Adoptive immunotherapies in neuro-oncology: classification, recent advances, and translational challenges

BACKGROUND: Adoptive immunotherapies are among the pillars of ongoing biological breakthroughs in neuro-oncology, as their potential applications are tremendously wide. The present literature review comprehensively classified adoptive immunotherapies in neuro-oncology, provides an update, and overviews the main translational challenges of this approach. METHODS: The PubMed/MEDLINE platform, Medical Subject Heading (MeSH) database, and ClinicalTrials.gov website were the sources. The MeSH terms "Immunotherapy, Adoptive," "Cell- and Tissue-Based Therapy," "Tissue Engineering," and "Cell Engineering" were combined with "Central Nervous System," and "Brain." "Brain tumors" and "adoptive immunotherapy" were used for a further unrestricted search. Only articles published in the last 5 years were selected and further sorted based on the best match and relevance. The search terms "Central Nervous System Tumor," "Malignant Brain Tumor," "Brain Cancer," "Brain Neoplasms," and "Brain Tumor" were used on the ClinicalTrials.gov website. RESULTS: A total of 79 relevant articles and 16 trials were selected. T therapies include chimeric antigen receptor T (CAR T) cell therapy and T cell receptor (TCR) transgenic therapy. Natural killer (NK) cell-based therapies are another approach; combinations are also possible. Trials in phase 1 and 2 comprised 69% and 31% of the studies, respectively, 8 of which were concluded. CAR T cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) was demonstrated to reduce the recurrence rate of glioblastoma after standard-of-care treatment. CONCLUSION: Adoptive immunotherapies can be classified as T, NK, and NKT cell-based. CAR T cell therapy redirected against EGFRvIII has been shown to be the most promising treatment for glioblastoma. Overcoming immune tolerance and immune escape are the main translational challenges in the near future of neuro-oncology

Rating the incidence of iatrogenic vascular injuries in thoracic and lumbar spine surgery as regards the approach: A PRISMA-based literature review

Purpose: To assess the rate, timing of diagnosis, and repairing strategies of vascular injuries in thoracic and lumbar spine surgery as their relationship to the approach. Methods: PubMed, Medline, and Embase databases were utilized for a comprehensive literature search based on keywords and mesh terms to find articles reporting iatrogenic vascular injury during thoracic and lumbar spine surgery. English articles published in the last ten years were selected. The search was refined based on best match and relevance. Results: Fifty-six articles were eligible, for a cumulative volume of 261 lesions. Vascular injuries occurred in 82% of instrumented procedures and in 59% during anterior approaches. The common iliac vein (CIV) was the most involved vessel, injured in 49% of anterior lumbar approaches. Common iliac artery, CIV, and aorta were affected in 40%, 28%, and 28% of posterior approaches, respectively. Segmental arteries were injured in 68% of lateral approaches. Direct vessel laceration occurred in 81% of cases and recognized intraoperatively in 39% of cases. Conclusions: Incidence of iatrogenic vascular injuries during thoracic and lumbar spine surgery is low but associated with an overall mortality rate up to 65%, of which less than 1% for anterior approaches and more than 50% for posterior ones. Anterior approaches for instrumented procedures are at risk of direct avulsion of CIV. Posterior instrumented fusions are at risk for injuries of iliac vessels and aorta. Lateral routes are frequently associated with lesions of segmental vessels. Suture repair and endovascular techniques are useful in the management of these severe complications

Working Corridors to Meckel’s Cave Trigeminal Schwannomas

Objectives: The present study focuses on the infratrochlear (IT) transcavernous, anteromedial (AM), and anterolateral (AL) approaches, analyzing their feasibility, indications, advantages, and limitations. Background: Understanding the working corridors used in the interdural approach to Meckel's cave is critical for the treatment of trigeminal schwannomas. Methods: Morphometric data of Meckel's cave, porus trigeminus, IT transcavernous, AM, and AL corridors were obtained from ten formalin-fixed, latex- injected cadaveric heads. Exposure areas, volumes, and opening angles of each corridor were calculated. Results: The volume of the IT transcavernous corridor was the largest, while the opening angle of the AM middle fossa triangle was the largest. Conclusions: The AM middle fossa corridor is strategic in schwannomas mainly involving Meckel's cave with a minor extension into the posterior fossa. It allows gross total resection through the opening of the porus trigeminus

Intraoperative Augmented Reality High-Definition Fiber Tractography for High-Grade Gliomas of The Primary Motor Area

Introduction The theoretical advantages of augmented reality (AR) with diffusion tensor imaging (DTI) based high-definition fiber tractography (HDFT) in high-grade glioma (HGG) surgery have not been investigated in detail. Objectives The present study aimed to evaluate the safety and efficacy profiles of HDFT-F microscope-based AR cytoreductive surgery for newly diagnosed HGGs involving the primary motor area. Methods A consecutive institutional series of patients with newly diagnosed HGGs of the central lobe that were operated on using the AR HDFT technique were reviewed and compared with that of a cohort of patients who underwent conventional white-light surgery assisted by infrared neuronavigation. The safety and efficacy of the technique were reported based on the postoperative Neurologic Assessment in Neuro-Oncology (NANO) scores, the extent of resection (EOR), and the Kaplan–Meier curves, respectively. A chi-squared test was conducted for categorical variables. A p-value < 0.05 was considered statistically significant. Results A total of 11 patients were operated on using the AR HDFT-F technique, and 9 underwent conventional white-light surgery. The average postoperative NANO scores were 5.4 ± 2 and 5.7 ± 3 in the AR HDFT-F and control group, respectively. The EOR was higher in the AR HDFT group than in the control group. On an average follow-up of 10.9 months, the rate of progression-free survival (PFS) was longer in the study group than in the control group (log-rank p = 0.045). Conclusions AR HDFT assisted surgery is safe and effective in maximizing the EOR and PFS rate, as well as in optimizing the patient’s functional outcomes, of newly diagnosed HGGs of the primary motor area

Supratentorial High-Grade Gliomas: Maximal Safe Anatomical Resection Guided by Intraoperative Augmented Reality High-Definition Fiber Tractography

Introduction The theoretical advantages of augmented reality (AR) with diffusion tensor imaging (DTI)–based high- definition fiber tractography (HDFT) in high-grade glioma (HGG) surgery have not been investigated in detail. Objectives In this study, the authors aimed to evaluate the safety and efficacy profiles of HDFT microscope-based AR cytoreductive surgery for newly diagnosed supratentorial HGGs. Methods Data of patients with newly diagnosed supratentorial HGGs who underwent surgery using the AR HDFT-F technique were reviewed and compared with those of a cohort of patients who underwent conventional white light surgery assisted by infrared neuronavigation. The safety and efficacy of the techniques were reported based on the postoperative Neurological Assessment in Neuro-Oncology (NANO) scores, the extent of resection (EOR), and Kaplan-Mei- er curves, respectively. The chi-square test was conducted for categorical variables. A p-value < 0.05 was considered statistically significant. Results A total of 54 patients underwent surgery using the AR HDFT technique, and 63 underwent conventional white-light surgery assisted by infrared neuronavigation. The mean postoperative NANO scores were 3.8 ± 2 and 5.2 ± 4 in the AR HDFT group and control group, respectively (p < 0.05). The EOR was higher in the AR HDFT group (p< 0.05) than in the control group. With a mean follow-up of 12.2 months, the rate of progression-free survival (PFS) was longer in the study group (log-rank test, p = 0.006) than in the control group. Moreover, the complication rates were 9.2% and 9.5% in the study and control groups, respectively. Conclusions Overall, AR HDFT–assisted surgery is safe and effective in maximizing the EOR and PFS rate for patients with newly diagnosed supratentorial HGGs, and in optimizing patient functional outcomes