title: Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma.
abstract: OBJECTIVE
  Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) therapy is an established treatment modality for relapsed/refractory neuroblastoma, most frequently administered according to fixed or weight-based criteria. We evaluate response and toxicity following a dosimetry-based, individualized approach.
  
  
  METHODS
  A review of 44 treatments in 25 patients treated with I-mIBG therapy was performed. Patients received I-mIBG therapy following relapse (n=9), in refractory disease (n=12), or with surgically unresectable disease despite conventional treatment (n=4). Treatment schedule (including mIBG dose and number of administrations) was individualized according to the clinical status of the patient and dosimetry data from either a tracer study or previous administrations. Three-dimensional tumour dosimetry was also performed for eight patients.
  
  
  RESULTS
  The mean administered activity was 11089±7222 MBq and the mean whole-body dose for a single administration was 1.79±0.57 Gy. Tumour-absorbed doses varied considerably (3.70±3.37 mGy/MBq). CTCAE grade 3/4 neutropenia was documented following 82% treatments and grade 3/4 thrombocytopenia following 71% treatments. Further acute toxicity was found in 49% of patients. All acute toxicities resolved with appropriate therapy. The overall response rate was 58% (complete or partial response), with a further 29% of patients having stable disease.
  
  
  CONCLUSIONS
  A highly personalized approach combining patient-specific dosimetry and clinical judgement enables delivery of high activities that can be tolerated by patients, particularly with stem cell support. We report excellent response rates and acceptable toxicity following individualized I-mIBG therapy.
authors.affiliation: aChildren's and Young Persons Unit bJoint Department of Physics, Institute of Cancer Research, Royal Marsden NHS Foundation Trust cDepartment of Nuclear Medicine, The Royal Marsden Hospital, Surrey, UK.
authors.forename: Sally L
authors.initials: SL
authors.lastname: George
authors.forename: Nadia
authors.initials: N
authors.lastname: Falzone
authors.forename: Sarah
authors.initials: S
authors.lastname: Chittenden
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Kirk
authors.forename: Donna
authors.initials: D
authors.lastname: Lancaster
authors.forename: Sucheta J
authors.initials: SJ
authors.lastname: Vaidya
authors.forename: Henry
authors.initials: H
authors.lastname: Mandeville
authors.forename: Frank
authors.initials: F
authors.lastname: Saran
authors.forename: Andrew D J
authors.initials: AD
authors.lastname: Pearson
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.forename: Simon T
authors.initials: ST
authors.lastname: Meller
authors.forename: Ana M
authors.initials: AM
authors.lastname: Denis-Bacelar
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Flux
mesh_terms: D019797:3-Iodobenzylguanidine / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000473:pathology / Q000532:radiotherapy*; D057285:Precision Medicine; D011874:Radiometry; D012008:Recurrence; D012189:Retrospective Studies; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D019797:3-Iodobenzylguanidine
references.citation: Br J Cancer. 1999 Dec;81(8):1378-84
references.pmid: 10604736
references.citation: J Nucl Biol Med. 1991 Oct-Dec;35(4):224-7
references.pmid: 1823823
references.citation: Eur J Cancer. 2014 Mar;50(4):801-15
references.pmid: 24333097
references.citation: Eur J Nucl Med Mol Imaging. 2013 Oct;40(11):1711-7
references.pmid: 23921531
references.citation: Eur J Nucl Med Mol Imaging. 2013 Oct;40(10):1516-22
references.pmid: 23740371
references.citation: Pediatr Blood Cancer. 2013 May;60(5):879-84
references.pmid: 23024113
references.citation: Q J Nucl Med Mol Imaging. 2013 Mar;57(1):66-78
references.pmid: 23474636
references.citation: J Nucl Med. 2012 Jul;53(7):1155-63
references.pmid: 22700000
references.citation: Clin Cancer Res. 2012 May 1;18(9):2679-86
references.pmid: 22421195
references.citation: Q J Nucl Med Mol Imaging. 2011 Apr;55(2):116-25
references.pmid: 21386786
references.citation: J Nucl Med. 2009 Sep;50(9):1518-24
references.pmid: 19713562
references.citation: Eur J Nucl Med Mol Imaging. 2008 May;35(5):1039-47
references.pmid: 18274745
references.citation: Eur J Cancer. 2008 Mar;44(4):551-6
references.pmid: 18267358
references.citation: Cancer Biother Radiopharm. 2007 Feb;22(1):105-12
references.pmid: 17627418
references.citation: Cancer Biother Radiopharm. 2007 Apr;22(2):243-9
references.pmid: 17600471
references.citation: J Clin Oncol. 2007 Mar 20;25(9):1054-60
references.pmid: 17369569
references.citation: Cancer Biother Radiopharm. 2005 Apr;20(2):195-9
references.pmid: 15869455
references.citation: J Clin Oncol. 1992 Dec;10(12):1889-96
references.pmid: 1453204
references.citation: J Nucl Med. 2001 Nov;42(11):1713-21
references.pmid: 11696644
references.citation: Phys Med Biol. 1968 Apr;13(2):205-17
references.pmid: 5649733
references.citation: J Nucl Biol Med. 1991 Oct-Dec;35(4):202-6
references.pmid: 1823819
references.citation: Med Phys. 2000 Mar;27(3):485-98
references.pmid: 10757601