Repeated Awake Surgical Resection(s) for Recurrent Diffuse Low-Grade Gliomas: Why, When, and How to Reoperate?

Early maximal surgical resection is the first treatment in diffuse low-grade glioma (DLGG), because the reduction of tumor volume delays malignant transformation and extends survival. Awake surgery with intraoperative mapping and behavioral monitoring enables to preserve quality of life (QoL). However, because of the infiltrative nature of DLGG, relapse is unavoidable, even after (supra)total resection. Therefore, besides chemotherapy and radiotherapy, the question of reoperation(s) is increasingly raised, especially because patients with DLGG usually enjoy a normal life with long-lasting projects. Here, the purpose is to review the literature in the emerging field of iterative surgeries in DLGG. First, long-term follow-up results showed that patients with DLGG who underwent multiple surgeries had an increased survival (above 17 years) with preservation of QoL. Second, the criteria guiding the decision to reoperate and defining the optimal timing are discussed, mainly based on the dynamic intercommunication between the glioma relapse (including its kinetics and pattern of regrowth) and the reactional cerebral reorganization-i.e., mechanisms underpinning reconfiguration within and across neural networks to enable functional compensation. Third, how to adapt medico-surgical strategy to this individual spatiotemporal brain tumor interplay is detailed, by considering the perpetual changes in connectome. These data support early reoperation in recurrent DLGG, before the onset of symptoms and before malignant transformation. Repeat awake resection(s) should be integrated in a global management including (neo)adjuvant medical treatments, to enhance long-lasting functional and oncological outcomes. The prediction of potential and limitation of neuroplasticity at each step of the disease must be improved to anticipate personalized multistage therapeutic attitudes.