Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5?mg/kg i.v. 3 weekly for 1?year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56?years (range 18-88?years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5?years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P?=?0.78). At 5?years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P?=?0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P?=?0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P?=?0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P?=?0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64

Some fundamental aspects of surface modelling

Attention is drawn to four aspects of surface modelling: (1) delineation of the (scale-dependent) geometrical boundary of a body via molecular considerations, (2) identification of the highly inhomogeneous interfacial region between a body and its exterior, and its modelling as a bidimensional continuum involving interfacial excess quantities, (3) the utility of co-ordinate-free notation for surfaces, and (4) the importance of surface effects for small-scale bodies exemplified within a thermoelastic context

Caracterização fenotípica e molecular de esporos de fungos micorrízicos arbusculares mantidos em banco de germoplasma Phenotypic and molecular characterization of arbuscular mycorrhizal fungal spores from cultures maintained in germplasm collection

O objetivo deste trabalho foi caracterizar fenotípica e genotipicamente isolados de espécies de fungos micorrízicos arbusculares (FMA) mantidos em cultura pura e avaliar a aplicabilidade da técnica PCR-DGGE desenvolvida para Gigaspora, na identificação molecular de espécies de FMA pertencentes a outros gêneros. A caracterização fenotípica das espécies foi realizada de acordo com critérios morfológicos, descritos pela taxonomia, e com uso de descrições originais das espécies presentes na literatura especializada. A análise genotípica foi feita com base na discriminação específica da região V9 do 18S rDNA, que permitiu a diferenciação das espécies e não revelou qualquer diferença entre os isolados geográficos de Glomus clarum, e entre os de Glomus etunicatum. Isto indica a aplicabilidade da técnica para a avaliação da pureza genética e discriminação de espécies de FMA.<br>The objective of this work was to characterize phenotypically and genotypically isolates of arbuscular mycorrhizal fungi (AMF) maintained in pure culture and to evaluate the applicability of PCR-DGGE analysis, developed for Gigaspora, for molecular identification of AMF species belonging to other genres. The species phenotypic characterization was done according to morphological criteria, as described by taxonomy, and according to original descriptions of species published in the specialized literature. The genotypic analysis was made through specific discrimination of the V9 region in the 18S rDNA, which allowed the distinction of species and showed no difference among geographical isolates of Glomus clarum, and among those of Glomus etunicatum. This indicates the applicability of this technique for assessment of genetic purity and discrimination of AMF species

Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids

Background: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. Patients and methods: Bibliographical searches were carried out in PubMed for the terms &apos;pulmonary neuroendocrine tumors&apos;, &apos;bronchial neuroendocrine tumors&apos;, &apos;bronchial carcinoid tumors&apos;, &apos;pulmonary carcinoid&apos;, &apos;pulmonary typical/atypical carcinoid&apos;, and &apos;pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis&apos;. A systematic review of the relevant literature was carried out, followed by expert review. Results: PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing the tumor and preserving as much lung tissue as possible. Resection of metastases should be considered whenever possible with curative intent. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however, temozolomide has shown most clinical benefit. Conclusions: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved