Clinical Features and Follow-up of Pure Seminoma Cases: Single Center Experience

Aim:Pure seminoma which is diagnosed in early stages is the most important tumor seen in young adults. Toxicity problems and patient preferences should be taken into consideration when making treatment decision. We aimed to present the data and survival rates of patients with pure seminoma who has been followed in our clinic.Materials and Methods:Documents of the pure seminoma patients who has been followed and treated in our clinic between the years of 2008 and 2018 were studied retrospectively. Patient features, tumour features, treatment regimens, prognosis and folow up after treatment were recorded.Results:86 of 125 patients(68,8%) who has been followed in our clinic with the diagnosis of seminoma were between the ages of 20 and 40. At the time of diagnosis,102 patients(81,6%) were at stage 1,14 patients(%11,2) were at stage 2 and 9 patients(7,2%) were at stage 3 disease. Metastases were detected in only 5 patients at the time of diagnosis. While 63 patients were treated with chemotherapy and 39 patients were treated with radiotherapy. Survival rate was 88,9% for 45 patients who filled in 10 years follow up time. 6 patients died because of disease recurrence and irresponsiveness to the therapy. The prominent features in deceased patients were late stage disease and lung parenchymal recurrence.Conclusion:Different treatment modalities for stage 1 disease were similar in aspect of overall survival. Pulmonary parenchyma recurrence and advanced stage disease were associated with mortality

Which factors help to determine the long-term response to first-line tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma: A Turkish multi-centre study

Many developing countries lack access to recommended first-line treatments for metastatic renal cell carcinoma (mRCC), such as immune checkpoint inhibitors (ICIs) or ICI-tyrosine kinase inhibitor (TKI) combinations. As a result, predictive markers are necessary to identify patients who may benefit from single-agent TKIs for long-term response. This study aims to identify such parameters. This was a multi-centre, retrospective study of patients with mRCC who were undergoing first-line treatment with sunitinib or pazopanib. Patients who had been diagnosed with mRCC and had not experienced disease progression for 36 months or more were deemed to have achieved a long-term response. Predictive clinical and pathological characteristics of patients who did not experience long-term disease progression were investigated. A total of 320 patients from four hospitals were included in the study. The median age of the patients was 60 years (range 20-89 years). According to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification, 109 patients were classified as having favourable risk and 211 were in the intermediate-poor risk group. The median progression-free survival (PFS) and overall survival (OS) for all patients were 12.5 months and 76.4 months, respectively. In the long-term responder’s group, the median PFS was 78.4 months. Among all patients, prior nephrectomy, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) <1, and the absence of brain metastasis were predictive factors for long-term response. For patients in the favourable risk group, the lack of brain metastasis was a predictor of long-term response. In the intermediate-poor risk group, prior nephrectomy and ECOG PS <1 were predictive factors for long-term response. Some individuals with mRCC may experience a durable response to TKIs. The likelihood of a long-term response can be determined by factors such as nephrectomy, ECOG PS < 1, and the absence of brain metastases

First-line treatment of patients with HER2-positive metastatic gastric and gastroesophageal junction cancer

Fluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of HER2-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (P = 0.495). 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (P = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, P = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, P = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, mFOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens

A Potential Treatment of Non-Alcoholic Fatty Liver Disease with SIRT1 Activators

Sirtuins (SIRTs) are members of the silent information regulator-2 family and act as nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases. The de-acetylation of proteins and histones results in an up- or down-regulation of gene transcription and protein function. In recent years, the regulatory action of the deacetylation activity of SIRT1 has been shown to have a positive impact on the pathophysiological mechanisms of nonalcoholic fatty liver disease (NAFLD). Among the effects of SIRT1 are: its healing activity on insulin sensitivity, thereby ameliorating glycemic regulation; its mimetic activity on calorie restriction; its antihyperlipidemic activity on lipid homeostasis via the liver, adipose tissues and skeletal muscles; its anti-inflammatory activities; its protective effects against cardiovascular events and endothelial dysfunction; its positive influence on autophagy, apoptosis and cancer; and finally, its anti-aging activity. The current approach for the treatment of NAFLD involves the treatment of etiological factors and recommendation of life-style changes including more physical activity and a low-calorie diet. However, there is no specific medical treatments for NAFLD. The therapeutic potential of SIRT1 activity in the treatment of NAFLD discovered in humans has been presented in this article. In this review, the potential effects of SIRT1 activation on NAFLD-related pathophysiological mechanisms and on the treatment of NAFLD are discussed

Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naive breast cancer: real-life practice outcomes

PurposeIn this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients.MethodsThis study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers.ResultsMedian age was 51 (22-82). Median PFS was 28.5months, while median OS was 40.3months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8m vs. 28.5m; p=0.002) and OS (26.7m vs. 40.3m; p=0.009). Patients older than 65years of age (n: 42, 13.2%) had significantly lower OS results (19.8m vs. 40.3m; p=0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure.ConclusionsOur RLP trial included only visceral metastatic, trastuzumab-naive BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences

Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum resistant urothelial carcinoma. Objective: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. Design, setting, and participants: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. Outcome measurements and statistical analysis: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. Results and limitations: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treat-ment response based on clinical notes and local radiographic studies. Conclusions: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. Patient summary: Atezolizumab is effective and well-tolerated in patients with meta-static urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting. (c) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab

Background Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. Patients and methods In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 >=), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p =) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. Conclusions This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience

Aim The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. Method Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. Findings Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). Discussion The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC

Is the prognostic nutritional index a prognostic and predictive factor in metastatic non-small cell lung cancer patients treated with first-line chemotherapy?

*Şakalar, Teoman ( Aksaray, Yazar )Purpose: We aimed to assess the prognostic and predictive significance of pretreatment Onodera’s prognostic nutritional index (OPNI) in metastatic non-small cell lung cancer patients (NSCLC) treated with first-line chemotherapy. Materials and methods: Patients with metastatic NSCLC who attended five different medical oncology clinics between December 2008 and January 2018 were retrospectively analyzed. The optimal cut-off point for OPNI was performed by a receiver operating characteristic (ROC) curve analysis. Patients were assigned to either the low OPNI group or high OPNI group. Results: A total of 333 patients were included in the study. Significant differences between the low and high OPNI groups were found regarding the rates of response to chemotherapy, sex, and hemoglobin level (p < 0.05). The patients in high OPNI group had a longer overall survival (OS) (15.3 vs. 10.6 months, p < 0.001) and progression-free survival (PFS) (6.7 vs. 5.3 months, p < 0.001) compared to the patients in low OPNI group. A multivariate analysis using Cox regression model revealed that a high OPNI score was an independent prognostic factor of OS (HR = 1.535, p = 0.002) and PFS (HR = 1.336, p = 0.014), but failed to demonstrate a statistical significance of pretreatment OPNI scores in predicting treatment response (p = 0.56). Conclusions: Pretreatment OPNI is an independent prognostic factor for OS and PFS in metastatic NSCLC patients treated with first-line chemotherapy. Thus, it may be used as easily calculated and low-cost prognostic tool in the routine clinical practice in this patient group

Predictive value of 18F-FDG PET/CT indices on extensive residual cancer burden in breast cancer patients treated with neoadjuvant chemotherapy [Valor predictivo de los índices 18F-FDG PET/TC sobre la carga tumoral residual en pacientes con cáncer de mama extenso tratadas con quimioterapia neoadyuvante]

Aim: We investigated the correlation between 18F-FDG PET/CT indices and pathological response in breast cancer treated with neoadjuvant chemotherapy (NACT) which was scored with Residual Cancer Burden (RCB) system after surgery. Our aim is to detect extensive residual cancer burden earlier by using PET/CT indices. Methods: Characteristics of patients were retrieved retrospectively. Baseline maximum Standart Uptake Value (SUVmax), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) indices and reduction rate (RR) between baseline and interim evaluation were calculated with FDG PET/CT scan. All patients were evaluated according to RCB scores after surgery. Pathological responses and PET/CT measurement results were analyzed with demographic and clinical parameters. Results: A total of 95 patients were included in the study. According to pathological responses, the distribution of RCB-0, -1, -2, -3 were 13 (13.7%), 11 (11.6%), 30 (31.6%), 41 (43.2%), respectively. Disease-free survival was significantly lower in the RCB-3 group compared to the pathological responder group (P=.01). According to multivariate analysis, RR of SUVmax was determined as an independent variable predicting extensive residual cancer burden with an optimal cut-off value of 86% (P&lt;.05). Conclusions: We determined RR of SUVmax as an independent factor for predicting extensive residual tumor burden. We believe that RR of SUVmax is sufficient to predict pathological response in daily practice. In addition, MTV and TLG measurements do not contribute additionally to SUVmax alone and can cause unnecessary labor loss. © 202