Ibrahim Yildiz

Noncutaneous Melanoma Have Distinct Features from Each Other and Cutaneous Melanoma

Objective: Compared to the cutaneous melanoma, noncutaneous melanomas are relatively rare and have a distinct pattern of behavior. We performed this study to define the clinical characteristics and outcomes of patients with noncutaneous melanomas and emphasize how they differ from cutaneous melanomas. Methods: 216 patients who were diagnosed with noncutaneous melanoma were assessed and their medical records between 2000 and 2010 were retrieved from the cancer registry. 475 patients with cutaneous melanoma were used for comparison. Results: Of the 216 noncutaneous melanoma patients, 83 had mucosal melanoma, 101 had ocular melanoma and 32 had unknown primaries. For mucosal melanoma, the head and neck was the most common anatomic site (53%), followed by the gastrointestinal tract (37%), female genital (6%) and urinary tract (4%). The majority of the ocular melanomas (94%) originated in the uvea. 32 patients demonstrated a primary unknown disease with regional metastasis as the dominant behavior (72%). Age was found to be statistically significantly different among melanoma patients (p < 0.001). Younger patients had more cutaneous and unknown primary melanomas, whereas older patients had more ocular and mucosal melanoma. In subset analyses, we found significant differences between cutaneous and ocular (p = 0.038) or mucosal (p < 0.001) melanomas. The ratios of metastasis on admission were higher in patients with mucosal (27.7%) and unknown primary (28.1%) melanomas, and lower for ocular (3%) melanomas (p < 0.001). Patients with cutaneous melanoma had an intermediate (12%) ratio. Patients with ocular melanoma had better outcome than patients with other melanoma sites (p < 0.05). While overall survival for cutaneous melanoma was significantly negatively correlated with male gender (p < 0.001), advanced stages (p < 0.001) and old age (p = 0.005), stage IV disease was the only independent prognostic factor in patients with ocular melanoma (p = 0.006). No prognostic factor for outcome was found for either mucosal or unknown primary melanomas. Conclusion: The clinical presentations and prognoses of different primary sites of melanoma are distinctive. Therefore, approaches to these melanomas should be different.

Response Rates and Adverse Effects of Continuous Once-daily Sunitinib in Patients with Advanced Renal Cell Carcinoma: A Single-center Study in Turkey

OBJECTIVE Therapy targeted against the vascular endothelial growth factor pathway is a standard of care for patients with metastatic renal cell carcinoma. This study assessed the response rates and toxicity profiles of sunitinib on a continuous once-daily dosing regimen in Turkish patients with metastatic renal cell carcinoma. METHODS Between April 2006 and August 2010, 74 patients with metastatic renal cell carcinoma who received sunitinib on a continuous, once-daily dosing regimen were included. Sunitinib was administered daily at a dose of either 37.5 mg (94% of the patients) or 25 mg (6% of the patients), without interruption, either as a second-line treatment after interferon-α or as a first-line treatment. Response, toxicity, progression-free survival and overall survival were evaluated. RESULTS Of the 74 patients, 65 (88%) were diagnosed with clear cell renal cell carcinoma. The median treatment duration was 10 months (range, 2-42 months). The most common treatment-related adverse events were fatigue (75%), stomatitis (51%) and hypertension (50%). The most common Grade 3 or 4 adverse events were anemia (10%) and hand-foot syndrome (7%). Dose reductions were required in 50% of the patients, and early treatment discontinuation was necessary in 16% of the patients. Cardiovascular events were the most common adverse events that resulted in drug discontinuation. The objective response rate and the disease control rate were 30 and 78%, respectively. The median progression-free survival and overall survival were 13 and 25 months, respectively. CONCLUSIONS Continuous, once-daily administration of sunitinib was generally well tolerated in Turkish patients with advanced renal cell carcinoma in a daily practice setting. This studys response rates were comparable to those in previous randomized trials.

Prognostic factors in metastatic pancreatic cancer: Older patients are associated with reduced overall survival

Pancreatic cancer is a major health concern worldwide and, despite the attempts at management, the prognosis of patients with metastatic pancreatic cancer remains poor, with a median survival of a few months. The aim of this study was to identify and evaluate clinicopathological factors and elucidate the clinical significance of patient age for the outcome of metastatic pancreatic cancer. Data from a total of 154 metastatic patients with a histologically confirmed diagnosis of pancreatic cancer, who were treated and followed-up in our clinic, were recorded from medical charts. The patient sample included 102 (66%) males with a median age of 58 years (range, 25–88 years). The majority of the patients had a poor performance status (64%), weight loss of >10% body weight (74%), tumor size of >3 cm (75%) and elevated tumor markers, including carcinoembryonic antigen (CEA) (66%) and carbohydrate antigen 19-9 (CA19-9) (85%). The distributions of prognostic factors depending on patient age were largely identical. The median survival time of patients with metastatic disease was 179 days and the 1-year survival rate was 7%. The median survival time of elderly patients was significantly lower compared to younger patients (148 vs. 198 days, respectively; P=0.039). The 1-year survival rates in elderly and younger patients were 3 and 10%, respectively. In the univariate and multivariate analyses, elderly patients had poorer outcomes compared with younger patients (P=0.04 and 0.05, respectively). In all patients, the univariate analysis demonstrated that similar prognostic factors, including the performance status of the patients and tumor markers, such as serum CEA and CA19-9 levels, were associated with survival. In the multivariate analysis, younger patients with a poor performance status had a significantly shorter overall survival compared to those with a good performance status (P=0.008). However, no significant prognostic factor affecting the outcome was identified in the elderly patients. In conclusion, patient age is a major prognostic factor affecting the survival of patients with metastatic pancreatic cancer and elderly patients without poor prognostic factors may be eligible for the available treatment options.

Prognostic factors associated with the response to sunitinib in patients with metastatic renal cell carcinoma.

OBJECTIVE We investigated the prognostic clinicopathologic factors associated with overall survival (os) and progression-free survival (pfs) in the once-daily continuous administration of first-line sunitinib in a consecutive cohort of Turkish patients with metastatic renal cell carcinoma (rcc). METHODS The study enrolled 77 Turkish patients with metastatic rcc who received sunitinib in a continuous once-daily dosing regimen between April 2006 and April 2011. Univariate analyses were performed using the log-rank test. RESULTS Median follow-up was 18.5 months. In univariate analyses, poor pfs and os were associated with 4 of the 5 factors in the Memorial Sloan-Kettering Cancer Center (mskcc) score: Eastern Cooperative Oncology Group performance status of 2 or higher, low hemoglobin, high corrected serum calcium, and high lactate dehydrogenase. In addition to those factors, hypoalbuminemia, more than 2 metastatic sites, liver metastasis, non-clear cell histology, and the presence of sarcomatoid features on pathology were also associated with poor pfs; and male sex, hypoalbuminemia, prior radiotherapy, more than 2 metastatic sites, lung metastasis, nuclear grade of 3 or 4 for the primary tumour, and the presence of sarcomatoid features were also associated with poorer os. The application of the mskcc model distinctly separated the pfs and os curves (p < 0.001). CONCLUSIONS Our study identified prognostic factors for pfs and os with the use sunitinib as first-line metastatic rcc therapy and confirmed that the mskcc model still appears to be valid for predicting survival in metastatic rcc in the era of molecular targeted therapy.

Serum M65 as a biomarker for metastatic renal cell carcinoma.

INTRODUCTION/BACKGROUND Effective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently need in metastatic RCC. M30 and M65 are released during apoptotic cell death and precisely reflect epithelial tumor cell death. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates for patients with metastatic RCC. PATIENTS AND METHODS Thirty-nine patients with metastatic RCC and 39 healthy control subjects were included in this study. Serum M30 and M65 levels were measured by ELISA. RESULTS The median ages of the patients and control subjects were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and control subjects (53.7 vs. 49.1 U/L; P = .31). The median serum M65 level was significantly higher in patients than in control subjects (334.0 vs. 179.1 U/L; P < .001). Receiver operating characteristic analysis revealed that the best cutoff value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/L. The median PFS of patients whose M65 levels were ≤ 313.6 U/L was better than that of patients whose M65 levels were > 313.6 U/L (P = .03). CONCLUSION To the best of our knowledge, this is the first study to evaluate serum M30 and M65 levels in patients with RCC. Serum M65 levels were significantly elevated in patients with metastatic RCC compared with healthy individuals. In addition, the serum M65 level could be predictive of PFS in patients with RCC.

Clinical significance of serum M30 and M65 levels in metastatic pancreatic adenocarcinoma

M30 and M65 are relatively new assays that detect different circulating forms of the epithelial cell structural protein cytokeratin 18. This study was conducted to investigate the serum levels of M30 and M65 in patients with metastatic pancreatic adenocarcinoma (MPA) and the relationship with tumor progression and known prognostic parameters. Twenty-six patients with MPA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum M30 and M65 levels were determined using enzyme-linked immunosorbent assay. The median age at diagnosis was 59 years, range 32–80 years; 14 patients were men. All patients had metastatic stage, and most (n = 21, 81 %) had hepatic metastasis. The baseline levels of both serum M30 and serum M65 were significantly higher in patients with MPA than those in the control group (p < 0.001, for both assays). Serum M65 level was only significantly higher in the patients with elevated serum LDH levels than in others with normal serum LDH levels (p = 0.03). For serum M30 levels, no correlation was found. The significant relationship was found between the serum levels of M30 and M65 (rs = 0. 926, n = 26, p < 0.001, Spearman’s correlation). The median survival for all patients was 31.7 ± 2.2 weeks (95 % CI = 27.31–36.08). Although only the serum LDH level was found to be a significant prognostic factor (p = 0.01), neither serum M30 nor serum M65 had significant effect on survival (p = 0.28 and p = 0.15, respectively). In conclusion, although both serum levels of M30 and M65 assays were found to be of diagnostic value, no predictive and prognostic values were determined in MPA patients.

The Behavior of Turkish Cancer Patients in Fasting During the Holy Month of Ramadan

OBJECTIVE Fasting during the holy month of Ramadan is one of the major obligations for all adult Muslims. We performed a survey of Turkish Muslim cancer patients to examine the extent of their fasting status and to compare various clinical characteristics of fasting and non-fasting cancer patients during the month of Ramadan. METHODS This study was conducted on 701 adult cancer patients who attended ambulatory patient care units answered the questionnaires. RESULTS The population comprised 445 women (63.5%), and the median age was 54 years. Before diagnosis of cancer, 93.1% of the patients used fast consists of completely (78.3%) and partial (14.8%). However, 15% of cases were fasting on the day of interview, either partially (7.4%) or completely (7.6%) with equal distributions. Patients who were females, those with good performance status, those without any comorbid disease, who had non-metastatic disease, those with history of surgery, those treated with radiotherapy and those being treated with oral chemotherapeutic agents were more likely to be fasting than others. The fasting ones had more prevalent among patients with lymphoma, urogenital cancer and breast cancer; conversely, the rate of fasting status among patients with lung and gastrointestinal cancer was quite low. Only 20.8% of all patients asked their physician whether it was alright for them to fast and physicians generally had a negative attitude towards fasting (83.2%). CONCLUSIONS Majority of cancer patients are not fasting during the month of Ramadan, and a small part of patients consult this situation to their physician.

Intolerance to Sunitinib Treatment in Hemodialysis Patients With Metastatic Renal Cell Carcinoma

Sunitinib is a multiple tyrosine kinase receptor inhibitor that is approved for the treatment of metastatic renal cell carcinoma (RCC). However, neither an appropriate dose nor dosing schedule of sunitinib has yet been established for patients with metastatic RCC who are on hemodialysis. Here, we report on two hemodialysis patients who received sunitinib to treat metastatic RCC. Sunitinib was planned to be administered at a dosage of 25 mg/d for 4 of every 6 weeks. Although sunitinib toxicity was manageable in one patient, disease progression occurred after 4 months of treatment. In the second patient, acute pulmonary edema, caused by uncontrolled hypertension, developed on the 15th day of sunitinib therapy and the drug had to be discontinued. Sunitinib is thus not well tolerated in a hemodialysis setting. Close monitoring of toxicity and dose manipulation may be required if such therapy is attempted.

Biweekly triplet chemotherapy with gemcitabine, cisplatin and vinorelbine for advanced chemotherapy naïve non-small cell lung cancer.

AIMS AND BACKGROUND To investigate the efficacy and tolerability of biweekly scheduled triplet chemotherapy consisting of gemcitabine, cisplatin and vinorelbine for chemotherapy-naïve advanced non-small cell lung cancer. METHODS AND STUDY DESIGN Patients with stage IIIB/IV non-small cell lung cancer and performance status of 0-2 were eligible. Patients who had brain metastasis and of an older age were also enrolled in the study. The triplet combination chemotherapy consisted of gemcitabine, cisplatin and vinorelbine at the doses of 1000 mg/m(2), 25 mg/m(2) and 50 mg/m(2), respectively, were administered on day 1 and 14, every 28 days, up to 6 cycles. RESULTS Thirty patients were enrolled in the study. Median age was 60 years (range, 42-74). Most of the patients (83%) had metastatic disease and 7 patients (23%) had brain metastasis. In assessing 24 patients for response evaluation, none had complete response. Partial responses were achieved in 18 (60%) patients. Four patients (13%) had stable disease and 2 (7%) progressed. Thirteen percent and 20% of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. Febrile neutropenia, severe thrombocytopenia, hepatic and renal toxicity were not seen. Overall and progression-free survival were 8.15 and 7.15 months, respectively. Patients who had no brain metastasis ( P = 0.069), who had more than 3 courses of chemotherapy (P <0.001), and who had chemotherapy applied without dose reduction (P = 0.018) had better survivals. CONCLUSIONS The biweekly schedule of the triplet chemotherapy combination including gemcitabine, cisplatin and vinorelbine was effective in advanced, mostly metastatic non-small cell lung cancer with acceptable and manageable side effects.

The role of surgical methods in the treatment of anorectal malignant melanoma (AMM).

Abstract Purpose : Anorectal malignant melanoma (AMM) is a rare tumor with a poor prognosis. The aim of this study was to investigate the clinicopathological characteristics and treatment outcomes in patients with AMM. Methods : The study included 21 patients diagnosed with AMM between 2000 and 2010 that were evaluated with regard to age, sex, disease stage, treatment modality, and survival. Stage I, II, and III were defined as localized primary malignant melanoma, regional lymph node metastasis, and distant metastasis, respectively. Results : In all, 12 (57%) patients were female and 9 (43%) were male; median age was 61 years (range: 30–84 years). Among the 21 patients, 7 (47%) underwent abdominoperineal resection and 8 (53%) were treated using wide local excision. Four (19%) patients were classified as stage I, 10 (48%) as stage II, and 7 (33%) patients as stage III. In total, 10 patients received adjuvant therapy. Median overall and progression-free survival was 12 and 9 months, respectively. The 1-year and 5-year overall survival estimates were 59% and 42%, and progression free survival were 49% and 7%, respectively. Patients aged > 60 years (P = 0.145), female patients (P = 0.076), patients with localized disease (P = 0.045), patients that underwent wide local excision (P = 0.619), and patients that received adjuvant therapy (P = 0.962) had longer survival. Conclusions : The prognosis of AMM remains very poor and disease stage is the only predictor of survival. Abdomino-perineal resection does not confer an advantage, in terms of survival, in patients with AMM.