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Tannock I.F.,Princess Margaret Cancer Center | Fizazi K.,University Paris - Sud | Karlsson C.T.,Onkologiska Kliniken Norrlands Universitetssjukhus | Flechon A.,CRLC Leon Berard | And 16 more authors.
The Lancet Oncology | Year: 2013

Background: Docetaxel plus prednisone is standard first-line chemotherapy for men with metastatic castrate-resistant prostate cancer. Aflibercept is a recombinant human fusion protein that binds A and B isoforms of VEGF and placental growth factor, thereby inhibiting angiogenesis. We assessed whether the addition of aflibercept to docetaxel and prednisone would improve overall survival in men with metastatic castrate-resistant prostate cancer compared with the addition of placebo to docetaxel and prednisone. Methods: VENICE was a phase 3, multicentre, randomised double-blind placebo-controlled parallel group study done in 31 countries (187 sites). Men with metastatic castrate-resistant prostate cancer, adequate organ function, and no prior chemotherapy were treated with docetaxel (75 mg/m2 intravenously every 3 weeks) and oral prednisone (5 mg twice daily) and randomly allocated (1:1) to receive aflibercept (6 mg/kg) or placebo, intravenously, every 3 weeks. Treatment allocation was done centrally via an interactive voice response system, using a computer-generated sequence with a permuted-block size of four and stratified according Eastern Co-operative Group performance status (0-1 vs 2). Patients, investigators, and other individuals responsible for study conduct and data analysis were masked to treatment assignment. Aflibercept or placebo vials were supplied in identical boxes. The primary endpoint was overall survival using intention-to-treat analysis. This is the primary analysis of the completed trial. The study is registered with ClinicalTrials.gov, number NCT00519285. Findings: Between Aug 17, 2007, and Feb 11, 2010, 1224 men were randomly allocated to treatment: 612 to each group. At final analysis, median follow-up was 35 months (IQR 29-41) and 873 men had died. Median overall survival was 22·1 months (95·6% CI 20·3-24·1) in the aflibercept group and 21·2 months (19·6-23·8) in the placebo group (stratified hazard ratio 0·94, 95·6% CI 0·82-1·08; p=0·38). We recorded a higher incidence of grade 3-4 gastrointestinal disorders (182 [30%] vs 48 [8·0%]), haemorrhagic events (32 [5·2%] vs ten [1·7%]), hypertension (81 [13%] vs 20 [3·3%]), fatigue (97 [16%] vs 46 [7·7%]), infections (123 [20%] vs 60 [10%]) and treatment-related fatal adverse events (21 [3·4%] vs nine [1·5%]) in the aflibercept group than in the placebo group. Interpretation: Aflibercept in combination with docetaxel and prednisone given as first-line chemotherapy for men with metastatic castrate-resistant prostate cancer resulted in no improvement in overall survival and added toxicity compared with placebo. Docetaxel plus prednisone remains the standard treatment for such men who need first-line chemotherapy. Funding: Sanofi and Regeneron Pharmaceuticals Inc. © 2013 Elsevier Ltd.


PubMed | Area Oncologia Digestiva, Hospital Universitario Of Antwerp, Institute Cancerologia, University of Chile and 20 more.
Type: Journal Article | Journal: Revista medica de Chile | Year: 2017

Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Via del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.


Muller B.G.,Instituto Nacional del Cancer | De Aretxabala X.,Instituto Nacional del Cancer | Gonzalez Domingo M.,Instituto Nacional del Cancer
American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting | Year: 2014

Gallbladder cancer is now considered a distinct clinical entity, allowing for a separate analysis from that of other malignancies of the biliary tree. Symptoms related to a malignant tumor of the gallbladder include jaundice and abdominal pain, or a palpable abdominal mass that occurs in a late stage of the disease. The majority of patients with operable gallbladder cancer are diagnosed by cholecystectomy performed for presumed benign disease, mostly cholelithiasis, a clinical entity known as incidental gallbladder cancer. Given the poor prognosis if tumor invasion beyond the muscular layer and/or nodal metastasis is found, adjuvant treatments have been implemented, but few data are available to guide treatment decisions in this setting. For advanced disease, a multidisciplinary treatment approach including biliary drainage procedures and palliative support is needed in the management of this aggressive disease. Palliative chemotherapy with a combination of gemcitabine and cisplatin or oxaliplatin is the standard treatment based on the findings of two phase III trials that showed improved overall survival compared to single-agent chemotherapy and best supportive care. Several phase II studies have been reported investigating the role of targeted agents against EGFR, VEGF, HER2, and MEK. International collaboration to enhance our knowledge of gallbladder cancer should be encouraged.


Figueroa R.G.,University of the Frontier | Lozano E.,Instituto Nacional del Cancer | Flores M.A.,University of the Frontier
International Journal of Morphology | Year: 2011

The knowledge of the concentration and spatial distribution that chemical elements present in different organs and tissues is a useful parameter for diagnosis of certain diseases or element levels above limits accepted as healthy. Therefore, development of techniques to identify the chemical elements present in a living tissue and obtaining information about their concentration and spatial distribution might be relevant to determine an individual's health status. This work presents an application of a new X-ray fluorescence technique, energy dispersive by scanning, which can be applied to samples of different composition and shape, unlike most of the existing techniques, only applicable to flat samples. This technique allows the acquisition of two-dimensional images of the chemical elements present in a sample in both mono and multielemental mode. In this work the technique is applied to a set of human bone samples and tarsus and fingers of a dead Gallus gallus (chicken), obtaining a 2D spatial distribution with different levels of fluorescence intensity, depending on the detected element and its concentration. The acquired images consider areas up to 104 mm2, with a spatial resolution of 400 mm2 and an acquisition time of about 20 min. Calculations of the radiation dose associated with this type of XRF analysis were also carried out, and the findings show that the levels applied to obtain an XRF image are tolerable. The latter leads to the conclusion that it would be possible to use this technique for an in vivo application.


Santibanez M.,University of the Frontier | Diaz A.,Instituto Nacional del Cancer | Figueroa R.G.,University of the Frontier
X-Ray Spectrometry | Year: 2016

When obtaining a chemical element image through energy dispersive X-ray fluorescence (EDXRF) scanning of a specific sample, it is important to determine the minimum detection time (MDT) required per dot (pixel) and per element in order to identify the minority and the trace elements present in the sample. Starting from the statistical criteria of limit of detection, quantitative estimations can be made regarding the concentration of elements present in the samples, determining the MDT which fits to the limit of detection previously established. Given that with this technique it is possible to implement in vivo applications, in this work, a process was developed for the MDT that is capable of generating the minimum radiation exposure in imaging EDXRF. For this proposal, the MDT is determined for metals, such as Fe, Cu, and Pb, given their great biomedical interest, in a series of equivalent bone and soft tissue phantom samples. Consequently, a criteria for global scanning time per dot was established, hence providing an elemental XRF image according to the As Low As Reasonably Achievable principles, i.e. as low an exposure as reasonably possible for each sample type studied by this sort of devices, in order to obtain appropriate information for each field of application. © 2016 John Wiley & Sons, Ltd.


Leo A.D.,Dell | Jerusalem G.,University of Liège | Petruzelka L.,Charles University | Torres R.,Instituto Nacional Del Cancer | And 11 more authors.
Journal of the National Cancer Institute | Year: 2014

BackgroundAt the time of the initial analysis of overall survival (OS) for the Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) randomized, double-blind, phase III trial, approximately 50% of patients had died. A final analysis of OS was subsequently planned for when 75% of patients had died.MethodsPatients were randomly assigned 1:1 to fulvestrant 500 mg administered as two 5-mL intramuscular injections on days 0, 14, and 28 and every 28 (±3) days thereafter or fulvestrant 250 mg administered as two 5-mL intramuscular injections (one fulvestrant and one placebo [identical in appearance to study drug]) on days 0, 14 (two placebo injections only), and 28 and every 28 (±3) days thereafter. OS was analyzed using an unadjusted log-rank test. No adjustments were made for multiplicity. Serious adverse events (SAEs) and best response to subsequent therapy were also reported. All statistical tests were two-sided.ResultsIn total, 736 women (median age = 61.0 years) were randomly assigned to fulvestrant 500mg (n = 362) or 250mg (n = 374). At the final survival analysis, 554 of 736 (75.3%) patients had died. Median OS was 26.4 months for fulvestrant 500mg and 22.3 months for 250mg (hazard ratio = 0.81; 95% confidence interval = 0.69-0.96; nominal P =. 02). There were no clinically important differences in SAE profiles between the treatment groups; no clustering of SAEs could be detected in either treatment group. Type of first subsequent therapy and objective responses to first subsequent therapy were well balanced between the two treatment groups.ConclusionsIn patients with locally advanced or metastatic estrogen receptor-positive breast cancer, fulvestrant 500mg is associated with a 19% reduction in risk of death and a 4.1-month difference in median OS compared with fulvestrant 250mg. Fulvestrant 500mg was well tolerated, and no new safety concerns were identified. © 2013 © The Author 2013. Published by Oxford University Press.


Figueroa R.G.,University of the Frontier | Lozano E.,Instituto Nacional del Cancer | Bongiovannic G.,CONICET
Revista Mexicana de Fisica | Year: 2013

Visualization of elemental distributions of biological tissue is gaining importance in many disciplines of biological, forensic, and medical research. Furthermore, the maps of elements have wide application in archeology for the understanding of the pigments, modes of preservation and environmental context. Since major advances in relation to collimators and detectors have yielded micro scale images, the chemical mapping via synchrotron scanning micro-X-ray fluorescence spectrometry (SR-μXRF) is widely used as microanalytical techniques. However, the acquisition time is a limitation of current SR-μXRF imaging protocols, doing tedious micro analysis of samples of more than 1 cm and very difficult to study of larger samples such as animal organ, whole organisms, work of art, etc. Recently we have developed a robotic system to image the chemistry of large specimens rapidly at concentration levels of parts per million. Multiple images of distribution of elements can be obtained on surfaces of 100×100 mm and a spatial resolution of up to 0.2 mm2 per pixel, with a spectral capture time up to 1 ms per point. This system has proven to be highly efficient for the XRF mapping of elements in large biological samples, achieving comparables results to those obtained by SR-μXRF. Thus, images of As and Cu accumulation in renal cortex of arsenic-exposed rats were obtained by both methodologies. However, the new imaging system enables the XRF scanning in few minutes, whereas SR-μXRF required several hours. These and other advantages as well as the potential applications of this system, will be discussed.


Britez M.E.M.,Clinical Hospital | Llano C.C.,Instituto Nacional del Cancer | Chaux A.,Research Laboratory
European Journal of Plastic Surgery | Year: 2012

Background Silicone gel-containing breast implants have been widely used for aesthetic and reconstructive mammoplasty. The development of a periprosthetic capsule is considered a local reparative process against the breast implant in which a variety of inflammatory cells may appear. Nevertheless, only few reports have evaluated the immunophenotypes of those inflammatory cells. Herein, we aim to provide more information in this regard evaluating 40 patients with breast implants. Methods We studied the immunophenotype of the inflammatory cells of capsular implants using antibodies against lymphocytes (CD3, CD4, CD8, CD20, CD45, and CD30) and histiocytes (CD68). Percentages of CD3 and CD20 positive cells were compared using the unpaired Student'st test. Fisher's test was also used to compare Baker grades by implant type, implant profile, and location and the presence of inflammatory cells by implant type. Results The associations between Baker grades and implant type and location were statistically nonsignificant (p00.42 in both cases). However, the use of low profile implants was significantly associated (p00.002) with a higher proportion of Baker grades 3 and 4. We found evidence of inflammation in 92.5 % of all implant capsules, with a statistically significant (p00.036) higher proportion in textured breast implants. T cells predominated over B cells. Textured implants elicited a more marked response to T cells than smooth implants, with a similar proportion of helper and cytotoxic T cells. Textured implants showed statistically significant higher percentages of CD3 positive cells than smooth implants. Percentages of CD20 positive cells were similar in textured and smooth implants. Conclusions These results suggest that textured breast implants might induce a stronger local T cell immune response. Our findings could shed some light to understand the association of silicone breast implants and some cases of anaplastic large cell lymphomas. Level of Evidence: Level III, prognostic study. © The Author(s) 2012.


Apt W.,University of Chile | Zulantay I.,University of Chile | Arnello M.,University of Chile | Oddo D.,Instituto Nacional del Cancer | And 5 more authors.
Transactions of the Royal Society of Tropical Medicine and Hygiene | Year: 2013

This study investigated the prevalence of Chagas disease (ChD) in pregnant women in Choapa Province (IV Region, Chile) and the vertical transmission of Trypanosoma cruziELISA and IFI IgG for ChD was performed for the pregnant women. PCR for T. cruzi was done for all chagasic mothers and their newborns. The congenital infection was confirmed by serial positive PCR and/or ELISA or IFI IgG after age of nine months. The placentas of mothers, with and without ChD, were submitted for histopathology and immunohistochemical study. Results: From 4831 deliveries in 2005-2009 with a serological coverage of 88.6%, it was established that 147 cases (3.4%) had ChD. More than 80% of the pregnancies had a physiological evolution and 90% of the newborn were term. Congenital transmission was demonstrated in six children (4.7%) of the 127 newborn studied by serial PCR (at birth and/or between 3-18 months) and/or ELISA or IIF IgG after age nine months. Most of congenital cases were asymptomatic (67%). The histopathology shows edema, necrosis, fibrinoid deposit in the placentas of 28 of 29 chagasic mothers. In three cases the immnunochemistry demonstrated a decrease in actin expression in trophoblast cells. In one congenital case amastigote nests was observed. Conclusions: These results indicate that T. cruzi infection in pregnant women and vertical transmission in Chile are still prevalent. For this reason it is important to propose control measures in endemic areas of the country. © Royal Society of Tropical Medicine and Hygiene 2012. All rights reserved.


Diaz A.,University of the Frontier | Parra C.,Instituto Nacional del Cancer | Valdes C.,Instituto Nacional del Cancer | Santibanez M.,University of the Frontier | Figueroa R.G.,University of the Frontier
X-Ray Spectrometry | Year: 2015

Knowing the spectrum near the output of the relatively new mini X-ray tube (MXRT) commercial models is fundamentally important in energy-dispersive X-ray fluorescence scan images, especially in the in vivo applications. This information is relevant for determining the absorbed dose during a measurement and for absolute quantification by a fundamental parameter method. However, it is not possible to measure it directly using a silicon drift detector (SDD) given the high saturation in the counts. In this work, an experimental methodology is developed for determining the kernel spectrum emitted by the MXRT, enabling the quantification of its energy flux density over short distances. Different distances were used: source-detector, solid emission angle (collimation), attenuation characteristics of the medium (air), and in a vacuum, within an energy range of 1-40keV, to determine the X-ray tube spectrum. The spectrum is measured by an SDD, taking its efficiency and dead time into account. In order to verify the method, a spectrum that is rebuilt starting with the kernel is compared, under the same conditions, with a reference spectrum that is directly measured in air and with a theoretical spectrum obtained by the Ebel model. The results are consistent and validate the methodology employed in this work. Additionally, low-energy peaks were detected, corresponding to the tube material's L lines, which are not present in the original spectrum reported by the manufacturer. © 2015 John Wiley & Sons, Ltd.

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