title: Pencil beam scanning proton therapy for pediatric intracranial ependymoma.
abstract: To assess the clinical outcome and late side effect profile of pencil beam scanning proton therapy (PT) delivered to children with intracranial ependymoma. Between July-2004 and March-2013, 50 patients with intracranial ependymoma (n = 46, grade 3) received involved-field PT at Paul Scherrer Institute (PSI). Median age at time of PT was 2.6 years (range 1.1-15.2). Thirty-six patients had infratentorial and 14 supratentorial ependymomas. Seventeen patients presented with macroscopic residual disease after subtotal resection before starting PT (8 with ≤1.5 cc and 9 with >1.5 cc residual tumor respectively). Forty-three (86 %) patients received post-operative chemotherapy before PT according to protocols; 44 (88 %) patients younger than 5 years required general anesthesia. Median prescribed dose was 59.4 Gy (RBE) (range 54-60) delivered in 1.8-2 Gy (RBE) per fraction. Late toxicity was assessed according to CTCAE v4.0. With a mean follow-up time of 43.4 months (range 8.5-113.7) seven patients experienced local failure (6 with infratentorial tumors and 1 with supratentorial tumor); four of the local failures were in patients with residual disease ≥1.5 cc at the time of PT and 3 without residual macroscopic disease. Five patients died from tumor progression. Actuarial 5-year Local Control rates were 78 ± 7.5 % and 5-year OS rates were 84 ± 6.8 %. Three patients developed grade ≥3 toxicity: 2 developed unilateral deafness (infratentorial tumors infiltrating into the internal acoustic canal), one patient developed a fatal brainstem necrosis. Repeated general anesthesia in children younger than 5 years was delivered without complications. Our data indicate the safety and the effectiveness of PT for pediatric ependymomas. Local control and survival rates are encouraging considering the high grade histology in 92 % of the patients and the number of patients with residual tumor ≥1.5 cc. The rates of late effects compare favorably with published photon-treated cohorts.
authors.affiliation: Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Switzerland. carmen.ares@hcuge.ch.|Department of Radiation Oncology, University Hospital of Geneva, Geneva, Switzerland. carmen.ares@hcuge.ch.
authors.forename: Carmen
authors.identifier: 0000-0002-3909-779X
authors.initials: C
authors.lastname: Ares
authors.affiliation: Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Albertini
authors.affiliation: Department of Anesthesia, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Frei-Welte
authors.affiliation: Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bolsi
authors.affiliation: Department of Pediatric Oncology, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grotzer
authors.affiliation: Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Switzerland.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Goitein
authors.affiliation: Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Switzerland.|University of Bern, Bern, Switzerland.
authors.forename: Damien C
authors.initials: DC
authors.lastname: Weber
mesh_terms: D000293:Adolescent; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D004307:Dose-Response Relationship, Radiation; D004806:Ependymoma / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D015192:Infratentorial Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D015173:Supratentorial Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome
keywords: Central nervous system; Intracranial pediatric ependymoma; Pencil beam scanning proton therapy; Radiotherapy; Tumor local control