both progression-free and overall survival.

Impact of active smoking on survival of patients with metastatic lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) mutation.

Lung cancer in smokers and non-smokers demonstrates distinct genetic profiles, and cigarette smoking affects epidermal growth factor receptor (EGFR) function and causes secondary EGFR tyrosine kinase resistance. We evaluated the effect of active smoking in patients with metastatic lung adenocarcinoma. A total of 132 metastatic lung adenocarcinoma patients, diagnosed between 2008 and 2013, with known EGFR mutation status, were evaluated retrospectively. Among these patients, 40 had an activating EGFR mutation. Patients who continued smoking during the treatment were defined as active smokers. Former smokers and never smokers were together defined as non-smokers. The outcomes of the treatment in relation to the EGFR mutation and smoking status were evaluated. The median follow-up time was 10.5 months. The overall response rate for the first-line therapy was significantly higher among the EGFR-mutant patients (p = 0.01), however, smoking status had no impact on the response rate (p = 0.1). The EGFR-mutant active smokers progressed earlier than the non-smokers (p < 0.01). The overall survival (OS) of the non-smokers and patients treated with erlotinib was significantly longer (p = 0.02 and p = 0.01, respectively). Smoking status did not affect the OS in EGFR wild type tumors (p = 0.49) but EGFR-mutant non-smokers had a longer OS than the active smokers (p = 0.01).The active smokers treated with erlotinib had poorer survival than the non-smokers (p = 0.03). Multivariate analysis of EGFR-mutant patients showed that erlotinib treatment at any line and non-smoking were independent prognostic factors for the OS (p = 0.04 and p = 0.01, respectively). Smoking during treatment is a negative prognostic factor in metastatic lung adenocarcinoma with an EGFR mutation.

KRAS Mutation in Small Cell Lung Carcinoma and Extrapulmonary Small Cell Cancer.

BACKGROUND Lung cancer is one of the most lethal cancers. It is mainly classified into 2 groups: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Extrapulmonary small cell carcinomas (EPSCC) are very rare. The Ras oncogene controls most of the cellular functions in the cell. Overall, 21.6% of human cancers contain a Kirsten Ras (KRAS) mutation. SCLC and EPSCC have several similar features but their clinical course is different. AIMS We investigated the KRAS mutation status in SCLC and EPSCC. STUDY DESIGN Mutation research. METHODS Thirty-seven SCLC and 15 EPSCC patients were included in the study. The pathological diagnoses were confirmed by a second pathologist. KRAS analysis was performed in our medical genetic department. DNA isolation was performed with primary tumor tissue using the QIAamp DNA FFPE Tissue kit (Qiagen; Hilden, Germany) in all patients. The therascreen KRAS Pyro Kit 24 V1 (Qiagen; Hilden, Germany) was used for KRAS analyses. RESULTS Thirty-four (91.9%) of the SCLC patients were male, while 11 (73.3%) of the EPSCC l patients were female. SCLC was more common in males, and EPSCC in females (p=0.001). A KRAS mutation was found in 6 (16.2%) if SCLC patients. The most common mutation was Q61R (CAA>CGA). Among the 15 EPSCC patients, 2 had a KRAS mutation (13.3%). When KRAS mutant and wild type patients were compared in the SCLC group, no difference was found for overall survival (p=0.6). CONCLUSION In previous studies, the incidence of KRAS mutation in SCLC was 1-3%; however, it was 16.2% in our study. Therefore, there may be ethnic and geographical differences in the KRAS mutations of SCLC. As a result, KRAS mutation should not be excluded in SCLC.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma.

BACKGROUND We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

A small cell carcinoma in the testis associated with testicular teratoma.

ture cyctic teratoma of the ovary. Pathol Int 1998;48:834-39. [CrossRef] 4. Abbosh PH, Zhang S, Maclennan GT. Germ cell origin of testicular carcinoid tumors. Clin Cancer Res 2008;14:1393-96. [CrossRef]

K-RAS and N-RAS mutations in testicular germ cell tumors

Testicular cancer is a relatively rare tumor type, accounting for approximately 1% of all cancers in men. However, among men aged between 15 and 40 years, testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell tumors (TGCTs) are classified as seminoma and non-seminoma. The RAS oncogene controls several cellular functions, including cell proliferation, apoptosis, migration, and differentiation. Thus, RAS signaling is important for normal germ cell development. Mutations of the Kirsten RAS (K-RAS) gene are present in over 20% of all cancers. RAS gene mutations have also been reported in TGCTs. We investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT patients. A total of 24 (55%) pure seminoma cases and 19 (45%) non-seminoma cases were included in the study. K-RAS and N-RAS analyses were performed in our molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen). In total, a RAS mutation was present in 12 patients (27%): 7 seminoma (29%) and 5 non-seminoma cases (26%) [p = 0.55]. A K-RAS mutation was present in 4 pure seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63], and an N-RAS mutation was observed in 4 seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: one with seminoma tumor and the other with non-seminoma tumor. To date, no approved targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS and N-RAS mutations in these tumors may provide more treatment options, especially in platinum-resistant tumors.

Increased dose single-agent gemcitabine in platinum-taxane resistant metastatic ovarian cancer.

Background In platinum-taxane resistant epithelial ovarian cancer (EOC), we aimed to determine the effectiveness. Patients and Methods Between 2004 and 2013, patients afflicted with platinum-taxane resistant EOC and who were administered a 30-minute i.v. infusion of single-agent gemcitabine at a dose of 1,250 mg/m2 on the 1st, 8th and 15th days, every 28 days, were examined retrospectively. Results Twenty-six patients with platinum-taxane resistant EOC were included in the study. The overall survival (OS) was 48 months. The median survival after becoming platinum-taxane resistant was 16 months for the study population. Median time to progression (TTP) and median survival after becoming platinum-taxane resistant for patients who received second-line treatment were 3.3 months and 16 months, respectively; for patients who received third-line treatment with gemcitabine, these were 3.7 months and 19 months, respectively. Administration of gemcitabine as second- and third-line chemotherapy in platinum-taxane resistant EOC, provides similar TTP and OS outcomes (p = 0.4, p = 0.9) with a similar response and toxicity rate. Conclusions Second- and third-line gemcitabine at a dose of 1,250 mg/m2 on days 1, 8 and 15 every 28 days as a 30-minute i.v. infusion in platinum-taxane resistant EOC is an effective treatment option with a tolerable and manageable toxicity.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma

ABSTRACT Aim: We examined impact of adjuvant treatment modalities in patients with curatively resected pancreatric adenocarcinoma (PAC). Methods: A total of 563 consecutive patients who were resected for PAC in 26 oncology centers were retrospectively analyzed between January 2003 and December 2013. Results: Of 563 patients, 472 received adjuvant treatment with chemotherapy alone (CT), chemoradiotherapy alone (CRT), and chemoradiotherapy with maintenance chemotherapy (CRT-CT) were analyzed. Of 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. Survival rates at 1st, 3rd, and 5th years were 70%, 23% and 16%, respectively. When CT and CRT-CT groups were compared, there was no difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT alone groups. To further investigate the impact of addition of radiation to chemotherapy on subgroups, patients were stratified according to lymph node status and resection margins, and then analyzed separately. When patients with positive lymph node disease were considered, both RFS (p = 0.004) and OS (p = 0.003) were significantly longer in CRT-CT group than CT group. In contrast, there was no difference between groups when patients with no metastatic lymph node disease or patients with or without positive surgical margins were considered. Conclusions: Although adjuvant chemotherapy is the standart treatment in curatively resected PAC, radiation should be a part of treatment at least in patients with positive lymph node disease. Disclosure: All authors have declared no conflicts of interest.