Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma

Abstract

ObjectiveIodine-131-labelled meta-iodobenzylguanidine (131I-mIBG) therapy is an established treatment modality for relapsed/refractory neuroblastoma, most frequently administered according to fixed or weight-based criteria. We evaluate response and toxicity following a dosimetry-based, individualized approach.Materials and methodsA review of 44 treatments in 25 patients treated with 131I-mIBG therapy was performed. Patients received 131I-mIBG therapy following relapse (n=9), in refractory disease (n=12), or with surgically unresectable disease despite conventional treatment (n=4). Treatment schedule (including mIBG dose and number of administrations) was individualized according to the clinical status of the patient and dosimetry data from either a tracer study or previous administrations. Three-dimensional tumour dosimetry was also performed for eight patients.ResultsThe mean administered activity was 11089±7222 MBq and the mean whole-body dose for a single administration was 1.79±0.57 Gy. Tumour-absorbed doses varied considerably (3.70±3.37 mGy/MBq). CTCAE grade 3/4 neutropenia was documented following 82% treatments and grade 3/4 thrombocytopenia following 71% treatments. Further acute toxicity was found in 49% of patients. All acute toxicities resolved with appropriate therapy. The overall response rate was 58% (complete or partial response), with a further 29% of patients having stable disease.ConclusionA highly personalized approach combining patient-specific dosimetry and clinical judgement enables delivery of high activities that can be tolerated by patients, particularly with stem cell support. We report excellent response rates and acceptable toxicity following individualized 131I-mIBG therapy.

Correlation of CT signs with lymphatic metastasis and pathology of neuroblastoma in children

“…CT scan showed low density and clearer border, as well as mild or no enhancement in enhanced scanning, indicating that CT features are closely correlated with the tumor cell components. NB is a kind of malignant tumor with aggressive growth along the paravertebral sympathetic chain, and NB usually invaded or wrapped around the surrounding tissues or organs with spindle- or irregular-shapes ( 18 ). During development, NB can easily cross the midline, and invade the spinal canal along the neural tube, thus expanding the intervertebral foramen, and causing damage to the vertebral body ( 19 ).…”

I-131 Metaiodobenzylguanidine Therapy of Neuroectodermal Tumors

“…However, this effect is usually transient and aggravated by combination chemo-radiotherapies [81,86]. Hypogonadism has been reported in higher frequencies with higher I-131 MIBG doses [11,73,87].…”

Individualized therapy in neuroblastoma

“…Преклинические данные об эффективности антиангиогенных препаратов проти-воречивы [59,60], в то время как клинические исследо-вания I фазы показывают обнадеживающие результаты [61,62]. Норэпинефриновая транспортная система яв-ляется молекулярной основой МЙБГ-терапии [63][64][65][66]. Высокодозная МЙБГ-терапия часто применяется в слу-чае наличия МЙБГ-позитивных очагов после индукци-онной ХТ, и это является примером ответ-адаптирован-ной индивидуальной терапии в случае применения ее в 1-й линии лечения [65].…”

“…Высокодозная МЙБГ-терапия часто применяется в слу-чае наличия МЙБГ-позитивных очагов после индукци-онной ХТ, и это является примером ответ-адаптирован-ной индивидуальной терапии в случае применения ее в 1-й линии лечения [65]. В дополнение МЙБГ-терапия также может применяться как продвинутый вариант лечения и в случае рецидивов МЙБГ-позитивных НБ [64,68,69]. Более того, патологический путь RAS/ MAPK играет важную роль в росте опухоли, в частности при рецидиве НБ [17, 70,71].…”