Abstract LB-138: Zero Childhood Cancer: A comprehensive precision medicine platform for children with high-risk cancer
Authors: Mould Emily , Lau Loretta , Arndt Greg , Barahona Paulette , Cowley Mark , Ekert Paul , Failes Tim , Fletcher Jamie , Gifford Andrew , Haber Michelle , Kamili Alvin , Kumar Amit , Lock Richard , Marshall Glenn , Mayoh Chelsea , Mead Scott , Norris Murray , O'Brien Tracey , Pinese Mark , Quang Dong Anh Khuong , Trahair Toby , Tsoli Maria , Tucker Katherine , Warby Meera , Wong Marie , Xie Jinhan , Ziegler David , Tyrrell Vanessa 
Published: August 2018

Abstract
Molecular genomics analyses aim to identify the subset of patients harbouring actionable mutations as a pathway to better targeted treatment selection. Low mutation rates and the paucity of clinical data linking targeted treatments with mutations in paediatric cancer suggests genomic analysis alone has limitations for translation into clinical benefit. The Zero Childhood Cancer program aims to assess the feasibility of a precision medicine platform to identify targeted therapeutic agents for high-risk (HR) paediatric malignancies (expected survival &lt;30%). We combine molecular genomic analysis (WGS (tumour, germline DNA), deep sequencing of a panel of cancer associated genes, and whole transcriptome (RNASeq)) with in vitro high-throughput drug screening, and patient-derived xenograft (PDX) drug efficacy testing, followed by assessment of and recommendations made by a national Multidisciplinary Tumour Board (MTB). The Pilot Feasibility Study enrolled 59 patients from June 2015 to October 2017 with a range of tumour types (47% central nervous system tumours, 20% sarcoma, 12% leukaemia, 9% neuroblastoma, 12% other rare cancers). The median age was 9 years (range 1-21 years) and 49% of patients were enrolled at diagnosis and 51% at relapse. In 54 curated cases, the complete molecular platform identified reportable somatic SNVs, fusions, and CNVs in 56%, 24% and 39% of patients, respectively. 5 patients had a reportable germline cancer predisposition variant and in 3 patients, the genomic findings changed the primary diagnosis. Fresh tissue collection in 48 of cases resulted in successful in vitro high-throughput drug screening (112 compound library single agent) in 23 cases and 23 successful patient-derived xenograft model engraftments. Overall, 57% of patients received a personalised medicine recommendation (targeted therapy, change in diagnosis, germline mutation referral), and 10 patients with a therapy recommendation went on to receive the recommended therapy. The Zero Childhood Cancer Pilot demonstrates the likelihood that oncologists will more frequently use a recommendation to benefit individual patients on the clinical trial who have typically exhausted other therapeutic approaches. Now, a national multicentre prospective study of the feasibility and clinical value of identifying therapeutic targets and recommending personalised treatment for children and adolescents with high-risk cancer (PRISM) opened in late 2017 for Australians up to 21 years with HR cancer.
Citation Format: Emily Mould, Loretta Lau, Greg Arndt, Paulette Barahona, Mark Cowley, Paul Ekert, Tim Failes, Jamie Fletcher, Andrew Gifford, Michelle Haber, Alvin Kamili, Amit Kumar, Richard Lock, Glenn Marshall, Chelsea Mayoh, Scott Mead, Murray Norris, Tracey O'Brien, Mark Pinese, Dong Anh Khuong Quang, Toby Trahair, Maria Tsoli, Katherine Tucker, Meera Warby, Marie Wong, Jinhan Xie, David Ziegler, Vanessa Tyrrell. Zero Childhood Cancer: A comprehensive precision medicine platform for children with high-risk cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-138.