Towards in silico oncology: adapting a four dimensional nephroblastoma treatment model to a clinical trial case based on multi-method sensitivity analysis.
In the past decades a great progress in cancer research has been made although medical treatment is still widely based on empirically established protocols which have many limitations. Computational models address such limitations by providing insight into the complex biological mechanisms of tumor progression. A set of clinically-oriented, multiscale models of solid tumor dynamics has been developed by the In Silico Oncology Group (ISOG), Institute of Communication and Computer Systems (ICCS)-National Technical University of Athens (NTUA) to study cancer growth and response to treatment. Within this context using certain representative parameter values, tumor growth and response have been modeled under a cancer preoperative chemotherapy protocol in the framework of the SIOP 2001/GPOH clinical trial. A thorough cross-method sensitivity analysis of the model has been performed. Based on the sensitivity analysis results, a reasonable adaptation of the values of the model parameters to a real clinical case of bilateral nephroblastomatosis has been achieved. The analysis presented supports the potential of the model for the study and eventually the future design of personalized treatment schemes and/or schedules using the data obtained from in vitro experiments and clinical studies.
In Silico Oncology Group, Institute of Communication and Computer Systems, School of Electrical and Computer Engineering, National Technical University of Athens, Greece.
Eleni Ch
ECh
Georgiadi
Dimitra D
DD
Dionysiou
Norbert
N
Graf
Georgios S
GS
Stamatakos
D000465:Algorithms; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002986:Clinical Trials as Topic; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology* / Q000628:therapy*; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000473:pathology; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D018875:Vocabulary, Controlled; D009396:Wilms Tumor / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery / Q000628:therapy*
D000970:Antineoplastic Agents