Advances in local therapy for glioblastoma — taking the fight to the tumour

Abstract

Despite advances in neurosurgery, chemotherapy and radiotherapy, glioblastoma remains one of the most treatment-resistant CNS malignancies, and the tumour inevitably recurs. The majority of recurrences appear in or near the resection cavity, usually within the area that received the highest dose of radiation. Many new therapies focus on combatting these local recurrences by implementing treatments directly in or near the tumour bed. In this Review, we discuss the latest developments in local therapy for glioblastoma, focusing on recent preclinical and clinical trials. The approaches that we discuss include novel intraoperative techniques, various treatments of the surgical cavity, stereotactic injections directly into the tumour, and new developments in convection-enhanced delivery and intra-arterial treatments. Glioblastoma is one of the most treatment-resistant CNS malignancies, and the tumour inevitably recurs, usually in or near the resection cavity. Here, the authors discuss local therapies for glioblastoma, examining treatment of the resection cavity and other direct approaches to the tumour. Glioblastoma almost always recurs at or near the resection cavity, within the radiotherapy field. Local therapy provides a unique opportunity to deliver high doses of therapeutics to the area with the highest concentration of glioblastoma cells, with limited systemic adverse effects. Many phase I and II trials experimenting with various forms of local therapy have been — and are being — conducted in glioblastoma, with many showing great potential for improving progression-free and overall survival. Large randomized phase III trials comparing local therapies with standard of care have been hindered by high cost, labour intensity and challenges in patient recruitment. Close collaboration between clinicians, researchers, companies and governmental institutions is needed to smooth the transition from laboratory to phase I and II trials to large-scale randomized controlled trials. Glioblastoma almost always recurs at or near the resection cavity, within the radiotherapy field. Local therapy provides a unique opportunity to deliver high doses of therapeutics to the area with the highest concentration of glioblastoma cells, with limited systemic adverse effects. Many phase I and II trials experimenting with various forms of local therapy have been — and are being — conducted in glioblastoma, with many showing great potential for improving progression-free and overall survival. Large randomized phase III trials comparing local therapies with standard of care have been hindered by high cost, labour intensity and challenges in patient recruitment. Close collaboration between clinicians, researchers, companies and governmental institutions is needed to smooth the transition from laboratory to phase I and II trials to large-scale randomized controlled trials.