‘In Silico’ Oncology for Clinical Decision Making in the Context of Nephroblastoma

Abstract

The present paper outlines the initial version of the ACGT (Advancing Clinico-Genomic Trials) – an Integrated Project, partly funded by the EC (FP6-2005-IST-026996)I-Oncosimulator as an integrated software system simulating in vivo tumour response to therapeutic modalities within the clinical trials environment aiming to support clinical decision making in individual patients. Cancer treatment optimization is the main goal of the system. The document refers to the technology of the system and the clinical requirements and the types of medical data needed for exploitation in the case of nephroblastoma. The outcome of an initial step towards the clinical adaptation and validation of the system is presented and discussed. Use of anonymized real data before and after chemotherapeutic treatment for the case of the SIOP 2001/GPOH nephroblastoma clinical trial constitutes the basis of the clinical adaptation and validation process. By using real medical data concerning nephroblastoma for a single patient in conjunction with plausible values for the model parameters (based on available literature) a reasonable prediction of the actual tumour volume shrinkage has been made possible. Obviously as more and more sets of medical data are exploited the reliability of the model “tuning” is expected to increase. The successful performance of the initial combined ACGT Oncosimulator platform, although usable up to now only as a test of principle, has been a particularly encouraging step towards the clinical translation of the system, being the first of its kind worldwide.

Zusammenfassung

Die vorliegende Arbeit beschreibt die erste Version des ACGT (Advancing Clinico-Genomic Trials) – ein integriertes Projekt, z. T. finanziert über EC (FP6-2005-IST-026996)I-Oncosimulators als eine integrierte Software, die das In-vivo-Ansprechen eines Tumors auf therapeutische Maßnahmen innerhalb von klinischen Studien simuliert. Diese Software zielt darauf ab, klinische Entscheidungsprozesse bei individuellen Patienten zu unterstützen. Die Technologie des ACGT-Oncosimulators als auch die klinischen Voraussetzungen und notwendigen medizinischen Daten werden beschrieben, um Ergebnisse am Beispiel des Nephroblastoms zu generieren. Die Anpassung an klinische Gegebenheiten als auch die Validierung des Systems werden besprochen. Der Gebrauch von anonymisierten realen Daten vor und nach präoperativer Chemotherapie beim Nephroblastom innerhalb der SIOP-2001/GPOH-Studie stellen die Basis dieses Adaptations- und Validierungsprozesses dar. Es kann gezeigt werden, dass mit Hilfe realer klinischer Daten eines Patienten und plausiblen Parametern des vorgestellten Modells des ACGT-Oncosimulators eine gute Vorhersage des wirklichen Tumoransprechens möglich ist. Da es sich um ein lernendes System handelt, ist zu erwarten, dass sich mit der Zunahme durchgeführter Simulationen die Reliabilität verbessern wird. Die erfolgreiche Durchführung einer solchen Simulation durch den ACGT-Oncosimulator am Beispiel des Nephroblastoms kann als ,Test of Principle‘ angesehen werden und ist ein wichtiger Schritt hin zur klinischen Anwendung und der erste seiner Art weltweit.

Key words

‘in silico’ oncology - Oncosimulator - nephroblastoma - decision making

Schlüsselwörter

‚In silico’-Onkologie - Onkosimulator - Nephroblastom - Entscheidungshilfe

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