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Conference Paper: Risk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinical-molecular analysis from the prospective, multi-center SJMB03 and SJYC07 trials

TitleRisk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinical-molecular analysis from the prospective, multi-center SJMB03 and SJYC07 trials
Authors
Issue Date2019
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1545-5017/
Citation
The 51th Congress of the Societe Internationale d’Oncologie Pediatrique (SIOP), Lyon, France, 23-26 October 2019. Abstracts In Pediatric Blood & Cancer, 2019, v. 66 n. S4, p. S27-S28 How to Cite?
AbstractBackground/Objectives: Pineoblastoma is an aggressive embryonal tumor conventionally treated with high‐dose CSI. We report outcome and molecular analysis of patients with pineoblastoma from two multi‐center risk‐adapted trials (SJMB03 for ≥3y, SJYC07 for <3y) and a non‐protocol SJMB03‐equivalent cohort (SJMB03‐like). Design/Methods: Fifty‐three patients with pineoblastoma treated on SJMB03 (N=30), SJMB03‐like (N=11), and SJYC07 (N=12) were included. High‐risk (HR) disease was defined by metastasis (M+) (SJMB03/SJMB03‐like/SJYC07) and/or residual tumor ≥1.5cm2 (R+) (SJMB03/SJMB03‐like). The SJMB03 protocol comprised risk‐adapted CSI (non‐HR=23.4Gy, HR=36Gy) with boost and chemotherapy (cisplatin/cyclophosphamide/vincristine); the SJYC07 protocol consisted of induction (methotrexate/cisplatin/cyclophosphamide/vincristine), consolidation (non‐HR=focal radiation, HR=cyclophosphamide/topotecan) and metronomic maintenance therapy. Available samples were profiled on MethylationEPIC array and analyzed with a reference brain tumor dataset. WES and RNA‐seq were performed in a subset. Results: Among SJMB03/SJMB03‐like patients, 18 were non‐HR and 23 HR (M+=17; R+ only=6). In SJYC07, 7 were non‐HR and 5 HR (M+). 5y‐PFS in patients on SJMB03/SJMB03‐like therapy with non‐HR and HR disease were 100% and 59.1±10.5% respectively (p=0.012). Patients on SJYC07 with non‐HR and HR disease had 5y‐PFS of 14.3±13.2% and 0% respectively (p=0.23). Unsupervised clustering of 40 methylation profiles resulted in 4 subgroups. Subgroup‐1 (N=7) patients were younger (median=1.2y; range=0.5‐5.7y), often metastatic (71%), and had epigenetic profiles that either associated with RB1‐driven pineoblastoma (“PB_A”) or formed a related cluster. Tumors in subgroup‐2 (N=9; median=1.9y; range=0.4‐14.4y) were heterogeneous and clustered with diverse reference classes. Subroups‐3 (N=6) and 4 (N=18) patients were older (median=8.4y; range=3.3‐17y) and less frequently metastatic (subgroup‐3=0%; subgroup‐4=44%). Profiles from subgroup‐3 formed a distinct cluster while those from subgroup‐4 overlapped with pineoblastoma methylation‐class “PB_B”. Pathogenic alterations in the microRNA processing pathway were enriched in subgroups‐3 and 4. Conclusions: Children ≥3y with non‐HR pineoblastoma can be successfully treated with 23.4Gy CSI and chemotherapy. Moreover, molecular analysis uncovers a biologically diverse disease, with subgroup‐specific differences in patient age and propensity for metastasis.
DescriptionOral presentation - no. FP041 SIOP19-1126
Young Investigator Award
Persistent Identifierhttp://hdl.handle.net/10722/288274
ISSN
2019 Impact Factor: 2.355
2015 SCImago Journal Rankings: 1.505

 

DC FieldValueLanguage
dc.contributor.authorLiu, APY-
dc.contributor.authorOrr, BA-
dc.contributor.authorKlimo, JR, P-
dc.contributor.authorLin, T-
dc.contributor.authorGudenas, B-
dc.contributor.authorBouffet, E-
dc.contributor.authorGururangan, S-
dc.contributor.authorCrawford, JR-
dc.contributor.authorKellie, SJ-
dc.contributor.authorChintagumpala, M-
dc.contributor.authorFisher, M-
dc.contributor.authorBowers, DC-
dc.contributor.authorHassall, T-
dc.contributor.authorEllison, D-
dc.contributor.authorBoop, FA-
dc.contributor.authorMerchant, TE-
dc.contributor.authorNorthcott, PA-
dc.contributor.authorRobinson, GW-
dc.contributor.authorGajjar, A-
dc.date.accessioned2020-10-05T12:10:28Z-
dc.date.available2020-10-05T12:10:28Z-
dc.date.issued2019-
dc.identifier.citationThe 51th Congress of the Societe Internationale d’Oncologie Pediatrique (SIOP), Lyon, France, 23-26 October 2019. Abstracts In Pediatric Blood & Cancer, 2019, v. 66 n. S4, p. S27-S28-
dc.identifier.issn1545-5009-
dc.identifier.urihttp://hdl.handle.net/10722/288274-
dc.descriptionOral presentation - no. FP041 SIOP19-1126-
dc.descriptionYoung Investigator Award-
dc.description.abstractBackground/Objectives: Pineoblastoma is an aggressive embryonal tumor conventionally treated with high‐dose CSI. We report outcome and molecular analysis of patients with pineoblastoma from two multi‐center risk‐adapted trials (SJMB03 for ≥3y, SJYC07 for <3y) and a non‐protocol SJMB03‐equivalent cohort (SJMB03‐like). Design/Methods: Fifty‐three patients with pineoblastoma treated on SJMB03 (N=30), SJMB03‐like (N=11), and SJYC07 (N=12) were included. High‐risk (HR) disease was defined by metastasis (M+) (SJMB03/SJMB03‐like/SJYC07) and/or residual tumor ≥1.5cm2 (R+) (SJMB03/SJMB03‐like). The SJMB03 protocol comprised risk‐adapted CSI (non‐HR=23.4Gy, HR=36Gy) with boost and chemotherapy (cisplatin/cyclophosphamide/vincristine); the SJYC07 protocol consisted of induction (methotrexate/cisplatin/cyclophosphamide/vincristine), consolidation (non‐HR=focal radiation, HR=cyclophosphamide/topotecan) and metronomic maintenance therapy. Available samples were profiled on MethylationEPIC array and analyzed with a reference brain tumor dataset. WES and RNA‐seq were performed in a subset. Results: Among SJMB03/SJMB03‐like patients, 18 were non‐HR and 23 HR (M+=17; R+ only=6). In SJYC07, 7 were non‐HR and 5 HR (M+). 5y‐PFS in patients on SJMB03/SJMB03‐like therapy with non‐HR and HR disease were 100% and 59.1±10.5% respectively (p=0.012). Patients on SJYC07 with non‐HR and HR disease had 5y‐PFS of 14.3±13.2% and 0% respectively (p=0.23). Unsupervised clustering of 40 methylation profiles resulted in 4 subgroups. Subgroup‐1 (N=7) patients were younger (median=1.2y; range=0.5‐5.7y), often metastatic (71%), and had epigenetic profiles that either associated with RB1‐driven pineoblastoma (“PB_A”) or formed a related cluster. Tumors in subgroup‐2 (N=9; median=1.9y; range=0.4‐14.4y) were heterogeneous and clustered with diverse reference classes. Subroups‐3 (N=6) and 4 (N=18) patients were older (median=8.4y; range=3.3‐17y) and less frequently metastatic (subgroup‐3=0%; subgroup‐4=44%). Profiles from subgroup‐3 formed a distinct cluster while those from subgroup‐4 overlapped with pineoblastoma methylation‐class “PB_B”. Pathogenic alterations in the microRNA processing pathway were enriched in subgroups‐3 and 4. Conclusions: Children ≥3y with non‐HR pineoblastoma can be successfully treated with 23.4Gy CSI and chemotherapy. Moreover, molecular analysis uncovers a biologically diverse disease, with subgroup‐specific differences in patient age and propensity for metastasis.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1545-5017/-
dc.relation.ispartofPediatric Blood & Cancer-
dc.relation.ispartofSIOP 2019: Congress of The International Society of Paediatric Oncology-
dc.titleRisk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinical-molecular analysis from the prospective, multi-center SJMB03 and SJYC07 trials-
dc.typeConference_Paper-
dc.identifier.emailLiu, APY: apyliu@hku.hk-
dc.identifier.authorityLiu, APY=rp01357-
dc.description.natureabstract-
dc.identifier.hkuros315007-
dc.identifier.volume66-
dc.identifier.issueS4-
dc.identifier.spageS27-
dc.identifier.epageS28-
dc.publisher.placeUnited States-
dc.identifier.partofdoi10.1002/pbc.27989-

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