Abstract
131I-meta-iodobenzylguanidine (131I-MIBG) radiotherapy has shown some survival benefits in metastatic neuroendocrine tumors (NETs). European Association of Nuclear Medicine clinical guidelines for 131I-MIBG radiotherapy suggest a repeated treatment protocol, although none currently exists. The existing single-high-dose 131I-MIBG radiotherapy (444 MBq/kg) has been shown to have some benefits for patients with metastatic NETs. However, this protocol increases adverse effects and requires alternative therapeutic approaches. Therefore, the aim of this study was to evaluate the effects of repeated 131I-MIBG therapy on tumor size and tumor metabolic response in patients with metastatic NETs. Methods: Eleven patients with metastatic NETs (aged 49.2 ± 16.3 y) prospectively received repeated 5,550-MBq doses of 131I-MIBG therapy at 6-mo intervals. In total, 31 treatments were performed. The mean number of treatments was 2.8 ± 0.4, and the cumulative 131I-MIBG dose was 15,640.9 ± 2,245.1 MBq (286.01 MBq/kg). Tumor response was observed by CT and 18F-FDG PET or by 18F-FDG PET/CT before and 3-6 mo after the final 131I-MIBG treatment. Results: On the basis of the CT findings with RECIST, 3 patients showed a partial response and 6 patients showed stable disease. The remaining 2 patients showed progressive disease. Although there were 2 progressive-disease patients, analysis of all patients showed no increase in summed length diameter (median, 228.7 mm [interquartile range (IQR), 37.0-336.0 mm] to 171.0 mm [IQR, 38.0-270.0 mm]; P = 0.563). In tumor region-based analysis with partial-response and stable-disease patients (n = 9), 131I-MIBG therapy significantly reduced tumor diameter (79 lesions; median, 16 mm [IQR, 12-22 mm] to 11 mm [IQR, 6-16 mm]; P < 0.001). Among 5 patients with hypertension, there was a strong trend toward systolic blood pressure reduction (P = 0.058), and diastolic blood pressure was significantly reduced (P = 0.006). Conclusion: Eighty-two percent of metastatic NET patients effectively achieved inhibition of disease progression, with reduced tumor size and reduced metabolic activity, through repeated 131I-MIBG therapy. Therefore, this relatively short-term repeated 131I-MIBG treatment may have potential as one option in the therapeutic protocol for metastatic NETs. Larger prospective studies with control groups are warranted.
Highlights
Beginning in 2017, the World Health Organization started defining pheochromocytoma and paraganglioma (PPGL) as a malignant disease, given that all those affected may develop metastatic lesions during their lifetime [1]
The largest study looking at the effects of chemotherapy showed decreased tumor size and facilitated blood pressure (BP) control in about a third of patients [6]
The concentrations of norepinephrine in the nervous systems are regulated by the norepinephrine transporter. 131I-MIBG accumulates in the nervous systems; unlike norepinephrine, 131I-MIBG has little or no affinity for adrenergic receptors [8]. 131I-MIBG radiotherapy has been used to treat neuroendocrine tumors (NETs), including metastatic
Summary
Beginning in 2017, the World Health Organization started defining pheochromocytoma and paraganglioma (PPGL) as a malignant disease, given that all those affected may develop metastatic lesions during their lifetime [1]. High-dose 131I-MIBG therapy combined with autologous bone marrow transplantation showed a high rate (83%) of complete remission (CR) or partial response (PR) [12] These data imply that controlling tumor progression or hormonal level may require a certain total accumulated dose of 131I-MIBG. In terms of side effects, Loh et al showed that radiationinduced toxicity such as bone marrow suppression was generally related to administered dose [11] Another analysis showed that 3 patients (9% of the study population) had 131I-MIBG treatment– related death from acute myocardial infarctions [13]. All these patients received 11,100 MBq of 131I-MIBG as a single dose and may have had an acute catecholamine crisis resulting from tumor necrosis. On the basis of this previous study and the EANM guidelines, we decided on an interval of 6 mo, which would be practical in a clinical setting
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