Taner Korkmaz

Review of the current role of targeted therapies as maintenance therapies in first and second line treatment of epithelial ovarian cancer; In the light of completed trials

Late and recurrent stage ovarian cancer has a high mortality and low response rate to therapy beyond first line treatment. Although first line platinum/taxane based regimens have a satisfactory response rate eventually in most cases disease recurrence is common and second-line treatments are not curative. Delaying progression or recurrence is the main goal of current ongoing clinical studies by means of establishing an effective maintenance regimen with acceptable toxicity profile. Clearly, the persistence of dormant and drug-resistant cells after front-line treatments results in the inability to cure the disease. Over the past several years, the idea of prolongation of therapy for ovarian cancer has garnered clinical attention and academic debate. As a result of a greater understanding of the molecular pathways involved in carcinogenesis and tumor growth, a large number of potential therapeutic targets have been identified and drugs to block receptors, ligands or pathways are being developed. Currently, numerous clinical trials with targeted agents have just been completed or are ongoing involving patients achieving a complete or durable response after first-line and beyond the first line chemotherapy in order to evaluate the efficacy of different therapeutic approaches in terms of progression-free survival and overall survival.

Primary renal carcinoid: Treatment and prognosis

Primary carcinoid tumors of the kidney are very rare, malignant tumors consisting of neuroendocrine cells. The pathogenesis of renal carcinoid is unclear because neuroendocrine cells are not normally found in adult renal parenchyma. Electron microscopy, immunohistochemistry, octreotide scan, positron emission tomography along with conventional radiographic imaging techniques are used in diagnosis and follow-up. Presenting symptoms usually include flank pain and haematuria. Early stage disease is treated with surgery only. However, randomized trials are lacking because of the very low number of reported cases. Thus, the role of debulking surgery, chemotherapy, radiotherapy, octreotide and targeted therapy in the management of advanced disease remains an open question. In this article the clinicopathologic features and prognosis of this very rare disease along with treatment outcomes of the reported cases are reviewed. In addition, we report a new case of a metastatic primary renal atypical carcinoid tumor treated with octreotide therapy.

Serum thymidine kinase 1 levels correlates with FDG uptake and prognosis in patients with non small cell lung cancer

Context: TK1 found to be elevated biomarker in many solid cancers. Objectives: The study aimed to assess the prognostic significance of a serum TK1 in patients with metastatic NSCLC. Methods: The study included 48 consecutive patients, newly diagnosed with metastatic NSCLC, and 10 healthy volunteers. Serum TK1 activity determined by ELISA method. Results: Patients with a bTK1 level >156 Du L–1 had significantly shorter survival. TK1 level showed a strong correlation with primary tumor SUVmax. Discussion and conclusion: The magnitude of maximum fluorodeoxyglucose uptake in primary tumors and the serum TK1 level in patients with metastatic NSCLC were found to be independent prognostic predictors of overall survival.

Primary small cell carcinoma of the breast: report of seven cases and review of the literature

AIMS AND BACKGROUND The aim of the study was to analyze the clinicopathological characteristics, treatment modalities, and clinical outcome of patients with primary small cell carcinoma of the breast. METHODS Fifty-three cases of primary small cell carcinoma of the breast were identified; 7 cases in this series and 46 from the English-language medical literature. RESULTS There were 52 females and 1 male. The mean age was 53 years. Tumor size ranged from 1 to 18 cm (mean, 4.53). Axillary node metastasis was present in 61.7%. Only one patient had distant metastases at presentation. The presence of hormone receptors was reported in 24.5% of the tumors. Modified radical mastectomy was the most common surgical procedure and was performed in 50.9% of the patients. Adjuvant radiotherapy was administered to 39.6% of the patients, and 69.8% underwent chemotherapy. Thirteen percent of patients received adjuvant tamoxifen therapy. The mean follow-up was 20.75 months (range, 3-60), and 10 of 53 cases (18.9%) died of metastatic disease. CONCLUSIONS The prognosis of primary small cell carcinoma of the breast largely depends on the initial stage of the disease. Multimodality treatment including surgery, radiotherapy and chemotherapy seems to be the most appropriate strategy for early disease. Chemotherapy is usually unsuccessful in treating metastatic disease.

Association between human papillomavirus and endometrial adenocarcinoma

Several studies have suggested a possible role of human papillomavirus (HPV) in the pathogenesis of endometrial carcinoma. The aim of the study was to investigate the presence of HPV DNA in endometrium cancers and nonneoplastic endometrium. Sixty endometrial adenocarcinomas with and without squamous differentiation and the nonneoplastic endometrium tissue of fifty-six of the same patients were analyzed for the presence of family 16 and family 6 HPV DNA by using chromogenic in situ hybridization technique on formalin-fixed and paraffin-embedded archival samples, and the results were confirmed by polymerase chain reaction method. HPV DNA was not detected either in the endometrial adenocarcinoma with or without squamous differentiation, or in the nonneoplastic endometrium tissue. It appears that HPV does not play any role in the pathogenesis of endometrial carcinoma, since endometrium may not to be a suitable host for HPV replication.

Inducible nitric oxide synthase expression in gastric adenocarcinoma: impact on lymphangiogenesis and lymphatic metastasis

BackgroundLymphatic metastasis is the most important parameter in the spread of gastric carcinomas. Nitric oxide (NO) is a signaling molecule that plays an important role in inflammation and carcinogenesis. In this study, the possible link between inducible nitric oxide synthase (iNOS) expression with lymphangiogenesis and the clinicopathological parameters of gastric carcinomas was investigated.MethodsIn this study, iNOS expression and D2-40 (lymphatic endothelium-specific marker monoclonal antibody) reactivity were examined immunohistochemically in 41 gastric adenocarcinoma and 20 non-neoplastic gastric tissues. iNOS expression was scored semiquantitatively in the tumor parenchyma and stroma. D2-40-positive lymphatic vessels were used in the determination of lymphatic invasion and intratumoral and peritumoral lymphatic vascular density.ResultsiNOS expression was higher in gastric carcinoma tissue compared with non-neoplastic tissue. Particularly, iNOS expression in tumor cells was found to be closely related to lymphangiogenesis and lymphatic metastasis. The density of lymphatic invasion as well as intratumoral and peritumoral lymphatic vascular density were positively correlated with lymph node metastasis.ConclusionsOur results suggest that iNOS-mediated NO formation plays an important role in gastric carcinogenesis, tumor lymphangiogenesis, and the development of lymphatic metastases. Inhibition of the NO pathway may be an alternative treatment of gastric carcinomas.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1713572940104388.

Netrin-1 concentrations in patients with advanced gastric cancer and its relation with treatment

Context: Netrin-1 is found to be elevated and usable as a diagnostic biomarker in many human cancers. Objectives: We evaluated serum Netrin-1 concentrations in patients with advanced gastric cancer compared with those in a healthy group. Material and methods: Thirty patients with advanced gastric cancer and thirty healthy people were included in the study. Serum netrin-1 concentrations were measured by quantitative ELISA method in both groups. Results: The mean serum Netrin-1 concentrations were found to be significantly higher in patients with gastric cancer than in healthy controls. The mean serum Netrin-1 concentrations were found to be significantly higher in patients with gastric cancer before the beginning of chemotherapy when compared after the completion of third cycle. Discussion and conclusion: Our results indicated that netrin-1 concentrations elevated in advanced gastric cancer compared to a healthy control group and netrin-1 concentrations decreased with chemotherapy.

Clinical Outcome of Turkish Metastatic Breast Cancer Patients with Currently Available Treatment Modalities - Single Center Experience

BACKGROUND Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. MATERIALS AND METHODS We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively. RESULTS A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). CONCLUSIONS All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature.

Pretreatment PET/CT Standardized Uptake Values Play a Role in Predicting Response to Treatment and Survival in Patients with Small Cell Lung Cancer

Background: We investigated the role of standardized uptake values (SUVs) of the primary tumor in small cell lung cancer (SCLC) patients. Patients and Methods: The relationship between SUV and response to treatment was investigated using receiver operating characteristic (ROC) curve analysis, and the efficient cut-off value for detecting response to treatment was determined. The effects of SUV on response to treatment and survival were investigated. Results: 90 patients with a median age of 58 years (range 39-83 years) were included. Median follow-up was 11 months. The suitable cut-off SUV for determination of response was found to be 10 in ROC analysis. The sensitivity and specificity of this value were 85.7% (95% confidence interval (95% CI) 63-96) and 61.8% (95% CI 49-73) (area under the curve 0.783; p = 0.0001), respectively. The overall objective response rate in patients with involvement above the cut-off value was 93.3% compared to 59.1% in those with involvement below the cut-off value (p < 0.0001). In uni- and multivariate analysis, favorable effects of limited-stage disease on response to treatment were established (p < 0.05). The effect of an SUV higher than the cut-off value on progression-free survival was borderline (p = 0.085). Conclusion: These data may contribute to identifying prognostic disease characteristics and response to treatment.

Metastasis-Induced Acute Pancreatitis Successfully Treated with Chemotherapy and Radiotherapy in a Patient with Small Cell Lung Cancer

Although involvement of pancreas is a common finding in small cell lung cancer (SCLC), metastasis-induced acute pancreatitis (MIAP) is very rare. A 50-year-old female with SCLC who had limited disease and achieved full response after treatment presented with acute pancreatitis during her follow-up. The radiologic studies revealed a small area causing obliteration of the pancreatic duct without mass in the pancreatic neck, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) confirmed the metastasis of SCLC. The patient was treated successfully with systemic chemotherapy and radiotherapy delivered to pancreatic field. In SCLC, cases of MIAP can be encountered with conventional computed tomography with no mass image, and positron emission tomography and EUS-FNA can be useful for diagnosis of such cases. Aggressive systemic and local treatment can prolong survival, especially in patients with good performance status.