Multiscale network perspectives on glioma: from tumour biology to symptoms, survival and treatment.

Adult glioma is associated with a wide range of symptoms and variable survival that are not fully explained by tumour location or subtype. Recent work suggests that the disease may be better understood using a network-based framework, as opposed to more traditional localizationist thinking. In this Review, we describe three major types of network scaffolds relevant in people with glioma: symptom networks, the connectome and tumour biology networks. We summarize current evidence on how symptoms co-occur to form patterns, how gliomas affect structural and functional brain connectivity beyond the lesion and how tumour cells form intricate networks that interact with their surroundings. We then explore the relationships between local and global perspectives within each scaffold, and how these three scaffolds are interrelated, for example, through associations among tumour connectivity, cognitive performance and survival. We examine how current treatments such as surgery, radiotherapy, chemotherapy and anti-seizure medication interact with various network scaffolds. Group-level findings often do not reflect individual variability, and we highlight the need for personalized, longitudinal, multimodal and standardized network studies. Finally, we outline future steps towards integration of these three, and potentially additional network scaffolds, to provide network-informed care to patients with glioma.