title: Proton radiotherapy for high-risk pediatric neuroblastoma: early outcomes and dose comparison.
abstract: OBJECTIVE
  To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed.
  
  
  METHODS
  All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, and laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost.
  
  
  RESULTS
  Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart.
  
  
  CONCLUSIONS
  Preliminary outcomes reveal excellent local control with proton therapy for high-risk neuroblastoma, although distant failures continu to occur. Dosimetric comparisons demonstrate the advantage of proton RT compared with IMRT in this setting, allowing more conformal treatment and better normal tissue sparing.
authors.affiliation: Harvard Radiation Oncology Program, Boston, MA, USA.
authors.forename: Jona A
authors.initials: JA
authors.lastname: Hattangadi
authors.forename: Barbara
authors.initials: B
authors.lastname: Rombi
authors.forename: Torunn I
authors.initials: TI
authors.lastname: Yock
authors.forename: George
authors.initials: G
authors.lastname: Broussard
authors.forename: Alison M
authors.initials: AM
authors.lastname: Friedmann
authors.forename: Mary
authors.initials: M
authors.lastname: Huang
authors.forename: Yen-Lin E
authors.initials: YL
authors.lastname: Chen
authors.forename: Hsiao-Ming
authors.initials: HM
authors.lastname: Lu
authors.forename: Hanne
authors.initials: H
authors.lastname: Kooy
authors.forename: Shannon M
authors.initials: SM
authors.lastname: MacDonald
mesh_terms: D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual; D009447:Neuroblastoma / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy* / Q000628:therapy; D059351:Organ Sparing Treatments / Q000379:methods; D058958:Organs at Risk; D017785:Photons / Q000627:therapeutic use; D061766:Proton Therapy; D011522:Protons / Q000009:adverse effects; D011859:Radiography; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D011522:Protons