Predicting regrowth of low-grade gliomas after radiotherapy.

Diffuse low grade gliomas are invasive and incurable brain tumors that inevitably transform into higher grade ones. A classical treatment to delay this transition is radiotherapy (RT). Following RT, the tumor gradually shrinks during a period of typically 6 months to 4 years before regrowing. To improve the patient's health-related quality of life and help clinicians build personalized follow-ups, one would benefit from predictions of the time during which the tumor is expected to decrease. The challenge is to provide a reliable estimate of this regrowth time shortly after RT (i.e. with few data), although patients react differently to the treatment. To this end, we analyze the tumor size dynamics from a batch of 20 high-quality longitudinal data, and propose a simple and robust analytical model, with just 4 parameters. From the study of their correlations, we build a statistical constraint that helps determine the regrowth time even for patients for which we have only a few measurements of the tumor size. We validate the procedure on the data and predict the regrowth time at the moment of the first MRI after RT, with precision of, typically, 6 months. Using virtual patients, we study whether some forecast is still possible just three months after RT. We obtain some reliable estimates of the regrowth time in 75% of the cases, in particular for all "fast-responders". The remaining 25% represent cases where the actual regrowth time is large and can be safely estimated with another measurement a year later. These results show the feasibility of making personalized predictions of the tumor regrowth time shortly after RT.

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

Diffuse low-grade gliomas are slowly growing tumors that always recur after treatment. In this paper, we revisit the modeling of the evolution of the tumor radius before and after the radiotherapy process and propose a novel model that is simple yet biologically motivated and that remedies some shortcomings of previously proposed ones. We confront this with clinical data consisting of time series of tumor radii from 43 patient records by using a stochastic optimization technique and obtain very good fits in all cases. Since our model describes the evolution of a tumor from the very first glioma cell, it gives access to the possible age of the tumor. Using the technique of profile likelihood to extract all of the information from the data, we build confidence intervals for the tumor birth age and confirm the fact that low-grade gliomas seem to appear in the late teenage years. Moreover, an approximate analytical expression of the temporal evolution of the tumor radius allows us to explain the correlations observed in the data.