title: Correlation of tumor and whole-body dosimetry with tumor response and toxicity in refractory neuroblastoma treated with (131)I-MIBG.
abstract: The purpose of our study was to determine the effect of tumor-targeted radiation in neuroblastoma by correlating administered (131)I-metaiodobenzylguanidine (MIBG) activity to tumor and whole-body dosimetry, tumor volume change, overall response, and hematologic toxicity.
  
  
  METHODS
  Eligible patients had MIBG-positive lesions and tumor-free, cryopreserved hematopoietic stem cells. Activity was administered according to body weight and protocol as part of a phase I and phase II study. The whole-body radiation dose was derived from daily 1-m exposure measurements, the tumor self-absorbed radiation dose (TSARD) was determined from scintillation-camera conjugate views, and the tumor volume was measured using CT or MRI.
  
  
  RESULTS
  Forty-two patients with refractory neuroblastoma (16 with prior hematopoietic stem cell transplant) received a median activity of 555 MBq/kg (15 mCi/kg) (range, 93-770 MBq/kg) and a median total activity of 11,470 MBq (310 mCi) (range, 3,330-30,969 MBq). The median whole-body radiation dose was 228 cGy (range, 57-650 cGy) and the median TSARD was 3,300 cGy (range, 312-30,500 cGy). Responses among evaluable patients included 16 partial response, 3 mixed response, 14 stable disease, and 9 progressive disease. Higher TSARD values predicted better overall disease response (P < 0.01). The median decrease in tumor volume was 19%; 18 tumors decreased, 4 remained stable, and 5 increased in size. Correlation was seen between administered activity per kilogram and whole-body dose as well as hematologic toxicity (assessed by blood platelet and neutrophil count nadir) (P < 0.05). The median whole-body dose was higher in the 11 patients who required hematopoietic stem cell infusion for prolonged neutropenia versus the 31 patients who did not (323 vs. 217 cGy; P = 0.03).
  
  
  CONCLUSIONS
  Despite inaccuracies inherent in dosimetry methods, (131)I-MIBG activity per kilogram correlated with whole-body radiation dose and hematologic toxicity. The TSARD by conjugate planar imaging predicted tumor volume decrease and also correlated with overall tumor response.
authors.affiliation: Department of Pediatrics, University of California, San Francisco, San Francisco, California 94143-0106, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Matthay
authors.forename: C
authors.initials: C
authors.lastname: Panina
authors.forename: J
authors.initials: J
authors.lastname: Huberty
authors.forename: D
authors.initials: D
authors.lastname: Price
authors.forename: D V
authors.initials: DV
authors.lastname: Glidden
authors.forename: H R
authors.initials: HR
authors.lastname: Tang
authors.forename: R A
authors.initials: RA
authors.lastname: Hawkins
authors.forename: J
authors.initials: J
authors.lastname: Veatch
authors.forename: B
authors.initials: B
authors.lastname: Hasegawa
mesh_terms: D019797:3-Iodobenzylguanidine / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D001853:Bone Marrow / Q000528:radiation effects; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006402:Hematologic Diseases / Q000097:blood; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000473:pathology / Q000532:radiotherapy*; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D014915:Whole-Body Counting
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine