Isolated central nervous system relapses in patients with high-risk neuroblastoma -clinical presentation and prognosis: experience of the Polish Paediatric Solid Tumours Study Group

Abstract

Although isolated central nervous system (CNS) relapses are rare, they may become a serious clinical problem in intensively treated patients with high-risk neuroblastoma (NBL). The aim of this study is the presentation and assessment of the incidence and clinical course of isolated CNS relapses. Retrospective analysis involved 848 NBL patients treated from 2001 to 2019 at 8 centres of the Polish Paediatric Solid Tumours Study Group (PPSTSG). Group characteristics at diagnosis, treatment and patterns of relapse were analysed. Observation was completed in December 2020. We analysed 286 high risk patients, including 16 infants. Isolated CNS relapse, defined as the presence of a tumour in brain parenchyma or leptomeningeal involvement, was found in 13 patients (4.5%; 8.4% of all relapses), all of whom were stage 4 at diagnosis. Isolated CNS relapses seem to be more common in young patients with stage 4 MYCN amplified NBL, and in this group they may occur early during first line therapy. The only or the first symptom may be bleeding into the CNS, especially in younger children, even without a clear relapse picture on imaging, or the relapse may be clinically asymptomatic and found during routine screening. Although the incidence of isolated CNS relapses is not statistically significantly higher in patients after immunotherapy, their occurrence should be carefully monitored, especially in intensively treated infants, with potential disruption of the brain-blood barrier.

Multimodality treatment for recurrent neuroblastoma in the central nervous system

“…An industry‐sponsored multicenter single‐arm phase 2/3 trial (NCT03275402) to evaluate the safety and feasibly of treating patients’ recurrent CNS neuroblastoma with 131 I‐omburtamab is ongoing. Our cases and others 5,12,13 indicate that favorable survival can be achieved in a subset of patients with isolated CNS relapsed neuroblastoma following gross total resection of the tumor and multimodality therapy without cRIT. Future studies testing the benefit of adding cRIT to multimodality therapy in patients with isolated CNS relapse and the efficacy of this treatment in unresectable recurrent CNS disease are warranted.…”

“…In a Chinese study of 106 stage 4 neuroblastoma patients, two of eight patients with recurrent CNS disease were alive 29–47 months following relapse after treatment with surgery, radiation, and chemotherapy 12 . Similarly, among 286 patients reported by the Polish Paediatric Solid Tumours Study Group (PPSTSG), two of 13 with isolated CNS relapse remained alive and disease‐free 9 and 2.5 years following multimodality therapy 13 . More recently, Berlanga and colleagues reported very poor survival among 53 high‐risk stage 4 patients enrolled on the high‐risk NBL1/SIOPEN study who developed a first relapse in the CNS 5 .…”

“…12 Similarly, among 286 patients reported by the Polish Paediatric Solid Tumours Study Group (PPSTSG), two of 13 with isolated CNS relapse remained alive and disease-free 9 and 2.5 years following multimodality therapy. 13 More recently, Berlanga and colleagues reported very poor survival among 53 high-risk stage 4 patients enrolled on the high-risk NBL1/SIOPEN study who developed a first relapse in the CNS. 5 However, three patients with isolated CNS recurrence remained alive 4.7, 4.9, and 10.1 years following complete surgical excision of the tumor and craniospinal radiotherapy, with or without a temozolomide-containing regimen.…”

Central Nervous System Metastasis in Neuroblastoma: From Three Decades Clinical Experience to New Considerations in the Immunotherapy Era

“…Out of the 6 patients with IM, 3 are still alive: 1 patient with CNS involvement at diagnosis after 121 months; and 2 patients with CNS relapses at 114 and 30 months. The survival time after the diagnosis of CNS involvement seems longer than reported in the Polish [ 32 ] and French [ 11 ] cohorts.…”

“…The CNS involvement may be asymptomatic, but rapid and fatal symptoms were reported and may represent a matter to debate for routine CNS imaging screening in HR NB [ 32 ]. Moreover, not only CNS involvement can be asymptomatic, but even the 123 I-MIBG may not reveal IM.…”