Molecular profile and clinical features of patients with gliomas using a broad targeted next generation-sequencing panel.

Gliomas are the most common malignant primary brain tumors characterized by poor prognosis. The genotyping of tumors using next generation sequencing (NGS) platforms enables the identification of genetic alterations that constitute diagnostic, prognostic and predictive biomarkers. The present study investigated the molecular profile of 32 tumor samples from 32 patients with high-grade gliomas by implementing a broad 80-gene targeted NGS panel while reporting their clinicopathological characteristics and outcomes.

Real-world management patterns in -mutant advanced non-small-cell lung cancer before first-line adoption of osimertinib: the REFLECT study in Greece.

To retrospectively characterize real-world therapeutic strategies, clinical outcomes and attrition rates with EGFR tyrosine kinase inhibitors (TKIs), before first-line osimertinib approval, in -mutated advanced/metastatic non-small-cell lung cancer patients in Greece. Among 160 patients, the discontinuation rate for first-line first- or second-generation EGFR-TKIs was 85%; among these patients, 43% did not receive any second-line therapy and 9.4% died during an 18.

Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations.

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.

MYC copy gain, chromosomal instability and PI3K activation as potential markers of unfavourable outcome in trastuzumab-treated patients with metastatic breast cancer.

Background: There is an unmet need for more efficient patient stratification for receiving trastuzumab in the metastatic breast cancer (mBC) setting, since only part of such patients benefit from the addition of this agent to chemotherapy. The aim of this study was to investigate the prognostic value of biomarkers including MYC and MET in mBC patients treated with trastuzumab-based regimens.

Methods: mBC patients, locally tested as HER2-positive, treated with trastuzumab and chemotherapy between 1998 and 2010 were evaluated.

Prognostic markers in early-stage colorectal cancer: significance of TYMS mRNA expression.

Background: Several studies have recently indicated the prognostic or predictive role of several biomarkers in colorectal cancer. We sought to investigate the prognostic value of prostaglandin synthase 2 (PTGS2), cyclooxygenase 2 (COX2), thymidylate synthetase (TYMS), thymidine phosphorylase (TYMP), dihydropyrimidine dehydrogenase (DPYD) and topoisomerase I (TOPO1) in colorectal cancer patients treated with 5-FU-based regimens, such as De Gramont and FOLFOX in the adjuvant setting.

Materials And Methods: In total, 96 formalin-fixed paraffin-embedded and 30 fresh-frozen tumor tissue samples were evaluated using immunohistochemistry, quantitative reverse transcription-polymerase chain reaction and microarray gene expression profiling, respectively.

Dose-dense sequential adjuvant chemotherapy followed, as indicated, by trastuzumab for one year in patients with early breast cancer: first report at 5-year median follow-up of a Hellenic Cooperative Oncology Group randomized phase III trial.

Background: Dose-dense sequential chemotherapy including anthracyclines and taxanes has been established in the adjuvant setting of high-risk operable breast cancer. However, the preferable taxane and optimal schedule of administration in a dose-dense regimen have not been defined yet.

Methods: From July 2005 to November 2008, 1001 patients (990 eligible) were randomized to receive, every 2 weeks, 3 cycles of epirubicin 110 mg/m2 followed by 3 cycles of paclitaxel 200 mg/m2 followed by 3 cycles of intensified CMF (Arm A; 333 patients), or 3 cycles of epirubicin followed by 3 cycles of CMF, as in Arm A, followed 3 weeks later by 9 weekly cycles of docetaxel 35 mg/m2 (Arm B; 331), or 9 weekly cycles of paclitaxel 80 mg/m2 (Arm C; 326).

Lack of association between KRAS mutations and 18F-FDG PET/CT in Caucasian metastatic colorectal cancer patients.

Background: Although Kirsten rat sarcoma (KRAS) gene mutational testing is essential for the optimal design of therapeutic strategies for colorectal cancer, it is not always feasible or reliable. In this retrospective study, we examined whether (18)F-Fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) scans can serve as a surrogate examination for KRAS mutational testing.

Patients And Methods: KRAS codon 12 and 13 mutational status was tested in 44 colorectal primary tumors and was compared with the (18)F-FDG PET/CT maximum standardized uptake value (SUVmax) values of the respective metastatic lesions.

A study of gene expression markers for predictive significance for bevacizumab benefit in patients with metastatic colon cancer: a translational research study of the Hellenic Cooperative Oncology Group (HeCOG).

Background: Bevacizumab, an antibody neutralizing Vascular Endothelial Growth Factor (VEGF), is licensed for the management of patients with advanced colon cancer. However, tumor biomarkers identifying the molecular tumor subsets most amenable to angiogenesis modulation are lacking.

Methods: We profiled expession of 24526 genes by means of whole genome 24 K DASL (c-DNA-mediated, Annealing, Selection and Ligation) arrays, (Illumina, CA) in 16 bevacizumab-treated patients with advanced colon cancer (Test set).

Dose selection trial of metronomic oral vinorelbine monotherapy in patients with metastatic cancer: a hellenic cooperative oncology group clinical translational study.

Background: Metronomic chemotherapy is considered an anti-angiogenic therapy that involves chronic administration of low-dose chemotherapy at regular short intervals. We investigated the optimal metronomic dose of oral vinorelbine when given as monotherapy in patients with metastatic cancer.

Methods: Patients with recurrent metastatic breast (BC), prostate (PC) or non-small cell lung cancer (NSCLC) and adequate organ functions were randomly assigned to 30, 40 or 50 mg vinorelbine, taken orally three times a week.

Evaluation of the prognostic role of centromere 17 gain and HER2/topoisomerase II alpha gene status and protein expression in patients with breast cancer treated with anthracycline-containing adjuvant chemotherapy: pooled analysis of two Hellenic Cooperative Oncology Group (HeCOG) phase III trials.

Background: The HER2 gene has been established as a valid biological marker for the treatment of breast cancer patients with trastuzumab and probably other agents, such as paclitaxel and anthracyclines. The TOP2A gene has been associated with response to anthracyclines. Limited information exists on the relationship of HER2/TOP2A gene status in the presence of centromere 17 (CEP17) gain with outcome of patients treated with anthracycline-containing adjuvant chemotherapy.

Biomarkers of benefit from cetuximab-based therapy in metastatic colorectal cancer: interaction of EGFR ligand expression with RAS/RAF, PIK3CA genotypes.

Background: More than half of patients with KRAS-wild type advanced colorectal cancer (CRC) fail anti-EGFR monoclonal antibodies. We studied EGFR-axis messenger RNA (mRNA) expression and RAS, RAF, PIK3CA mutations in order to identify additional biomarkers of cetuximab efficacy.

Methods: Previously genotyped (KRAS, NRAS, BRAF, PIK3CA mutations) formalin-fixed paraffin-embedded tumour biopsies of 226 cetuximab-treated CRC patients (1st to 3rd line therapy) were assessed for mRNA expression of epidermal growth factor receptor (EGFR) and its ligands EGF, Transofrming Growth Factor-a (TGFA), Amphiregulin (AREG) and Epiregulin (EREG) with real time quantitative PCR.

Prospective, open-label, randomized, phase III study of two dose-dense regimens MVAC versus gemcitabine/cisplatin in patients with inoperable, metastatic or relapsed urothelial cancer: a Hellenic Cooperative Oncology Group study (HE 16/03).

Background: The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied.

Topoisomerase II alpha gene amplification is a favorable prognostic factor in patients with HER2-positive metastatic breast cancer treated with trastuzumab.

Background: The vast majority of patients with HER2-positive metastatic breast cancer (MBC) treated with trastuzumab eventually develop resistance to this agent. There is an unmet need therefore, for identifying biological markers with possible prognostic/predictive value in such patients. The aim of this study was to investigate the prognostic role of topoisomerase II alpha gene (TOP2A) amplification and protein (TopoIIa) expression in patients treated with trastuzumab-containing regimens.

XELIRI-bevacizumab versus FOLFIRI-bevacizumab as first-line treatment in patients with metastatic colorectal cancer: a Hellenic Cooperative Oncology Group phase III trial with collateral biomarker analysis.

Background: The aim was to compare two standard chemotherapy regimens combined with bevacizumab as first-line treatment in patients with metastatic colorectal cancer.

Methods: Patients previously untreated for metastatic disease were randomized in: group A (irinotecan, capecitabine, bevacizumab, every 3 weeks; XELIRI-bevacizumab) and group B (irinotecan, leucovorin, fluorouracil, bevacizumab, every 2 weeks; FOLFIRI-bevacizumab). Primary endpoint was progression-free survival (PFS).

Irinotecan/fluorouracil/leucovorin or the same regimen followed by oxaliplatin/fluorouracil/leucovorin in metastatic colorectal cancer.

Background: This study reports the long-term follow-up of patients with metastatic colorectal cancer (CRC) participating in a randomised phase II study that compared the efficacy and toxicity of the combination of irinotecan (IRI), fluorouracil (FU) with leucovorin (LV) (arm A) versus sequential chemotherapy with IRI plus FU/LV followed by oxaliplatin (OXA) plus FU/LV (arm B) as first line therapy.

Materials And Methods: Intent-to-treat analysis was performed on 417 patients (211 in arm A and 206 in arm B). Treatment schedules of weekly IRI 80 mg/m(2) or OXA 45 mg/m(2) plus LV 200 mg/m(2) immediately followed by intravenous bolus FU 450 mg/m(2) for 6 weeks were followed by a 2-week rest period.

Prognostic stratification of patients with advanced renal cell carcinoma treated with sunitinib: comparison with the Memorial Sloan-Kettering prognostic factors model.

Background: The treatment paradigm in advanced renal cell carcinoma (RCC) has changed in the recent years. Sunitinib has been established as a new standard for first-line therapy. We studied the prognostic significance of baseline characteristics and we compared the risk stratification with the established Memorial Sloan Kettering Cancer Center (MSKCC) model.

Pegfilgrastim administered on the same day with dose-dense adjuvant chemotherapy for breast cancer is associated with a higher incidence of febrile neutropenia as compared to conventional growth factor support: matched case-control study of the Hellenic Cooperative Oncology Group.

Objective: Recombinant human granulocyte-colony-stimulating factors such as filgrastim and pegfilgrastim have been employed as primary and secondary prophylaxis against neutropenia in cancer patients receiving chemotherapy. This study was conducted to evaluate the rate of febrile neutropenia in patients with high-risk early breast cancer receiving dose-dense chemotherapy and, as primary prophylaxis, either pegfilgrastim 6 mg fixed dose on the same day as chemotherapy or filgrastim on days 2-10 of each cycle. Secondary objectives included the rate of severe neutropenia, treatment delays and dose reductions.

Solitary large hepatic metastasis in an elderly patient with anaplastic thyroid carcinoma: a case report.

Background: We present the case of a patient who presented with anaplastic thyroid carcinoma with a solitary large liver metastasis. Hepatic metastases are extremely rare in anaplastic thyroid carcinoma.

Case Presentation: We report the case of a 78-year old Greek man who presented with voice hoarseness, dyspnoea and a large mass on the anterior surface of the cervical region (neck), as well as constitutional symptoms such as anorexia, weight loss and malaise.

Clear cell ovarian carcinoma following polymyositis diagnosis: a case report and review of the literature.

Background: The association of ovarian malignancy with dermatomyositis (DM) is well established from previous reports, while the relationship with polymyositis (PM) is rare.

Case Report: We report a case of a 50 years old nulliparous woman who developed clear cell ovarian cancer four years after the PM diagnosis. The patient presented with deep lower abdominal pain and distension.

Potential value of PTEN in predicting cetuximab response in colorectal cancer: an exploratory study.

Background: The epidermal growth factor receptor (EGFR) is over-expressed in 70-75% of colorectal adenocarcinomas (CRC). The anti-EGFR monoclonal antibody cetuximab has been approved for the treatment of metastatic CRC, however tumor response to cetuximab has not been found to be associated with EGFR over-expression by immunohistochemistry (IHC). The aim of this study was to explore EGFR and the downstream effector phosphatase and tensin homologue deleted on chromosome 10 (PTEN) as potential predictors of response to cetuximab.

Intensive weekly chemotherapy with docetaxel, epirubicin and carboplatin with G-CSF support in patients with advanced gastric cancer: a Hellenic Cooperative Oncology Group (HeCOG) phase II study.

Chemotherapy is an established modality in the management of patients with advanced gastric cancer but the optimal regimen has not been defined yet. Platinum and the anthracyclines and more recently docetaxel have shown activity in this tumor. The primary objective of this phase II study was to assess the efficacy and safety of an intensified regimen of weekly docetaxel/epirubicin/carboplatin (DECb) with growth factor support in previously untreated patients with advanced gastric cancer.

Prognostic factors in patients with colorectal cancer receiving adjuvant chemotherapy or chemoradiotherapy: a pooled analysis of two randomized studies.

Background: Although the TNM system is useful in predicting survival in resected colorectal cancer, heterogeneity within the same stages regarding prognosis exists. We are presenting a pooled analysis of prognostic factors from two randomized studies of adjuvant treatment conducted by the Hellenic Cooperative Oncology Group.

Patients And Methods: Patients with stage II or III colon (n = 279) or rectal (n = 220) cancer were included in this analysis.

Relative bioavailability study of two nifedipine tablet formulations in healthy male volunteers.

Objective: To assess the bioequivalence of two oral formulations containing 10 mg of nifedipine. The test preparation were Macorel tablets, the reference preparation were Adalat tablets.

Subjects, Material And Methods: The study was designed as a single-dose, three-period crossover randomized design to 18 non-smoker, healthy male volunteers under fasting conditions.