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

Abstract

BackgroundNeuroblastoma is the most common pediatric extracranial tumor with varied prognoses, but the survival of treated refractory or relapsing patients remains poor.ObjectiveThis analysis presents the outcomes of children with neuroblastoma undergoing MIBG therapy in Poland in 2006-2019.Study DesignA retrospective cohort of 55 patients with refractory or relapsed neuroblastoma treated with I-131 MIBG in Poland in 2006-2019 was analyzed. The endpoints were overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of second cancers and CI of hypothyroidism. Survival curves were estimated using the Kaplan-Meier method and compared between the cohorts by the log-rank test. Cox modeling was adopted to estimate hazard ratios for OS and EFS, considering factors with P < 0.2.ResultsFifty-five patients with a median age of 78.4 months (range 18-193) with neuroblastoma underwent one or more (4 patients) courses of MIBG I-131 therapy. Fifteen patients were not administered chemotherapy, 3 children received standard-dose chemotherapy, and 37 patients were administered high-dose chemotherapy (HDCT) (busulfan-melphalan in 24 and treosulfan-based in 12 patients). Forty-six patients underwent stem cell transplantation, with autologous (35 patients), haploidentical (6), allogeneic (4), and syngeneic grafts (1). The median time from first MIBG therapy to SCT was 22 days. Children with relapsing tumors had inferior OS compared to those with primary resistant disease (21.2% vs 58.7%, p=0.0045). Survival was better in patients without MYCN gene amplification. MIBG therapy was never curative, except in patients further treated with HDCT with stem cell rescue irrespective of the donor type. 31 patients were referred for immune therapy after MIBG therapy, and the 5-year OS in this group was superior to the untreated children (55.2% vs 32.7%, p=0.003), but the difference in the 5-year EFS was not significant (25.6% vs 32.9%, p=ns). In 3 patients, a second malignancy was diagnosed. In 19.6% of treated children, hypothyroidism was diagnosed within 5 years after MIBG therapy.ConclusionMIBG therapy can be incorporated into the therapeutic strategy of relapsed or resistant neuroblastoma patients as preconditioning with HDCT rather than stand-alone therapy. Follow-up is required due to the incidence of thyroid failure and risk of second cancers.

Phase II study of 131I‐metaiodobenzylguanidine with 5 days of topotecan for refractory or relapsed neuroblastoma: Results of the French study MIITOP

“…Four of the 10 patients who received BuMel immediately after MIITOP had long‐term survival. From data available, none of these 10 patients experienced severe veno‐occlusive disease, supporting the feasibility of such a combination in children with NBL 40–42 …”

“…From data available, none of these 10 patients experienced severe veno-occlusive disease, supporting the feasibility of such a combination in children with NBL. [40][41][42] Pasqualini et al evaluated tandem HDC with thiotepa and BuMel in 26 VHR-NBL patients (i.e., stage 4 NBL at diagnosis or relapse, age more than 1 year at diagnosis, less than a PR of metastases, and more than 3 mIBG spots after two lines of conventional chemotherapy in patients <10 years old or no CR of metastases after one line of conventional chemotherapy in patients >10 years old). 43 In this study, the 3-year EFS and OS rates after the diagnosis were 37.3% (95% CI: 21.3%−56.7%) and 69.0% (95% CI: 49.7%−83.4%), respectively.…”

Pediatric Neuroendocrine Neoplasms: Rare Malignancies with Incredible Variability

“…Patients with norepinephrine and somatostatin receptor avid tumors detected with the functional imaging discussed above can be treated with similarly structured therapeutic radiopharmaceuticals. Nonresectable neuroblastomas, pheochromocytomas, and paragangliomas with elevated MIBG uptake are often treated with 131I-MIBG alone or in combination with chemotherapeutics [ 135 , 136 , 137 ]. A therapy still in evolution that offers improved outcomes over 131I-MIBG, is peptide receptor radionuclide therapy (PRRT).…”

Thyroid function after diagnostic 123I-metaiodobenzylguanidine in children with neuroblastic tumors

“…Due to the fact that KI does not protect the thyroid gland sufficiently [ 3 ], thiamazole (blocking the binding of iodide to thyroglobulin in the thyroid follicular cell resulting in a shorter exposure time to 131 I) and thyroxine (T4) (lower uptake of 131 I − due to lowering of the serum TSH) or perchlorate (CIO4) (lowering the uptake of 131 I − by blocking the sodium-iodide transporter) can be added to KI [ 5 – 7 ]. Despite these preventive measures, thyroid dysfunction occurs frequently [ 3 , 4 , 7 , 8 ], which raises the question whether the administered thyroid protection measures are sufficient or if NBL survivors are more susceptible to thyroid dysfunction regardless of given treatment. The 131 I/ 123 I-MIBG scintigraphy procedure guidelines for tumor imaging from the European Association of Nuclear Medicine (EANM) recommend the use of thyroid prophylaxis during both 131 I and 123 I-MIBG[ 9 ].…”