title: Sirolimus improves pain in NF1 patients with severe plexiform neurofibromas.
abstract: Plexiform neurofibromas (PNs) are common and potentially debilitating complications of neurofibromatosis 1 (NF1). These benign nerve-sheath tumors are associated with significant pain and morbidity because they compress vital structures. The mammalian target of rapamycin (mTOR) pathway is a major mediator involved in tumor growth in NF1. We present 3 cases of patients with NF1, aged 8, 16, and 17 years, followed for inoperable and symptomatic PNs; patients received sirolimus for life-threatening and painful neurofibromas after multidisciplinary consultation. Epidemiologic, clinical, and radiologic data were retrospectively collected. The volume of PNs did not differ between baseline and 12-month follow-up and pain was alleviated, with withdrawal of analgesics in 2 cases at 6 months, and significantly decreased for the third case. Sirolimus for inoperable symptomatic PNs in patients with NF1 permitted stabilization of mass and produced unpredictable and important alleviation of pain in all cases with good tolerance. This treatment was proposed in extreme cases, in absence of therapeutic alternatives, after multidisciplinary consensus. The mTOR pathway may be both a major mediator of NF1 tumor growth and regulator of nociceptor sensitivity. mTOR inhibitors clinically used as anticancer and immunosuppressant drugs could be a potential treatment of chronic pain.
authors.forename: Camille
authors.initials: C
authors.lastname: Hua
authors.forename: Ouidad
authors.initials: O
authors.lastname: Zehou
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ducassou
authors.forename: Véronique
authors.initials: V
authors.lastname: Minard-Colin
authors.forename: Dominique
authors.initials: D
authors.lastname: Hamel-Teillac
authors.forename: Pierre
authors.initials: P
authors.lastname: Wolkenstein
authors.forename: Laurence
authors.initials: L
authors.lastname: Valeyrie-Allanore
mesh_terms: D000008:Abdominal Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D000293:Adolescent; D002648:Child; D059350:Chronic Pain / Q000175:diagnosis / Q000188:drug therapy*; D003299:Cooperative Behavior; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D033183:Interdisciplinary Communication; D008297:Male; D018318:Neurofibroma, Plexiform / Q000175:diagnosis / Q000188:drug therapy*; D009456:Neurofibromatosis 1 / Q000175:diagnosis / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D020123:Sirolimus