Ilhan Hacibekiroglu

Is sunitinib-induced hypothyroidism a predictive clinical marker for better response in metastatic renal cell carcinoma patients?

Background: The main goal of this study was to examine whether the occurrence of hypothyroidism during sunitinib therapy in patients with metastatic renal cell carcinoma (mRCC) is associated with a better outcome. Methods: The study enrolled 81 patients with pathologically proven mRCC who were treated with sunitinib between March 2008 and June 2013.Thyroid function evaluation comprised (free-thyroxine) FT4 and thyroid-stimulating hormone (TSH) before treatment and at day 1 of each 6-week cycle. Survival analysis was performed using the Kaplan–Meier method, and the differences among the groups were determined using the log-rank test. Results: Hypothyroidism occurred in 30 (37%) of 81 patients within a median 3 months (range 1–18) of treatment initiation. There was a statistically significant correlation between the occurrence of hypothyroidism during treatment and the rate of objective remission (ORR) (hypothyroid patients vs euthyroid patients: 46.7 vs 13.7%, respectively; P = 0.001). Median progression-free survival (PFS) was 10 (95% CI 6.13–13.8) months in the euthyroid patients, and 17 (95% CI 9.33–24.6) months in the hypothyroid patients (P = 0.001). The median overall survival (OS) was 39 (95% CI 25.4–52.5) months in the hypothyroid patients and 20 (95% CI 14.7–25.2) months in the euthyroid patients (P = 0.019). Conclusions: The occurrence of hypothyroidism during treatment in patients was significantly associated with longer PFS, OS and better ORR in the current study.

Is Late Recurrence a Predictive Clinical Marker for Better Sunitinib Response in Metastatic Renal Cell Carcinoma Patients

BACKGROUND We investigated the clinicopathological features in patients with recurrent renal cell carcinoma (RCC) within 5 years or more than 5 years after nephrectomy and determined predictors of overall survival (OS) and progression-free survival (PFS) after disease recurrence in the administration of first-line sunitinib in the treatment of metastatic RCC (mRCC). PATIENTS AND METHODS In this study we enrolled 86 Turkish patients with mRCC who received sunitinib. Univariate analyses were performed using the log rank test. RESULTS Fifty-six patients (65%) were diagnosed with disease recurrence within 5 years after radical nephrectomy (early recurrence) and 30 patients (35%) were diagnosed with recurrence more than 5 years after radical nephrectomy (late recurrence). Fuhrman grade was statistically significantly different between the 2 groups (P = .013). The late recurrence patients were significantly associated with the Memorial Sloan Kettering Cancer Center favorable risk group compared with patients with early recurrence (P = .001). There was a statistically significant correlation between recurrence time and the rate of objective remission (ORR) (the late recurrence group vs. the early recurrence group: 43.3% vs. 14.3%, respectively; P = .004). From the time of disease recurrence, the median OS was 42.0 (95% confidence interval [CI], 24.4-59.5) months in the late recurrence group, and 16 (95% CI, 11.5-20.4) months in the early recurrence group (P = .001). Median PFS was 8 (95% CI, 4.05-11.9) months in the early recurrence group, and 20 (95% CI, 14.8-25.1) months in the late recurrence group (P ≤ .001). CONCLUSION The study demonstrated a potential prognostic value of late recurrence in terms of PFS, OS, and ORR.

XELOX plus bevacizumab vs. FOLFIRI plus bevacizumab treatment for first-line chemotherapy in metastatic colon cancer: a retrospective study of the Anatolian Society of Medical Oncology.

BACKGROUND XELOX plus bevacizumab (XELOX-Bev) and FOLFIRI plus Bevacizumab (FOLFIRI - Bev) treatments are an effective strategies patients with metastatic colorectal cancer (mCRC).The aim of this study was to compare efficacy of first-line XELOX-Bev treatment vs FOLFIRI-Bev treatment for mCRC. MATERIALS AND METHODS A total of 409 patients with mCRC who received chemotherapy were included and divided into 2 groups. Group 1 (n=298) received XELOX-Bev and Group 2 (n=111) FOLFIRI-Bev. Comparisons were made in terms of overall (OS) and progression-free (PFS) survival, response rate (RR), and grade 3-4 toxicity. RESULTS Median follow-up was 11 months in Group 1 and 15 months for Group 2. Complete remission was observed in 29 (9.7%) and 2 (1.8%) patients, partial remission in 139 (46.6%) and 27 (24.5%) , stable disease in 88 (29.5%) and 49 (44.1%) and progressive disease in 42 (14.1%) and 33 (30.0%) patients in Group 1 and 2, respectively. Median OS was 25 months (range 2-57 months, 95%CI; 22.2-27.7) for Group 1 and 20 months (range 1-67 months, 95%CI; 16.8-23.1) for Group 2 (p=0.036). Median PFS was 9.6 months (range 2-36 months, 95%CI; 8.8-10.4) for Group 1 and 9 months (range 1-44 months, 95%CI; 7.4-10.5) for Group 2 (p=0.019). Objective RR was 56.4% in Group 1 and 26.1% in Group 2 (p<0.001). CONCLUSIONS First-line XELOX-Bev is more effective with a better response rate, prolongation of median PFS/OS, and a superior safety profile compared with FOLFIRI-Bev.

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.

Prognostic factors of patients who received chemotherapy after cranial irradiation for non-small cell lung cancer with brain metastases: A retrospective analysis of multicenter study (Anatolian Society of Medical Oncology)

Purpose: Almost half of all patients diagnosed with non-small cell lung cancer (NSCLC) have distant metastases at presentation. One-third of patients with NSCLC will have brain metastases. Without effective treatment, the median survival is only 1 month. However, it is difficult to treat brain metastases with systemic chemotherapy since the agents have difficulty crossing the blood-brain barrier. Therefore, it is important to estimate the patients survival prognosis. The aim of this study was to analyze prognostic factors for survival in Turkish patients who received chemotherapy after cranial irradiation for NSCLC with brain metastases. Methods: We retrospectively reviewed 698 patients with brain metastases resulting from NSCLC. Ten potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with overall survival (OS). Results: Among the 10 variables for univariate analysis, six were identified to have prognostic significance; these included sex, smoking history, histology, number of brain metastases, extracranial metastases, and neurosurgical resection. Multivariate analysis by the Cox proportional hazard model showed that a smoking history, extracranial metastases, and neurosurgical resection were independent negative prognostic factors for OS. Conclusion: Smoking history, extracranial metastases, and neurosurgical resection were considered independent negative prognostic factors for OS. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for more appropriate treatment options.

Comparison of survival with somatostatin analog and chemotherapy and prognostic factors for treatment in 165 advanced neuroendocrine tumor patients with Ki-67 20% or less.

The objectives of this study were to compare progression-free survival (PFS) with somatostatin analog (SSA) versus chemotherapy (CTx) in first-line therapy and to determine the patient group in which these treatments were more effective in neuroendocrine tumors (NETs) with a Ki-67 index of 20% or less. Patients who received SSA or CTx and had unresectable locally advanced and metastatic NETs with a Ki-67 index of 20% or less were retrospectively selected from 13 centers in the Turkish database between 2000 and 2015. One hundred and sixty-five patients were enrolled. The median age was 56 years and the male-to-female ratio was 1.09. Seventy-four (45%) patients were of grade 1 NET and 91 (55%) were of grade 2. SSA was given to 104 patients, whereas 61 were treated with CTx. The objective response rate after SSA was 15.4%; another 73.1% had stable disease. The objective response rate after CTx was 36.1%, and 40.9% had stable disease (P=0.008). The median PFS in SSA patients was 21 months (95% confidence interval: 12.4–29.6), and 8 months for CTx (95% confidence interval: 5.5–10.6) (P<0.001). There was no significant difference between PFS of receiving SSA and CTx in pancreatic neuroendocrine tumor (PNET) patients; however, the PFS of receiving SSA was longer in non-PNET patients (P<0.001). SSA was better treatment in advanced NET patients with a Ki-67 index of less than 5%, having a primary resected and a performance status of 0 (P<0.05). SSA may be preferred over CTx in advanced NET patients with low-to-intermediate grade.

A rare cause in etiology of left atrial mass: metastatic testicular germ cell tumor.

Although intracardiac metastasis of germ cell tumors is rare, it can be localized in the right or left heart by disseminating spread and give their cardiac symptoms depending on the location of metastatic mass. We present a 38-year-old male patient with a preliminary diagnosis of testicular tumor who was followed by the medical oncology clinic with cerebrovascular event and heart failure symptoms.