Small cell ovarian cancer in adolescents: report of two cases and review of the literature.

Ovarian small cell carcinoma is a rare and highly malignant neoplasm carrying a poor prognosis. Although combination chemotherapy remains the cornerstone of treatment due to the rarity of these tumors, no regimen can be recommended as standard of care although in the majority of cases platinum-based regimens are used. Herein, we report two cases of small cell carcinoma of the ovaries along with a review of the relevant literature.

DNA methylation of tumor suppressor and metastasis suppressor genes in circulating tumor cells.

Background: Circulating tumor cells (CTCs) are associated with prognosis in a variety of human cancers and have been proposed as a liquid biopsy for follow-up examinations. We show that tumor suppressor and metastasis suppressor genes are epigenetically silenced in CTCs isolated from peripheral blood of breast cancer patients.

Methods: We obtained peripheral blood from 56 patients with operable breast cancer, 27 patients with verified metastasis, and 23 healthy individuals.

Immunohistochemical study of the angiogenetic network of VEGF, HIF1α, VEGFR-2 and endothelial nitric oxide synthase (eNOS) in human breast cancer.

Background: The role of Nitric Oxide (NO) in angiogenesis has not been fully clarified yet. A dual role for NO, either inductive or inhibitory, has been proposed on the basis of different effects that high or low concentrations of NO may exert on the angiogenic process. Additionally, it has been referred that NO may induce VEGF production, while VEGF may induce NO production via up-regulation of the endothelial nitric oxide synthase (eNOS), the two pathways being reverse.

Docetaxel vs. vinorelbine in elderly patients with advanced non--small-cell lung cancer: a hellenic oncology research group randomized phase III study.

Background/purpose: This study compared front-line treatment with docetaxel or vinorelbine in elderly patients with advanced/metastatic non-small-cell lung cancer (NSCLC).

Patients And Methods: Chemotherapy-naive patients with inoperable stage IIIB and stage IV NSCLC who were > 65 years of age with performance status (PS) of 0-2 were enrolled. Patients were assigned to receive either docetaxel 38 mg/m(2) or vinorelbine 25 mg/m(2) by intravenous (I.

Cytokeratin-19 mRNA-positive circulating tumor cells during follow-up of patients with operable breast cancer: prognostic relevance for late relapse.

Background: The detection of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTC) before and/or after adjuvant chemotherapy in patients with operable breast cancer is associated with poor clinical outcome. Reliable prognostic markers for late disease relapse are not available. In this study we investigated the value of CTC detection during the first five years of follow-up in predicting late disease relapse.

Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients.

Introduction: Epithelial to mesenchymal transition (EMT) is considered an essential process in the metastatic cascade. EMT is characterised by upregulation of vimentin, Twist, Snail, Slug and Sip1 among others. Metastasis is also associated with the presence of circulating tumour cells (CTCs) and disseminated tumour cells in the blood and bone marrow, respectively, of breast cancer patients, but the expression of EMT markers in these cells has not been reported so far.

Mini Nutritional Assessment (MNA) and biochemical markers of cachexia in metastatic lung cancer patients: interrelations and associations with prognosis.

Purpose: Lung cancer patients frequently present with weight loss in the context of the cachexia syndrome. Despite its high clinical significance, definite diagnostic criteria of cachexia are lacking. Nutritional screening questionnaires, like the Mini Nutritional Assessment (MNA), have been proposed for the timely diagnosis of the syndrome.

A phase I trial of oral metronomic vinorelbine plus capecitabine in patients with metastatic breast cancer.

Purpose: To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTD) of oral metronomic vinorelbine with capecitabine in patients with metastatic breast cancer (MBC).

Patients And Methods: Escalated doses of oral metronomic vinorelbine (starting dose 30 mg) every other day continuously and capecitabine (starting dose 800 mg/m(2) bid) on days 1-14 every 21 days were administered. DLTs were evaluated during the first cycle.

Second-line paclitaxel/carboplatin versus vinorelbine/carboplatin in patients who have advanced non-small-cell lung cancer pretreated with non-platinum-based chemotherapy: a multicenter randomized phase II study.

Purpose: This study evaluates the activity and toxicity of the paclitaxel/carboplatin (PC) doublet versus vinorelbine/carboplatin (VC) doublet as second-line treatment in patients who have advanced non-small-cell lung cancer (NSCLC).

Patients And Treatment: Patients pretreated with front-line docetaxel and gemcitabine were randomized to receive either PC (n = 75), which consisted of paclitaxel at a dose of 140 mg/m(2) and carboplatin area under the curve (AUC3), or VC (n = 78), which consisted of vinorelbine at a dose of 45 mg/m(2) orally and carboplatin AUC3; both drugs were administered on days 1 and 15.

Results: The overall response rate was 18.

Identification of the M541L sequence variation of the transmembrane KIT domain in Merkel cell carcinoma.

Background: Merkel cell carcinoma (MCC) is an aggressive KIT-positive cutaneous tumor. KIT mutations are considered to play a key role in the pathogenesis of various neoplasms, but have not been found so far in MCC. The aim of the present study was therefore to investigate the presence of KIT mutations in MCC.

Efficacy and treatment tolerance in older patients with NSCLC: a meta-analysis of five phase III randomized trials conducted by the Hellenic Oncology Research Group.

Background: Approximately 50% of newly diagnosed cases of non-small-cell lung cancer (NSCLC) are observed in patients >65 years, while 30%-40% of cases occur in patients >70 years.

Patients And Methods: The objective of the current study was to determine (i) the number of elderly (>70 years) patients with advanced/metastatic NSCLC enrolled in phase III trials of the Hellenic Oncology Research Group, (ii) the treatment-related toxicity observed in these patients compared with their younger counterparts, and (iii) the differences in terms of response rate, time to tumor progression (TTP), and overall survival (OS) between younger and older patients.

Results: Pooled data from five clinical trials including 1845 patients were analyzed; 1421 (77%) and 424 (23%) were <70 years and ≥70 years, respectively.

Crescentic glomerulonephritis associated with vascular endothelial growth factor (VEGF) inhibitor and bisphosphonate administration.

Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, has been widely used in a variety of malignancies offering substantial clinical benefit. Hypertension and proteinuria are the most commonly reported manifestations of bevacizumab-related nephrotoxicity with the risk increasing along with the dose and with the concomitant use of bisphosphonates. We describe the first case of a patient with small-cell lung cancer who developed diffuse extracapillary necrotizing crescentic glomerulonephritis, temporarily necessitating haemodialysis, following administration of bevacizumab and zolendronate.

Assessment of the effect of surgery on the kinetics of circulating tumour cells in patients with operable breast cancer based on cytokeratin-19 mRNA detection.

Aims: The aim of this study was to evaluate the effect of surgery on the kinetics of CTCs in breast cancer patients.

Methods: The detection of CK-19 mRNA-positive CTCs in the blood by RT-PCR was analysed in 104 stage 0-IIIA patients at 4 time-points: prior to surgery, upon completion, 24 h after surgery and 15 days after surgery. Furthermore, a late sample was assessed prior to initiation of adjuvant chemotherapy in a subgroup of 53 patients.

Impact of KRAS, BRAF, PIK3CA mutations, PTEN, AREG, EREG expression and skin rash in ≥ 2 line cetuximab-based therapy of colorectal cancer patients.

Background: To investigate the predictive significance of KRAS, BRAF, PIK3CA mutational status, AREG- EREG mRNA expression, PTEN protein expression and skin rash in metastatic colorectal cancer (mCRC) patients treated with cetuximab containing salvage chemotherapy.

Methods: Primary tumors from 112 mCRC patients were analyzed. The worst skin toxicity during treatment was recorded.

Prophylactic and therapeutic strategies in chemotherapy-induced neutropenia.

Introduction: Neutropenia poses a serious threat to patients on chemotherapy. It exposes them to the risk of infection--including potentially fatal infections--and also leads to delays in treatment and reductions in dose intensity, which can compromise the possibility of a favorable outcome.

Areas Covered: The use of granulocyte colony-stimulating factors (G-CSF) and antibiotics to prevent febrile neutropenia (FN) and to ameliorate cancer chemotherapy-induced myelosuppression is discussed, based on a systematic search of Pubmed for clinical trials, reviews and meta-analysis published in the last 20 years.

Molecular characterization of circulating tumor cells in breast cancer by a liquid bead array hybridization assay.

Background: Molecular characterization of circulating tumor cells (CTCs) is crucial to identify novel diagnostic and therapeutic targets for individualized therapies. We developed a multiplexed PCR-coupled liquid bead array to detect the expression of multiple genes in CTCs.

Methods: mRNA isolated from immunomagnetically enriched CTCs was subjected to multiplex PCR for KRT19 (keratin 19; also known as CK19), ERBB2 [v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian); also known as HER2], SCGB2A2 (secretoglobin, family 2A, member 2; also known as MGB1, mammaglobin A), MAGEA3 (melanoma antigen family A, 3), TWIST-1 [twist homolog 1 (Drosophila)], and HMBS (hydroxymethylbilane synthase; also known as PBGD).

Targeting the insulin-like growth factor I receptor inhibits proliferation and VEGF production of non-small cell lung cancer cells and enhances paclitaxel-mediated anti-tumor effect.

The effects of AVE1642, a human monoclonal antibody against IGF-IR, were examined in NSCLC cell lines in order to characterize its anti-proliferative and anti-angiogenic activity as a single agent and in combination with chemotherapy. AVE1642 inhibited IGF-IR signaling and suppressed IGF-I-induced, serum-stimulated or autocrine-mediated proliferation of NSCLC cells in vitro. Furthermore, the combination of paclitaxel and AVE1642 resulted in a sequence-dependent increase in the inhibition of cell proliferation, compared to each agent alone, which was associated with a dose-dependent increase in phosphorylated IGF-IR and Akt.

Correlation of BRCA1, TXR1 and TSP1 mRNA expression with treatment outcome to docetaxel-based first-line chemotherapy in patients with advanced/metastatic non-small-cell lung cancer.

Background: We explored the predictive significance of BRCA1, TXR1 and TSP1 expression in non-small-cell lung cancer (NSCLC) patients treated with docetaxel in association with cisplatin or gemcitabine.

Methods: To analyse BRCA1, TXR1 and TSP1 mRNA expression from microdissected primary tumours of 131 patients with stage IIIB (wet) and IV NSCLC, RT-qPCR was used.

Results: The mRNA levels of TXR1/TSP1 were inversely correlated (Spearman's test: -0.

Hypofractionated accelerated CT-guided interstitial ¹⁹²Ir-HDR-Brachytherapy as re-irradiation in inoperable recurrent cervical lymphadenopathy from head and neck cancer.

Background: Despite significant improvements in the treatment of head and neck cancer (HNC), lymph node recurrences remain a clinical challenge after primary radiotherapy. The value of interstitial (IRT) brachytherapy (BRT) for control of lymph node recurrence remains unclear. In order to clarify its role a retrospective review was undertaken on the value of computed tomography (CT)-guided IRT high-dose-rate (HDR)-BRT in isolated recurrent disease from HNC.

A randomized phase III study of the docetaxel/carboplatin combination versus docetaxel single-agent as second line treatment for patients with advanced/metastatic non-small cell lung cancer.

Background: To compare the activity and toxicity of docetaxel/carboplatin (DC) doublet vs single agent docetaxel (D) as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC).

Methods: Patients pre-treated with front-line platinum-free regimens, were randomized to receive either docetaxel/carboplatin (DC), (docetaxel 50 mg/m2; carboplatin AUC4; both drugs administered on days 1 and 15) or docetaxel single-agent (D), (docetaxel 50 mg/m2 on days 1 and 15).

Results: Response rate was similar between the two arms (DC vs D: 10.

Prognostic significance of the detection of peripheral blood CEACAM5mRNA-positive cells by real-time polymerase chain reaction in operable colorectal cancer.

Purpose: To evaluate the clinical relevance of circulating CEACAM5mRNA-positive cells in patients with operable colorectal cancer (CRC).

Methods: Peripheral blood was obtained from 265 patients with operable CRC before the initiation of adjuvant systemic therapy from 96 normal donors and RNA prepared from the Lovo and ARH-77 CRC and leukemic cell lines, respectively, was used as positive and negative controls. The detection of CEACAM5mRNA-positive cells was done using a real-time PCR assay.

A dose-escalation study of pemetrexed and docetaxel in non-small-cell lung cancer.

A phase I study was conducted to determine the maximum tolerated doses (MTD) and the dose-limiting toxicities (DLT) of pemetrexed and docetaxel in patients with advanced unresectable or metastatic non-small-cell lung cancer (NSCLC). Patients were treated with escalating doses of pemetrexed (400-600 mg/m(2) as a 10-min intravenous infusion) and docetaxel (65-85 mg/m(2) as a 1-h intravenous infusion) on day 1, every 3 weeks. An expanded accrual at the level of the recommended dose (RD) had been scheduled.

A retrospective analysis of non-platinum-based first- and second-line chemotherapy in patients with advanced non-small cell lung cancer.

Background: Platinum-based chemotherapy represents the standard of care for advanced non-small cell lung cancer (NSCLC) while non-platinum-based regimens are frequently administered in patients with relapse. A retrospective analysis of the sequence administration of these regimens in the first- and second-line setting was performed.

Patients And Methods: The records of patients enrolled in the Hellenic Oncology Research Groups's randomized advanced NSCLC trials from February 1997 to September 2006 were retrospectively reviewed.

Baseline nutritional evaluation in metastatic lung cancer patients: Mini Nutritional Assessment versus weight loss history.

Background: Cancer cachexia adversely affects survival and quality of life but its timely recognition is problematic. Nutritional questionnaires, like the Mini Nutritional Assessment (MNA), could identify early those patients at risk. The aim of the study was to compare MNA with 5% weight loss, a common criterion used in oncologic evaluation.

Salvage treatment in metastatic breast cancer with weekly paclitaxel and bevacizumab.

Background: Weekly paclitaxel (P) in combination with bevacizumab (B) is an effective regimen as initial treatment of metastatic breast cancer (MBC). We investigated in a phase II study the activity of the same regimen as salvage therapy in MBC.

Methods: Pretreated women with MBC received weekly P (90 mg/m(2) days 1, 8, 15) and B (10 mg/kg days 1, 15) every 28 days.