title: Acute neurovascular events in cancer patients receiving anti-vascular endothelial growth factor agents: Clinical experience in Paris University Hospitals.
abstract: Despite the increasing and broadening use of agents targeting the vascular endothelial growth factor (VEGF) pathway, little is known on their acute neurovascular toxicities.
  
  
  
  This retrospective, multi-centre study examined the characteristics of patients with solid tumours who experienced an ischaemic or haemorrhagic stroke, a transient ischaemic accident (TIA) or a posterior reversible encephalopathy syndrome (PRES) while under anti-VEGF and until 8 weeks after termination of treatment and evaluated their management in our institutions from 2004 to 2014. Patients with newly diagnosed or progressive cerebral metastases at the time of the acute neurovascular event were excluded.
  
  
  
  Thirty-four patients (55.9% men) were identified, and experienced either ischaemic stroke (n = 18), PRES (n = 9), TIA (n = 6) or haemorrhagic stroke (n = 1). At initiation of anti-VEGF agents, 64.7% of patients had previous cardiovascular risk factors, and 52.9% had hypertension. Eight patients (23.5%) had received cerebral radiotherapy, five of which concomitantly to anti-VEGF treatment. Six (17%) patients died in the 8 weeks following the acute neurovascular event, and only 55.9% recovered their initial neurological status. Overall, 1-year and 2-year survival rates after the acute neurovascular event were 67.9% and 50%, respectively. When anti-VEGF agents were reintroduced (n = 6), severe vascular toxicity recurred in two patients.
  
  
  
  Neurovascular events under VEGF treatments are potentially severe, and the management of comorbid conditions has to be improved. A prospective collection of data and standardised management of such events is therefore being structured in our institutions.
authors.affiliation: Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Paris Descartes University, 27, rue du faubourg Saint-Jacques, 75014 Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Tlemsani
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Cancer Campus, University of Paris Sud, 114, rue Edouard Vaillant, 94800 Villejuif, France. Electronic address: olivier.mir@gustaveroussy.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mir
authors.affiliation: Department of Neurology Mazarin, Pitié-Salpétrière Teaching Hospital, AP-HP, University Pierre et Marie Curie Paris VI, 47-83, boulevard de l'Hôpital, 75013 Paris, France; Department of Neurology, OncoNeuroTox Center, Paris, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Psimaras
authors.affiliation: Department of Medical Oncology, Georges Pompidou Teaching Hospital (HEGP), AP-HP, Paris Descartes University, 20, rue Leblanc, 75015 Paris, France.
authors.forename: Yann-Alexandre
authors.initials: YA
authors.lastname: Vano
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Cancer Campus, University of Paris Sud, 114, rue Edouard Vaillant, 94800 Villejuif, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Cancer Campus, University of Paris Sud, 114, rue Edouard Vaillant, 94800 Villejuif, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.affiliation: Department of Medical Oncology, Henri Mondor Teaching Hospital, AP-HP, University of Paris Est, 51, avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Rousseau
authors.affiliation: Department of Medical Oncology, Curie Institute, 26, rue d'ULM, 75005 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Loirat
authors.affiliation: Department of Medical Oncology, Val-de-Grâce Teaching Hospital, Service de Santé des Armées, 74, boulevard de Port Royal, 75005 Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ceccaldi
authors.affiliation: Department of Medical Oncology, Saint-Antoine Teaching Hospital, AP-HP, University Pierre et Marie Curie Paris VI, 184, rue du Faubourg Saint Antoine, 75012 Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: André
authors.affiliation: Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Paris Descartes University, 27, rue du faubourg Saint-Jacques, 75014 Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Goldwasser
authors.affiliation: Department of Neurology, OncoNeuroTox Center, Paris, France; Department of Neurology, Val-de-Grâce Teaching Hospital, Service de Santé des Armées, 74, boulevard de Port Royal, 75005 Paris, France; Department of Neurology, Cognition an Action Group (COGNAC-G) UMR 8257 Centre National de la Recherche Scientifique, Service de Santé des Armées, Paris Descartes University, 45, rue des Saints-Pères, 75006 Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Ricard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects; D002545:Brain Ischemia / Q000139:chemically induced; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006785:Hospitals, University / Q000706:statistics & numerical data; D006801:Humans; D002546:Ischemic Attack, Transient / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010297:Paris; D054038:Posterior Leukoencephalopathy Syndrome / Q000139:chemically induced*; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis inhibitors; Cancer; Cardiovascular risk factors; Cerebral radiotherapy; Hypertension; Posterior reversible encephalopathy syndrome; Stroke; Toxicity; Vascular endothelial growth factor A