Personalized dosimetry for a deeper understanding of metastatic response to high activity 131I-mIBG therapy in high risk relapsed refractory neuroblastoma

Background: Dosimetry in molecular radiotherapy for personalized treatment is assuming a central role in clinical management of aggressive/relapsed tumors. Relapsed/refractory metastatic high-risk neuroblastoma (rrmHR-NBL) has a poor prognosis and high-activity I-131-mIBG therapy could represent a promising strategy. The primary aim of this case series study was to report the absorbed doses to whole-body (D-WB), red marrow (D-RM) and lesions (D-Lesion). A secondary aim was to correlate D-Lesion values to clinical outcome. Methods: Fourteen patients affected by rrmHR-NBL were treated with high-activity I-131-mIBG therapy (two administrations separated by 15 days). The first administration was weight-based whereas the second one was dosimetry-based (achieving D-WB equals to 4 Gy). In all patients D-WB and D-RM was assessed; 9/14 patients were selected for D-Lesion evaluation using planar dosimetric approach (13 lesions evaluated). Treatment response was classified as progressive and stable disease (PD and SD), partial and complete response (PR and CR) according to the International Neuroblastoma Response Criteria. Patients were divided into two groups: Responder (CR, PR, SD) and Non-Responder (PD), correlating treatment response to D-Lesion value. Results: The cumulative D-WB, D-RM and D-Lesion ranged from (1.5; 4.5), (1.0; 2.6) and (44.2; 585.8) Gy. A linear correlation between D-WB and D-RM and a power law correlation between the absorbed dose to WB normalized for administered activity and the mass of the patient were observed. After treatment 3, 2, 4 and 5 patients showed CR, PR, SD and PD respectively, showing a correlation between D-Lesion and the two response group. Conclusions: Our experience demonstrated feasibility of high activity therapy of I-131-mIBG in rrmHR-NBL children as two administration intensive strategy. Dosimetric approach allowed a tailored high dose treatment maximizing the benefits of radionuclide therapy for pediatric patients while maintaining a safety profile. The assesment of D-Lesion contributed to have a deeper understaning of metabolic treatment effects.