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Haibe-Kains B.,Institute Jules Bordet | Haibe-Kains B.,Free University of Colombia | Haibe-Kains B.,Ontario Cancer Institute | Desmedt C.,Institute Jules Bordet | And 26 more authors.
Genomics Data | Year: 2013

Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant Trial of Principle (TOP) study, in which patients with estrogen receptor (ER)-negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase II-alpha (TOP2A) and develop a gene expression signature to identify those patients who do not benefit from anthracyclines. Here we describe in details the contents and quality controls for the gene expression and clinical data associated with the study published by Desmedt and colleagues in the Journal of Clinical Oncology in 2011 (Desmedt et al., 2011). We also provide R code to easily access the data and perform the quality controls and basic analyses relevant to this dataset. © 2013 The Authors. Source


De Azambuja E.,Free University of Colombia | Ameye L.,Free University of Colombia | Diaz M.,Hopital Ambroise Pare | Vandenbossche S.,Neuropsychologue CHIRECBrussels | And 12 more authors.
European Journal of Cancer | Year: 2015

Background Epirubicin-based chemotherapy improves the outcome of early breast cancer (BC) patients. However, cardiotoxicity remains an important side effect. Methods We re-consented node-positive BC patients enrolled in a phase III trial between 1988 and 1996 which compared six cycles of oral cyclophosphamide, methotrexate, fluorouracil (CMF) versus two epirubicin-cyclophosphamide regimens differing by the anthracycline cumulative dose [standard-dose epirubicin and cyclophosphamide (SDE) (8 × 60 mg/m2) and higher-dose epirubicin and cyclophosphamide (HDE) (8 × 100 mg/m2)]. Eligible patients were those who were alive and free of disease and had no contra-indications to the proposed tests (cardiac evaluation). Cardiotoxicity was defined as asymptomatic systolic dysfunction (left ventricular ejection fraction (LVEF) < 50%, New York Heart Association (NYHA) Class I) or symptomatic heart failure (NYHA Class II-IV). Differences in cardiotoxicity between CMF and SDE/HDE were assessed using chi-square and Fisher Exact tests for binary variables and t-test and Wilcoxon test for continuous variables. Results Among the 777 patients, 20 cases of CHF were reported (CMF = 1, SDE = 5, HDE = 14; p < 0.001). Between September 2010 and June 2013, 82 patients (30%) out of 269 eligible patients accepted to participate in this substudy. Median follow-up was 18 years (range 15-24). Epirubicin-treated patients had significantly higher heart rate, more abnormal echocardiograms and LVEF by magnetic resonance imaging (MRI) compared to CMF-treated ones. A trend towards higher BNP was also observed in the SDE/HDE group (P = 0.08). No differences were observed in LVEF assessed by echocardiogram or troponin T levels. Conclusions Participation rate in this substudy was lower than expected highlighting the complexity of re-calling patients several years after the initial BC diagnosis. After 18 years, epirubicin-treated patients had a lower LVEF by MRI, more abnormal echocardiograms, higher heart rates compared to patients treated with CMF. However, no major delayed cardiotoxicity was observed. © 2015 Elsevier Ltd. Source


Van Esch A.,7Sigma | Huyskens D.P.,7Sigma | Behrens C.F.,Copenhagen University | Samose E.,Copenhagen University | And 6 more authors.
Medical Physics | Year: 2011

Purpose: With the increased commercial availability of intensity modulated arc therapy (IMAT) comes the need for comprehensive QA programs, covering the different aspects of this newly available technology. This manuscript proposes such a program for the RapidArc (RA) (Varian Medical Systems, Palo Alto) IMAT solution. Methods: The program was developed and tested out for a Millennium120 MLC on iX Clinacs and a HighDefinition MLC on a Novalis TX, using a variety of measurement equipment including Gafchromic film, 2D ion chamber arrays (Seven29 and StarCheck, PTW, Freiburg, Germany) with inclinometer and Octavius phantom, the Delta4 systam (ScandiDos, Uppsala, Sweden) and the portal imager (EPID). First, a number of complementary machine QA tests were developed to monitor the correct interplay between the accelerating/decelerating gantry, the variable dose rate and the MLC position, straining the delivery to the maximum allowed limits. Second, a systematic approach to the validation of the dose calculation for RA was adopted, starting with static gantry and RA specific static MLC shapes and gradually moving to dynamic gantry, dynamic MLC shapes. RA plans were then optimized on a series of artificial structures created within the homogeneous Octavius phantom and within a heterogeneous lung phantom. These served the double purpose of testing the behavior of the optimization algorithm (PRO) as well as the precision of the forward dose calculation. Finally, patient QA on a series of clinical cases was performed with different methods. In addition to the well established in-phantom QA, we evaluated the portal dosimetry solution within the Varian approach. Results: For routine machine QA, the Snooker Cue test on the EPID proved to be the most sensitive to overall problem detection. It is also the most practical one. The Twinkle and Sunrise tests were useful to obtain well differentiated information on the individual treatment delivery components. The AAA8.9 dose calculations showed excellent agreement with all corresponding measurements, except in areas where the 2.5 mm fixed fluence resolution was insufficient to accurately model the tongue and groove effect or the dose through nearly closed opposing leafs. Such cases benefited from the increased fluence resolution in AAA10.0. In the clinical RA fields, these effects were smeared out spatially and the impact of the fluence resolution was considerably less pronounced. The RA plans on the artificial structure sets demonstrated some interesting characteristics of the PRO8.9 optimizer, such as a sometimes unexpected dependence on the collimator rotation and a suboptimal coverage of targets within lung tissue. Although the portal dosimetry was successfully validated, we are reluctant to use it as a sole means of patient QA as long as no gantry angle information is embedded. Conclusions: The all-in validation program allows a systematic approach in monitoring the different levels of RA treatments. With the systematic approach comes a better understanding of both the capabilities and the limits of the used solution. The program can be useful for implementation, but also for the validation of major upgrades. © 2011 American Association of Physicists in Medicine. Source

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