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Perez-Garcia19 - Computational design of improved standardized chemotherapy protocols for grade 2 oligodendrogliomas

ABSTRACT: This is a model built by COPASI4.24(Build 197) This a model from the article: Computational design of improved standardized chemotherapy protocols for grade II oligodendrogliomas Víctor M. Pérez-García, Luis E. Ayala-Hernández, Juan Belmonte-Beitia, Philippe Schucht, Michael Murek, Andreas Raabe, Juan Sepúlveda. PLoS Comput Biol. 2019 Jul; 15(7): e1006778. Abstract: Here we put forward a mathematical model describing the response of low-grade (WHO grade II) oligodendrogliomas (LGO) to temozolomide (TMZ). The model describes the longitudinal volumetric dynamics of tumor response to TMZ of a cohort of 11 LGO patients treated with TMZ. After finding patient-specific parameters, different therapeutic strategies were tried computationally on the ‘in-silico twins’ of those patients. Chemotherapy schedules with larger-than-standard rest periods between consecutive cycles had either the same or better long-term efficacy than the standard 28-day cycles. The results were confirmed in a large trial of 2000 virtual patients. These long-cycle schemes would also have reduced toxicity and defer the appearance of resistances. On the basis of those results, a combination scheme consisting of five induction TMZ cycles given monthly plus 12 maintenance cycles given every three months was found to provide substantial survival benefits for the in-silico twins of the 11 LGO patients (median 5.69 years, range: 0.67 to 68.45 years) and in a large virtual trial including 2000 patients. We used 220 sets of experiments in-silico to show that a clinical trial incorporating 100 patients per arm (standard intensive treatment versus 5 + 12 scheme) could demonstrate the superiority of the novel scheme after a follow-up period of 10 years. Thus, the proposed treatment plan could be the basis for a standardized TMZ treatment for LGO patients with survival benefits. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92

SUBMITTER: Szeyi Ng

PROVIDER: BIOMD0000000814 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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			Action	DRS
	BIOMD0000000814?filename=Fig%203e.png	Other
	BIOMD0000000814?filename=Nuevo_Modelo_P105.m	Other
	BIOMD0000000814?filename=Nuevo_Modelo_TMZ_P105.m	Other
	BIOMD0000000814?filename=Perez-Garcia19%20Computational%20design%20of%20improved%20standardized%20chemotherapy%20protocols%20for%20grade%202%20oligodendrogliomas.cps	Other
	BIOMD0000000814?filename=Perez-Garcia19%20Computational%20design%20of%20improved%20standardized%20chemotherapy%20protocols%20for%20grade%202%20oligodendrogliomas.sedml	Other

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Computational design of improved standardized chemotherapy protocols for grade II oligodendrogliomas.

Pérez-García Víctor M VM Ayala-Hernández Luis E LE Belmonte-Beitia Juan J Schucht Philippe P Murek Michael M Raabe Andreas A Sepúlveda Juan J

PLoS computational biology 20190715 7

Here we put forward a mathematical model describing the response of low-grade (WHO grade II) oligodendrogliomas (LGO) to temozolomide (TMZ). The model describes the longitudinal volumetric dynamics of tumor response to TMZ of a cohort of 11 LGO patients treated with TMZ. After finding patient-specific parameters, different therapeutic strategies were tried computationally on the 'in-silico twins' of those patients. Chemotherapy schedules with larger-than-standard rest periods between consecutive ...[more]

PMID: 31306418

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