New concepts in the management of diffuse low-grade glioma: Proposal of a multistage and individualized therapeutic approach

Abstract

Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a "wait and see" policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associated with a longer overall survival (OS) while minimizing morbidity. However, most studies have investigated the role of only one specific treatment (surgery, radiotherapy, chemotherapy) without taking a global view of managing the cumulative time while preserving quality of life (QoL) versus time to anaplastic transformation. Our aim is to switch towards a more holistic concept based upon the anticipation of a personalized and long-term multistage therapeutic approach, with online adaptation of the strategy over the years using feedback from clinical, radiological, and histomolecular monitoring. This dynamic strategy challenges the traditional approach by proposing earlier therapy, by repeating treatments, and by reversing the classical order of therapies (eg, neoadjuvant chemotherapy when maximal resection is impossible, no early radiotherapy) to improve OS and QoL. New individualized management strategies should deal with the interactions between the course of this chronic disease, reaction brain remapping, and oncofunctional modulation elicited by serial treatments. This philosophy supports a personalized, functional, and preventive neuro-oncology.

Keywords: awake surgery; diffuse low-grade gliomas; individualized management; multistage therapeutic approach; quality of life.

Fig. 1.

(A) Preoperative axial, sagittal, and coronal FLAIR-weighted MRI showing a left frontal DLGG incidentally discovered (headaches) in a young right-handed adult with a normal neurological examination and enjoying a normal life. The preoperative neuropsychological examination demonstrated slight attentional disorders. (B) Intraoperative photograph. Left: view before resection showing the tumor limits (letter tags) identified by ultrasonography as well as the eloquent cortical structures (number tags) detected by IEM. Right: view after glioma removal, performed according to functional boundaries and detected by IEM, both at the cortical and subcortical levels throughout the resection (no neuronagivation, no intraoperative MRI). In other words, a functional-mapped guided resection was achieved, not an image-guided resection. (C) Postoperative axial and sagittal FLAIR-weighted MRI as well as coronal T2-weighted MRI, demonstrating a complete resection of the DLGG (histologically confirmed), including its part involving the so-called Broca's area as well as within the corpus callosum. Despite an extensive left frontal lobectomy, the patient recovered and returned to a normal social and professional live (working full time) 3 months after surgery, with no symptoms. Interestingly, there was an improvement of the objective cognitive assessment performed 3 months following the resection in comparison with the presurgical evaluation, thanks to a specific cognitive rehabilitation. No antiepileptic drugs and no adjuvant oncological treatments were given.

Fig. 2.

Proposal of dynamic therapeutic strategy in DLGG before malignant transformation, with special emphasis on the role of early and maximal surgical resection(s) as well as multistage therapies tailored to each patient over years (modified from).

Fig. 3.

(A) Axial FLAIR-weighted MRI revealing a wide DLGG, which involved the right frontal and central areas as well as the corona radiata, in a woman who experienced intractable epilepsy. (B) After 20 cycles of neo-adjuvant chemotherapy (temozolomide) a dramatic shrinkage was observed, and awake surgery with resection guided by functional mapping was achieved. (C) Postoperative axial FLAIR-weighted MRI, demonstrating a subtotal resection in a patient who returned to a normal life with no seizures.