The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study.

PURPOSE: We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC). METHODS: Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times. RESULTS: Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS (p = 0.079, and p = 0.147, respectively). Among grade 1-2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1-2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3-4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups (p = 0.063, and p = 0.210, respectively). CONCLUSION: In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.

Outcomes of surveillance versus adjuvant chemotherapy for patients with stage IA and IB nonseminomatous testicular germ cell tumors.

BACKGROUND: Currently, it is accepted that risk assessment of clinical stage I (CS I) nonseminomatous germ cell tumors (NSGCT) patient is mainly dependent on the presence of lymphovascular invasion (LVI). Initial active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection (RPLND) are acceptable treatment options for these patients, but there is no uniform consensus. The purpose of this study was to compare outcomes of active surveillance with adjuvant chemotherapy. METHODS: A total of 201 patients with CS I NSGCT after orchiectomy were included. Outcomes of active surveillance and adjuvant chemotherapy were retrospectively analyzed. The prognostic significance of risk factors for survival and relapse was evaluated. RESULTS: Of the 201 patients, 110 (54.7%) received adjuvant chemotherapy, while the remaining 91 patients (45.3%) underwent surveillance. Relapses were significantly higher for patients underwent surveillance compared to adjuvant chemotherapy group (18.3 vs. 1.2%, p < 0.001). The 5-year relapse-free survival (RFS) rate for patients who were treated with adjuvant chemotherapy was significantly better than those of patients underwent surveillance (97.6 vs. 80.8%, respectively; p < 0.001). Univariate analysis showed that the presence of LVI (p = 0.01) and treatment option (p < 0.001) were prognostic factors for RFS and pT stage (p = 0.004) and invasion of rete testis (p = 0.004) and the presence of relapse (p < 0.001) were significant prognostic factors for OS. Multivariate analysis revealed that the treatment strategy was an independent prognostic factor for RFS (p < 0.001, HR 0.54). A logistic regression analysis demonstrated that treatment options (p = 0.031), embryonal carcinoma (EC) >50% (p = 0.013) and tumor diameter (p = 0.016) were found to be independent factors for predicting relapse. CONCLUSIONS: Our results indicate that adjuvant chemotherapy is associated with improved RFS compared with surveillance for CS I NSGCT patients. Moreover, the treatment strategy is an important prognostic indicator for RFS and a predictive factor for relapse. Although adjuvant chemotherapy seems to be a suitable treatment for patients with risk factors for relapse, surveillance is still preferred management option.

Treatment preferences in stage IA and IB testicular seminoma: multicenter study of Anatolian Society of Medical Oncology.

BACKGROUND: Approximately 75 % of patients with testicular seminoma present with stage I disease, and the probability of long-term survival approaches 100 %. However, the standard adjuvant treatment for stage I seminoma patients remains controversial, and there is no uniform consensus in the literature. The present study was performed to evaluate treatment preference and outcomes for men with stage I testicular seminoma. MATERIALS AND METHODS: From 1997 to 2013, 282 patients with histologically confirmed stage IA and IB testicular seminoma who underwent orchiectomy were included. The outcomes of three management options and survivals were retrospectively analyzed. The prognostic significance of risk factors for relapse on survival was evaluated by univariate and multivariate analysis; in addition, the factors predicting relapse were also evaluated by logistic regression analysis. RESULTS: Of the 282 patients with stage I seminoma, 130 (46.1) received adjuvant radiotherapy (RT), 80 (28.4 %) were treated with adjuvant carboplatin, while the remaining 72 patients (25.5 %) underwent surveillance. At the time of analysis, the median follow-up period of 38.5 months; relapses were observed in 16 patients (22.3 %) on surveillance, in one patient (1.2 %) treated with adjuvant carboplatin and in ten patients (%7.7) who received adjuvant RT. The 5-year disease-free survival (DFS) rate for patients who underwent surveillance was worse than those of patients treated with adjuvant carboplatin and RT (64.2 vs. 97.7 vs. 91.9 %, respectively; p < 0.001). However, the 5-year overall survival (OS) rate for patients on surveillance was similar compared with the adjuvant treatment groups (100 vs. 92.3 vs. 97.4 %, respectively; p = 0.44). Univariate analysis showed that only the treatment approach (surveillance vs. adjuvant carboplatin vs. adjuvant RT) for DFS (p < 0.001), invasion of the rete testis (p = 0.041) and the presence of relapse (p < 0.001) for OS were important prognostic indicators. Multivariate analysis indicated that the treatment strategy for DFS (p < 0.001, HR 0.34) was an independent prognostic factor. Furthermore, a logistic regression analysis showed that adjuvant treatment was found to be an independent factor for predicting relapse (p = 0.004, odds ratio: 0.39). CONCLUSIONS: Our results indicate that adjuvant treatment with carboplatin or RT is associated with improved DFS compared with surveillance for men with stage I testicular seminoma after orchiectomy. Moreover, the treatment strategy is an important prognostic indicator for DFS and a predictive factor for relapse. Although adjuvant treatment, especially carboplatin, seems to be a suitable treatment for patients with risk factors for relapse, surveillance is still feasible and the preferred management option after radical orchiectomy in men with stage I seminoma. More reliable predictive factors are needed to make treatment decisions.

Primary Tumor Resection Offers Higher Survival Advantage in KRAS Mutant Metastatic Colorectal Cancer Patients.

BACKGROUND/AIMS: Colorectal cancer is the fourth most common cancer diagnosed in the United States, and the third most common cause of death from cancer. Approximately 20% of the patients with colorectal cancer have distant metastasis during diagnosis. Primary tumor resection is controversial in unresectable metastatic colorectal cancer (CRC). We studied the survival effect of primary tumor resection in unresectable metastatic CRC according to kirsten ras (KRAS) mutation status. METHODOLOGY: Seventy eight CRC cases with unresectable metastasis were included in the study. The KRAS status was known in all patients. 34 patients had undergone primary tumor resection before 1st chemotherapy. RESULTS: ThE median time from primary tumor resection to first chemotherapy was 6 (3-17) weeks. The survival was better in the unresectable metastatic colon patients with resected primary tumor, but it was statistically non-significant (P = 0.07). The median OS was similar (P = 0.91) in the KRAS wild patients with or without primary tumor resection. The median OS was 28 months in KRAS mutant patients with primary tumor resection, 14 months in KRAS mutant patients without primary tumor resection (P = 0.002). CONCLUSION: Primary tumor resection offers survival advantage in KRAS mutant patients, but randomized prospective studies are required.

Importance of Ki-67 in human epidermal growth factor receptor 2 positive breast cancer.

PURPOSE: The aim of this study was to evaluate the importance of Ki-67 in Human Epidermal Growth Factor Receptor 2 (Her-2) positive breast cancer patients. METHODS: We reviewed the records of patients diagnosed with Her-2-positive non-metastatic breast cancer between 2005 and 2011. Paraffin-embedded tissue samples were stained with MIB-1 mouse monoclonal antibody to find Ki-67 levels. Patients were grouped as low Ki-67<20% and high Ki-67≥20%. Demographic and clinical features were compared. RESULTS: One hundred and six patients were included in the study. Median follow up time was 41 months (range 15-100). Median age was 49.5 years (range 29-79). Twenty-nine patients (27.4%) were in the Ki-67 low group. Demographic features were similar in both groups. Lymphovas cular invasion was more frequent in the Ki-67 high group, and hormone receptor (HR) positivity was more frequent in the Ki-67 low group (p=0.03, p=0.03, respectively). Recurrence rate was not significantly different in both groups (p=0.36). T stage (p=0.02), stage (p<0.01), lymphovascular invasion (p=0.02), ER status (p=0.02), and HR status (p<0.01) were related with recurrence. In multivariate analysis, stage and HR negativity were independent factors for recurrence (p<0.01, p=0.01, respectively). Recurrence sites were also similar in both groups. Survival rates at the third year for Ki-67 low group and Ki-67 high group were 94% and 92%, respectively. CONCLUSION: Her-2 positive patients with low Ki-67 and high Ki-67 had similar demographic and pathologic features except lymphovascular invasion and HR status. HR status was an important factor for disease course. Clinical course was determined by HR status rather than Ki-67.

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.

Incidence of contrast-induced nephropathy in hospitalised patients with cancer.

OBJECTIVES: To determine the frequency of and possible factors related to contrast-induced nephropathy (CIN) in hospitalised patients with cancer. METHODS: Ninety adult patients were enrolled. Patients with risk factors for acute renal failure were excluded. Blood samples were examined the day before contrast-enhanced computed tomography (CT) and serially for 3 days thereafter. CIN was defined as an increase in serum creatinine (Cr) of 0.5 mg/dl or more, or elevation of Cr to 25 % over baseline. Relationships between CIN and possible risk factors were investigated. RESULTS: CIN was detected in 18/90 (20 %) patients. CIN developed in 25.5 % patients who underwent chemotherapy and in 11 % patients who did not (P = 0.1). CIN more frequently developed in patients who had undergone CT within 45 days after the last chemotherapy (P = 0.005); it was also an independent risk factor (P = 0.017). CIN was significantly more after treatment with bevacizumab/irinotecan (P = 0.021) and in patients with hypertension (P = 0.044). CONCLUSIONS: The incidence of CIN after CT in hospitalised oncological patients was 20 %. CIN developed 4.5-times more frequently in patients with cancer who had undergone recent chemotherapy. Hypertension and the combination of bevacizumab/irinotecan may be additional risk factors for CIN development. KEY POINTS: • Contrast-induced nephropathy (CIN) is a concern for oncological patients undergoing CT. • CIN occurs more often when CT is performed <45 days after chemotherapy. • Hypertension and treatment with bevacizumab appear to be additional risk factors.

Performance status is an important prognostic factor in second line treatment of pancreaticobiliary adenocarcinoma.

BACKGROUND/AIMS: To define the factors related with disease control and survival in patients with pancreaticobiliary adenocarcinoma treated with second-line therapy. METHODOLOGY: We retropectively reviewed the data of 39 pancreaticobiliary adenocarcinoma patients treated with second-line chemotherapy between 2000 and 2012. Age, gender, origin of tumor, location of tumor, stage at diagnosis, Eastern Cooperative Oncology Group (ECOG) performance status, progression site, progression free survival (PFS) for first-line therapy, disease control at first-line therapy and chemotherapy protocols are analyzed for disease control rate, PFS and overall survival (OS). RESULTS: Disease control was recorded in 21 (53.8%) patients (20 stable disease, 1 partial response). Disease control rate was higher in patients with good performance status (p=0.03). Disease control at first-line therapy was not a predictor of disease control at second-line (p=0.6). Response to first-line therapy and other prognostic factors was not related with disease control. Progression free survival and OS was significantly longer in patients with good ECOG performance status (0-1) (p=0.01, p=0.006). Choice of chemotherapy (single agent or combination) and other factors did not have any impact on PFS and OS. In multivariate analysis; disease control was independent prognostic factor for both PFS and OS (p<0.001), (p<0.001). CONCLUSIONS: Disease control and performance status are two important prognostic factors. Chemotherapy regimen has no impact on disease control and survival. Salvage chemotherapy can be considered for patients with good performance status whether they are resistant to first-line therapy or not.

Major and minor salivary gland cancers: A multicenter retrospective study.

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.

Clinical features of the patient with multiple primary tumors: Single center experience.

OBJECTIVE: Multiple primary tumors are the ones that develop in the same patient at the same or different times. They are usually examined under two groups. If the second tumor is diagnosed 6 months after the first tumor is diagnosed, it is named as metachronous tumor. If it is diagnosed in 6 months after the first diagnosis, it is called as synchronous tumor. The malignancy of tumors should be proved histologically. At least 2 cm of solid tissue should be present between two tumors. If they are at localized at the same place, a gap of at least 5 years should be present between them. Metastatic disease should be eliminated. This study aimedto review the clinical, demographic, and pathological features of multiple primary tumors, detect the prevalence, compare the results with literature findings, and evaluate and improve the approach to multiple primary tumors. METHODS: A total of 170 patients diagnosed with multiple primary tumors were included in this study. Patient data were obtained from pathology and medical reports of the patients. RESULTS: Most of the multiple primary tumors were metachronous. The number of male patients was more than that of female patients. The median time between double tumors was 3 monthsforsynchronous tumorsand 26 months for metachronous tumors. Synchronous tumors with the highest prevalence of comorbidity were lung-larynx and lung-colon, whereas metachronous tumors with the highest prevalence of comorbidity were lung-bladder, lung-larynx, breast-endometrium, and breast-colon. The history of smoking and alcohol was found to be higher in male patients andsynchronous tumors. CONCLUSION: The detection of the first tumor in the metastatic stage and an accompanying synchronous secondary tumor was found to be a poor prognostic factor. The treatment of the first tumor, smoking, squamous cell histology, and male gender were among the other factors negatively affecting survival, although they were not statistically significant.

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.

Transcatheter closure of ventricular septal defects using the Amplatzer Duct Occluder II device: a single-center experience.

INTRODUCTION: Off-label use of different devices has been described for percutaneous closure of ventricular septal defects (VSD) because of the unacceptable rate of post-procedure heart block associated with special VSD devices. AIM: To describe the early single-center clinical experience with closure of a VSD using the Amplatzer Duct Occluder II (ADO II) device in children. MATERIAL AND METHODS: Between May 2013 and June 2015, 26 patients between 13 days and 16 years of age underwent percutaneous closure of a VSD with an ADO II device at our institute. The decision to use the ADO II device was based primarily on lower risk of total atrioventricular block (TAVB) after VSD closure reported in the literature, reduction of the cost of the procedure and the need to close symptomatic VSDs in young patients. RESULTS: The location of the VSD was perimembranous in 21 patients, postsurgical residual in 2, midmuscular in 2 and apical muscular in 1. Complex procedures including newborn, combined procedures and postsurgical residual VSD were performed in 5 (19%) patients. The median duration of follow-up was 12 months. The complete VSD closure rate was 81% immediately after the procedure, 85% at 24 h, and 93% at the last follow-up. There was no device embolization. During the entire follow-up period, TAVB did not develop. CONCLUSIONS: The ADO II constitutes a safe and effective therapeutic alternative for morphologically varied VSDs in all pediatric age groups. A larger range of sizes and configurations of this occluder may be required to successfully occlude a wider range of VSDs.

Post progression survival analysis of metastatic gastric and gastroesophageal junction cancer patients after second-line treatment.

PURPOSE: The aim of this study was to define the factors that -affect response and post-progression survival of metastatic gastric cancer (MGC) and gastroesophageal junction cancer (GEJ) -patients treated with second-line chemotherapy. METHODS: We retrospectively reviewed the data of 59 patients with MGC or GEJ adenocarcinoma who received second-line treatment. RESULTS: The median age was 54 years old (26-77). Response to second-line treatment was strongly associated with disease control with first-line treatment (p < 0.01). Median progression-free survival (PFS), overall survival (OS) and post-progression survival (PPS) were 3.2 (95% CI : 2.63-3.80), 6.5 (95% CI : 3.78-9.35) and 2.7 months (95% CI : 1.89-3.68), respectively. PFS (r = 0.55, p < 0.01) and PPS (r = 0.89, p < 0.01) were correlated with OS. Response to second-line treatment was independently related to PFS (HR : 0.12 95%CI : 0.53-0.26, p < 0.001). Having an ECOG 0 performance status (HR : 0.42 ; 95%CI : 0.21-0.86, p = 0.02) and response to second-line therapy (HR : 0.47 ; 95%CI : 0.25-0.85, p = 0.01) were independently associated with OS. CONCLUSION: PPS and PFS were correlated with OS after second-line treatment of MGC. Response to second-line treatment prolonged OS by increasing PFS, and having an ECOG 0 PS prolonged OS by increasing PPS.

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.

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 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.

Predictive and Prognostic Factors in Ovarian and Uterine Carcinosarcomas.

BACKGROUND: Prognostic factors and the standard treatment approach for gynaecological carcinosarcomas have not yet been clearly defined. Although carcinosarcomas are more aggressive than pure epithelial tumours, they are treated similarly. Serous/clear cell and endometrioid components may be predictive factors for the efficacy of adjuvant chemotherapy (CT) or radiotherapy (RT) or RT in patients with uterine and ovarian carcinosarcomas. Heterologous carcinosarcomas may benefit more from adjuvant CT. AIMS: We aimed to define the prognostic and predictive factors associated with treatment options in ovarian (OCS) and uterine carcinosarcoma (UCS). STUDY DESIGN: Retrospective cross-sectional study. METHODS: We retrospectively reviewed the medical records of patients with ovarian and uterine carcinosarcoma from 2000 to 2013, and 127 women were included in this study (24 ovarian and 103 uterine). Patients admitted to seventeen oncology centres in Turkey between 2000 and December 2013 with a histologically proven diagnosis of uterine carcinosarcoma with FIGO 2009 stage I-III and patients with sufficient data obtained from well-kept medical records were included in this study. Stage IV tumours were excluded. The patient records were retrospectively reviewed. Data from 104 patients were evaluated for this study. RESULTS: Age (≥70 years) was a poor prognostic factor for UCS (p=0.036). Pelvic±para aortic lymph node dissection did not affect overall survival (OS) (p=0.35). Macroscopic residual disease was related with OS (p<0.01). The median OS was significantly longer in stage I-II patients than stage III patients (p=0.03). Adjuvant treatment improved OS (p=0.013). Adjuvant radiotherapy tended to increase the median OS (p=0.075). However, this tendency was observed in UCS (p=0.08) rather than OCS (p=0.6).Adjuvant chemotherapy had no effect on OS (p=0.15).Adjuvant radiotherapy significantly prolonged the median OS in patients with endometrioid component (p=0.034). A serous/clear cell component was a negative prognostic factor (p=0.035). Patients with serous/clear cell histology for whom adjuvant chemotherapy was applied had significantly longer OS (p=0.019), and there was no beneficial effect of adjuvant radiotherapy (p=0.4). Adjuvant chemotherapy was effective in heterologous tumours (p=0.026). In multivariate analysis, the stage and chemotherapy were prognostic factors for all patients. Age was an independent prognostic factor for UCS. However, serous/clear cell histology and radiotherapy tended to be significant prognostic factors. CONCLUSION: The primary location, the histological type of sarcomatous and the epithelial component may be predictive factors for the efficacy of chemotherapy or radiotherapy in UCS and OCS.

Comparative analysis of the efficacy and safety of modified FOLFOX-6 and DCF regimens as first-line treatment in advanced gastric cancer.

The aim of this study was to retrospectively compare the efficacy and toxicity of the oxaliplatin + 5-fluorouracil (5-FU) + leucovorin (LV) regimen [modified (m)FOLFOX-6] with that of the docetaxel + cisplatin + 5-FU regimen (DCF) in patients with advanced gastric cancer (AGC). A total of 72 patients received DCF (75 mg/m2 docetaxel and 75 mg/m2 cisplatin on day 1 and 750 mg/m2 5-FU on days 1-5) every 21 days, whereas 54 patients received mFOLFOX-6 (85 mg/m2 oxaliplatin and 400 mg/m2 LV as a 2-h infusion, followed by a 5-FU bolus of 400 mg/m2 and 2,400 mg/m2 5-FU as a 46-h continuous infusion) every 14 days. In the DCF arm, 55 (76.4%) of the patients received prophylactic granulocyte colony-stimulating factor (G-CSF), 48-72 h following completion of chemotherapy. The median follow-up of the study was 12.1 months. The overall response rate (ORR) was 37.0% for mFOLFOX-6 and 40.3% for DCF (P=0.72). The median time to progression was 6.5 and 6.2 months in the mFOLFOX-6 and DCF arms, respectively (P=0.70). The median overall survival was 11.4 and 13.5 months in the mFOLFOX-6 and DCF arms, respectively (P=0.72). The rates of hematological toxicity did not differ between the two arms. However, in the subgroup analysis, grade 3-4 neutropenia and febrile neutropenia were significantly more common among patients who had not received G-CSF prophylaxis in the DCF arm. The incidence of grade 3-4 nausea/vomiting and diarrhea were significantly higher in the DCF arm. In conclusion, the present study demonstrated that the efficacy of the mFOLFOX-6 regimen was comparable to that of the DCF regimen in AGC patients. In addition, the benefit of G-CSF prophylaxis in conjunction with the DCF regimen was demonstrated.

Association between specific KRAS mutations and the clinicopathological characteristics of colorectal tumors.

The aim of this study was to investigate the clinicopathological characteristics and distribution by tumor localization of KRAS point mutations in metastatic colorectal cancer. A total of 189 patients diagnosed with colorectal cancer between 2007 and 2014, who were either metastatic at the time of diagnosis or developed metastasis subsequently, were included in this study. KRAS mutation analysis was performed in the primary tumor tissues and KRAS mutations were identified in 47.6% of the patients. There was a high frequency of the p.G13D point mutation in left-colon tumors (P=0.011), while the p.G12D point mutation was more frequent in right-colon tumors (P=0.004). KRAS wild-type frequency (P=0.02) was higher among patients aged <40 years. A comparison of codon 12 and 13 mutations revealed that codon 12 mutations were more common in the >50-year-old group (P=0.03) and codon 13 mutations were more common in the <70-year-old group (P=0.04). KRAS wild-type tumors were localized in the right colon (P=0.005) and tumors with the p.G13D point mutation (P=0.018) were diagnosed at non-metastatic stages. In conclusion, KRAS point mutations in colorectal cancer exhibited a heterogeneous distribution in terms of tumor localization. In addition, the p.G13D point mutation was found to differ from other mutations in several aspects.

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.