2402 - Radiation Oncology at the Interface of Pediatric Cancer Biology and Data Science
Presenter(s)
D. E. Kozono1, S. Mueller2, S. G. Dubois3, D. Chowdhury4, D. S. Bitterman1, B. H. Kann1, H. Aerts1, S. Pal5, G. K. Savova6, Y. Seo7, P. Doyle8, M. G. Filbin9, A. M. Molinaro10, B. D. Crompton5, L. R. Diller5, J. L. Nakamura11, R. I. Berbeco12, C. Stiles5, F. Michor13, and D. A. Haas-Kogan14; 1Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 2University of California San Francisco, San Francisco, CA, 3Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, 4Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, 5Dana-Farber Cancer Institute, Boston, MA, 6computational Health Informatics Program, Boston Children's Hospital, Boston, MA, 7University of California, San Francisco, San Francisco, CA, 8Brigham and Women's Hospital/Dana-Farber, Boston, MA, United States, 9Boston Children's Hospital, Bosotn, MA, 10University of California San Francisco, Department of Epidemiology and Biostatistics, San Francisco, CA, 11Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 12Department of Radiation Oncology, Brigham and Women’s Hospital, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, 13Dana Farber Cancer Institute, Boston, MA, 14Brigham and Women's Hospital and Dana-Farber Cancer Institute/ Harvard, Boston, MA, Boston, MA
Purpose/Objective(s): KIDSROBIN is one of five Radiation Oncology-Biology Integration Networks (ROBINs) funded by National Cancer Institute U54 grants to perform high-depth molecular characterization of serial patient samples to deepen understanding of the mechanisms underlying variable responses to radiotherapy (RT). KIDSROBIN focuses on two pediatric cancers of neuro-ectodermal origin, diffuse midline glioma (DMG) and high-risk neuroblastoma (NBL), the former treated by external beam RT, and the latter by the radiopharmaceutical 131I-MIBG. The relatively low tumor mutational burden of these pediatric malignancies permits representative characterization despite small sample sizes, allowing resources to be dedicated toward comprehensive multiomics assays to identify tumor cell extrinsic and intrinsic causes of heterogeneity.
Materials/Methods: The KIDSROBIN Molecular Characterization Trial coordinates the collection of biospecimens and clinical data from ongoing cooperative group studies. These include PNOC023 and COG ANBL1531 for 18-23 children with DMG and 24 with NBL, respectively. Blood samples are obtained from all subjects before, during and after RT. Cerebrospinal fluid samples are obtained before and after RT for DMG. Tumor samples are obtained before and after treatment; for DMG they may be obtained at autopsy. Serial imaging and health-related quality of life questionnaires are obtained longitudinally. Molecular assays performed for the two disease-focused Projects include immunohistochemistry for DNA damage repair markers (?-H2AX, RAD51, p53BP1, pXRCC1), single cell RNA sequencing, single-cell ATAC sequencing, microRNA sequencing, and circulating tumor DNA sequencing. The Clinical Artificial Intelligence and Imaging Core coordinates natural language processing and radiomics analyses. The Molecular Data Science and Advanced Dosimetry Core performs predictive computational modeling, advanced dosimetry, and serves as the data management hub. ROBIN-NEST (Next generation Education and Scientific Training) is a Cross Training Core that provides educational and research opportunities to junior investigators. Annually, there will be solicitation of grant-funded Collaborative Pilot Projects that leverage collaborative opportunities supported by ROBIN resources.
Results: TBD
Conclusion: TBD. ClinicalTrials.gov: NCT06000787.