Rationale for irradiation of persisting oligo-skeletal metastases to improve survival of metastatic neuroblastoma patients with a poor response to chemotherapy: A retrospective study.
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BACKGROUND: Persistent metaiodobenzylguanidine (mIBG)-positive skeletal metastases post induction in high-risk neuroblastoma correlate with a poor outcome. The aim of this study was to investigate the potential rationale for a prospective randomized study evaluating the impact on event-free survival of the irradiation of residual oligo-skeletal metastases. PROCEDURE: Patients over 1 year with a stage M neuroblastoma treated between 2000 and 2020 at Gustave Roussy were identified. Patients with a positive mIBG scan at diagnosis and persistent skeletal metastases after high-dose chemotherapy (HDC) were included. Data were retrospectively collected and mIBG scans reviewed by two nuclear medicine physicians. RESULTS: Persistent skeletal uptake after HDC was observed in 30/201 patients (15%). Four patients reached a complete response at the end of maintenance treatment and did not relapse (median follow-up [FU] 8 years [1.8-11.8]), while two patients had progressive disease during maintenance. Among the 24 patients with persistent skeletal uptakes at the end of treatment, seven had a persistent response (median FU 8.2 years [4-15.6]). Median SIOPEN (International Society of Paediatric Oncology European Neuroblastoma) scores post consolidation and at the end of treatment were, respectively, 2 [1-6] and 2 [0-4] for patients with persistent responses compared to 4 [1-28] and 2 [1-17] for patients with progressive diseases. Median SIOPEN score at progression was 34 [2-56]. CONCLUSIONS: Our study underlines that only a minority of patients had persistent skeletal mIBG-positive scans after HDC. Recurrence mainly occurred in disease sites present at diagnosis that cleared with chemotherapy. On-therapy control of the disease is the main challenge. These results highlight the complexity of conducting a randomized study exploring this strategy.