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The current state of immunotherapy for gliomas: an eye toward the future

JNSPG 75th Anniversary Invited Review Article

Peter E. Fecci and John H. Sampson

The last decade has seen a crescendo of FDA approvals for immunotherapies against solid tumors, yet glioblastoma remains a prominent holdout. Despite more than 4 decades of work with a wide range of immunotherapeutic modalities targeting glioblastoma, efficacy has been challenging to obtain. Earlier forms of immune-based platforms have now given way to more current approaches, including chimeric antigen receptor T-cells, personalized neoantigen vaccines, oncolytic viruses, and checkpoint blockade. The recent experiences with each, as well as the latest developments and anticipated challenges, are reviewed.

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Darrin J. Lee, Christopher S. Lozano, Robert F. Dallapiazza, and Andres M. Lozano

Deep brain stimulation (DBS) has evolved considerably over the past 4 decades. Although it has primarily been used to treat movement disorders such as Parkinson’s disease, essential tremor, and dystonia, recently it has been approved to treat obsessive-compulsive disorder and epilepsy. Novel potential indications in both neurological and psychiatric disorders are undergoing active study. There have been significant advances in DBS technology, including preoperative and intraoperative imaging, surgical approaches and techniques, and device improvements. In addition to providing significant clinical benefits and improving quality of life, DBS has also increased the understanding of human electrophysiology and network interactions. Despite the value of DBS, future developments should be aimed at developing less invasive techniques and attaining not just symptom improvement but curative disease modification.

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Michael T. Lawton and Michael J. Lang

Despite the erosion of microsurgical case volume because of advances in endovascular and radiosurgical therapies, indications remain for open resection of pathology and highly technical vascular repairs. Treatment risk, efficacy, and durability make open microsurgery a preferred option for cerebral cavernous malformations, arteriovenous malformations (AVMs), and many aneurysms. In this paper, a 21-year experience with 7348 cases was reviewed to identify trends in microsurgical management. Brainstem cavernous malformations (227 cases), once considered inoperable and managed conservatively, are now resected in increasing numbers through elegant skull base approaches and newly defined safe entry zones, demonstrating that microsurgical techniques can be applied in ways that generate entirely new areas of practice. Despite excellent results with microsurgery for low-grade AVMs, brain AVM management (836 cases) is being challenged by endovascular embolization and radiosurgery, as well as by randomized trials that show superior results with medical management. Reviews of ARUBA-eligible AVM patients treated at high-volume centers have demonstrated that open microsurgery with AVM resection is still better than many new techniques and less invasive approaches that are occlusive or obliterative. Although the volume of open aneurysm surgery is declining (4479 cases), complex aneurysms still require open microsurgery, often with bypass techniques. Intracranial arterial reconstructions with reimplantations, reanastomoses, in situ bypasses, and intracranial interpositional bypasses (third-generation bypasses) augment conventional extracranial-intracranial techniques (first- and second-generation bypasses) and generate innovative bypasses in deep locations, such as for anterior inferior cerebellar artery aneurysms. When conventional combinations of anastomoses and suturing techniques are reshuffled, a fourth generation of bypasses results, with eight new types of bypasses. Type 4A bypasses use in situ suturing techniques within the conventional anastomosis, whereas type 4B bypasses maintain the basic construct of reimplantations or reanastomoses but use an unconventional anastomosis. Bypass surgery (605 cases) demonstrates that open microsurgery will continue to evolve. The best neurosurgeons will be needed to tackle the complex lesions that cannot be managed with other modalities. Becoming an open vascular neurosurgeon will be intensely competitive. The microvascular practice of the future will require subspecialization, collaborative team effort, an academic medical center, regional prominence, and a large catchment population, as well as a health system that funnels patients from hospital networks outside the region. Dexterity and meticulous application of microsurgical technique will remain the fundamental skills of the open vascular neurosurgeon.