title: Fractionated low-dose radiotherapy after myeloablative stem cell transplantation for local control in patients with high-risk neuroblastoma.
abstract: BACKGROUND
  The optimal administration of radiotherapy for patients with high-risk neuroblastoma (NB) currently is undefined in the context of modern therapy using myeloablative chemotherapy with autologous stem cell rescue (hematopoietic stem cell transplantation [HSCT]).
  
  
  METHODS
  The authors conducted a retrospective review of the records of 21 consecutive patients with high-risk NB to assess local control and toxicity of external beam radiotherapy (XRT). Therapy included multiagent induction chemotherapy and delayed surgical resection, consolidation of HSCT and local XRT, and 13-cis-retinoic acid maintenance therapy. XRT was delivered to the primary site, using postchemotherapy volumes, and to initial metastatic sites with 1-2 cm margins to 2100 centigrays (cGy) using 14 fractions administered once daily.
  
  
  RESULTS
  Four of 21 patients did not receive XRT due to toxic death (n = 2), disease progression before XRT (n = 1), or parental refusal (n = 1). The median time to XRT post-HSCT was 54 days. Thirteen patients received a second peripheral blood stem cell infusion after completing XRT. Twelve of the 14 patients who received XRT post-HSCT and for whom toxicity data were available had Grade 3-4 acute toxicities, including gastrointestinal toxicity (n = 8), hematologic toxicity (n = 9), and infection (n = 1). Nonrecurrent long-term toxicities included prolonged nutritional deficiency (n = 9) and leg-length discrepancy (n = 1). Tumors recurred in 7 of 21 patients (5 of 17 patients who received radiotherapy), either within a radiation field (n = 1) or at distant nonirradiated sites (n = 6). The estimated local failure rate was 7% (95% confidence interval [95% CI], 0-14%), with a 2-year event-free survival rate of 48% (95% CI, 26-70%).
  
  
  CONCLUSIONS
  Post-HSCT, fractionated XRT to 2100 cGy was a tolerable and effective treatment for patients with high-risk NB, and minimal recurrences were observed at designated XRT sites.
authors.affiliation: Department of Pediatric Hematology/Oncology, Children's Hospital and Regional Medical Center, Seattle, Washington 98105-5371, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Bradfield
authors.forename: James G
authors.initials: JG
authors.lastname: Douglas
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Hawkins
authors.forename: Jean E
authors.initials: JE
authors.lastname: Sanders
authors.forename: Julie R
authors.initials: JR
authors.lastname: Park
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002675:Child, Preschool; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009447:Neuroblastoma / Q000401:mortality* / Q000628:therapy*; D011878:Radiotherapy / Q000009:adverse effects; D012189:Retrospective Studies; D016896:Treatment Outcome