Critical observations on neuroblastoma treatment with 131‐I‐metaiodobenzylguanidine at diagnosis

Abstract

Results of treatment with 131-I-Metaiodobenzylguanidine (131-I-MIBG) in patients with resistant neuroblastoma appear encouraging if one considers that most of the patients had far advanced, intensively pre-treated disease. To further explore the potential role of this new drug in untreated patients, we treated 3 children with stage III neuroblastoma. All three of our cases received 131-I-MIBG at relatively low dose with the complete disappearance of the tumor mass in case 1, whereas in cases 2 and 3 CT scan showed a significant reduction of the tumor mass and, interestingly enough, no evidence of 131-I-MIBG uptake of a tracer dose in the remaining tumor. Particularly, in case 2, the persistence and subsequent progression of part of the tumor mass without 131-I-MIBG uptake after a therapeutic dose of 131-I-MIBG, which apparently destroyed the 131-I-MIBG-positive cell population, clearly suggest heterogeneity at diagnosis, with a dual neuroblastoma cell population, one with 131-I-MIBG uptake and the other without. Besides the biological implications of the 131-I-MIBG uptake heterogeneity in neuroblastoma at diagnosis, our findings suggest that in stage III neuroblastoma patients even a relatively small dose of 131-I-MIBG administered at diagnosis is sufficient to destroy either the primary tumor completely (case 1) or the part of the tumor (case 2 and 3) which shows 131-I-MIBG uptake, without any significant hematologic toxicity. Furthermore, a single course of 131-I-MIBG at the dosage employed does not appear to jeopardize the subsequent use of chemotherapy. In conclusion, if our data are confirmed by further investigation, 131-I-MIBG may be included as a front line drug shortly followed by chemotherapy in future treatment strategies of advanced neuroblastoma without or with minimal bone marrow infiltration.