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.

Clinicopathologic Features and Efficacy of Induction Chemotherapy in Nasopharyngeal Carcinoma: Real-World Experience.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) accounts for 0.01% of all carcinomas, and 70% of patients have locally advanced disease with a poor prognosis. The mainstay therapy is chemoradiotherapy (CRT), and concurrent administration of platinum-based agents and irradiation provides high local control rates. However, induction (neoadjuvant) chemotherapy (ICT) prior to CRT is recommended for large tumors with a high tumor burden at the category 1 level. For ICT, platinum-based doublet or triplet combination regimens are recommended. Selected patients with a high tumor burden at the time of diagnosis who did not receive ICT before CRT were given adjuvant (consolidation) therapy after CRT. This multicenter study aimed to share our experience in treatment of NPC and evaluate the factors associated with survival. METHODS: The study included patients diagnosed with NPC who were followed and treated between 2008 and 2022. Hundred and forty-two patients from 6 centers were evaluated. The factors associated with disease-free survival (DFS) and overall survival (OS) were evaluated. RESULTS: The median age of our patients was 51 years (IQR: 16-81 years), and the male:female ratio was 2.5:1. A majority of patients (71%) had stage 3-4 disease. They had locally advanced disease, and 48 patients (34%) received ICT. Twenty patients (14%) received adjuvant therapy. The median follow-up was 41 months (range, 2.7-175.1 months). The median DFS in NPC was 92.6 months (range, 71.9-113.3 months), with a 40th month DFS of 70.9%. The median OS was 113 months (range, 91-135 months), with a 40th month OS of 84.7%. Median DFS was 95.3 months (range, 64.2-126.4 months) in patients who received ICT before CRT, which was longer than in the CRT-only group (p = 0.6). DFS at the 40th month was 75.1% in patients treated with ICT compared to 65.1% in the CRT-only group. Median OS was 117 months (range, 92-142 months) in patients receiving ICT, which was longer than in the CRT-only group (p = 0.4). OS at the 40th month was 86.7% in patients receiving ICT but 83.6% in the CRT-only group. CONCLUSIONS: Both the objective response rate and survival were longer in patients who radiologically responded to CRT following ICT. Nonresponse to ICT is a negative predictive indicator. The role of ICT in locally advanced NPC is increasing.

The prognostic factors in patients with advanced hepatocellular carcinoma: impact of treatment sequencing.

The prognosis of patients with advanced HCC can vary widely depending on factors such as the stage of the cancer, the patient's overall health, and treatment regimens. This study aimed to investigate survival outcomes and associated factors in patients with hepatocellular carcinoma (HCC). In this retrospective study, data from 23 medical oncology clinics were analyzed. Progression-free survival (PFS) and overall survival (OS) values were estimated using the Kaplan-Meier method. Prognostic factors associated with survival which were identified in univariate analysis were subsequently evaluated in a multivariate Cox-regression survival analysis was conducted using the backward stepwise (Conditional LR) method to determine the independent predictors of PFS and OS. Of 280 patients, 131 received chemotherapy and 142 received sorafenib, 6 received atezolizumab plus bevacizumab and 1 received nivolumab for first-line setting. The median follow-up time was 30.4 (95%CI 27.1-33.6) months. For-first line, median PFS was 3.1 (95%CI2.7-3.5) months, and it was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab (PFS 5.8 (95%CI 4.2-7.5) than in those received chemotherapy (PFS 2.1 (95%CI 1.9-2.3) in the first-line setting (p < 0.001). Multivariate analysis revealed that male gender (HR: 2.75, 95% CI: 1.53-4.94, p = 0.01), poor ECOG performance score (HR: 1.88, 95% CI: 1.10-3.21, p = 0.02), higher baseline AFP level (HR: 2.38, 95% CI: 1.54-3.67, p < 0.001) and upfront sorafenib treatment (HR,0.38; 95% CI: 0.23-0.62, p < 0.001) were significantly associated with shorter PFS. The median OS was 13.2 (95%CI 11.1-15.2) months. It was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab in the first-line setting followed by TKIs (sorafenib or regorafenib, OS 18.6 (95%CI 13.8-23.5)) compared to those who received chemotherapy (OS 10.3 (95%CI 6.6-14.1)) in the first-line setting. The multivariate analysis revealed that upfront chemotherapy treatment approach, male gender (HR: 1.77, 95% CI: 1.07-2.94, p = 0.02), poor ECOG performance score (HR: 1.96, 95% CI: 1.24-3.09, p = 0.004) and Child-Pugh score, presence of extrahepatic disease (HR: 1.54, 95% CI: 1.09-2.18, p = 0.01), and higher baseline AFP value (HR: 1.50, 95% CI: 1.03-2.19, p = 0.03) were significantly associated with poor prognosis. Additionally, regarding of treatment sequence, upfront sorafenib followed by regorafenib showed a significantly lower risk of mortality (HR: 0.40, 95% CI: 0.25-0.66, p < 0.001). Sorafenib followed by regorafenib treatment was associated with a significantly lower risk of mortality rather than upfront sorafenib followed by BSC group or upfront chemotherapy followed by TKIs. These findings underscore the importance of the optimal treatment sequences to improve survival in patients with advanced HCC.

SGLT2 inhibitors improve plasma atherogenic biomarkers in patients with type 2 diabetes: a real-world retrospective observational study.

BACKGROUND: There are cost-effective, non-invasive, and predictive tools used to predict the CVD risk in patients with diabetes such as the "atherogenic index of plasma (AIP)" which is defined as the logarithm to the base 10 of the ratio of fasting plasma TG (mg/dL) to HDL-C [log (TG/HDL-C)], triglyceride to high density lipoprotein (TG-to-HDL-C) ratio and the triglyceride glucose (TyG) index which is calculated as Ln (fasting TG [mg/dL] × fasting blood glucose (mg/dL)/2). These tools are indirect markers of atherosclerosis. Dapagliflozin and empagliflozin have exhibited cardiovascular beneficial effects and this study evaluated the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on AIP, TyG index and TG-to-HDL-C ratio in patients with type 2 diabetes. METHODS: This single center, retrospective, observational study involved patients with type 2 diabetic patients who were prescribed SGLT2i in the endocrinology outpatient clinic between January 2017 and June 2019. Demographic and clinical data were collected from patient files. AIP, TyG index and TG-to-HDL-C ratio were calculated obtained at the first visit and the sixth month visit. RESULTS: Overall, 143 patients with T2DM (75 women, 68 men) were recruited in this study. Sixty-six patients were prescribed dapagliflozin (46.2%), and 77 were prescribed empagliflozin (53.8%). SGLT2i treatment did not alter the lipid profile except the serum triglyceride (TG) levels. Serum TG levels were significantly reduced after 6 months of SGLT2i therapy (P=0.045). All patients had significant reductions in AIP at 6-month follow-up (P<0.001), accompanied by a significant reduction in TyG index (P<0.001). Both empagliflozin and dapagliflozin caused significant decrease in AIP (P=0.043 and P<0.001, respectively) and TyG index (P=0.010 and P<0.001, respectively). CONCLUSIONS: Both dapagliflozin and empagliflozin were noted to significantly affect AIP and TyG indexes, which indicate atherosclerotic cardiovascular risk, with or without statin treatment regardless of lipid parameters.

Hyperandrogenism-related metabolic changes in drug-naïve transmen compared to cisgender women: a case-controlled study.

INTRODUCTION: The aetiology of gender dysphoria is still unclear. Although prior studies have shown that trans men have higher androgen levels than cisgender women, they all concluded unselected populations. Our reason for performing this study is to evaluate trans men's hormone profile and metabolic status to compare with cisgender women in a more selected population. This is the first case-controlled study to compare anthropometric, metabolic, and endocrinological parameters of drug-naïve trans men with those of cisgender women. MATERIAL AND METHODS: We designed this study as a single-centre observational cohort study. We included 70 drug naïve trans men, and the control group comprised 34 healthy cisgender women. We measured and compared hormone profiles and metabolic parameters in the 2 groups. RESULTS: Of the 70 trans men individuals, 16 (22.85%) met the Rotterdam criteria and were diagnosed with polycystic ovary syndrome (PCOS); 4 individuals in the control group met the criteria (11.7%). Although we matched body mass index in the groups, total testosterone, free androgen index, androstenedione, 17 hydroxyprogesterone, muscle strength, triglyceride, and homeostatic model assessment of insulin resistance levels were significantly higher in the trans men than in the cisgender women (p < 0.05). Even after were excluded PCOS patients, hyperandrogenaemia was apparent in the trans men. CONCLUSION: Our study showed that trans men have clearly higher androgen levels, which may have been the reason for metabolic changes compared to cisgender women. However, the main reason for hyperandrogenism in drug-naïve trans men is still not known, and more comprehensive studies are needed.