Determination of breast cancer prognosis after neoadjuvant chemotherapy: comparison of Residual Cancer Burden (RCB) and Neo-Bioscore

Background To compare RCB (Residual Cancer Burden) and Neo-Bioscore in terms of prognostic performance and see if adding pathological variables improve these scores.Methods We analysed 750 female patients with invasive breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) at Institut Curie between 2002 and 2012. Scores were compared in global population and by BC subtype using Akaike information criterion (AIC), C-Index (concordance index), calibration curves and after adding lymphovascular invasion (LVI) and pre-/post-NAC TILs levels.Results RCB and Neo-Bioscore were significantly associated to disease-free and overall survival in global population and for triple-negative BC. RCB had the lowest AICs in every BC subtype, corresponding to a better prognostic performance. In global population, C-Index values were poor for RCB (0.66; CI [0.61–0.71]) and fair for Neo-Bioscore (0.70; CI [0.65–0.75]). Scores were well calibrated in global population, but RCB yielded better prognostic performances in each BC subtype. Concordance between the two scores was poor. Adding LVI and TILs improved the performance of both scores.Conclusions Although RCB and Neo-Bioscore had similar prognostic performances, RCB showed better performance in BC subtypes, especially in luminal and TNBC. By generating fewer prognostic categories, RCB enables an easier use in everyday clinical practice.Subject terms: Breast cancer, Breast cancer, Chemotherapy     

From bedside to bench: an evaluation of expectations and challenges encountered by young surgeons facing basic science

Abstract

Background: The evolution of surgical practice may lead to increasing difficulties for surgeons to perform fundamental research. The aim of this study was to evaluate the expectations and the challenges encountered by young surgeons when starting basic science.

Methods: A qualitative study was conducted in France. A written questionnaire was anonymously filled by the participants attending to the Master Degree in surgical science.

Results: The study included 47 participants (median age: 28 years, 59.6% of men); 37 (78.7%) participants had applied for a grant for their salary and 32 (68.1%) had obtained it. Nine (19.1%) participants had planned to keep their usual clinical activity. The main motivations were the perspective to embark on an academic career (55.3%) and improvement of knowledge in science (38.3%). The main barriers encountered were the lack of time (70.2%), the lack of interest (27.7%), the lack of financial support (23.4%) and administrative difficulties (12.8%).

Conclusion: This study identified main barriers that young surgeons have to face when getting involved in basic science underlining the need to improve institutional and financial support to ensure involvement of new generations of surgeons in surgical research.     

Penta-block copolymer microspheres: Impact of polymer characteristics and process parameters on protein release

Here, we aimed to develop protein loaded microspheres (MSs) using penta-block PLGA-based copolymers to obtain sustained and complete protein release. We varied MS morphology and studied the control of protein release. Lysozyme was used as a model protein and MSs were prepared using the solid-in-oil-in-water emulsion solvent extraction method. We synthesized and studied various penta-block PLGA-based copolymers. Copolymer characteristics (LA/GA ratio and molecular weight of PLGA blocks) influenced MS morphology. MS porosity was influenced by process parameters (such as solvent type, polymer concentration, emulsifying speed), whereas the aqueous volume for extraction and stabilizer did not have a significant effect. MSs of the same size, but different morphologies, exhibited different protein release behavior, with porous structures being essential for the continuous and complete release of encapsulated protein. These findings suggest strategies to engineer the morphology of MSs produced from PLGA-based multi-block copolymers to achieve appropriate release rates for a protein delivery system.     

Parallel indirect solution of optimal control problems

This paper presents an algorithm for the indirect solution of optimal control problems that contain mixed state and control variable inequality constraints. The necessary conditions for optimality lead to an inequality constrained two‐point BVP with index‐1 differential‐algebraic equations (BVP‐DAEs). These BVP‐DAEs are solved using a multiple shooting method where the DAEs are approximated using a single‐step linearly implicit Runge–Kutta (Rosenbrock–Wanner) method. An interior‐point Newton method is used to solve the residual equations associated with the multiple shooting discretization. The elements of the residual equations, and the Jacobian of the residual equations, are constructed in parallel. The search direction for the interior‐point method is computed by solving a sparse bordered almost block diagonal (BABD) linear system. Here, a parallel‐structured orthogonal factorization algorithm is used to solve the BABD system. Examples are presented to illustrate the efficiency of the parallel algorithm. It is shown that an American National Standards Institute C implementation of the parallel algorithm achieves significant speedup with the increase in the number of processors used. Copyright © 2013 John Wiley & Sons, Ltd.