High-dose 131I-metaiodobenzylguanidine therapy in patients with high-risk neuroblastoma in Japan.

OBJECTIVE: The aim of the study was to investigate the outcomes and prognostic factors of high-dose 131I-metaiodobenzylguanidine (131I-MIBG) therapy in patients with refractory or relapsed neuroblastoma (NBL) in Japan. METHODS: We retrospectively analyzed 20 patients with refractory or relapsed high-risk NBL who underwent 131I-MIBG therapy with an administration dose ranging from 444 to 666 MBq/kg at Kanazawa University Hospital, Japan, between September 2008 and September 2013. We focused on measurements regarding their initial responses, prognostic factors, survivals, and toxicities following 131I-MIBG therapy using our hospital data and questionnaires from the hospitals that these patients were initially referred from. Furthermore, we performed Kaplan-Meier survival analysis to evaluate event-free survival (EFS) and overall survival (OS). RESULTS: In 19 patients with complete follow-up data, the median age at first 131I-MIBG treatment was 7.9 years (range 2.5-17.7 years). Following 131I-MIBG therapy, 17 of the 19 patients underwent stem-cell transplantations, and their treatment response was either complete (CR) or partial (PR) in three and two cases, respectively. The EFS and OS rates at 1 year following 131I-MIBG therapy were 42% and 58%, respectively, and those at 5 years following 131I-MIBG therapy were 16% and 42%, respectively. Using the two-sample log-rank test, the OS time following 131I-MIBG therapy was significantly longer for < 3-year time interval between the initial diagnosis and 131I-MIBG therapy (p = 0.017), Curie score < 16 just before 131I-MIBG therapy (p = 0.002), without pain (p = 0.002), without both vanillylmandelic acid (VMA) and homovanillic acid (HVA) elevation (p = 0.037) at 131I-MIBG therapy, and with CR or PR following 131I-MIBG therapy (p = 0.015). Although severe hematological toxicities were identified in all 19 patients, severe nonhematological toxicity was not recorded in any patient, except for one patient with grade 3 anorexia and nausea. CONCLUSIONS: High-dose 131I-MIBG therapy in patients with refractory or relapsed high-risk NBL can provide a favorable prognosis without severe nonhematological toxicities. Better prognosis may be anticipated in patients with the initial good response, no pain at 131I-MIBG therapy, no VMA and HVA elevation at 131I-MIBG therapy, low Curie score (< 16) just before 131I-MIBG therapy, and short time interval (< 3 years) between the initial diagnosis and 131I-MIBG therapy.

Extremity Radioactive Iodine Uptake on Post-therapeutic Whole Body Scan in Patients with Differentiated Thyroid Cancer.

OBJECTIVES: We investigated a frequency of lower extremity uptake on the radioactive iodine (RAI) whole body scan (WBS) after RAI treatment in patients with differentiated thyroid cancer, in order to retrospectively examine whether or not the frequency was pathological. METHODS: This retrospective study included 170 patients with thyroid cancer, undergoing RAI treatment. Overall, 99(58%) and 71(42%) patients received single and multiple RAI treatments, respectively. Post-therapeutic WBS was acquired after 3 days of RAI administration. For patients with multiple RAI treatments, the WBS of their last RAI treatment was evaluated. Lower extremity uptake on post-therapeutic WBS was classified into 3 categories: bilateral femoral uptake (type A), bilateral femoral and tibia uptake (type B), and uptake in bilateral upper and lower extremities (type C). Then, the patients with RAI uptake in the lower extremities on WBS were analyzed with clinical parameters. RESULTS: Overall, 99 patients (58%) had the extremity uptake on their posttherapeutic RAI WBS. As the results indicated, 42, 53, and 4 patients had type A, type B, and type C uptakes, respectively. Lower extremity uptake was significantly associated with younger age, not only in subjects with multiple RAI treatments but also in all the patients (P<0.05). Accumulation in patients with multiple RAI treatments was more frequent than patients with single RAI treatment (P<0.05). Lower extremity uptake was not associated with counts of the white blood cell count, hemoglobin level, platelet count, estimated glomerular filtration rate, effective half-time of RAI, serum TSH level, and anti-Tg concentration. CONCLUSION: About half of the patients had lower extremity uptake on the posttherapeutic RAI WBS, especially younger patients and those with multiple courses of RAI treatment. Bilateral lower extremity's RAI uptake on the posttherapeutic WBS should be considered as physiological RAI distribution in bone marrow.

Effects and safety of ¹³¹I-metaiodobenzylguanidine (MIBG) radiotherapy in malignant neuroendocrine tumors: results from a multicenter observational registry.

Effective treatments for malignant neuroendocrine tumors are under development. While iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG) radiotherapy has been used in the treatment of malignant neuroendocrine tumors, there are few studies evaluating its therapeutic effects and safety in a multicenter cohort. In the current study, we sought to evaluate the effects and safety of ¹³¹I-MIBG therapy for conditions including malignant pheochromocytoma and paraganglioma within a multicenter cohort. Forty-eight malignant neuroendocrine tumors (37 pheochromocytoma and 11 paraganglioma) from four centers underwent clinical ¹³¹I-MIBG radiotherapy. The tumor responses were observed before and 3 to 6 months after the ¹³¹I-MIBG radiotherapy in accordance with RECIST criteria. We also evaluated the data for any adverse effects. The four centers performed a total of 87 ¹³¹I-MIBG treatments on 48 patients between January 2000 and March 2009. Of the treatments, 65 were evaluable using RECIST criteria. One partial response (PR), 40 stable disease (SD), and 9 progressive disease (PD) in malignant pheochromocytoma were observed after each treatment. Fourteen SD and one PD-were observed in paraganglioma. Patients with normal hypertension (systolic blood pressure (BP) > 130 mmHg) showed significantly reduced systolic BP after the initial follow-up (n=10, 138.1±8.2 to 129.5±13.5 mmHg, P=0.03). In adult neuroendocrine tumors with a treatment-basis analysis, there were side effects following 41 treatments (47.1%) and most of them (90.2%) were minor. In this multicenter registry, PR or SD was achieved in 84.6% of the treatment occasions in adult neuroendocrine tumors through ¹³¹I-MIBG radiotherapy. This indicated that most of the ¹³¹I-MIBG radiotherapy was performed safely without significant side effects.