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Introduction: Kidney dysfunction is prevalent in oncology patients and has an impact on their treatment and quality of life. The aim of our study was to analyze the prevalence of CKD in a large cohort of several types of cancer patients in an East European Region. Material and methods: We conducted an observational retrospective cohort study on 5831 consecutive, biopsy-diagnosed cancer patients between January 2019 –December 2020 in the largest oncology hospital and outpatient clinic in Western Romania. 4342 subjects were included in the statistical analysis. Results and discussion: From the 24 cancer types, the most prevalent cancers were represented by: breast (22.02%), lung (10.18%) and colonic cancer (9.51%). The prevalence of CKD (G3 –G5) was 12.27% after the first year of follow-up and 13.42 after the second year. The prevalence of CKD was higher in patients with renal (50%), urinary tract (33.6%) and pancreatic cancers (19.6%) and lower in patients with colonic cancers (5.3%) and brain tumors (2.5%). At the end of our 2-year survey period, 0,7% of the CKD cases had an eGFR around 6 ml/min/1.73m2 –an indication for renal replacement therapy. Conclusion: Oncology patients have a significantly higher prevalence of CKD compared to the general population, dependent of the age of the patients and the type of cancer. The prevalence of advanced CKD was surprisingly high (stages G4-G5 Pre-Dialysis 22.15%) one third of the CKD- G5 patients having indication for initiation of renal replacement therapy. An onco- nephrology team should be needed for the best medical care of these patients. [ABSTRACT FROM AUTHOR]

Background: Hereditary cancer predisposition syndromes are responsible for approximately 5-10% of all diagnosed cancer cases. In the past, single-gene analysis of specific high risk genes was used for the determination of the genetic cause of cancer heritability in certain families. The application of Next Generation Sequencing (NGS) technology has facilitated multigene panel analysis and is widely used in clinical practice, for the identification of individuals with cancer predisposing gene variants. The purpose of this study was to investigate the extent and nature of variants in genes implicated in hereditary cancer predisposition in individuals referred for testing in our laboratory.Methods: In total, 1197 individuals from Greece, Romania and Turkey were referred to our laboratory for genetic testing in the past 4 years. The majority of referrals included individuals with personal of family history of breast and/or ovarian cancer. The analysis of genes involved in hereditary cancer predisposition was performed using a NGS approach. Genomic DNA was enriched for targeted regions of 36 genes and sequencing was carried out using the Illumina NGS technology. The presence of large genomic rearrangements (LGRs) was investigated by computational analysis and Multiplex Ligation-dependent Probe Amplification (MLPA).Results: A pathogenic variant was identified in 264 of 1197 individuals (22.1%) analyzed while a variant of uncertain significance (VUS) was identified in 34.8% of cases. Clinically significant variants were identified in 29 of the 36 genes analyzed. Concerning the mutation distribution among individuals with positive findings, 43.6% were located in the BRCA1/2 genes whereas 21.6, 19.9, and 15.0% in other high, moderate and low risk genes respectively. Notably, 25 of the 264 positive individuals (9.5%) carried clinically significant variants in two different genes and 6.1% had a LGR.Conclusions: In our cohort, analysis of all the genes in the panel allowed the identification of 4.3 and 8.1% additional pathogenic variants in other high or moderate/low risk genes, respectively, enabling personalized management decisions for these individuals and supporting the clinical significance of multigene panel analysis in hereditary cancer predisposition. [ABSTRACT FROM AUTHOR]

Purpose: The Romanian Patient Access Program (Ro-PAP, CA 184-427), part of the European Expanded Access Program (EAP), was developed to evaluate the effectiveness and safety profile ipilimumab in previously treated patients with advanced melanoma (unresectable or metastatic melanoma). The objective of our retrospective observational study of patients included in this program was to provide data recorded in real-life settings., Methods: We analysed 89 patients enrolled in Ro-PAP, CA 184-427 (54 men and 35 women) aged between 29 and 89 years. The patients received ipilimumab 3mg/kg, administered with short 30-min i.v. infusion every 3 weeks, having a total of 4 doses. Patients were assessed for tumor response, overall survival (OS) and progression-free survival (PFS), and were monitored for adverse events (AE)., Results: At 12 weeks after the completion of therapy, the complete and partial response rates were 6.74% each, stable disease 15.73%, with the best overall response rate 13.48% and disease control rate 29.21%. Median OS was 189.00 days (95% CI 69.50-308.49) and median PFS 124.00 days (95% CI 85.05-162.94). The level of patient functionality at the beginning of ipilimumab treatment showed to be an important predictor of outcome, as patients with ECOG performance status (PS) (0) before therapy with ipilimumab had a higher OS compared with those with impaired functionality., Conclusions: The use of ipilimumab in daily clinical practice demonstrated to be effective and safe, consistent with data coming from randomized clinical trials or other observational studies.

Objectives: Treatment decision-making in colorectal cancer is often guided by tumour tissue molecular analysis. The aim of this study was the development and validation of a high-resolution melting (HRM) method for the detection of KRAS, NRAS and BRAF mutations in Greek and Romanian patients with colorectal cancer and determination of the frequency of these mutations in the respective populations., Setting: Diagnostic molecular laboratory located in Athens, Greece., Participants: 2425 patients with colorectal cancer participated in the study., Primary and Secondary Outcome Measures: 2071 patients with colorectal cancer (1699 of Greek and 372 of Romanian origin) were analysed for KRAS exon 2 mutations. In addition, 354 tumours from consecutive patients (196 Greek and 161 Romanian) were subjected to full KRAS (exons 2, 3 and 4), NRAS (exons 2, 3 and 4) and BRAF (exon 15) analysis. KRAS, NRAS and BRAF mutation detection was performed by a newly designed HRM analysis protocol, followed by Sanger sequencing., Results: KRAS exon 2 mutations (codons 12/13) were detected in 702 of the 1699 Greek patients with colorectal carcinoma analysed (41.3%) and in 39.2% (146/372) of the Romanian patients. Among the 354 patients who were subjected to full KRAS, NRAS and BRAF analysis, 40.96% had KRAS exon 2 mutations (codons 12/13). Among the KRAS exon 2 wild-type patients 15.31% harboured additional RAS mutations and 12.44% BRAF mutations. The newly designed HRM method used showed a higher sensitivity compared with the sequencing method., Conclusions: The HRM method developed was shown to be a reliable method for KRAS, NRAS and BRAF mutation detection. Furthermore, no difference in the mutation frequency of KRAS, NRAS and BRAF was observed between Greek and Romanian patients with colorectal cancer., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)