An open-label, single-arm, multi-center, phase II clinical trial of single-dose [131I]meta-iodobenzylguanidine therapy for patients with refractory pheochromocytoma and paraganglioma.

OBJECTIVE: In this phase II study, we aimed to investigate the efficacy and safety of single-dose [131I]meta-iodobenzylguanidine (131I-mIBG) therapy in patients with refractory pheochromocytoma and paraganglioma (PPGL). PATIENTS AND METHODS: This study was designed as an open-label, single-arm, multi-center, phase II clinical trial. The enrolled patients were administered 7.4 GBq of 131I-mIBG. Its efficacy was evaluated 12 and 24 weeks later, and its safety was monitored continuously until the end of the study. We evaluated the biochemical response rate as the primary endpoint using the one-sided exact binomial test based on the null hypothesis (≤ 5%). RESULTS: Seventeen patients were enrolled in this study, of which 16 were treated. The biochemical response rate (≥ 50% decrease in urinary catecholamines) was 23.5% (90% confidence interval: 8.5-46.1%, p = 0.009). The radiographic response rates, determined with CT/MRI according to the response evaluation criteria in solid tumors (RECIST) version 1.1 and 123I-mIBG scintigraphy were 5.9% (0.3%-25.0%) and 29.4% (12.4%-52.2%), respectively. The most frequent non-hematologic treatment-emergent adverse events (TEAEs) were gastrointestinal symptoms including nausea, appetite loss, and constipation, which were, together, observed in 15 of 16 patients. Hematologic TEAEs up to grade 3 were observed in 14 of 16 patients. No grade 4 or higher TEAEs were observed. All patients had experienced at least one TEAE, but no fatal or irreversible TEAEs were observed. CONCLUSION: A single dose 131I-mIBG therapy was well tolerated by patients with PPGL, and statistically significantly reduced catecholamine levels compared to the threshold response rate, which may lead to an improved prognosis for these patients.

131 I-Meta-iodobenzylguanidine followed by busulfan and melphalan and autologous stem cell rescue in high-risk neuroblastoma.

INTRODUCTION: Despite the progress in current treatments, the event-free survival of high-risk neuroblastoma (HR-NB) patients does not exceed 40%-50%, and the prognosis of refractory or relapsed patients is poor, still representing a challenge for pediatric oncologist. Therapeutic Iodine-131 meta-iodobenzylguanidine (Th-131 I-MIBG) is a recognized safe and potentially effective treatment for NB. MATERIALS: This retrospective study reports the outcomes of 28 MIBG-avid NB patients with advanced disease either refractory or relapsed, which was undertaken from 1996 to 2014. Th-131 I-MIBG was administered shortly before (median: 17 days) high-dose chemotherapy with busulfan and melphalan (HD-BuMel) and autologous stem cell rescue (ASCR) at the Gaslini Institute in Genoa, with the aim of analyzing the feasibility, safety, and efficacy of this approach. RESULTS: Engraftment occurred in all patients after a median of 14 (11-29) and 30 days (13-80) from ASCR for neutrophils and platelets, respectively. No treatment-related deaths were observed. The main high-grade (3-4) toxicity observed was oral and gastrointestinal mucositis in 78.6% and 7.1% of patients, respectively, whereas high-grade hepatic toxicity was observed in 10.7%. Two patients developed veno-occlusive-disease (7.1%), completely responsive to defibrotide. Hypothyroidism was the main late complication that occurred in nine patients (31.1%). After Th-131 MIBG and HD-BuMel, 19 patients (67.8%) showed an improvement in disease status. Over a median follow-up of 15.9 years, the three-year and five-year overall survival (OS) probabilities were 53% (CI 0.33-0.69) and 41% (CI 0.22-0.59), and the three-year and five-year rates of cumulative risk of progression/relapse were 64% (CI 0.47-0.81) and 73% (CI 0.55-0.88), respectively. MYCN amplification emerged as the only risk factor significantly associated with OS (HR, 3.58;P = 0.041). CONCLUSION: Th-131 I-MIBG administered shortly before HD-BuMel is a safe and effective regimen for patients with advanced MIBG-avid NB. These patients should be managed in centers with proven expertise.

Glow in the dark.

OBJECTIVE: To highlight the importance of radiation safety and handling of radioactive secretions following 131I-meta iodobenzylguanidine (131I-mIBG) use in the treatment of neuroblastoma. METHODS: We report a 4-year-old girl with stage 4 neuroblastoma, on whom's single-photon emission computer tomography (SPECT) scan we demonstrate four extra-corporal areas of radioactivity confirming radiation uptake in the four corners of her 'comfort blanket' that had been used to cover her during the scan. It transpired that she had been sucking on the four corners of this blanket. RESULTS: The patient's secretions remain radioactive for some time following scintigraphy, as evidence of radioactivity in the patient's comfort blanket. CONCLUSIONS: Radioactive uptake of 131I-mIBG in the salivary glands of patients has previously been reported. This illustrative case emphasizes that patient's secretions remain radioactive following treatment and highlights the importance of careful handling of radioactive secretions.

A systematic review of 131I-meta iodobenzylguanidine molecular radiotherapy for neuroblastoma.

The optimal use and effectiveness of (131)I-meta iodobenzylguanidine ((131)I-mIBG) molecular radiotherapy for neuroblastoma remain unclear despite extensive clinical experience. This systematic review aimed to improve understanding of the current data and define uncertainties for future clinical trials. Bibliographic databases were searched for neuroblastoma and (131)I-mIBG. Clinical trials and non-comparative case series of (131)I-mIBG therapy for neuroblastoma were included. Two reviewers assessed papers for inclusion using the title and abstract with consensus achieved by discussion. Data were extracted by one reviewer and checked by a second. Studies with multiple publications were reported as a single study. The searches yielded 1216 citations, of which 51 publications reporting 30 studies met our inclusion criteria. No randomised controlled trials (RCTs) were identified. In two studies (131)I-mIBG had been used as induction therapy and in one study it had been used as consolidation therapy. Twenty-seven studies for relapsed and refractory disease were identified. Publication dates ranged from 1987 to 2012. Total number of patients was 1121 with study sizes ranging from 10 to 164. There was a large amount of heterogeneity between the studies with regard to patient population, treatment schedule and response assessment. Study quality was highly variable. The objective tumour response rate reported in 25 studies ranged from 0% to 75%, mean 32%. We conclude that (131)I-mIBG is an active treatment for neuroblastoma, but its place in the management of neuroblastoma remains unclear. Prospective randomised trials are essential to strengthen the evidence base.