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author:("puberty, John")
1.  Thyroid and Hepatic Function After High Dose 131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Neuroblastoma 
Pediatric blood & cancer  2010;56(2):191-201.
Background
131I-Metaiodobenzylguanidine (131I-MIBG) provides targeted radiotherapy for children with neuroblastoma, a malignancy of the sympathetic nervous system. Dissociated radioactive iodide may concentrate in the thyroid, and MIBG is concentrated in the liver after MIBG therapy. The aim of our study was to analyze the effects of 131I-MIBG therapy on thyroid and liver function.
Procedure
Pre and post therapy thyroid and liver functions were reviewed in a total of 194 neuroblastoma patients treated with 131I-MIBG therapy. The cumulative incidence over time was estimated for both thyroid and liver toxicities. The relationship to cumulative dose/kg, number of treatments, time from treatment to follow-up, sex, and patient age was examined.
Results
In patients who presented with Grade 0 or Grade 1 thyroid toxicity at baseline, 12±4% experienced onset or worsening to Grade 2 hypothyroidism and one patient developed Grade 2 hyperthyroidism by two years after 131I-MIBG therapy. At two years post 131I-MIBG therapy, 76±4% patients experienced onset or worsening of hepatic toxicity to any grade, and 23±5% experienced onset of or worsening to Grade 3 or 4 liver toxicity. Liver toxicity usually was transient asymptomatic transaminase elevation, frequently confounded by disease progression and other therapies.
Conclusion
The prophylactic regimen of potassium iodide and potassium perchlorate with 131I-MIBG therapy resulted in a low rate of significant hypothyroidism. Liver abnormalities following 131I-MIBG therapy were primarily reversible and did not result in late toxicity. 131I-MIBG therapy is a promising treatment for children with relapsed neuroblastoma with a relatively low rate of symptomatic thyroid or hepatic dysfunction.
doi:10.1002/pbc.22767
PMCID: PMC3006009  PMID: 20830775
Neuroblastoma; 131I-MIBG; Hypothyroidism
2.  Phase II Study of High-Dose [131I]Metaiodobenzylguanidine Therapy for Patients With Metastatic Pheochromocytoma and Paraganglioma 
Journal of Clinical Oncology  2009;27(25):4162-4168.
Purpose
To evaluate the safety and efficacy of high-dose [131I]metaiodobenzylguanidine ([131I]MIBG) in the treatment of malignant pheochromocytoma (PHEO) and paraganglioma (PGL).
Methods
Fifty patients with metastatic PHEO or PGL, age 10 to 64 years, were treated with [131I]MIBG doses ranging from 492 to 1,160 mCi (median, 12 mCi/kg). Cumulative [131I]MIBG administered ranged from 492 to 3,191 mCi. Autologous hematopoietic stem cells were collected and cryopreserved before treatment with [131I]MIBG greater than 12 mCi/kg or with a total dose greater than 500 mCi. Sixty-nine [131I]MIBG infusions were given, which included infusions to 35 patients treated once and infusions to 15 patients who received two or three treatments. Response was evaluated by [123I]MIBG scans, computed tomography/magnetic resonance imaging, urinary catecholamines/metanephrines, and chromogranin A.
Results
The overall complete response (CR) plus partial response (PR) rate in 49 evaluable patients was 22%. Additionally, 35% of patients achieved a CR or PR in at least one measure of response without progressive disease, and 8% of patients maintained stable disease for greater than 12 months. Thirty-five percent of patients experienced progressive disease within 1 year after therapy. The estimated 5-year overall survival rate was 64%. Toxicities included grades 3 to 4 neutropenia (87%) and thrombocytopenia (83%). Grades 3 to 4 nonhematologic toxicity included acute respiratory distress syndrome (n = 2), bronchiolitis obliterans organizing pneumonia (n = 2), pulmonary embolism (n = 1), fever with neutropenia (n = 7), acute hypertension (n = 10), infection (n = 2), myelodysplastic syndrome (n = 2), and hypogonadism (n = 4).
Conclusion
Although serious toxicity may occur, the survival and response rates achieved with high-dose [131I]MIBG suggest its utility in the management of selected patients with metastatic PHEO and PGL.
doi:10.1200/JCO.2008.21.3496
PMCID: PMC2734428  PMID: 19636009
3.  Iodine-131—Metaiodobenzylguanidine Double Infusion With Autologous Stem-Cell Rescue for Neuroblastoma: A New Approaches to Neuroblastoma Therapy Phase I Study 
Journal of Clinical Oncology  2009;27(7):1020-1025.
Purpose
Iodine-131—metaiodobenzylguanidine (131I-MIBG) provides targeted radiotherapy with more than 30% response rate in refractory neuroblastoma, but activity infused is limited by radiation safety and hematologic toxicity. The goal was to determine the maximum-tolerated dose of 131I-MIBG in two consecutive infusions at a 2-week interval, supported by autologous stem-cell rescue (ASCR) 2 weeks after the second dose.
Patients and Methods
The 131I-MIBG dose was escalated using a 3 + 3 phase I trial design, with levels calculated by cumulative red marrow radiation index (RMI) from both infusions. Using dosimetry, the second infusion was adjusted to achieve the target RMI, except at level 4, where the second infusion was capped at 21 mCi/kg.
Results
Twenty-one patients were enrolled onto the study at levels 1 to 4, with 18 patients assessable for toxicity and 20 patients assessable for response. Cumulative 131I-MIBG given to achieve the target RMI ranged from 22 to 50 mCi/kg, with cumulative RMI of 3.2 to 8.92 Gy. No patient had a dose-limiting toxicity. Reversible grade 3 nonhematologic toxicity occurred in six patients at level 4, establishing the recommended cumulative dose as 36 mCi/kg. The median time to absolute neutrophil count more than 500/μL after ASCR was 13 days (4 to 27 days) and to platelet independence was 17 days (6 to 47 days). Responses included two partial responses, eight mixed responses, three stable disease, and seven progressive disease. Responses by semiquantitative MIBG score occurred in eight patients, soft tissue responses occurred in five of 11 patients, but bone marrow responses occurred in only two of 13 patients.
Conclusion
The lack of toxicity with this approach allowed dramatic dose intensification of 131I-MIBG, with minimal toxicity and promising activity.
doi:10.1200/JCO.2007.15.7628
PMCID: PMC2738616  PMID: 19171714

Results 1-3 (3)