TY  - JOUR
N2  - Background Disease: relapse occurs in around 30% of children with medulloblastoma, and is almost universally fatal.
We aimed to establish whether the clinical and molecular characteristics of the disease at diagnosis are associated
with the nature of relapse and subsequent disease course, and whether these associations could inform clinical
management.
Methods: In this multicentre cohort study we comprehensively surveyed the clinical features of medulloblastoma
relapse (time to relapse, pattern of relapse, time from relapse to death, and overall outcome) in centrally reviewed
patients who relapsed following standard upfront therapies, from 16 UK Children?s Cancer and Leukaemia Group
institutions and four collaborating centres. We compared these relapse-associated features with clinical and molecular
features at diagnosis, including established and recently described molecular features, prognostic factors, and
treatment at diagnosis and relapse.
Findings: 247 patients (175 [71%] boys and 72 [29%] girls) with medulloblastoma relapse (median year of diagnosis
2000 [IQR 1995?2006]) were included in this study. 17 patients were later excluded from further analyses because they
did not meet the age and treatment criteria for inclusion. Patients who received upfront craniospinal irradiation
(irradiated group; 178 [72%] patients) had a more prolonged time to relapse compared with patients who did not
receive upfront craniospinal irradiation (non-irradiated group; 52 [21%] patients; p<0·0001). In the non-irradiated
group, craniospinal irradiation at relapse (hazard ratio [HR] 0·27, 95% CI 0·11?0·68) and desmoplastic/nodular
histology (0·23, 0·07?0·77) were associated with prolonged time to death after relapse, MYC amplification was
associated with a reduced overall survival (23·52, 4·85?114·05), and re-resection at relapse was associated with longer
overall survival (0·17, 0·05?0·57). In the irradiated group, patients with MBGroup3 tumours relapsed significantly more
quickly than did patients with MBGroup4 tumours (median 1·34 [0·99?1·89] years vs 2·04 [1·39?3·42 years; p=0·0043).
Distant disease was prevalent in patients with MBGroup3 (23 [92%] of 25 patients) and MBGroup4 (56 [90%] of 62 patients)
tumour relapses. Patients with distantly-relapsed MBGroup3 and MBGroup4 displayed both nodular and diffuse patterns of
disease whereas isolated nodular relapses were rare in distantly-relapsed MBSHH (1 [8%] of 12 distantly-relapsed MBSHH
were nodular alone compared with 26 [34%] of 77 distantly-relapsed MBGroup3 and MBGroup4). In MBGroup3 and MBGroup4,
nodular disease was associated with a prolonged survival after relapse (HR 0·42, 0·21?0·81). Investigation of secondgeneration MBGroup3 and MBGroup4 molecular subtypes refined our understanding of heterogeneous relapse
characteristics. Subtype VIII had prolonged time to relapse and subtype II had a rapid time from relapse to death.
Subtypes II, III, and VIII developed a significantly higher incidence of distant disease at relapse whereas
subtypes V and VII did not (equivalent rates to diagnosis).
Interpretation: This study suggests that the nature and outcome of medulloblastoma relapse are biology and therapydependent, providing translational opportunities for improved disease management through biology-directed disease
surveillance, post-relapse prognostication, and risk-stratified selection of second-line treatment strategies
A1  - Hill, RM
A1  - Richardson, S
A1  - Schwalbe, EC
A1  - Hicks, D
A1  - Lindsey, JC
A1  - Crosier, S
A1  - Rafiee, G
A1  - Grabovska, Y
A1  - Wharton, SB
A1  - Jacques, TS
A1  - Michalski, A
A1  - Joshi, A
A1  - Pizer, B
A1  - Williamson, D
A1  - Bailey, S
A1  - Clifford, SC
EP  - 874
SP  - 865
IS  - 12
AV  - public
UR  - https://doi.org/10.1016/S2352-4642(20)30246-7
Y1  - 2020/12//
ID  - discovery10116096
N1  - This is an Open Access article under the CC BY 4·0 license
https://creativecommons.org/licenses/by/4.0/
TI  - Time, pattern, and outcome of medulloblastoma relapse and their association with tumour biology at diagnosis and therapy: a multicentre cohort study
VL  - 4
JF  - The Lancet Child & Adolescent Health
ER  -