Faculty Bibliography

PURPOSE OF REVIEW:This review summarizes the modern approach to surgical management of malignant brain tumors, highlighting new technology and multimodal treatment paradigms. RECENT FINDINGS:Outcomes in patients with glioblastoma are strongly correlated with extent of initial surgical resection. Intraoperative MRI, 5-ALA, and neuronavigation are surgical tools that can help achieve a maximal safe resection. Stereotactic radiosurgery and brachytherapy can be used to enhance local control for brain metastases in conjunction with surgery, while combinatorial approaches are increasingly employed in patients with multiple metastases. Advances in surgical techniques allow for minimally invasive approaches, including the use of tubular retractors, endoscopes, and laser interstitial thermal therapy. Primary and metastatic brain tumors require a multimodal, multidisciplinary approach to treatment. Surgical resection can be paired with radiation for metastases to maximize tumor control, expanding systemic options. Technological innovations have improved the safety of surgical resection, while expanding the surgical options and indications for treatment.

PURPOSE:Small-molecule inhibitors have had a major impact on cancer care. While treatments have demonstrated clinically promising results, they suffer from dose-limiting toxicities and the emergence of refractory disease. Considerable efforts made to address these issues have more recently focused on strategies implementing particle-based probes that improve drug delivery and accumulation at target sites, while reducing off-target effects. EXPERIMENTAL DESIGN:biological and therapeutic properties of a prototype epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib. Novel surface chemical components were used to conjugate gefitinib-dipeptide drug-linkers and deferoxamine (DFO) chelators for therapeutic delivery and PET imaging labels, respectively. RESULTS:= 6.21 nmol/L vs. 3 μmol/L, respectively). In human non-small cell lung cancer mice, efficacious Gef-C' dot doses were at least 200-fold lower than that needed for gefitinib (360 nmoles vs. 78 μmoles, respectively), noting fairly equivalent tumor growth inhibition and prolonged survival. Gef-C' dot-treated tumors also exhibited low phosphorylated EFGR levels, with no appreciable wild-type EGFR target inhibition, unlike free drug. CONCLUSIONS:Results underscore the clinical potential of DFO-Gef-C' dots to effectively manage disease and minimize off-target effects at a fraction of the native drug dose.

OBJECTIVE:The utility and safety of intraoperative MRI (iMRI) for resection of pituitary adenomas is not clearly established in the context of advances in endoscopic approaches. The goal in this study was to evaluate the safety and efficacy of iMRI for pituitary adenoma resection, with endoscopic transsphenoidal (ETS) versus microscopic transsphenoidal (MTS) approaches. METHODS:Radiographic and clinical outcomes of all pituitary adenomas resected using iMRI between 2008 and 2017 at a single institution were retrospectively evaluated. RESULTS:Of 212 tumors treated, 131 (62%) underwent further resection based on iMRI findings, resulting in a significant increase in gross-total resection on postoperative MRI compared with iMRI (p = 0.0001) in both ETS and MTS groups. iMRI increased rates of gross-total resection for cavernous sinus invasion Knosp grades 1 and 2, but not in Knosp ≥ 3 across treatment groups (p < 0.0001). The extent of resection on postoperative MRI was significantly correlated with increased progression-free survival (p < 0.0001). Initial hormone remission off medical therapy was achieved in 64%, with a significantly higher rate of remission in tumors resected via the ETS approach (81%) compared with the MTS approach (55%) (p = 0.02). The rate of persistent new hormone deficit was low at 8%, including a 2.8% rate of permanent diabetes insipidus, and 45% of patients had improvement in preoperative hormone deficit following surgery. Serious postoperative complications including CSF leaks requiring reoperation were rare at 1%, with no postoperative infections. CONCLUSIONS:These results suggest that iMRI is a safe and effective method of increasing the extent of resection for pituitary adenomas while preserving hormone function. When paired with the endoscope, iMRI may offer the ability to tailor more aggressive removal of tumors while optimizing pituitary function, resulting in high rates of secretory hormone remission. Secretory tumors and adenomas with Knosp grade < 3 cavernous sinus invasion may benefit most from the use of iMRI.

PURPOSE:Small-molecule inhibitors have revolutionized treatment of certain genomically defined solid cancers. Despite breakthroughs in treating systemic disease, central nervous system (CNS) metastatic progression is common, and advancements in treating CNS malignancies remain sparse. By improving drug penetration across a variably permeable blood-brain barrier and diffusion across intratumoral compartments, more uniform delivery and distribution can be achieved to enhance efficacy. EXPERIMENTAL DESIGN:autoradiography, fluorescence microscopy, and p-S6RP IHC. RESULTS:Improvements in brain tumor delivery and penetration, as well as enhancement in the ADR, were observed following administration of integrin-targeted C' dots, as compared with a nontargeted control. Furthermore, attachment of the small-molecule inhibitor, dasatinib, led to its successful drug delivery throughout mGBM, demonstrated by downstream pathway inhibition. CONCLUSIONS:These results demonstrate that highly engineered C' dots are promising drug delivery vehicles capable of navigating the complex physiologic barriers observed in a clinically relevant brain tumor model.

OBJECTIVE:The use of multidisciplinary teams (MDTs) comprised of all members of the patient care team is becoming increasingly popular in the field of oncology. Here, we present a single center experience on the utility and uniqueness of a MDT in the setting of brain and spine stereotactic radiosurgery (SRS) patients. METHODS:The weekly stereotactic radiosurgery conference brings together neurosurgeons, radiation oncologists, neuroradiologists, physicists, dosimetrists, therapists, advanced practice providers, and trainees in these fields, as well as researchers from a variety of disciplines with a goal of optimizing patient care. A survey of 20 conference attendees from seven different facets of the treatment team was conducted for feedback. RESULTS:The survey results revealed that most believed that the conference was beneficial in terms of increasing educational opportunities, providing opportunity for research and collaborations, helping streamline patient care, and being beneficial to their practice. CONCLUSION/CONCLUSIONS:We present our institutional MDT model, a framework and workflow that can be incorporated at other large academic centers. We believe that the conference has educational, academic, and patient-care value.

Recent technological advancements in intraoperative imaging are shaping the way for a new era in brain tumor surgery. Magnetic resonance thermometry has provided intraoperative real-time imaging feedback for safe and effective application of laser interstitial thermal therapy (LITT) in neuro-oncology. Thermal ablation has also established itself as a surgical option in epilepsy surgery and is currently used in spine oncology with promising results. This article reviews the principles and rationale as well as the clinical application of LITT for brain tumors. It also discusses the technical nuances of the current commercially available systems.