Thyroid and hepatic function after high-dose 131 I-metaiodobenzylguanidine ( 131 I-MIBG) therapy for neuroblastoma.

Background 131 I-Metaiodobenzylguanidine ( 131 I-MIBG) provides targeted radiotherapy for children with neuroblastoma, a malignancy of the sympathetic nervous system. Dissociated radioactive iodide may concentrate in the thyroid, and 131 I-MIBG is concentrated in the liver after 131 I-MIBG therapy. The aim of our study was to analyze the effects of 131 I-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 131 I-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 1 thyroid toxicity at baseline, 12 ± 4% experienced onset of or worsening to Grade 2 hypothyroidism and one patient developed Grade 2 hyperthyroidism by 2 years after 131 I-MIBG therapy. At 2 years post- 131 I-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 was usually transient asymptomatic transaminase elevation, frequently confounded by disease progression and other therapies. Conclusion The prophylactic regimen of potassium iodide and potassium perchlorate with 131 I-MIBG therapy resulted in a low rate of significant hypothyroidism. Liver abnormalities following 131 I-MIBG therapy were primarily reversible and did not result in late toxicity. 131 I-MIBG therapy is a promising treatment for children with relapsed neuroblastoma with a relatively low rate of symptomatic thyroid or hepatic dysfunction. Pediatr Blood Cancer 2011;56:191–201. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78497/1/22767_ftp.pd

Different outcomes for relapsed versus refractory neuroblastoma after therapy with 131I-metaiodobenzylguanidine (131I-MIBG)

Background(131)I-metaiodobenzylguanidine ((131)I-MIBG) is a targeted radiopharmaceutical with significant activity in high-risk relapsed and chemotherapy-refractory neuroblastoma. Our primary aim was to determine if there are differences in response rates to (131)I-MIBG between patients with relapsed and treatment-refractory neuroblastoma.MethodsThis was a retrospective cohort analysis of 218 patients with refractory or relapsed neuroblastoma treated with (131)I-MIBG at UCSF between 1996 and 2014. Results were obtained by chart review and database abstraction. Baseline characteristics and response rates between relapsed patients and refractory patients were compared using Fisher exact and Wilcoxon rank sum tests, and differences in overall survival (OS) were compared using the log-rank test.ResultsThe response rate (complete and partial response) to (131)I-MIBG-based therapies for all patients was 27%. There was no difference in response rates between relapsed and refractory patients. However, after (131)I-MIBG, 24% of relapsed patients had progressive disease compared to only 9% of refractory patients, and 39% of relapsed patients had stable disease compared to 59% of refractory patients (p=0.02). Among all patients, the 24-month OS was 47.0% (95% confidence interval (CI) 39.9-53.9%). The 24-month OS for refractory patients was significantly higher at 65.3% (95% CI 51.8-75.9%), compared to 38.7% (95% CI 30.4-46.8%) for relapsed patients (p<0.001).ConclusionsAlthough there was no significant difference in overall response rates to (131)I-MIBG between patients with relapsed versusrefractory neuroblastoma, patients with prior relapse had higher rates of progressive disease and had lower 2-year overall survival after (131)I-MIBG compared to patients with refractory disease

Semiquantitative mIBG scoring as a prognostic indicator in patients with stage 4 neuroblastoma: a report from the Children\u27s oncology group

Radiolabeled metaiodobenzylguanidine (mIBG) is a highly sensitive and specific marker for detecting neuroblastoma. A semiquantitative mIBG score (Curie score [CS]) was assessed for utility as a prognostic indicator for a cohort of patients with high-risk metastatic disease. METHODS: mIBG scans from 280 patients with mIBG-avid, stage 4 neuroblastoma enrolled on the Children\u27s Oncology Group (COG) protocol A3973 were evaluated at diagnosis (n = 280), after induction chemotherapy (n = 237), and after an autologous stem cell transplantation (n = 178). Individual mIBG scans were evaluated at 10 different anatomic regions, with the scoring of each site (0-3) based on the extent of disease at that anatomic region. RESULTS: There was no correlation between CS at diagnosis and subsequent treatment outcome. Patients with a CS \u3e 2 after induction therapy had a significantly worse event-free survival (EFS) than those with scores 2 identified a cohort of patients at greater risk for an event, independent of other known neuroblastoma factors, including age, MYCN status, ploidy, mitosis-karyorrhexis index, and histologic grade. For MYCN-amplified tumors, the presence (CS \u3e 0) versus absence (CS = 0) of residual mIBG avidity after induction was associated with a significantly worse outcome (3-y EFS: 11.8% +/- 7.8% vs. 49.6% +/- 7.7%, respectively; P = 0.003). After transplantation, patients with a CS \u3e 0 had an EFS inferior to that of patients with a CS of 0 (3-y EFS: 28.9% +/- 6.8% vs. 49.3% +/- 4.9%, respectively [n = 133]; P = 0.009). CONCLUSION: Curie scoring carries prognostic significance in the management of patients with high-risk neuroblastoma. In particular, patients with CSs \u3e 2 after induction have extremely poor outcomes and should be considered for alternative therapeutic strategies

Semiquantitative mIBG Scoring as a Prognostic Indicator in Patients with Stage 4 Neuroblastoma: A Report from the Children’s Oncology Group

UnlabelledRadiolabeled metaiodobenzylguanidine (mIBG) is a highly sensitive and specific marker for detecting neuroblastoma. A semiquantitative mIBG score (Curie score [CS]) was assessed for utility as a prognostic indicator for a cohort of patients with high-risk metastatic disease.MethodsmIBG scans from 280 patients with mIBG-avid, stage 4 neuroblastoma enrolled on the Children's Oncology Group (COG) protocol A3973 were evaluated at diagnosis (n = 280), after induction chemotherapy (n = 237), and after an autologous stem cell transplantation (n = 178). Individual mIBG scans were evaluated at 10 different anatomic regions, with the scoring of each site (0-3) based on the extent of disease at that anatomic region.ResultsThere was no correlation between CS at diagnosis and subsequent treatment outcome. Patients with a CS > 2 after induction therapy had a significantly worse event-free survival (EFS) than those with scores ≤ 2 (3-y EFS: 15.4% ± 5.3% vs. 44.9% ± 3.9%, respectively; P < 0.001). A postinduction CS > 2 identified a cohort of patients at greater risk for an event, independent of other known neuroblastoma factors, including age, MYCN status, ploidy, mitosis-karyorrhexis index, and histologic grade. For MYCN-amplified tumors, the presence (CS > 0) versus absence (CS = 0) of residual mIBG avidity after induction was associated with a significantly worse outcome (3-y EFS: 11.8% ± 7.8% vs. 49.6% ± 7.7%, respectively; P = 0.003). After transplantation, patients with a CS > 0 had an EFS inferior to that of patients with a CS of 0 (3-y EFS: 28.9% ± 6.8% vs. 49.3% ± 4.9%, respectively [n = 133]; P = 0.009).ConclusionCurie scoring carries prognostic significance in the management of patients with high-risk neuroblastoma. In particular, patients with CSs > 2 after induction have extremely poor outcomes and should be considered for alternative therapeutic strategies

Expression of Neuroblastoma-Related Genes in Bone Marrow at End of High-Risk Neuroblastoma Therapy

BACKGROUND: Minimal disease quantification may predict event-free survival (EFS) and overall survival (OS). METHODS: We evaluated mRNA expression of five neuroblastoma-associated genes (NB5 assay) in bone marrows (BM) of patients with newly diagnosed high-risk neuroblastoma who received consistent immunotherapy. mRNA expression of CHGA, DCX, DDC, PHOX2B, and TH genes in BM of 479 patients enrolled on the immunotherapy arm of Children\u27s Oncology Group trials ANBL0032 and ANBL0931 was evaluated using real-time polymerase chain reaction (PCR)-based TaqMan low-density array. Results from end-consolidation and end-therapy were analyzed for association with five-year EFS/OS and patient and tumor characteristics. Tests of statistical significance were two-sided. RESULTS: NB5 assay detected neuroblastoma-related mRNA in 222 of 286 (77.6%) of BMs obtained at end-consolidation and 188 of 304 (61.8%) at end-therapy. Any mRNA level detected in end-therapy BM correlated with significantly worse EFS (57% [49.6%-63.7%] vs 73.0% [63.5%-80.4%]; P = 0.005), but not OS. Analysis limited to patients in complete response at end-therapy still found a significant difference in EFS with detectable versus not detectable NB5 assay results (58.9% [49.5%-67.1%] vs 76.6% [66.1%-84.2%]; P = 0.01). End-consolidation results did not correlate with EFS or OS. Multivariable analysis determined end-therapy NB5 assay BM results (P = 0.02), age at diagnosis (P = 0.002), and preconsolidation response (P = 0.02) were significantly associated with EFS independent of other clinical and biological parameters evaluated, including end-therapy response. CONCLUSIONS: If further validated in additional patient cohorts, the NB5 assay\u27s ability to independently predict EFS from end-therapy could improve patient stratification for novel maintenance therapy trials after current end-therapy to improve outcome