MBRS-44. Time, pattern and outcome of medulloblastoma relapse are associated with tumour biology at diagnosis and upfront therapy: a cohort study

Rebecca Hill, Stacey Richardson, Edward Schwalbe, Debbie Hicks, Janet Lindsey, Stephen Crosier, Gholamreza Rafiee, Yura Grabovska, Stephen Wharton, Thomas Jacques, Anthony Michalski, Abhijit Joshi, Barry Pizer, Daniel Williamson, Simon Bailey, Steven Clifford

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Disease relapse occurs in ~30% of children with medulloblastoma, and is fatal in the majority. We sought to establish whether clinico-molecular characteristics at diagnosis are associated with the nature of relapse, subsequent disease-course, and whether these associations could inform clinical management. We surveyed the clinical features of medulloblastoma relapse (time-to-relapse, pattern-of-relapse, time-to-death and overall outcome) in 247 centrally-reviewed patients who relapsed following standard-upfront-therapies. We related these to clinico-molecular features at diagnosis, prognostic factors, and first-line/relapse treatment. Patients who received upfront craniospinal irradiation (CSI-treated) displayed prolonged time-to-relapse compared to CSI naïve patients (p<0.001). Similarly, in CSI naïve patients, CSI at relapse, alongside re-resection and desmoplastic/nodular histology, were associated with long-term survival. In CSI-treated patients, the nature of relapse was subgroup-dependent. Local-nodular relapse patterns were enriched in relapsed-MBSHH patients (p<0.001), but a notable proportion (65%) also acquired distant-diffuse disease (p=0.010). MBGroup3 relapsed quickly (median 1.3 years), MBGroup4 slowly (median 2.1 years). Distant-disease was prevalent in MBGroup3 and MBGroup4 relapses (90%) but, in contrast to relapsed-MBSHH, nodular and diffuse patterns of distant-disease were observed. Furthermore, nodular disease was associated with a prolonged time-to-death post-relapse (p=0.006). Investigation of second-generation MBGroup3/4 subtypes refined our understanding of heterogeneous relapse characteristics. Subtype VIII had prolonged time-to-relapse; subtype II a rapid time-to-death. Subtypes II/III/VIII developed a significantly higher incidence of distant-disease at relapse, whereas subtypes V/VII did not. The nature of medulloblastoma relapse are biology and therapy-dependent, providing immediate translational opportunities for improved disease management through biology-directed surveillance, post-relapse prognostication and risk-stratified selection of second-line treatment.
Original languageEnglish
Pages (from-to)iii405-iii406
JournalJournal of Neuro-Oncology
Issue numberSupplement_3
Publication statusPublished - 04 Dec 2020
Externally publishedYes


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