Feasibility and effectiveness of treatment strategy of tandem high‐dose chemotherapy and autologous stem cell transplantation in combination with ¹³¹I‐MIBG therapy for high‐risk neuroblastoma

Abstract

This study was performed to evaluate the safety and effectiveness of tandem HDCT/ASCT combined with targeted radiotherapy using 131I‐MIBG for high‐risk neuroblastoma. Patients with high‐risk neuroblastoma were treated with 8 to 10 cycles of induction chemotherapy before tandem HDCT/ASCT. Patients received 131I‐MIBG treatment before the second HDCT/ASCT. Local radiotherapy and maintenance therapy were performed after tandem HDCT/ASCT. Between 2012 and 2016, 19 patients were diagnosed with high‐risk neuroblastoma in our institution and 18 of them received tandem HDCT/ASCT combined with 131I‐MIBG therapy. For the first HDCT/ASCT regimen, 12 patients received busulfan/melphalan and six patients received melphalan/etoposide/carboplatin. The second HDCT included ThioCy. The median dose of 131I‐MIBG was 17.2 mCi/kg for the first eight patients, while 12 patients in the latter period of the study received reduced dose of 10.7 mCi/kg. The 5‐year OS and EFS rates were 79% and 61%, respectively, for all 19 patients with high‐risk neuroblastoma, and 83% and 64%, respectively, for 18 patients who completed tandem HDCT/ASCT combined with 131I‐MIBG therapy. Six patients experienced disease relapse and five patients died. Treatment‐related mortality was not observed. Among 15 evaluable patients, 11 patients (73%) developed hypothyroidism, six patients (40%) had CKD, and six patients (40%) had growth failure. Hypothyroidism and growth failure were less frequent in patients who received reduced doses of 131I‐MIBG therapy. Tandem HDCT/ASCT combined with HD 131I‐MIBG therapy could be feasible for patients with high‐risk neuroblastoma with acceptable toxicity profiles and favorable outcomes.

Diagnostic Use of Post-therapy 131I-Meta-Iodobenzylguanidine Scintigraphy in Consolidation Therapy for Children with High-Risk Neuroblastoma

“…Hickeson et al showed that 210 lesions were detected on the post-therapy 131 I-mIBG scintigraphy compared with 151 on the 123 I-mIBG scintigraphy in 16 patients (89%) [ 17 ]. For the patients with neuroblastoma without mIBG-avid lesions on diagnostic 123 I-mIBG scintigraphy, post-therapy 131 I-mIBG WBS images detected occult lesions in five of five (100%) [ 13 ] and post-therapy 131 I-mIBG scan with no information about SPECT in three of fifteen (20%) patients [ 5 ]. This study found that the detection rate of 32% in patients without mIBG-avid lesions was less compared to that in most reports on patients with mIBG-avid lesions using 123 I-mIBG scintigraphy.…”

“…123 I-meta-iodobenzylguanidine ( 123 I-mIBG) scintigraphy has been used for evaluating disease extent in children with neuroblastoma, and 131 I-mIBG therapy has been used for children with high-risk neuroblastoma and mIBG-avid lesions [ 1 , 2 , 3 ]. Consolidation therapy incorporating high-dose 131 I-mIBG has yielded good overall and event-free survival in children with high-risk neuroblastoma with complete response (CR) to primary therapy as demonstrated by diagnostic 123 I-mIBG scintigraphy [ 4 , 5 ].…”

“…Johnson et al demonstrated that five of five relapsed/refractory neuroblastoma patients with CR by diagnostic 123 I-mIBG scintigraphy showed abnormal uptake in post-therapy 131 I-mIBG whole-body scan (WBS) images [ 13 ]. Suh et al demonstrated that three of fifteen newly diagnosed neuroblastoma patients with CR by diagnostic 123 I-mIBG scintigraphy showed abnormal uptake in post-therapy 131 I-mIBG images [ 5 ]. The percentage varies depending on the study; high-risk neuroblastoma patients have hidden mIBG-avid lesions, which is under the level of detection by diagnostic 123 I-mIBG images.…”

Factors Modifying Outcome After MIBG Therapy in Children With Neuroblastoma—A National Retrospective Study

“…The post MIBG therapy whole body scan in high-risk neuroblastoma patients may reveal hidden mIBG-avid lesions, which are under the level of detection by diagnostic 123I-MIBG images (27)(28)(29). The fact, that in 13 patients the MIBG uptake was absent can be explained by a time interval between the qualification and administration of the therapy, during which patients received chemotherapy.…”

Theragnostic Aspects and Radioimmunotherapy in Pediatric Tumors

“…The authors reported an overall survival of 83% after five years. Of note, no treatment-related mortality was registered [15]. High dose 131 I-MIBG targeted therapy has been applied recently in Japan to treat children with relapsed neuroblastoma, who were administered with treatment ranging from 444 to 666 MBq/kg.…”