188 results match your criteria: "institut universitaire du cancer-Oncopole[Affiliation]"

Evolutionary design of explainable algorithms for biomedical image segmentation.

Nat Commun

November 2023

University of Toulouse - Institut de Recherche en Informatique de Toulouse (IRIT) - UMR5505, Artificial and Natural Intelligence Toulouse Institute, Toulouse, France.

An unresolved issue in contemporary biomedicine is the overwhelming number and diversity of complex images that require annotation, analysis and interpretation. Recent advances in Deep Learning have revolutionized the field of computer vision, creating algorithms that compete with human experts in image segmentation tasks. However, these frameworks require large human-annotated datasets for training and the resulting "black box" models are difficult to interpret.

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Germline pathogenic variants in the exonuclease domain of the replicative DNA polymerase Pol ε encoded by the gene, predispose essentially to colorectal and endometrial tumors by inducing an ultramutator phenotype. It is still unclear whether all the alterations influence similar strength tumorigenesis, immune microenvironment, and treatment response. In this review, we summarize the current understanding of the mechanisms and consequences of mutations in human malignancies; we highlight the heterogeneity of mutation rate and cancer aggressiveness among POLE variants, propose some mechanistic basis underlining such heterogeneity, and discuss novel considerations for the choice and efficacy of therapies of POLE tumors.

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Background: The French phase II AcSé-crizotinib trial aimed to evaluate the safety and efficacy of crizotinib in patients with ALK, ROS1, and MET-driven malignancies, including ALK-positive anaplastic large-cell lymphoma (ALK ALCL).

Methods: ALK ALCL patients 12 months or older with measurable disease and no standard care options available received crizotinib twice daily at 165 mg/m in children and adolescents and 250 mg in adults. The primary end-point was the response rate at 8 weeks.

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Background: Genomic tests are a useful tool for adjuvant chemotherapy decision-making in the case of hormone receptor-positive (HR+), and human epidermal growth factor receptor 2-negative (HER2-) breast cancer with intermediate prognostic factors. Real-life data on the use of tests can help identify the target population for testing.

Methods: French multicentric study (8 centers) including patients, all candidates for adjuvant chemotherapy for HR-positive, HER2-negative early breast cancer.

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Cell-free DNA in human blood plasma (cfDNA) is now widely used and studied as a biomarker for several physiological and pathological situations. In addition to genetic and epigenetic alterations that provide information about the presence and the nature of non-constitutive DNA in the body, cfDNA concentration and size distribution may potentially be independent biomarkers suitable for monitoring at-risk patients and therapy efficacy. Here, we describe a simple, in-line, method, which measures cfDNA concentration and size distribution from only a few microliters of plasma without the need to extract and/or concentrate the DNA prior to the analysis.

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We conducted a single-centre retrospective cohort study in a French University Hospital between 2010 and 2018 to describe the risk of severe infectious event (SIE) within 2 years after the date of first rituximab infusion (T0) prescribed after the evidence of acquired hypogammaglobulinemia (gamma globulins [GG] ≤ 6 g/L) in the setting of autoimmune diseases (AID) other than rheumatoid arthritis. SIE occurred in 26 out of 121 included patients. Two years cumulative incidence rates were 12.

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Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer.

N Engl J Med

June 2023

From the Royal Marsden Hospital, Institute of Cancer Research, London (N.C.T.), the Christie NHS Foundation Trust, Manchester (S.J.H.), and Oncology Research and Development, AstraZeneca, Cambridge (E.C.B., L.G., G.S., A.F.) - all in the United Kingdom; the Department of Medical Oncology, Vall d'Hebron University Hospital (M. Oliveira), the Breast Cancer Unit, Vall d'Hebron Institute of Oncology (M. Oliveira), the Department of Oncology, International Breast Cancer Center, Pangaea Oncology, Quiron Group, Medica Scientia Innovation Research (J.C.), and Institut de Recerca Biomèdica (S.M.M.), Barcelona, and the Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid (J.C.) - all in Spain; Institut Claudius Regaud, Institut Universitaire du Cancer-Oncopole Toulouse, Toulouse, France (F.D.); Departamento de Oncología Médica, Instituto Nacional de Enfermedades Neoplásicas, and Universidad Ricardo Palma - both in Lima, Peru (H.L.G.M.); Shanghai Cancer Center, Fudan University, Shanghai, China (X.H.); Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College - both in New York (K.J.); Petrov Research Institute of Oncology, St. Petersburg (P.K.), and Loginov Moscow Clinical Scientific Center, Moscow (L.Z.) - both in Russia; GBG Forschungs, Neu-Isenburg, and the Center for Hematology and Oncology, Bethanien, Frankfurt - both in Germany (S.L.); Icon Cancer Centre, Adelaide, SA, Australia (M. Okera); Sungkyunkwan University School of Medicine, Samsung Medical Center (Y.H.P.), and Yonsei University College of Medicine, Yonsei Cancer Center (J.S.) - both in Seoul; Kyoto University Hospital, Kyoto (M.T.), and National Hospital Organization Kyushu Cancer Center, Fukuoka (E.T.) - both in Japan; Emek Medical Center, Afula, Israel (S.Y.); and the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.).

Article Synopsis
  • The study investigates the efficacy and safety of the AKT inhibitor capivasertib when combined with fulvestrant therapy for patients with hormone receptor-positive advanced breast cancer.
  • In a phase 3 trial, patients who had previously experienced disease progression while on aromatase inhibitors were randomly assigned to receive either capivasertib with fulvestrant or a placebo with fulvestrant.
  • Results showed that the combination therapy significantly improved progression-free survival: 7.2 months for the capivasertib group compared to 3.6 months for placebo, with higher rates of adverse events, such as rash and diarrhea, in the capivasertib group.
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Animal toxicological studies often fail to mimic the complexity of the human exposome, associating low doses, combined molecules and long-term exposure. Since the reproductive potential of a woman begins in the fetal ovary, the literature regarding the disruption of its reproductive health by environmental toxicants remains limited. Studies draw attention to follicle development, a major determinant for the quality of the oocyte, and the preimplantation embryo, as both of them are targets for epigenetic reprogramming.

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CD8 cytotoxic T lymphocytes (CTL) play a key role in anti-tumor immune response. They are therefore at the heart of current immunotherapy protocols against cancer. Despite current strategies to potentiate CTL responses, cancer cells can resist CTL attack, thus limiting the efficacy of immunotherapies.

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Investigating the clinical impact of dose-banding for weekly paclitaxel in patients with breast cancer: A retrospective and monocentric study.

Br J Clin Pharmacol

July 2023

Centre de Recherches en Cancérologie de Toulouse (CRCT), Team 14, INSERM UMR1037, Université de Toulouse, 2 avenue Hubert Curien, CS53717, Toulouse, France.

Aims: Dose-banding (DB) consists in approximating the theoretical dose of anticancer drugs calculated according to the body surface area (Dose-BSA) of patients. This concept is supported by pharmacokinetic but not by clinical data. The aim of this study was to assess the clinical outcome of DB defined as dose-fitting up to ±10%.

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Patients treated by radical prostatectomy (RP) for localized prostate cancer (PCa) may experience biochemical recurrence (BCR) in approximately 30% of cases. Recently, advances in imaging modalities and in particular Positron-Emission Tomography with computed tomography (PET/CT) imaging allow for better detection and characterization of lesions outside the prostatic bed at recurrence. Thus, treatment at BCR can be significantly improved by a tailored strategy based on new generation imaging.

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BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib.

Blood Adv

June 2023

Division of Experimental Oncology, B cell Neoplasia Unit, IRCCS Ospedale San Raffaele, Milan, Italy.

Article Synopsis
  • Patients with chronic lymphocytic leukemia (CLL) on ibrutinib treatment often develop resistance due to mutations in the BTK and PLCG2 genes, with varying frequencies impacting patient outcomes.
  • A study of 98 CLL patients revealed that 65% of those who relapsed exhibited at least one mutation in BTK or PLCG2, while 12% of responding patients also had mutations, indicating a potential for progression.
  • The findings suggest that other genetic mutations may contribute to resistance, with BTK mutation profiles differing between relapsing patients, but no significant impact on TP53 mutations was observed, highlighting the complexity of treatment resistance.
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Resisting T cell attack: tumor-cell-intrinsic defense and reparation mechanisms.

Trends Cancer

March 2023

INSERM U1037, Centre de Recherche en Cancérologie de Toulouse (CRCT), Université de Toulouse III-Paul Sabatier, 31057 Toulouse, France; Department of Pathology, Institut Universitaire du Cancer-Oncopole de Toulouse, 31059 Toulouse, France. Electronic address:

Cytotoxic T lymphocytes (CTLs) are antigen-specific killer cells equipped to identify and eliminate host cells that have been altered through infection or transformation. Both chimeric antigen-receptor (CAR) T cell therapies and immune checkpoint blockade (ICB) therapies are based on successful elimination of tumor cells by cytotoxic effectors. In this opinion article, we outline cell-intrinsic mechanisms by which tumor cells defend against CTLs, highlighting pathways that confer resistance and proposing opportunities for combination therapies.

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Background: Recently, the combination of venetoclax plus a hypomethylating agent (HMA; azacitidine ordecitabine) or low-dose cytarabine (LDAC) showed promise in Phase III trials in previously untreated AML. In France at the time of this study, venetoclax was not yet approved for AML and there were therefore no formal usage recommendations. Here we report the first study in a French cohort that assessed venetoclax in combination with existing treatments for AML under real-life conditions.

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Chimeric antigen receptor (CAR) T cell immunotherapy is a revolutionary pillar in cancer treatment. Clinical experience has shown remarkable successes in the treatment of certain hematological malignancies but only limited efficacy against B cell chronic lymphocytic leukemia (CLL) and other cancer types, especially solid tumors. A wide range of engineering strategies have been employed to overcome the limitations of CAR T cell therapy.

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PERFECT is a multicentre randomised controlled clinical trial that evaluates the efficiency of fusion magnetic resonance imaging-targeted biopsies in the transperineal (TP) versus transrectal (TR) approach in terms of the detection of significant cancers. Our study builds on the hypothesis that the TP approach for prostate biopsies has at least the same diagnostic accuracy as the TR approach, with lower morbidity. Here, we describe the clinical protocol, study population, and primary and secondary outcomes.

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Article Synopsis
  • * A new 67-gene expression prognostic signature called CINSARC has been developed, which has shown effectiveness in predicting outcomes across various cancers and can be used on preserved tissue samples through NanoString® technology.
  • * In studies of CRC patients, CINSARC effectively differentiated between groups with different survival rates, demonstrating strong prognostic capacity that surpasses traditional TNM staging and CMS classification, making it a valuable tool for clinical practice.
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The Emerging Role of Extracranial Stereotactic Ablative Radiotherapy for Metastatic Renal Cell Carcinoma: A Systematic Review.

Eur Urol Focus

January 2023

Department of Radiation Oncology, Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland; Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland; Università della Svizzera Italiana, Lugano, Switzerland. Electronic address:

Context: Although the management of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of new systemic agents, still few patients experience a long-term durable response. Stereotactic ablative radiotherapy (SABR) is nowadays commonly used as metastasis-directed therapy (MDT), but limited data exist on how best to implement this strategy as part of a multimodal approach.

Objective: To evaluate the potential role of extracranial SABR in mRCC and to identify future therapeutic developments of SABR in different disease settings.

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Article Synopsis
  • * A total of 133 patients were assessed, and of the 86 who were identified as underdosed, those in the TDM group had higher imatinib levels and a significantly better major molecular response (MMR) at 12 months (67% for TDM vs. 39% for control).
  • * TDM proved to be a feasible approach that not only heightened drug levels but also maintained a positive impact on treatment outcomes for up to three years.
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Effectiveness of Early Radical Cystectomy for High-Risk Non-Muscle Invasive Bladder Cancer.

Cancers (Basel)

August 2022

Sorbonne Université, Department of Urology, GRC n°5 Predictive Onco-Urology, AP-HP, Pitié-Salpêtrière Hospital, 75013 Paris, France.

Purpose: The purpose of this study is to compare perioperative and oncological outcomes of upfront vs. delayed early radical cystectomy (eRC) for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). Methods: All consecutive HR-NMIBC patients who underwent eRC between 2001 and 2020 were retrospectively included and divided into upfront and delayed groups, according to the receipt or not of BCG.

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What Is Known And Objective: Bispecific drugs (BDs) belong to the family of immunotherapies along with checkpoint inhibitors and CAR-T cells. In the field of oncology, BDs are designed to simultaneously bind a tumour antigen on the one side and an antigen present on the surface of effector cells on the other. This review summarizes the information available to date on the first marketed BiTE-format bispecific antibody, blinatumomab BLINCYTO® in acute lymphoblastic leukaemia.

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In order to standardize cellular hematology practices, the French-speaking Cellular Hematology Group (Groupe Francophone d'Hématologie Cellulaire, GFHC) focused on Perls' stain. A national survey was carried out, leading to the proposal of recommendations on insoluble iron detection and quantification in bone marrow. The criteria presented here met with a "strong professional agreement" and follow the suggestions of the World Health Organization's classification of hematological malignancies.

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