Efficacy and Safety of ¹²⁴I-MIBG Dosimetry-Guided High-Activity ¹³¹I-MIBG Therapy of Advanced Pheochromocytoma or Neuroblastoma.

Abstract

We aim to evaluate the efficacy and safety of ¹²⁴I-metaiodobenzylguanidine (MIBG) dosimetry-guided high-activity ¹³¹I-MIBG therapy of advanced pheochromocytoma or neuroblastoma. <b>Methods:</b> Fourteen patients with advanced pheochromocytoma or neuroblastoma, age 9-69 y, underwent ¹²⁴I-MIBG PET scans and whole-body retention measurements to assess the whole-body dose as a surrogate of bone marrow toxicity and tumor (absorbed) dose per unit of administered activity. Dosimetry results together with individual patient characteristics were combined to guide a single therapeutic activity to achieve a high tumor dose without exceeding toxicity threshold. Toxicity was assessed for hematologic, hepatic, and renal function. Response was evaluated by RECIST, International Society of Pediatric Oncology Europe Neuroblastoma-like score, change in PET uptake, and quantitative PET parameters (SUV_max, SUV_peak, metabolic tumor volume, total lesion glycolysis), as well as visual decrease in number or in visual intensity of lesions on baseline to follow-up ¹²⁴I-MIBG PET/CT. <b>Results:</b> The average therapeutic activity was 14 GBq. Eleven of 14 patients (79%) received each more than 10 GBq. One male patient was treated with a single activity of 50 GBq. Three patients were treated with lower activities between 3.5 and 7.0 GBq. Median overall survival was 85 mo (95% CI), and median progression-free survival was 25 mo (95% CI). Four (29%) and 5 (36%) patients demonstrated response (complete response or partial response) by RECIST and functional imaging, respectively. One patient exceeded whole-body dose of 2 Gy and demonstrated grade 3 hematologic toxicity, which resolved spontaneously within 12 mo after the therapy without the need for further treatment. Three patients (21%) demonstrated transient grade 1 renal toxicity. <b>Conclusion:</b> ¹²⁴I-MIBG dosimetry-guided high-activity ¹³¹I-MIBG therapy in patients with advanced pheochromocytoma or neuroblastoma resulted in durable responses with a low rate of manageable adverse events. Efficacy of ¹²⁴I-MIBG-guided activity escalation should further be assessed in a prospective setting.