title: Radiation therapy and concurrent topotecan followed by maintenance triple anti-angiogenic therapy with thalidomide, etoposide, and celecoxib for pediatric diffuse intrinsic pontine glioma.
abstract: BACKGROUND
  Despite major treatment attempts, the prognosis for pediatric diffuse intrinsic pontine gliomas (DIPGs) remains dismal. Gliomas are highly vascularized tumors, suggesting that the prevention of vessel formation by anti-angiogenic treatment might be effective.
  
  
  METHODS
  Forty-one pediatric patients with DIPG were treated according to the Angiocomb protocol, starting with radiotherapy combined with topotecan and followed by anti-angiogenic triple medication consisting of thalidomide, etoposide, and celecoxib. Overall survival, radiological response, quality of life, requirement of corticosteroids, and adverse effects were monitored. Eight patients treated with only radiotherapy were used as controls.
  
  
  RESULTS
  For study patients, the 12 and 24 months overall survival was 61% and 17%, respectively. The median overall survival was 12 months (range 4-60 months). Four radiological complete responses were seen, of which two were transient. Radiologically, 56% of the tumors reduced in size and 78% in signal intensity. Study patients were able to visit school or daycare and walk for a significantly longer time compared to controls (Log Rank 0.036 and 0.008, respectively). Adverse effects were generally minor.
  
  
  CONCLUSIONS
  The Angiocomb protocol created a noticeable share of long-term survivors and was well tolerated, suggesting that anti-angiogenic therapy for patients with DIPG should be studied more in the future.
authors.affiliation: Division of Hematology-Oncology and Stem Cell Transplantation, Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Porkholm
authors.forename: Leena
authors.initials: L
authors.lastname: Valanne
authors.forename: Tuula
authors.initials: T
authors.lastname: Lönnqvist
authors.forename: Stefan
authors.initials: S
authors.lastname: Holm
authors.forename: Birgitta
authors.initials: B
authors.lastname: Lannering
authors.forename: Pekka
authors.initials: P
authors.lastname: Riikonen
authors.forename: Dorota
authors.initials: D
authors.lastname: Wojcik
authors.forename: Astrid
authors.initials: A
authors.lastname: Sehested
authors.forename: Niels
authors.initials: N
authors.lastname: Clausen
authors.forename: Arja
authors.initials: A
authors.lastname: Harila-Saari
authors.forename: Eckhard
authors.initials: E
authors.lastname: Schomerus
authors.forename: Halldora K
authors.initials: HK
authors.lastname: Thorarinsdottir
authors.forename: Päivi
authors.initials: P
authors.lastname: Lähteenmäki
authors.forename: Mikko
authors.initials: M
authors.lastname: Arola
authors.forename: Harald
authors.initials: H
authors.lastname: Thomassen
authors.forename: Ulla M
authors.initials: UM
authors.lastname: Saarinen-Pihkala
authors.forename: Sanna-Maria
authors.initials: SM
authors.lastname: Kivivuori
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D020295:Brain Stem Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016022:Case-Control Studies; D000068579:Celecoxib; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007223:Infant; D008297:Male; D060787:Neoplasm Grading; D011379:Prognosis; D011720:Pyrazoles / Q000008:administration & dosage; D011788:Quality of Life; D012074:Remission Induction; D013449:Sulfonamides / Q000008:administration & dosage; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; D013792:Thalidomide; D005047:Etoposide; D019772:Topotecan; D000068579:Celecoxib
keywords: anti-angiogenic therapy; celecoxib; etoposide; pediatric; pontine glioma; thalidomide