Nausicaa Malissen

Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor–Related Cardiotoxicity

Immune checkpoint inhibitors (ICIs) represent a major advance in the treatment of cancer. Although clinical trials reported a low incidence of immune-related cardiovascular adverse events,1 the number of published life-threatening cases of cardiotoxicity is increasing.2 In this descriptive observational analysis, we aimed to describe the clinical manifestations, management, and outcomes of patients who developed ICI-related cardiotoxicity. The medical records of patients with a clinical suspicion of ICI-related cardiotoxicity were reviewed from the databases of 2 cardio-oncology units between March 2015 and April 2017. The patients are managed according to similar protocols. Because no specific follow-up had previously been established for patients receiving ICIs during the study period, the oncologists referred patients receiving ICIs only on the basis of their clinical suspicion of cardiovascular events. These patients had a standardized evaluation including clinical consultation, ECG, transthoracic echocardiography, and measurement of brain natriuretic peptide and troponin I serum levels. The management of cardiotoxicity was left to the physician’s discretion. The study was approved by our institutional review board, and informed consent has been obtained from the subjects. To create a pooled analysis, we also searched PubMed for English articles reporting cases of ICI-related cardiotoxicity until April 2017. We selected …

The scalp hair collar and tuft signs: A retrospective multicenter study of 78 patients with a systematic review of the literature

Background: Hair collar sign (HCS) and hair tuft of the scalp (HTS) are cutaneous signs of an underlying neuroectodermal defect, but most available data are based on case reports. Objective: We sought to define the clinical spectrum of HCS and HTS, clarify the risk for underlying neurovascular anomalies, and provide imaging recommendations. Methods: A 10‐year multicenter retrospective and prospective analysis of clinical, radiologic, and histopathologic features of HCS and HTS in pediatric patients was performed. Results: Of the 78 patients included in the study, 56 underwent cranial and brain imaging. Twenty‐three of the 56 patients (41%) had abnormal findings, including the following: (1) cranial/bone defect (30.4%), with direct communication with the central nervous system in 28.6%; (2) venous malformations (25%); or (3) central nervous system abnormalities (12.5%). Meningeal heterotopia in 34.6% (9/26) was the most common neuroectodermal association. Sinus pericranii, paraganglioma, and combined nevus were also identified. Limitations: The partial retrospective design and predominant recruitment from the dermatology department are limitations of this study. Conclusions: Infants with HCS or HTS are at high risk for underlying neurovascular anomalies. Magnetic resonance imaging scans should be performed in order to refer the infant to the appropriate specialist for management.

Study of metastatic kinetics in metastatic melanoma treated with B-RAF inhibitors: Introducing mathematical modelling of kinetics into the therapeutic decision

Background Evolution of metastatic melanoma (MM) under B-RAF inhibitors (BRAFi) is unpredictable, but anticipation is crucial for therapeutic decision. Kinetics changes in metastatic growth are driven by molecular and immune events, and thus we hypothesized that they convey relevant information for decision making. Patients and methods We used a retrospective cohort of 37 MM patients treated by BRAFi only with at least 2 close CT-scans available before BRAFi, as a model to study kinetics of metastatic growth before, under and after BRAFi. All metastases (mets) were individually measured at each CT-scan. From these measurements, different measures of growth kinetics of each met and total tumor volume were computed at different time points. A historical cohort permitted to build a reference model for the expected spontaneous disease kinetics without BRAFi. All variables were included in Cox and multistate regression models for survival, to select best candidates for predicting overall survival. Results Before starting BRAFi, fast kinetics and moreover a wide range of kinetics (fast and slow growing mets in a same patient) were pejorative markers. At the first assessment after BRAFi introduction, high heterogeneity of kinetics predicted short survival, and added independent information over RECIST progression in multivariate analysis. Metastatic growth rates after BRAFi discontinuation was usually not faster than before BRAFi introduction, but they were often more heterogeneous than before. Conclusions Monitoring kinetics of different mets before and under BRAFi by repeated CT-scan provides information for predictive mathematical modelling. Disease kinetics deserves more interest

A novel anti-CD146 antibody specifically targets cancer cells by internalizing the molecule

CD146 is an adhesion molecule present on many tumors (melanoma, kidney, pancreas, breast, ...). In addition, it has been shown to be expressed on vascular endothelial and smooth muscle cells. Generating an antibody able to specifically recognize CD146 in cancer cells (designated as tumor CD146), but not in normal cells, would thus be of major interest for targeting tumor CD146 without affecting the vascular system. We thus generated antibodies against the extracellular domain of the molecule produced in cancer cells and selected an antibody that specifically recognizes tumor CD146. This antibody (TsCD146 mAb) was able to detect CD146-positive tumors in human biopsies and in vivo, by PET imaging, in a murine xenograft model. In addition, TsCD146 mAb antibody was able to specifically detect CD146-positive cancer microparticles in the plasma of patients. TsCD146 mAb displayed also therapeutic effects since it was able to reduce the growth of human CD146-positive cancer cells xenografted in nude mice. This effect was due to a decrease in the proliferation and an increase in the apoptosis of CD146-positive cancer cells after TsCD146-mediated internalization of the cell surface CD146. Thus, TsCD146 mAb could be of major interest for diagnostic and therapeutic strategies against CD146-positive tumors in a context of personalized medicine.

L’utilisation clinique des anticorps anti-CTLA-4

L’utilisation d’anticorps monoclonaux anti-CTLA-4 dans le melanome metastatique a fourni la premiere preuve clinique que le ciblage des points de controle immunitaires pouvait avoir un interet therapeutique en cancerologie. Le concept est le blocage par des anticorps monoclonaux de l’activite de corecepteurs inhibiteurs exprimes a la surface des lymphocytes T infiltrant les tumeurs. Ce blocage permet de stimuler les reponses immunitaires dirigees contre les cellules tumorales. Dans cet article, l’utilisation des anticorps anti-CTLA-4 en therapeutique est decrite, avec ses succes initiaux qui ont encourage la recherche en immunotherapie, et ses limites liees a son faible taux de reponse.