title: Likelihood of bone recurrence in prior sites of metastasis in patients with high-risk neuroblastoma.
abstract: OBJECTIVE
  Despite recent improvements in outcomes, 40% of children with high-risk neuroblastoma will experience relapse, facing a guarded prognosis for long-term cure. Whether recurrences are at new sites or sites of original disease may guide decision making during initial therapy.
  
  
  METHODS
  Eligible patients were retrospectively identified from institutional databases at first metastatic relapse of high-risk neuroblastoma. Included patients had disease involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and first relapse, achieved a complete or partial response with no more than one residual MIBG-avid site before first relapse, and received no total body irradiation or therapy with (131)I-MIBG before first relapse. Anatomically defined metastatic sites were tracked from diagnosis through first relapse to determine tendency of disease to recur at previously involved versus uninvolved sites and to assess whether this pattern was influenced by site irradiation.
  
  
  RESULTS
  Of 159 MIBG-avid metastatic sites identified among 43 patients at first relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at diagnosis. This distribution was similar for bone sites, but patterns of relapse were more varied for the smaller subset of soft tissue metastases. Among all metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3 of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%) unirradiated sites.
  
  
  CONCLUSIONS
  Metastatic bone relapse in neuroblastoma usually occurs at anatomic sites of previous disease. Metastatic sites identified at diagnosis that did not receive radiation during frontline therapy appeared to have a higher risk of involvement at first relapse relative to previously irradiated metastatic sites. These observations support the current paradigm of irradiating metastases that persist after induction chemotherapy in high-risk patients. Furthermore, they raise the hypothesis that metastatic sites appearing to clear with induction chemotherapy may also benefit from radiotherapeutic treatment modalities (external beam radiation or (131)I-MIBG).
authors.affiliation: Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Alexei L
authors.initials: AL
authors.lastname: Polishchuk
authors.affiliation: Division of Radiation Oncology, Dana Farber/Boston Children's Cancer and Blood Disorders Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Richard
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Christine
authors.initials: C
authors.lastname: Hill-Kayser
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Anthony
authors.initials: A
authors.lastname: Little
authors.affiliation: Department of Radiology, University of California at San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Randall A
authors.initials: RA
authors.lastname: Hawkins
authors.affiliation: Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hamilton
authors.affiliation: Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Lau
authors.affiliation: Division of Hematology/Oncology, Children's Hospital of Los Angeles, Los Angeles, California.
authors.forename: Hung Chi
authors.initials: HC
authors.lastname: Tran
authors.affiliation: Division of Hematology and Oncology, Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Caron
authors.initials: C
authors.lastname: Strahlendorf
authors.affiliation: Division of Pediatric Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Lemons
authors.affiliation: Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Vivian
authors.initials: V
authors.lastname: Weinberg
authors.affiliation: Department of Pediatrics, University of California at San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
authors.affiliation: Department of Pediatrics, University of California at San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Steven G
authors.initials: SG
authors.lastname: DuBois
authors.affiliation: Division of Radiation Oncology, Dana Farber/Boston Children's Cancer and Blood Disorders Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Marcus
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Bagatell
authors.affiliation: Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California. Electronic address: dhaaskogan@radonc.ucsf.edu.
authors.forename: Daphne A
authors.initials: DA
authors.lastname: Haas-Kogan
mesh_terms: D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics; D000293:Adolescent; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D009447:Neuroblastoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012189:Retrospective Studies
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine