Purpose of Review: This review will discuss the challenges facing chimeric antigen receptor (CAR)-T cell application for solid tumors and opportunities to overcome these obstacles. In addition, this review will examine therapies that are in development for pediatric solid tumors. Recent Findings: The similar success of CAR-T cell treatment for hematological malignancies has not been observed in solid tumors because of the hostile tumor microenvironment and tumor heterogeneity. Most strategies developed to combat these limitations emphasize combinatorial techniques that still require further testing. Preliminary results of multiple clinical trials, including GD2- and HER2-CAR-T cells, are encouraging but must be reproduced and validated on a larger scale. Summary: CAR-T cell application in solid tumors remains challenging, and most research is in development. Several clinical trials are ongoing for pediatric solid tumors. Early results are promising but demonstrate the need for CAR-T cell modification to prevent tumor recurrence.

Surgical extent‐of‐resection has been shown to have an impact on high‐grade glioma (HGG) outcomes; however, complete resection is rarely achievable in difficult‐to‐access (DTA) tumors. Controlled thermal damage to the tumor may have the same impact in DTA‐HGGs. We report our multicenter results of laser interstitial thermal therapy (LITT) in DTA‐HGGs. We retrospectively reviewed 34 consecutive DTA‐HGG patients (24 glioblastoma, 10 anaplastic) who underwent LITT at Cleveland Clinic, Washington University, and Wake Forest University (May 2011–December 2012) using the NeuroBlate^® System. The extent of thermal damage was determined using thermal damage threshold (TDT) lines: yellow TDT line (43°C for 2 min) and blue TDT line (43°C for 10 min). Volumetric analysis was performed to determine the extent‐of‐coverage of tumor volume by TDT lines. Patient outcomes were evaluated statistically. LITT was delivered as upfront in 19 and delivered as salvage in 16 cases. After 7.2 months of follow‐up, 71% of cases demonstrated progression and 34% died. The median overall survival (OS) for the cohort was not reached; however, the 1‐year estimate of OS was 68 ± 9%. Median progression‐free survival (PFS) was 5.1 months. Thirteen cases who met the following two criteria—(1) <0.05 cm³ tumor volume not covered by the yellow TDT line and (2) <1.5 cm³ additional tumor volume not covered by the blue TDT line—had better PFS than the other 21 cases (9.7 vs. 4.6 months; P = 0.02). LITT can be used effectively for treatment of DTA‐HGGs. More complete coverage of tumor by TDT lines improves PFS which can be translated as the extent of resection concept for surgery.

Adoptive cellular immunotherapy (ACT) employing engineered T lymphocytes expressing chimeric antigen receptors (CARs) has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. We anticipate these modifications will further expand CAR T cell therapy in clinical practice.

BACKGROUND: Women represent a growing cohort of US neurosurgeons. OBJECTIVE: To describe postresidency fellowship, practice environment, and updated academic rank among female neurosurgeons. METHODS: Databases from the American Association of Neurological Surgeons (AANS) and the American Board of Neurological Surgery (ABNS) from 1964 to 2013 were reviewed for female neurosurgery residency graduates. Data on postresidency fellowships, practice environment (private vs academic), academic rank, board certification, and AANS/CNS (Congress of Neurological Surgeons) Joint Section on Women in Neurosurgery (WINS) membership were collected in 2016. Academic rank was verified from program websites and electronic correspondence. Faculty members were asked to report directorships and tenure. The AANS/CNS Joint Section on Women in Neurosurgery verified WINS membership. RESULTS: A total of 379 female neurosurgery residency graduates were identified in this 50-yr span. Of these, 70% became ABNS certified, and 2.1% left neurosurgery. Twenty-seven percent of women (n = 103) pursued fellowships, with pediatric neurosurgery (33%) the most common. Regarding practice environment, 26% entered academic medicine (n = 91), with 42 at the rank of assistant professor, 33 at the rank of associate professor, and 16 reaching the rank of full professor. CONCLUSION: Upon completion of training, 27% of women pursue fellowships. The distribution of women in private vs academic practice environments is proportionate to male neurosurgeons; however, the number women in academic leadership positions remains exceedingly low, with disproportionate representation in higher academic ranks. Women in national organized neurosurgery are increasing. Tracking the career paths of women in neurosurgery is a necessary step to identifying current achievements and opportunities for future progress.

The blood–brain barrier remains a main hurdle to drug delivery to the brain. The prognosis of glioblastoma remains grim despite current multimodal medical management. We review neurosurgical technologies that disrupt the blood–brain barrier (BBB). We will review superselective intra-arterial mannitol infusion, focused ultrasound, laser interstitial thermotherapy, and non-thermal irreversible electroporation (NTIRE). These technologies can lead to transient BBB and blood–brain tumor barrier disruption and allow for the potential of more effective local drug delivery. Animal studies and preliminary clinical trials show promise for achieving this goal.