Non-standard radiotherapy fractionations delay the time to malignant transformation of low-grade gliomas

Abstract

Grade II gliomas are slowly growing primary brain tumors that affect mostly young patients. Cytotoxic therapies (radiotherapy and/or chemotherapy) are used initially only for patients having a bad prognosis. These therapies are planned following the “maximum dose in minimum time” principle, i. e. the same schedule used for high-grade brain tumors in spite of their very different behavior. These tumors transform after a variable time into high-grade gliomas, which significantly decreases the patient’s life expectancy. In this paper we study mathematical models describing the growth of grade II gliomas in response to radiotherapy. We find that protracted metronomic fractionations, i.e. therapeutical schedules enlarging the time interval between low-dose radiotherapy fractions, may lead to a better tumor control without an increase in toxicity. Other non-standard fractionations such as protracted or hypoprotracted schemes may also be beneficial. The potential survival improvement depends on the tumor’s proliferation rate and can be even of the order of years. A conservative metronomic scheme, still being a suboptimal treatment, delays the time to malignant progression by at least one year when compared to the standard scheme.

Optimization of Dose Fractionation for Radiotherapy of a Solid Tumor with Account of Oxygen Effect and Proliferative Heterogeneity

“…The model simulations showed that only a rather moderate increase of it can be achieved for the considered parameter values under the restriction of maximum treatment duration of 6 weeks. However, the results suggested that sufficient tumor growth delays might be obtained for much longer treatments of slowly-proliferating tumors, which is in agreement with other theoretical studies [59,60]. Moreover, the presented model did not account for the drainage of necrotic tissue, which should be crucial for such problem.…”

Computational design of improved standardized chemotherapy protocols for grade II oligodendrogliomas

“…This result was later extended for different doses per fraction and time spacing between doses in Ref. [27]. Mazocco et al [31] found a similar result using in-silico simulations of the Ribba’s et al model [29].…”

“…Some previous models have explored different therapeutic regimens for low-grade gliomas [27, 28, 31, 34]. First, in Ref.…”

The Effect of Radiotherapy on Diffuse Low-Grade Gliomas Evolution: Confronting Theory with Clinical Data

“…The advantage of this model is that it contains a spatial structure and also allows a slow decrease in the tumor radius after the end of the RT treatment. The authors used the model to study the impact of a fractionation of the RT treatment [ 20 , 24 ]. However, these studies are theoretical, and the model was not applied to real clinical data.…”