title: Factors affecting response to everolimus therapy for subependymal giant cell astrocytomas associated with tuberous sclerosis.
abstract: BACKGROUND
  The aim of the study was to investigate factors affecting response to everolimus, a mammalian-target-of-rapamycin (mTOR) inhibitor, of subependymal giant cell astrocytomas (SEGA) in patients with tuberous sclerosis complex (TSC).
  
  
  METHODS
  The study group consisted of 15 children with a diagnosis of TSC-related SEGA. Median therapy duration was 13 months. Age, sex, previous neurosurgical or mTOR inhibitor treatment, everolimus blood concentration and anticonvulsant therapy were analyzed as potential factors affecting reduction of SEGA tumor volume.
  
  
  RESULTS
  Significant reductions in SEGA volumes were noted at 3 and 6 months (median tumor volume 0.97 cm(3) and 0.70 cm(3) , respectively, versus 2.70 cm(3) at baseline, P = 0.001). Responses were observed in 11/15 (73.3%) and 10/12 (83.3%) patients at 3 and 6 months, respectively. The most rapid reduction of SEGA volume (58.6%) was found during the initial 3 months of treatment. There was no statistical difference in the extent of SEGA volume reduction between patients with everolimus trough levels <5 ng/ml and ≥5 ng/ml. Patients treated with ≤1 anticonvulsant had greater tumor reduction after 6 months of treatment.
  
  
  CONCLUSIONS
  Everolimus is an effective and safe treatment option for TSC-related SEGA. Drug dose titration according to blood concentration did not appear to be crucial to achieve clinical efficacy; however, concomitant anticonvulsant therapy may affect response to mTOR inhibitors.
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Trelinska
authors.forename: Iwona
authors.initials: I
authors.lastname: Dachowska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kotulska
authors.forename: Dobromila
authors.initials: D
authors.lastname: Baranska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fendler
authors.forename: Sergiusz
authors.initials: S
authors.lastname: Jozwiak
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics; D001254:Astrocytoma / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D016609:Neoplasms, Second Primary / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D012737:Sex Factors; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D013997:Time Factors; D014402:Tuberous Sclerosis / Q000097:blood / Q000188:drug therapy / Q000473:pathology
chemical_list: D000927:Anticonvulsants; D007166:Immunosuppressive Agents; D009363:Neoplasm Proteins; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: SEGA; everolimus; mTOR inhibitor; tuberous sclerosis complex