Abstract

Developing Personalized Medicine in Oncology

Christof von Kalle, Head of Translational Oncology, German Cancer Research Center

The Precision Oncology Program (NCT POP) at the National Center for Tumor Diseases employs a center-wide NCT MASTER (Molecularly Aided Stratification for Tumor Eradication) umbrella protocol that provides all components of a clinical implementation workflow for high-throughput molecular diagnostics. Steps include: quality-assured sample acquisition by surgery or biopsy; histopathological evaluation; quality-managed analyte extraction; NGS and other “omics” technologies; bioinformatic processing according to standardized pipelines; GLP-certified validation of variants; and and clinical evaluation by a molecular tumor board. NCT MASTER makes it possible to perform and evaluate molecular diagnostics on materials from all consenting NCT patients, with the explicit purpose of stratifying each patient for the best treatment or trial strategy. The Heidelberg-led INFORM study, which enrolls all children and adolescents with relapsed or refractory cancers in Germany for comprehensive molecular profiling, is the first nationally comprehensive initiative to translate personalized treatment into clinical practice. The NCT MASTER MATCH trial focuses on all adult patients with systemic cancers who are younger than 50 and undergo biopsy or resection of their tumors at NCT/HUMS. The NCT Neuro MASTER MATCH trial uses obligatory genome-wide methylation analyses and a glioma gene panel to treat newly diagnosed glioma as a paradigm for other entities. In order to best integrate and exploit the data produced in all NCT programs, a central NCT DataThereHouse contains a working copy of every patient-related dataset from all IT sources to enable efficient retrieval, aggregation, and evaluation of molecular and clinical data for clinical decision making and translational research. NCT’s overall aim is to provide optimal individualization of treatment decisions according to the specific needs of each individual patient by reaching across traditional disciplines and academic departments.