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000178484 1001_ $$aRitzmann, Timothy A$$b0
000178484 245__ $$aSIOP Ependymoma I: Final results, long term follow-up and molecular analysis of the trial cohort: A BIOMECA Consortium Study.
000178484 260__ $$aOxford$$bOxford Univ. Press$$c2022
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000178484 520__ $$aSIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) of non-metastatic intracranial ependymoma in children aged 3 to 21 years treated with a staged management strategy. A further aim was to assess the response rate (RR) of subtotally resected (STR) ependymoma to vincristine, etoposide and cyclophosphamide (VEC). We report final results with 12-year follow-up and post hoc analyses of recently described biomarkers.74 participants were eligible. Children with gross total resection (GTR) received radiotherapy, whilst those with STR received VEC before radiotherapy. DNA methylation, 1q, hTERT, ReLA, Tenascin-C, H3K27me3 and pAKT status were evaluated.Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. GTR was achieved in 33/74 (44.6%) and associated with improved EFS (p=0.003, HR=2.6, 95% confidence interval (CI) 1.4-5.1). Grade 3 tumours were associated with worse OS (p=0.005, HR=2.8, 95%CI 1.3-5.8). 1q gain and hTERT expression were associated with poorer EFS (p=0.003, HR=2.70, 95%CI 1.49-6.10 and p=0.014, HR=5.8, 95%CI 1.2-28) and H3K27me3 loss with worse OS (p=0.003, HR=4.6, 95%CI 1.5-13.2). Methylation profiles showed expected patterns. 12 participants with STR did not receive chemotherapy; a protocol violation. However, best chemotherapy RR was 65.5% (19/29, 95%CI 45.7-82.1), exceeding the prespecified 45%.Participants with totally resected ependymoma had the best outcomes. RR of STR to VEC exceeded the pre-specified efficacy criterion. However, cases of inaccurate stratification highlighted the need for rapid central review. 1q gain, H3K27me3 loss and hTERT expression were all associated with poorer survival outcomes.
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000178484 650_7 $$2Other$$aChemotherapy
000178484 650_7 $$2Other$$aEpendymoma
000178484 650_7 $$2Other$$aRadiotherapy
000178484 650_7 $$2Other$$aRecurrence
000178484 650_7 $$2Other$$aResection
000178484 7001_ $$00000-0001-8050-8426$$aChapman, Rebecca J$$b1
000178484 7001_ $$00000-0002-0539-215X$$aKilday, John-Paul$$b2
000178484 7001_ $$aThorp, Nicola$$b3
000178484 7001_ $$aModena, Piergiorgio$$b4
000178484 7001_ $$00000-0002-9523-2546$$aDineen, Robert A$$b5
000178484 7001_ $$aMacarthur, Donald$$b6
000178484 7001_ $$00000-0002-5509-0547$$aMallucci, Conor$$b7
000178484 7001_ $$aJaspan, Timothy$$b8
000178484 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian$$b9$$udkfz
000178484 7001_ $$aGiagnacovo, Marzia$$b10
000178484 7001_ $$aJacques, Thomas S$$b11
000178484 7001_ $$00000-0002-1434-3931$$aPaine, Simon M L$$b12
000178484 7001_ $$aEllison, David W$$b13
000178484 7001_ $$00000-0002-6832-6539$$aBouffet, Eric$$b14
000178484 7001_ $$00000-0002-2585-2539$$aGrundy, Richard G$$b15
000178484 7001_ $$aconsortium, BIOMECA$$b16$$eCollaboration Author
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