Quantitative Approach of the Natural Course of Diffuse Low-Grade Gliomas

Abstract

Supratentorial hemispheric diffuse low-grade gliomas (LGG), i.e., World Health Organization grade II gliomas, are a heterogeneous group of tumors with distinct clinical, histological and molecular characteristics. The prognosis of LGG varies between series and reflects their heterogeneity with different subgroups harboring specific intrinsic properties. The natural course of LGG, as observed in clinical practice can be summarized as a three-step process although there is an actual continuum from “low-grade” to “high-grade” of malignancy. The two first steps correspond to the histological “low-grade” of malignancy with an initial silent period before clinical revelation followed by a symptomatic period. The third step corresponds to the progression to a higher grade of malignancy leading to neurological disability and ultimately to death. It has been well demonstrated that LGG are progressive tumors that present a systematic, spontaneous and continuous radiological growth all along their natural course, even during the initial silent period and during the symptomatic period before any transformation into a higher grade of malignancy. The Velocity of Diametric Expansion (VDE), estimated from the evolution of the mean tumor diameter over time, can easily quantify the radiological tumor growth. The median VDE is at about 4 mm/year for LGG albeit with a great heterogeneity. Several intrinsic factors may influence spontaneous VDE (1p19q codeletion and p53 overexpression) or not (histological subtype) and extrinsic factors may modify VDE (hormonal changes during pregnancy). The spontaneous VDE has a strong prognostic significance on overall and progression free survivals. As a consequence, the analysis of the spontaneous VDE, a dynamic macroscopic parameter easily available in clinical practice, may be a useful tool to overcome biological diversity of LGG and could be integrated along with the other “static” parameters (histological and molecular analyses) in a multi-scale approach to understand better the individual natural course of LGG. The VDE remains unchanged after surgical resection, whereas it decreases markedly during and after chemotherapy with temozolomide or PCV. Thus, a precise assessment of the VDE obtained before and after treatment would help guiding and analyzing the effects of different oncological treatment modalities on an individual basis.