New Therapeutic Strategies in Low-grade Gliomas: Who Grade 2 Gliomas

Low-grade glioma (LGG) (grade 2 or G2G) is a brain infiltrative neoplasia, often invading cortical and subcortical functional structures, while displaying as a rule a somewhat indolent course initially (no patent deficit). It affects essentially young, fully active patients, who usually present with seizures. However, these lesions progress relentlessly, and their final fate is anaplastic transformation, leading to neurological impairment and death, with an overall median survival of around 10 years since the onset of symptoms. Due to their apparent biological variability, commonly admitted spontaneous prognostic factors are of limited use if not questionable; consequently, the management of LGGs remains difficult to define (individually), and subject to controversies in the literature. However, most studies have evaluated the eventual impact of treatment(s) independently of the individual natural history and of the global therapeutic strategy. Thus, the goal of the present review is to give new insights regarding the different therapeutic strategies that need to be considered for each patient, and the parameters that can help the decision making. First, it is now possible to benefit from data allowing a better understanding of the natural history of a given LGG: (1) initial tumoral volume (2) tumoral growth rate evaluated on at least two MRIs (3) tumoral metabolic profile, using new radiological methods such as PET and SRM (4) tumoral molecular biology, completing the information provided by classical histopathology. Second, it is mandatory to perform a complete neurological examination, extensive neuropsychological assessment and evaluation of the quality of life from the time of diagnosis throughout the follow-up. Moreover, the analysis of the brain functional (re)organisation and connectivity is needed via the use of new neurofunctional imaging methods (PET, MEG, fMRI, DTI), in order to understand the individual mechanisms of functional compensation in reaction to the glioma growth -- explaining the frequent lack of deficit despite a classical invasion of so called "eloquent" areas. Third, the advantages and limits of each treatment have to be considered for each patient. In this way, the use of intraoperative electrical functional mapping as well as the integration, up to the operating room, of preoperative anatomo-functional data, has allowed the minimisation of the risk of postoperative sequelae, while improving the quality of tumor removal, even in eloquent regions. However, the actual long-term impact of surgery on survival still remains to ascertain. Concerning radiotherapy, the adaptation of doses, fractionation and volume of irradiation has enabled to decrease its risks, especially regarding cognitive functions. Nevertheless, despite an impact on the progression free survival, the effect on the overall survival is not proven. Finally, the recent use of new chemotherapeutic drugs has allowed a better tolerance and a frequent improvement of the quality of life via an impact on seizures, with a stabilisation or even partial regression of the LGG; however, the follow-up is still too short to conclude. On the basis of these (non exhaustive) parameters, we propose in the last part of this book to consider not "a standard treatment", but rather alternative "multiple dynamic therapeutic strategies" adapted to each patient, to be evaluated according to the clinico-radiological evolution of the LGG.