Multi‐institutional analysis of central nervous system germ cell tumors in patients with Down syndrome

Abstract

Purpose: Primary germ cell tumors (GCTs) are the most common central nervous system (CNS) neoplasm in patients with Down syndrome (DS). However, a standard of care has not been established due to paucity of data. Methods:A retrospective multi-institutional analysis was conducted, in addition to a comprehensive review of the literature.Results: Ten patients from six institutions (five USA, one Brazil) were identified, in addition to 31 patients in the literature from 1975 to 2021. Of the 41 total patients (mean age 9.9 years; 61% male), 16 (39%) had non-germinomatous germ cell tumors (NGGCTs), 16 (39%) had pure germinomas, and eight (19.5%) had teratomas. Basal ganglia was the most common tumor location (n = 13; 31.7%), followed by posterior fossa (n = 7; 17%). Nine patients (22%) experienced disease relapse or progression, of which four died from tumor progression (one germinoma, three teratomas). Sixteen patients (39%) experienced treatment-related complications, of which eight (50%) died (five germinomas, three NGGCTs). Of the germinoma patients, two died from chemotherapy-related sepsis, one from postsurgery cardiopulmonary failure, one from pneumonia, and one from moyamoya following radiation therapy (RT). Of the NGGCT patients, one died from chemotherapy-related sepsis, one from postsurgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival was 66% for all histological types: 62% germinomas, 79% for NGGCTs, and 53% for teratomas. Conclusion:Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered to mitigate treatment-related complications and long-term neurocognitive sequelae.

Intracranial non-germinomatous germ cell tumors in children and adolescents: how can the experience from an uppermiddle-income country contribute to the worldwide effort to improve outcomes?

“…Notably, the rarity of NGGCT, though linked with Down Syndrome in just one case in our series, warrants careful attention. A recent publication by Harris et al revealed an increased risk of treatment-related adverse events and long-term neurocognitive sequelae in this patient group, necessitating alternative therapeutic approaches (24). Some innovative cases have been reported, such as ASCT and brentuximab-vedotin for those with CD30-positive embryonal carcinoma (25).…”

Down syndrome-associated leukaemias: current evidence and challenges

“… 18 A specific example in children with DS is that germ cell tumours make up a disproportionate number of central nervous system tumours, with a higher percentage located in the basal ganglia, compared to the non-DS population. 19 …”