Superior orbital fissure narrowing and tumor-associated pain in spheno-orbital meningiomas.

INTRODUCTION: Spheno-orbital meningiomas (SOMs) represent a distinct subtype of meningioma characterized by their unique multi-compartmental invasion pattern. Previous studies have investigated correlations between SOMs and visual manifestations. However, our comprehension of pain associated with SOMs remains limited. This study aims to provide insight into the pathophysiology underlying SOM-related pain through measurements of tumor volume and superior orbital fissure (SOF) narrowing. METHODS: This retrospective study included patients who underwent surgical resection of a SOM between 2000 and 2022. Preoperative CT and/or MRI scans were analyzed, and the tumor volume of each segment was measured. Bony 3D reconstructions were used to measure the area of the SOF, and SOF narrowing was calculated. RESULTS: The study cohort included 66 patients diagnosed with SOMs, among which 25.8% (n = 17) presented with pain. Postoperatively, 14/17 (82.4%) of patients reported pain improvement. There was no significant correlation between the total volume or the volume of tumor within each compartment and the presence of pain on presentation (p > 0.05). The median SOF narrowing was significantly different between patients presenting with and without tumor-associated pain with median of 11 mm2 (IQR 2.8-22.3) and 2 mm2 (IQR 0-6), respectively (p = 0.005). Using logistic regression, a significant correlation between the degree of SOF narrowing and the presence of SOM-associated pain on presentation was identified, with an aOR of 1.2 (95% CI 1.12-1.3, p = 0.02). CONCLUSION: While the exact cause of tumor-associated pain remains unclear, SOF narrowing seems to play a role in pain among SOM patients. Based on the radiological characteristics, SOF neurovascular decompression is recommended in SOM patients.

The vectorial technique: a novel neuronavigation-based tool to measure angles of exposure during skull base dissections.

The angle of exposure (AnE) represents a metric that is particularly useful for analyzing circular bony structures during skull base dissections. The authors aimed to develop and validate a neuronavigation-based method to measure the AnE. A formula based on vectorial geometry and the coordinates of three points collected with a neuronavigation system was developed to measure the AnE. The method was validated using a plexiglass phantom head. To demonstrate its applicability, the authors measured the AnE in 6 cadaveric specimens after exposure of the hypoglossal canal using a far-medial approach (FMA) and a far-lateral transtubercular approach (FLTA) and in 6 different specimens after exposure of the jugular foramen using an FLTA and a retrosigmoid approach (RSA). The mean angles measured at 45°, 90°, and 180° using a goniometer during the validation test were 44.8° ± 1.1°, 90.8° ± 1.2°, and 179.7° ± 0.8° using the novel formula (p > 0.05). In the first illustrative application, the mean AnEs for the FMA and FLTA were 129° ± 0.9° and 243° ± 1.9°, respectively. In the second scenario, the mean AnEs were 192° ± 1.3° for the FTLA and 143° ± 2.1° for the RSA. The neuronavigation-based technique described is a highly accurate method to measure the AnE.

Oculomotor nerve cavernous malformation: case report and operative video.

BACKGROUND: Cavernous malformations (CMs) are clusters of thin-walled sinusoidal vessels without well-defined walls. Though they can occur anywhere in the neuroaxis, cranial nerve (CN) CMs are rare. METHOD: We report a 47-year-old male with gradual CN III palsy. Initial imaging showed no significant findings, but a follow-up MRI revealed a growing lesion along CN III. Intraoperative findings confirmed a CN III CM. Diagnosing and treating CN III CM are complex. Radiological findings lack specificity, requiring consideration of various diagnoses for patients with isolated CN III palsy and abnormal radiological findings. CONCLUSION: Surgery is the gold standard, aiming for complete lesion removal while minimizing neurological complications.

Pediatric infectious aneurysms: individual patient pooled analysis on presentation, management and outcomes.

BACKGROUND: Infectious intracranial aneurysms (IIAs) are a rare sequel of systemic infection and occur most commonly in patients with infective endocarditis (IE). Despite the increasing use of non-invasive screening angiography in patients with IE, the incidence remains low, yielding limited data on the management of IIAs in pediatric populations. We performed a pooled analysis of all published series of pediatric patients with IIAs to study the disease landscape including presentation, management, and outcomes. METHODS: Data included in this study were pooled from published literature on IIAs between 1960 and 2023. Abstracts were selected for full review to include only manuscripts reporting at least one case of pediatric IIA (age 0-18 years). RESULTS: A total of 145 pediatric patients with 178 IIAs were included. Patients presented with rupture in 68% of cases, of which 36% had intraparenchymal hemorrhage and 39% had subarachnoid hemorrhage. Using multivariate logistic regression, independent predictors of rupture were posterior location (aOR 10, P=0.041) and history of IE (aOR 7.2, P=0.001). Primary medical management was successful in 82% of cases with unruptured aneurysms while, in those with ruptured IIAs, medical management was successful in 26% of cases. The 90-day mortality rate was 28%. Using multivariate logistic regression, ruptured IIAs (aOR 5.4, P<0.01) and failure of medical management (aOR 11.1, P<0.05) were independent predictors of 90-day mortality. CONCLUSION: Pediatric IIAs remain a rare complication of systemic or localized CNS infection in the pediatric population. Medical management of unruptured aneurysms is highly successful, while ruptured aneurysms have a remarkably high rate of failure of medical management and should be treated by early surgical or endovascular intervention when feasible.

Comparison of Resection Assisting Devices in the Process of Collecting Brain Tumor Tissue for Basic Research: Microdebrider Versus Ultrasonic Aspirator.

INTRODUCTION: Brain tumors display significant inter and intratumoral heterogeneity, impacting disease progression and outcomes. Preserving surgically resected tissue is vital for ensuring accurate research results to enhance understanding of tumor pathophysiology. This study evaluates tissue integrity and viability of tissue resected using 2 surgical devices for tumor resection: a mechanical microdebrider (MD) and an ultrasonic aspirator (UA). METHODS: Tumor samples were obtained from patients undergoing surgical resection of primary and secondary intracranial tumors. Cell viability was assessed, and histopathological analysis of Hematoxylin and Eosin -stained tissues was performed. Adherent monolayer and neurospheres cell cultures were established from paired samples. RNA isolation and quantitative polymerase chain reaction of housekeeping genes were conducted to compare genetic integrity. RESULTS: The cellular viability was comparable between samples obtained using both the MD and the UA, with a mean viability of 75.2% ± 15.6 and 70.7% ± 16.8, respectively (P = 0.318). Histopathological evaluation indicated no discernible differences in cellular integrity between the devices. Cell culture success rates and growth characteristics were similar for both devices. RNA concentration and integrity were well-maintained in both MD and UA samples, with no significant differences (P = 0.855). Quantitative polymerase chain reaction analysis of housekeeping genes showed consistent results across matched tissues from both devices and different tumor pathologies. CONCLUSIONS: Surgical handheld devices provide valuable, high-quality tissue samples for research. Surgeon preference, tumor pathology, and anatomical location dictate device choice. Both MD and UA devices are reliable for obtaining quality tissue specimens, facilitating translational neuro-oncology research.

An Artificial Neural Network Model for Predicting Postoperative Facial Nerve Outcomes After Vestibular Schwannoma Surgery.

BACKGROUND AND OBJECTIVES: The emergence of machine learning models has significantly improved the accuracy of surgical outcome predictions. This study aims to develop and validate an artificial neural network (ANN) model for predicting facial nerve (FN) outcomes after vestibular schwannoma (VS) surgery using the proximal-to-distal amplitude ratio (P/D) along with clinical variables. METHODS: This retrospective study included 71 patients who underwent VS resection between 2018 and 2022. At the end of surgery, the FN was stimulated at the brainstem (proximal) and internal acoustic meatus (distal) and the P/D was calculated. Postoperative FN function was assessed using the House-Brackmann grading system at discharge (short-term) and after 9-12 months (long-term). House-Brackmann grades I-II were considered good outcome, whereas grades III-VI were considered fair/poor. An ANN model was constructed, and the performance of the model was evaluated using the area under the ROC curve for internal validation and accuracy, sensitivity, specificity, and positive and negative predictive values for external validation. RESULTS: The short-term FN outcome was grades I-II in 57.7% and grades III-VI in 42.3% of patients. Initially, a model using P/D had an area under the curve of 0.906 (internal validation) and an accuracy of 89.1% (95% CI: 68.3%-98.8%) (external validation) for predicting good vs fair/poor short-term FN outcomes. The model was then refined to include only muscles with a P/D with a proximal latency between 6 and 8 ms. This improved the accuracy to 100% (95% CI: 79%-100%). Integrating clinical variables (patient's age, tumor size, and preoperative HB grade) in addition to P/D into the model did not significantly improve the predative value. A model was then created to predict the long-term FN outcome using P/D with latencies between 6 and 8 ms and had an accuracy of 90.9% (95% CI: 58.7%-99.8%). CONCLUSION: ANN models incorporating P/D can be a valuable tool for predicting FN outcomes after VS surgery. Refining the model to include P/D with latencies between 6 and 8 ms further improves the model's prediction. A user-friendly interface is provided to facilitate the implementation of this model.

Volumetric Analysis of Spheno-Orbital Meningiomas: Prognostic Correlation and a Compartmentalized Approach.

BACKGROUND AND OBJECTIVES: Spheno-orbital meningiomas arise from the arachnoid villi cap cells at the sphenoid ridge and have the ability to spread through soft tissue extension and cranial bone invasion. Owing to their orbital hyperostosis and intraorbital soft tissue extension, they commonly present with ophthalmologic manifestations. This study aims to investigate the correlation between tumor volume with the presenting symptoms and postoperative outcomes. METHODS: This retrospective study analyzed patients who underwent surgical resection of spheno-orbital meningiomas. Tumor volumes in different compartments were measured using preoperative and postoperative imaging. Linear and logistic regression analyses were used to identify correlations between tumor volumes and presenting symptoms preoperatively and postoperative outcomes. RESULTS: Sixty-six patients were included in this study, of whom 86.4% had proptosis, 80.3% had decreased visual acuity (VA), 30.3% had visual field defects, and 13.6% had periorbital edema. Preoperatively, proptosis linearly correlated with intraosseous tumor volume (coefficient = 0.6, P < .001), while the decrease in baseline VA correlated with the intraorbital tumor volume (coefficient = 0.3, P = .01). The odds of periorbital edema were found to increase with an increase in intraosseous tumor volume with an adjusted odds ratio of 1.4 (95% CI, 1.1-1.7, P = .003), while the odds of visual field defects were found to increase with an increase in intraorbital tumor volume with an adjusted odds ratio of 2.7 (95% CI, 1.3-5.6, P = .01). Postoperatively, the volume of intraosseous tumor resected linearly correlated with the improvement in proptosis (coefficient = 0.7, P < .001), while the volume of intraorbital tumor resected linearly correlated with improvement in VA (coefficient = 0.5, P < .001) and with a larger effect size in patients presenting with moderate-to-severe decrease in VA preoperatively (coefficient = 0.8). CONCLUSION: Underscoring the importance of each tumor compartment relative to the patient's symptomatology serves as a valuable guide in implementing a compartmentalized resection approach tailored to the surgical objectives.

Sellar atypical teratoid/rhabdoid tumor in adults: survival analysis of treatment strategies. Illustrative case.

BACKGROUND: Atypical teratoid/rhabdoid tumor (ATRT) is a rare, highly aggressive central nervous system tumor predominantly found in children. Limited information exists on ATRT in adults, posing challenges in diagnosis and treatment. This study presents the case of an adult patient with ATRT in the sellar region and explores the impact of different treatment regimens on patient survival. OBSERVATIONS: A 60-year-old female with an ATRT underwent resection of the tumor, followed by adjuvant chemoradiotherapy. Molecular genetic analysis revealed compound heterozygous SMARCB1 point mutations. Survival analysis was performed on previously published adult ATRT cases, comparing treatment approaches. The cohort's overall median survival was 6 months, with patients receiving combined chemoradiotherapy showing the longest median survival of 23.5 months. Statistical analysis demonstrated a significant difference in survival between patients treated with surgery alone and those receiving surgery followed by chemoradiotherapy (p < 0.001). However, no significant difference was observed between patients treated with surgery alone and those with postoperative radiotherapy (p = 0.105). LESSONS: Early initiation of adjuvant chemoradiotherapy following surgery improves survival outcomes in adult patients with ATRT. Because of limited data on standardized treatment protocols for adults with ATRT, further research and larger-scale studies are needed to establish effective treatment guidelines for this population.

Therapeutic response to pazopanib: case report and literature review on molecular abnormalities of aggressive prolactinomas.

Introduction: Aggressive prolactinomas (APRLs) pose a significant clinical challenge due to their high rate of regrowth and potentially life-threatening complications. In this study, we present a case of a patient with an APRL who had a trial of multiple therapeutic modalities with the aim to provide a review of molecular abnormalities and management of APRLs by corroborating our experience with previous literature. Methods: A total of 268 articles were reviewed and 46 were included. Case reports and series, and studies that investigated the molecular and/or genetic analysis of APRLs were included. Special care was taken to include studies describing prolactinomas that would fall under the APRL subtype according to the European Society of Endocrinology guidelines; however, the author did not label the tumor as "aggressive" or "atypical". Addiontionally, we present a case report of a 56-year-old man presented with an invasive APRL that was resistant to multiple treatment modalities. Results: Literature review revealed multiple molecular abnormalities of APRLs including mutations in and/or deregulation of ADAMTS6, MMP-9, PITX1, VEGF, POU6F2, CDKN2A, and Rb genes. Mismatch repair genes, downregulation of microRNAs, and hypermethylation of specific genes including RASSF1A, p27, and MGMT were found to be directly associated with the aggressiveness of prolactinomas. APRL receptor analysis showed that low levels of estrogen receptor (ER) and an increase in somatostatin receptors (SSTR5) and epidermal growth factor receptors (EGFR) were associated with increased invasiveness and higher proliferation activity. Our patient had positive immunohistochemistry staining for PD-L1, MSH2, and MSH6, while microarray analysis revealed mutations in the CDKN2A and POU6F2 genes. Despite undergoing two surgical resections, radiotherapy, and taking dopamine agonists, the tumor continued to progress. The patient was administered pazopanib, which resulted in a positive response and the patient remained progression-free for six months. However, subsequent observations revealed tumor progression. The patient was started on PD-L1 inhibitor pembrolizumab, yet the tumor continued to progress. Conclusion: APRLs are complex tumors that require a multidisciplinary management approach. Knowledge of the molecular underpinnings of these tumors is critical for understanding their pathogenesis and identifying potential targets for precision medical therapy.

Symptomatic intracranial tumors in pregnancy: an updated management algorithm. Illustrative case.

BACKGROUND: Intracranial tumors are infrequently encountered during pregnancy, and their diagnosis and management require a multidisciplinary approach to ensure the best possible outcomes for the mother and fetus. The pathophysiology and manifestations of these tumors are influenced by hormonal changes, hemodynamic modifications, and alterations in immunological tolerance that occur during pregnancy. Despite the complexity of this condition, no standardized guidelines exist. This study aims to highlight the key points of this presentation, along with the discussion of a possible management algorithm. OBSERVATIONS: The authors report the case of a 35-year-old woman who presented during the third trimester of pregnancy with severe signs of increased intracranial pressure (ICP) due to a posterior cranial fossa mass. The decision was made to stabilize the patient by placing an external ventricular drain to temporize her increased ICPs until the baby could be safely delivered via cesarean section. The mass was resected via suboccipital craniectomy 1 week postpartum. LESSONS: In considering treatment modalities and their timing in patients presenting with intracranial tumors during pregnancy, each patient should be managed on the basis of an individual treatment algorithm. Symptoms, prognosis, and gestational age should be taken into account to optimize the surgical and perioperative outcomes of both the mother and fetus.

Thermal Analysis of an Ultrasonic Aspirator Micro Claw Tool Compared With Standard High-Speed Drilling During Internal Auditory Canal Opening in a Cadaveric Model.

BACKGROUND: The ultrasonic aspirator micro claw tool (UAmCT) can be used to remove the bone of the internal auditory canal (IAC) during vestibular schwannoma resection via the retrosigmoid approach (RSA) without the risk of a spinning drill shaft. However, the thermal profile of the UAmCT during IAC removal has not been reported. OBJECTIVE: To compare the thermal profile of the UAmCT during access of the IAC to that of a conventional high-speed drill (HSD) and to present an illustrative case of this application. METHODS: IAC opening via RSA was performed in 5 embalmed cadaveric specimens using the UAmCT with 3, 8, and 15 mL/min irrigation on the left and the HSD at 75 000 revolutions per minute and 0%, 14%, and 22% irrigation on the right. Peak bone surface temperatures were measured 4 times in 20-second intervals, and statistical analyses were performed using SPSS software. An illustrative case of a vestibular schwannoma resected via an RSA using the UAmCT to access the IAC is presented. RESULTS: The IAC was opened in all 5 specimens using both the UAmCT and HSD without complication. The mean peak bone surface temperatures were significantly lower with the UAmCT compared with the HSD ( P < .001). The UAmCT did not meaningfully prolong the operating time in the illustrative case, and the IAC was accessed without complication. CONCLUSION: The UAmCT may be a safe and effective alternative to HSD for IAC opening during vestibular schwannoma resection via the RSA. Larger studies under clinical conditions are required to further validate these findings.

Radial Forearm Free Flap with Parapharyngeal Pedicle Corridor for Reconstruction of Anterior Skull Base Defects.

BACKGROUND: The radial forearm free flap (RFFF) is an indispensable tool for the reconstruction of a range of defects, including those of the skull base. Several options for routing of the RFFF pedicle have been described, and the parapharyngeal corridor (PC) has been proposed as an option and employed for a nasopharyngeal defect. However, there are no reports of its use for the reconstruction of anterior skull base defects. The objective of this study is to describe the technique for free tissue reconstruction of anterior skull base defects using the RFFF and routing of the pedicle via the PC. METHODS: Relevant neurovascular landmarks and critical surgical steps for reconstruction of anterior skull base defects with an RFFF and routing of the pedicle via the PC are reported using an illustrative clinical case and cadaveric dissections. RESULTS: We present a case of a 70-year-old man who underwent endoscopic transcribriform resection of cT4N0 sinonasal squamous cell carcinoma and was left with a large anterior skull base defect that persisted despite several repair attempts. An RFFF was utilized to repair the defect. This report is the first description of the clinical use of the PC for free tissue repair of an anterior skull base defect. CONCLUSIONS: The PC is an option for routing the pedicle during the reconstruction of anterior skull base defects. When the corridor is prepared as described in this case, a direct route exists from the anterior skull base to cervical vessels, simultaneously maximizing the reach of the pedicle and minimizing the risk of kinking.

Surgical management of spontaneous middle cranial fossa defects: a systematic review and meta-analysis of available reconstructive techniques and materials.

Different materials and techniques have been proposed for surgical repair of spontaneous middle cranial fossa (MCF) defects. However, conclusive evidence supporting their selection and impact on clinical outcomes is lacking. The study aims to conduct a systematic review and meta-analysis on materials and techniques employed to repair MCF defects and evaluate complications and rates of recurrent cerebrospinal fluid (CSF) leaks. A PRISMA-guided systematic review and meta-analysis were performed using MESH terms and specific keywords including studies published before May 2022. Primary outcomes included recurrence of CSF leak and complication rates by type of reconstructive material and technique utilized. Meta-analyses of proportions were performed using random effects and confidence intervals for individual proportions were calculated using the Clopper-Pearson method. Twenty-nine studies were included (n = 471 cases). Materials employed for repair were categorized according to defect size: 65% of defects were of unknown size, 24% were small (< 1 cm), and 11% were large (≥ 1 cm). Rigid reconstruction (RR) was significantly favored over soft reconstruction (SR) for larger defects (94% of cases, p < 0.05). Complications and recurrent CSF leak rates of SR and RR techniques were comparable for defects of all sizes (p > 0.05). Complication rates reported for these procedures are low regardless of technique and material. RR was universally preferred for larger defects and analysis of complication and recurrence rates did not reveal differences regardless of defect size. While RR was more frequently reported in smaller defects, SR was used by several centers, particularly for smaller MCF floor defects.

Contralateral Transmaxillary Approach to Petrous Apex Granuloma with Lateral Maxillotomy: 2-Dimensional Operative Video.

The endoscopic endonasal approach (EEA) has proven to be a valuable tool to access the petrous apex (PA).1 Although lesions located medial to the PA can be easily accessed through an EEA with minimal risk to the internal carotid artery (ICA), more laterally seated lesions represent a surgical challenge. The contralateral transmaxillary approach is an effective extension of the normal EEA to the PA, allowing a more lateral trajectory and thereby reducing the risks connected to paraclival ICA manipulation.2-4 This is a 47-year-old female presenting with tinnitus, hearing loss, and right facial twitching. The preoperative audiogram showed a 60 dB sensorineural hearing loss, and magnetic resonance imaging demonstrated an expansive lesion of the PA with high signal intensity in T1- and T2-weighted sequences. A high-riding jugular bulb ruled out the use of an infracochlear infralabyrinthine approach, and a middle cranial fossa approach was felt to render a high risk of recurrence due to the potential for incomplete resection. Ultimately, a contralateral transmaxillary approach was selected. Due to the extreme lateral position of the lesion, the maxillotomy was created in the lateral wall of the maxillary sinus to allow a coaxial approach to the PA. Postoperatively, the patient did not report new neurologic deficits. Anatomic pathology was consistent with cholesterol granuloma (Video 1). In the surgical management of PA granulomas, recognizing relevant anatomic structures such as the paraclival ICA, cochlea, jugular bulb, and vestibule preoperatively is of paramount importance to tailor the surgical approach and reduce its risks.

A Cost-Effective and Reproducible Cadaveric Training Model for Internal Carotid Artery Injury Management During Endoscopic Endonasal Surgery: The Submersible Peristaltic Pump.

BACKGROUND: Internal carotid artery injury (ICAI) represents one of the most challenging complications in endoscopic endonasal neurosurgery and its rarity results in limited opportunities for trainees and surgeons to achieve proficiency in its management. Currently, available models for ICAI have employed costly systems that prevent their widespread use. The objective of this study is to validate an affordable submersible peristaltic pump (SPP)-based model as a reproducible and realistic paradigm for ICAI management training. METHODS: A laceration of the left parasellar internal carotid artery was purposely carried out in 2 human cadaveric heads. A blood substitute was perfused to ensure a perfusion flow of 1 L/min using an affordable SPP. A cohort of 20 neurosurgery and otolaryngology residents, fellows, and attendings were enrolled to evaluate the realism and content validity of the model using a validated 5-grade questionnaire. RESULTS: The model proved to mimic a real intraoperative scenario of ICAI with an expected output flow of 1 L/min. Questionnaire responses reported a realistic experience and the impact of this model on improving trainee surgical coordination and capability to rehearse the most accepted repair technique. The use of a fixed noninjected head allowed the reproducibility of the training session without the additional cost of new fresh-frozen heads. The affordable SPP allowed an impactful reduction of ICAI model training expenses maintaining high realism. CONCLUSIONS: The SPP-based ICAI model with noninjected cadaveric specimens is an affordable and cost-effective system that allows reproducibility and realism. These qualities favor greater adoption in neurosurgery and otolaryngology training curricula.

Exoscope-Assisted Middle Cranial Fossa Approach for Repair of Tegmental Defects: A Cadaveric and Clinical Study.

BACKGROUND: Recent studies highlighted how exoscopes may be employed to approach the lateral skull base. The use of exoscope-assisted procedures to repair middle cranial fossa (MCF) defects has not been fully explored. The surgical microscope in the same circumstances has been associated with relevant limitations, such as its physical obstruction, among others. The aim of this study was to present a proof of concept of exoscope-assisted surgery for MCF defects. METHODS: A detailed step-by-step MCF approach was performed on 2 alcohol-preserved, latex-injected cadaveric specimens under exoscopic magnification. An illustrative clinical case of encephalocele secondary to a spontaneous tegmen tympani defect repaired via an exoscope-assisted MCF approach was presented. RESULTS: The most common sites of MCF defects, the tegmen tympani and the arcuate eminence, were successfully exposed under exoscopic magnification. Dissection was easily performed; no damage to the dura mater or to vascular or neural structures occurred. In the clinical case, the exoscope-assisted technique demonstrated adequate maneuverability and magnification quality. After localization, the encephalocele was resected, and the MCF defect was repaired. The surgeon's position was comfortable, and operative time was not prolonged. CONCLUSIONS: The exoscope allows adequate exposure of the MCF floor with identification and preservation of key anatomical structures. The exoscope represents a valuable alternative to the microscope in reconstruction of MCF defects, offering high-quality magnification and proven maneuverability.

EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation.

The epidermal growth factor receptor (EGFR) is a prime oncogene that is frequently amplified in glioblastomas. Here we demonstrate a new tumour-suppressive function of EGFR in EGFR-amplified glioblastomas regulated by EGFR ligands. Constitutive EGFR signalling promotes invasion via activation of a TAB1-TAK1-NF-κB-EMP1 pathway, resulting in large tumours and decreased survival in orthotopic models. Ligand-activated EGFR promotes proliferation and surprisingly suppresses invasion by upregulating BIN3, which inhibits a DOCK7-regulated Rho GTPase pathway, resulting in small hyperproliferating non-invasive tumours and improved survival. Data from The Cancer Genome Atlas reveal that in EGFR-amplified glioblastomas, a low level of EGFR ligands confers a worse prognosis, whereas a high level of EGFR ligands confers an improved prognosis. Thus, increased EGFR ligand levels shift the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastomas by suppressing invasion. The tumour-suppressive function of EGFR can be activated therapeutically using tofacitinib, which suppresses invasion by increasing EGFR ligand levels and upregulating BIN3.