59 research outputs found

    The association between adiposity and anti-proliferative response to neoadjuvant endocrine therapy with letrozole in post-menopausal patients with estrogen receptor positive breast cancer

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    The impact of adiposity on the efficacy of endocrine treatment in patients with estrogen receptor positive breast cancer is poorly investigated. Here, we retrospectively investigated in a cohort of 56 patients whether body mass index and/or mammary adiposity are associated with anti-proliferative response in the neoadjuvant setting. Anti-proliferative response was defined as high Ki67 at baseline (Ki67(bl)) and low Ki67 at surgery (Ki67(srg)), using the 14% cut-off. Mammary adipocyte size was assessed on hematoxylin and eosin slides from the surgical samples using digital pathology. A higher proportion of tumors with an anti-proliferative response was observed in patients with obesity (54.5%) as compared to patients with normal weight (9.0%) and patients with overweight (40.0%) (p = 0.031), confirmed by multivariable regression analysis adjusted for baseline Ki67 (OR, obese vs normal weight: 13.76, 95%CI: 1.49–207.63, p = 0.020). Larger adipocyte diameter was identified as predictor of anti-proliferative response (OR per increase in diameter of 5 μm for adipocytes distant from the tumor: 2.24, 95%CI: 1.01–14.32, p = 0.046). This study suggests that anti-proliferative response to neoadjuvant letrozole might be more frequent in patients with increased systemic or mammary adiposity

    Contactos entre los Países Bajos y el mundo ibérico /

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    Includes bibliographical references.Estudios. Contactos entre los Países Bajos y el mundo ibérico. A modo de introducción / Jan Lechner; Españoles y portugueses en los medios universitarios de Lovaina (siglos XV y XVI) / Gustaaf Janssens; El Duque de Alba en la conciencia colectiva de los flamencos / Lieve Behiels; El hombre que intentó convertir al rey de España: Hans Avontroot (1559-1633) / Werner Thomas; La "Guerra de Flandes". Una sinopsis de su leyenda negra (1550-1650) / Hugo de Schepper; Marineros flamencos en la carrera de Indias, 1598-1610 / Auke P. Jacobs; España: ¿La gran desconocida? Los viajes y su importancia en relación con el problema de los contactos culturales hispano-holandeses a partir de la sublevación de los Países Bajos / P. J. A. N. Rietbergen; España y los escritires sefardíes de Amsterdam / Harm den Boer; Neerlandofobia en Goa a principos del siglo XVII / B. N. Teensma;Análisis. Lectura de 'En bética no bella' de Carlos Germá, Belli / F. Lasarte;Artículos-reseña. Claude Cymerman (ed.), Le roman hispano-américain des années 80. Actes du colloque de Rouen 26-28 Avril 1990 / Leo Serrano; R. Lemm, De literatuur als filosoof. De innerlijke biografie van Jorge Luis Borges / Charo Crego y Ger Groot; Jacques de Coutre, Andanzas asiáticas / Maxim P. A. M. Kerkhof;Reseñas. J. A. de Moor y H. Ph. Vogel, Duizend miljoen maal vervloekt land. De Hollandse Brigade in Spanje 1808-1913 / Wim Klooster; Germán Gullón, La novela del siglo XIX: estudio sobre su evolución formal / Lieve Behiels; Elisabeth van Elsen y Doortje ter Horst, El juego de hacer versos. Spaanse en Spaans-Amerikaanse poëzie voor het onderwijs / Lily Coenen;Agenda del Hispanismo / Jenny Fraai-Roem y Tineke Groot; Colaboran

    Comparison of PSMA immunohistochemistry scoring systems to parametric [18F]PSMA-1007 PET/MRI in primary prostate cancer

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    Purpose Quantification of PSMA expression via PSMA PET is well-established, however quantification of PSMA via immunohistochemistry (IHC) is not standardized. Our aim was to determine the most optimal PSMA IHC scoring system to quantify PSMA expression with PSMA PET as reference standard. Methods Primary intermediate- and high-risk prostate cancer patients received an [F-18]PSMA-1007 PET/MRI followed by radical prostatectomy. SUVmax, SUVmean and K-i of the prostate tumor was determined. Prostate tumors were stained with anti-PSMA antibodies and scored by 2 readers via 10 IHC scoring systems: histochemical score (H-score), immunoreactivity score(predominant intensity) (IRSpredominant intensity), IRS classification(predominant intensity), IRSmean intensity, IRS classification(mean intensity), Allred score, predominant expression pattern, Shannon diversity index (SDI), percentage negatively stained cells and total percentage positively stained cells. Spearman's rank correlation coefficients (rho) were calculated between PET parameters and IHC scoring systems. Interreader agreement for the IHC scoring systems was measured by the intraclass correlation coefficient (ICC). Results Fifty tumors in 46 patients were analysed. H-score had the best correlation with SUVmax (rho 0.615 p < 0.0001) and SUVmean (rho 0.570, p < 0.0001) and the second best correlation with Ki (rho 0.411, p = 0.0030). SDI had the best correlation with Ki (rho -0.440, p = 0.0014) and the second best correlation with SUVmax (rho -0.516, p = 0.0001) and SUVmean (rho -0.490, p = 0.0003). A moderate interreader agreement was observed for H-score (ICC 0.663, 95% CI 0.495-0.797) and SDI (ICC 0.546, 95% CI 0.354-0.725). Conclusion H-score had the best correlation with PSMA PET quantification and an acceptable interreader agreement. Therefore, we deem H-score the most optimal PSMA IHC scoring system.Funding This work was supported by the Agency for Innovation By Science and Technology (IWT, grant number IWT.140193). Acknowledgements The authors are grateful to the study participants and to Kwinten Porters, Jef Van Loock, Stefan Ghysels, Kris Byloos and Guido Putzeys for their contribution to the scanning and data handling, and to Kathleen Van den Eynde, Nele Crama, Sabrina D’Haese and Sofie De Block for their contribution to the processing of the pathology specimens. Steven Joniau, Wouter Everaerts, Christophe M. Deroose are senior clinical investigators at the Research FoundationFlanders (FWO). Niloefar Ahmadi Bidakhvidi is a PhD fellow at the Research Foundation-Flanders (FWO)

    Digital analysis of distant and cancer-associated mammary adipocytes

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    Adipocytes and cancer-associated adipocytes (CAAs) are poorly investigated cells in the tumor microenvironment. Different image analysis software exist for identifying and measuring these cells using scanned hematoxylin and eosin (H&E)-stained slides. It is however unclear which one is the most appropriate for breast cancer (BC) samples. Here, we compared three software (AdipoCount, Adiposoft, and HALO®). HALO® outperformed the other methods with regard to adipocyte identification, (> 96% sensitivity and specificity). All software performed equally good with regard to area and diameter measurement (concordance correlation coefficients > 0.97 and > 0.96, respectively). We then analyzed a series of 10 BCE samples (n = 51 H&E slides) with HALO®. Distant adipocytes were defined >2 mm away from cancer cells or fibrotic region, whereas CAAs as the first three lines of adipocytes close to the invasive front. Intra-mammary heterogeneity was limited, implying that measuring a single region of ∼500 adipocytes provides a reliable estimation of the distribution of their size features. CAAs had smaller areas (median fold-change: 2.62) and diameters (median fold-change: 1.64) as compared to distant adipocytes in the same breast (both p = 0.002). The size of CAAs and distant adipocytes was associated with the body mass index (BMI) of the patient (area: rho = 0.89, p = 0.001; rho = 0.71, p = 0.027, diameter: rho = 0.87 p = 0.002; rho = 0.65 p = 0.049, respectively). To conclude, we demonstrate that quantifying adipocytes in BC sections is feasible by digital pathology using H&E sections, setting the basis for a standardized analysis of mammary adiposity in larger series of patients.sponsorship: This studywas funded by the Belgian Cancer Foundation (FAF-C/2018/1302) and the Luxemburg Cancer Foundation (FC/2018/07). (Belgian Cancer Foundation|FAF-C/2018/1302, Luxemburg Cancer Foundation|FC/2018/07)status: Publishe

    Treatment Response, Tumor Infiltrating Lymphocytes and Clinical Outcomes in Inflammatory Breast Cancer-Treated with Neoadjuvant Systemic Therapy

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    Inflammatory breast cancer (IBC) is a rare (1%-5%), aggressive form of breast cancer, accounting for approximately 10% of breast cancer mortality. In the localized setting, standard of care is neoadjuvant chemotherapy (NACT) ± anti-HER2 therapy, followed by surgery. Here we investigated associations between clinicopathologic variables, stromal tumor-infiltrating lymphocytes (sTIL), and pathologic complete response (pCR), and the prognostic value of pCR. We included 494 localized patients with IBC treated with NACT from October 1996 to October 2021 in eight European hospitals. Standard clinicopathologic variables were collected and central pathologic review was performed, including sTIL. Associations were assessed using Firth logistic regression models. Cox regressions were used to evaluate the role of pCR and residual cancer burden (RCB) on disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS). Distribution according to receptor status was as follows: 26.4% estrogen receptor negative (ER-)/HER2-; 22.0% ER-/HER2+; 37.4% ER+/HER2-, and 14.1% ER+/HER2+. Overall pCR rate was 26.3%, being highest in the HER2+ groups (45.9% for ER-/HER2+ and 42.9% for ER+/HER2+). sTILs were low (median: 5.3%), being highest in the ER-/HER2- group (median: 10%). High tumor grade, ER negativity, HER2 positivity, higher sTILs, and taxane-based NACT were significantly associated with pCR. pCR was associated with improved DFS, DRFS, and OS in multivariable analyses. RCB score in patients not achieving pCR was independently associated with survival. In conclusion, sTILs were low in IBC, but were predictive of pCR. Both pCR and RCB have an independent prognostic role in IBC treated with NACT. SIGNIFICANCE: IBC is a rare, but very aggressive type of breast cancer. The prognostic role of pCR after systemic therapy and the predictive value of sTILs for pCR are well established in the general breast cancer population; however, only limited information is available in IBC. We assembled the largest retrospective IBC series so far and demonstrated that sTIL is predictive of pCR. We emphasize that reaching pCR remains of utmost importance in IBC

    Deadline-aware TCP congestion control for HTTP adaptive streaming services

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    Abstract: Over the last decades, video streaming services have gained a lot of popularity, representing over 70% of the total consumer Internet traffic worldwide. While originally dedicated streaming protocols have been used to deliver these services, for several years, the video streaming industry is steadily shifting to HTTP adaptive streaming (HAS)-based delivery over TCP. With each video segment, implicit delivery deadlines are associated in order to avoid playout interruptions. However, TCP is known to be far from minimizing the number of deadline-missing streams. In this paper, 2 deadline-aware congestion control mechanisms are proposed, based on a parametrization of the traditional TCP New Reno congestion control strategy. By introducing deadline awareness at the transport layer, the modulation of the congestion window size is dynamically adapted to steer the aggressiveness of the considered stream to optimize the delivery of video streaming services. The proposed approaches are thoroughly evaluated in an HAS video-on-demand scenario over tree-based delivery networks. It was shown that in a realistic scenario, the proposed approaches can outperform traditional congestion control strategies by up to 12% in terms of estimated mean opinion score, mainly by reducing the average video freezing time by more than 85%

    Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer

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    Invasive lobular carcinoma (ILC) represents the second most common subtype of breast cancer (BC), accounting for up to 15% of all invasive BC. Loss of cell adhesion due to functional inactivation of E-cadherin is the hallmark of ILC. Although the current world health organization (WHO) classification for diagnosing ILC requires the recognition of the dispersed or linear non-cohesive growth pattern, it is not mandatory to demonstrate E-cadherin loss by immunohistochemistry (IHC). Recent results of central pathology review of two large randomized clinical trials have demonstrated relative overdiagnosis of ILC, as only ~60% of the locally diagnosed ILCs were confirmed by central pathology. To understand the possible underlying reasons of this discrepancy, we undertook a worldwide survey on the current practice of diagnosing BC as ILC. A survey was drafted by a panel of pathologists and researchers from the European lobular breast cancer consortium (ELBCC) using the online tool SurveyMonkey®. Various parameters such as indications for IHC staining, IHC clones, and IHC staining procedures were questioned. Finally, systematic reporting of non-classical ILC variants were also interrogated. This survey was sent out to pathologists worldwide and circulated from December 14, 2020 until July, 1 2021. The results demonstrate that approximately half of the institutions use E-cadherin expression loss by IHC as an ancillary test to diagnose ILC and that there is a great variability in immunostaining protocols. This might cause different staining results and discordant interpretations. As ILC-specific therapeutic and diagnostic avenues are currently explored in the context of clinical trials, it is of importance to improve standardization of histopathologic diagnosis of ILC diagnosis
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