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. Electronic supplementary material The online version of this article (10.1186/s12885-019-5756-4) contains supplementary material, which is available to authorized users.

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Background/Aims: This study aimed to determine the epidemiological characteristics of colorectal cancer in Turkey. Materials and Methods: In this multicenter, prospective, and cross-sectional registry study, data for 968 patients with colorectal cancer from 21 centers in 7 geographic regions were analyzed. Results: Diagnosis was colon cancer in 662 (68.4%) and rectum cancer in 306 (31.6%) patients. In total, 60.9% of patients was male; mean age was 58.9±12.6 years. Among patients, 15.0% was drinking alcohol, 17.5% was smoking, 1.5% had familial history of polyposis, 15.0% had diabetes mellitus, 1.0% had inflammatory bowel disease. Fruit and vegetable consumption was low (<3 times/week) in 35.5% and red meat consumption was high (≥3 times/ week) in 47.4% of the patients. Median time-to diagnosis was 3.0 months and 4.0 months for patients with colon and rectum cancer, respectively. Mean body mass index was >25 in all group of patients. Distal rectum (61.3%) and sigmoid colon (36.8%) were the most common locations of cancer, for rectum and colon respectively. In total, 85.6% of patients were operated; 25.8% had emergency surgery. Low anterior resection rate was 64.2% in rectum cancer. In majority (89.8%) of the patients with rectum cancer who received preoperative treatment, conventional chemo-radiotherapy regimen was given. pTNM staging at diagnosis showed that stage III and IV patients were in majority (35.9% and 29.7%, respectively). Conclusion: Colon cancer is more frequent than rectum cancer in Turkey. Colorectal cancer patients are diagnosed at later stages. Most of the cases were operated. Interregional differences for risk factors are worthwhile for evaluation in future trials.

In this study, we estimated the response rate, duration of response, and type, severity and reversibility of toxicities in patients with Stage IV adenocarcinoma of the pancreas treated with docetaxel. Twenty-one patients with locally advanced or metastatic pancreatic cancer, previously untreated or treated with surgery or radiation alone, were treated with 100 mg/m2 docetaxel as a 1 hr infusion once every 21 days. All the patients were pretreated with dexamethasone and diphenhydramine. Twenty patients were assessable for both response and toxicity. One patient was assessable for toxicity alone. However, all the patients were assessed for survival. The major side effect of the drug was neutropenia, which required a dose reduction to 75 mg/m2 in approximately half of the patients. Nine patients were hospitalized with neutropenic fever. Fluid retention was not a significant problem. One patient had a partial response lasting for 21 weeks and 7 patients had stable disease. The remaining patients had progressive disease. The median survival for all the patients was 5.9 months. Docetaxel as a single agent showed limited activity against adenocarcinoma of the pancreas. Since the completion of this study, molecular predictors of in vitro response to docetaxel have been described. Confirmation of the clinical relevance of such predictors in humans could allow for the identification of a subgroup of patients with a higher rate of response to docetaxel.

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Background Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed. Methods We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m² doxorubicin-loaded nanoparticles (30 mg/m² group), 20 mg/m² doxorubicin-loaded nanoparticles (20 mg/m² group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01655693.

Background The aim of this study was to explore the relationship between follow-up imaging characteristics and overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients under sorafenib treatment. Methods Associations between OS and objective response (OR) by mRECIST or early tumor shrinkage (ETS; ≥20% reduction in enhancing tumor diameter at the first follow-up imaging) were analyzed in HCC patients treated with sorafenib within a multicenter phase II trial (SORAMIC). 115 patients were included in this substudy. The relationship between survival and OR or ETS were explored. Landmark analyses were performed according to OR at fixed time points. Cox proportional hazards models with OR and ETS as a time-dependent covariate were used to compare survival with factors known to influence OS. Results The OR rate was 29.5%. Responders had significantly better OS than non-responders (median 30.3 vs. 11.4 months; HR, 0.38 [95% CI, 0.22–0.63], p < 0.001), and longer progression-free survival (PFS; median 10.1 vs. 4.3 months, p = 0.015). Patients with ETS ≥ 20% had longer OS (median 22.1 vs. 11.4 months, p = 0.002) and PFS (median 8.0 vs. 4.3 months, p = 0.034) than patients with ETS < 20%. Besides OR and ETS, male gender, lower bilirubin and ALBI grade were associated with improved OS in univariate analysis. Separate models of multivariable analysis confirmed OR and ETS as independent predictors of OS. Conclusion OR according to mRECIST and ETS in patients receiving sorafenib treatment are independent prognostic factors for OS. These parameters can be used for assessment of treatment benefit and optimal treatment sequencing in patients with advanced HCC.

Impairment of liver function can be seen in cancer patients for a variety of reasons including metastasis, biliary obstruction, toxicity of chemotherapy or other concomittant drugs, can be paraneoplastic or can be due to infections, especially with hepatotropic viruses. Mostly reported in hematological malignancies, reactivation of hepatitis B virus (HBV) is a complication of chronic HBV infection in patients under cytotoxic or immunosuppressive therapy. Up to now, only a few cases of hepatitis B reactivation have been described in patients with solid tumors. We report an acute reversible deterioration of liver function tests following cytotoxic chemotherapy in an HBsAg-positive patient with metastatic pancreatic cancer due to hepatitis B reactivation. As far as we know, this is the first case of pancreatic carcinoma with reactivation following chemotherapy. As experience with acute flares of HBV carriers in solid tumors increases, the establishment of guidelines for the management of these patients has become more crucial.