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

Abstract

Central nervous system (CNS) metastatic spread in neuroblastoma (NB) is rare and occurs more often at relapse/progression. We report on CNS involvement in high risk (HR) NB over 25 years. For this retrospective study, we reviewed the CNS imaging of all the patients treated at Bambino Gesù Children Hospital from 1 July 1996 to 30 June 2022. A total of 128 patients with HR NB were diagnosed over 26 years. Out of 128 patients, CNS metastatic spread occurred in 6 patients: 3 patients presented a metastatic spread at diagnosis, while in 3 patients, CNS was involved at relapse. Overall, the rate of occurrence of CNS spread is 4.7% with the same distribution at diagnosis and at relapse, namely 2.3%. Interestingly, CNS spread at diagnosis was observed only before 2012, whereas CNS was observed at relapse only after 2012, in the immunotherapy era. CNS metastases presented similar imaging features at diagnosis and at relapse, with a peculiar hemorrhagic aspect and mainly hemispheric localization in patients with bone skull involvement at the time of diagnosis. The outcome is dismal, and 3 out of 6 patients died for progressive disease.

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“…NB metastasis to the CNS is rare and often occurs in recurrent or progressive cases (53). Even with aggressive treatment strategies, the treatment outcomes of patients with NB with CNS metastasis remain poor.…”

Targeting B7-H3—A Novel Strategy for the Design of Anticancer Agents for Extracranial Pediatric Solid Tumors Treatment

“…The metastatic lesions of NB are present in more than 50% of patients, being most commonly located in bone marrow, bone, and liver. Secondary lesions in CNS are rare with an overall estimated prevalence of 1.7-11.7% [133]. In 2010, Kramer et al published the results of a clinical study testing compartmental intrathecal antibody-based radioimmunotherapy in patients with recurrent metastatic CNS NB.…”

Adaptation of the Th-MYCN Mouse Model of Neuroblastoma for Evaluation of Disseminated Disease

“…NB metastasizes to bone marrow, bone, liver, and lymph nodes in almost 70% of patients [10,11], with ~20% of patients presenting with two metastatic sites [11]. In some cases, NB can also metastasize to the brain, skin, and lungs [11][12][13][14]. Both lymphatic and blood circulation are involved in spreading NB cells [15,16].…”