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

Pérez-García, Víctor M; Ayala-Hernández, Luis E; Belmonte-Beitia, Juan; Schucht, Philippe; Murek, Michael; Raabe, Andreas; Sepúlveda, Juan (2019). Computational design of improved standardized chemotherapy protocols for grade II oligodendrogliomas. PLoS computational biology, 15(7), e1006778. Public Library of Science 10.1371/journal.pcbi.1006778

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery

UniBE Contributor:

Schucht, Philippe; Murek, Michael and Raabe, Andreas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1553-734X

Publisher:

Public Library of Science

Language:

English

Submitter:

Nicole Söll

Date Deposited:

27 Aug 2019 09:21

Last Modified:

22 Oct 2019 21:18

Publisher DOI:

10.1371/journal.pcbi.1006778

PubMed ID:

31306418

BORIS DOI:

10.7892/boris.132390

URI:

https://boris.unibe.ch/id/eprint/132390

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