Effects of Repeated I-Iodobenzylguanidine Radiotherapy on Tumor Size and Tumor Metabolic Activity in Patients with Metastatic Neuroendocrine Tumors.

I-iodobenzylguanidine (I-MIBG) radiotherapy has shown some survival benefits in metastatic neuroendocrine tumors (NETs). European Association of Nuclear Medicine clinical guidelines for I-MIBG radiotherapy suggest a repeated treatment protocol, although none currently exists. The existing single-high-dose I-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 I-MIBG therapy on tumor size and tumor metabolic response in patients with metastatic NETs. Eleven patients with metastatic NETs (aged 49.2 ± 16.3 y) prospectively received repeated 5,550-MBq doses of I-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 I-MIBG dose was 15,640.9 ± 2,245.1 MBq (286.01 MBq/kg). Tumor response was observed by CT and F-FDG PET or by F-FDG PET/CT before and 3-6 mo after the final I-MIBG treatment. 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]; = 0.563). In tumor region-based analysis with partial-response and stable-disease patients ( 9), I-MIBG therapy significantly reduced tumor diameter (79 lesions; median, 16 mm [IQR, 12-22 mm] to 11 mm [IQR, 6-16 mm]; < 0.001). Among 5 patients with hypertension, there was a strong trend toward systolic blood pressure reduction ( 0.058), and diastolic blood pressure was significantly reduced ( 0.006). Eighty-two percent of metastatic NET patients effectively achieved inhibition of disease progression, with reduced tumor size and reduced metabolic activity, through repeated I-MIBG therapy. Therefore, this relatively short-term repeated I-MIBG treatment may have potential as one option in the therapeutic protocol for metastatic NETs. Larger prospective studies with control groups are warranted.