ID #1104 Tolerability of intraventricular and intrathecal chemotherapy in paediatric patients with central nervous system tumours: a case series

Background Central nervous system (CNS) tumours in young children remain challenging to treat, due to poor survival rates and the desirability of sparing or deferring radiation. The addition of intraventricular/intrathecal (IVT) chemotherapy may improve response rates and/or delay disease progression, although its tolerability on intensive chemotherapy backbones has been a concern. Objective To review the side effects associated with addition of IVT chemotherapy to systemic chemotherapy. Method This was a retrospective case series of paediatric patients with CNS tumours (atypical teratoid rhabdoid tumour (n = 6), embryonal tumour with multilayered rosettes (n = 2), choroid plexus carcinoma (n = 1), medulloblastoma (n = 1), pineoblastoma (n = 1)), who received standard of care chemotherapy (as per COG ACNS0334 or CCG99703 backbones with or without maintenance therapies) with addition of IVT chemotherapy, across two centres in Australia between 2016 and 2025. Results Eleven patients were included with a mean age of 27 months [5-63] at diagnosis, with stage 0-3 disease according to the Chang classification. These patients received IVT methotrexate (n = 1), topotecan (n = 3) or hydrocortisone and cytarabine (n = 8), four via a reservoir and seven via lumbar puncture. Four patients received IVT added to their maintenance therapy. The most common toxicities (graded as per CTCAE version 5.0) experienced were grade 3 and 4 cytopenias (100%), grade 3 febrile neutropenia (91%), grade 2-3 vomiting (91%) and grade 2-3 mucositis (73%). Two patients experienced intracranial haemorrhage (grades 2-3) associated with marked thrombocytopaenia. Three patients received radiotherapy in their primary treatment. Follow up ranged from 7-88 months; four patients experienced disease progression by the time of last follow up (mean time to progression 13 months [6-21]), and three patients had died from disease. Conclusion These patients experienced similar rates of adverse events as previously reported with systemic chemotherapy alone; IVT chemotherapy did not appear to contribute additional toxicity.