Unraveling molecular advancements in chordoma tumorigenesis and treatment response: a review of scientific discoveries and clinical implications.

Chordomas are tumors thought to originate from notochordal remnants that occur in midline structures from the cloves of the skull base to the sacrum. In adults, the most common location is the sacrum, followed by the clivus and then mobile spine, while in children a clival origin is most common. Most chordomas are slow growing. Clinical presentation of chordomas tend to occur late, with local invasion and large size often complicating surgical intervention. Radiation therapy with protons has been proven to be an effective adjuvant therapy. Unfortunately, few adjuvant systemic treatments have demonstrated significant effectiveness, and chordomas tend to recur despite intensive multimodal care. However, insight into the molecular underpinnings of chordomas may guide novel therapeutic approaches including selection for immune and molecular therapies, individualized prognostication of outcomes, and real-time noninvasive assessment of disease burden and evolution. At the genomic level, elevated levels of brachyury stemming from duplications and mutations resulting in altered transcriptional regulation may introduce druggable targets for new surgical adjuncts. Transcriptome and epigenome profiling have revealed promoter- and enhancer-dependent mechanisms of protein regulation, which may influence therapeutic response and long-term disease history. Continued scientific and clinical advancements may offer further opportunities for treatment of chordomas. Single-cell transcriptome profiling has further provided insight into the heterogeneous molecular pathways contributing to chordoma propagation. New technologies such as spatial transcriptomics and emerging biochemical analytes such as cell-free DNA have further augmented the surgeon-clinician's armamentarium by facilitating detailed characterization of intra- and intertumoral biology while also demonstrating promise for point-of-care tumor quantitation and assessment. Recent and ongoing clinical trials highlight accelerating interest to translate laboratory breakthroughs in chordoma biology and immunology into clinical care. In this review, the authors dissect the landmark studies exploring the molecular pathogenesis of chordoma. Incorporating this into an outline of ongoing clinical trials and discussion of emerging technologies, the authors aimed to summarize recent advancements in understanding chordoma pathogenesis and how neurosurgical care of chordomas may be augmented by improvements in adjunctive treatments.

The role of systemic therapy in advanced skull base chordomas: overview of the current state and the MD Anderson protocol.

The role of systemic therapy in primary or advanced and metastatic chordoma has been traditionally limited because of the inherent resistance to cytotoxic therapies and lack of specific or effective therapeutic targets. Despite resection and adjuvant radiation therapy, local recurrence rates in clival chordoma remain high and the risk of systemic metastases is not trivial, leading to significant morbidity and mortality. Recently, molecular targeted therapies (MTTs) and immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic avenues in chordoma. In recent years, preclinical studies have identified potential targets based on intrinsic genetic dependencies, epigenetic modulators, or newly identified tumor-associated cell populations driving treatment resistance and recurrence. Nonetheless, the role of systemic therapies in the neoadjuvant or adjuvant setting for primary, locally progressive, and distant metastatic chordomas is still being investigated. Herein, an overview of current and emerging systemic treatment strategies in advanced clival chordoma is provided. Furthermore, several molecular biomarkers have been recently uncovered as potential predictors of the response to specific molecular therapeutics. The authors describe the recently discovered role of 1p36 and 9p21 deletions as biomarkers capable of guiding drug selection. Then they discuss completed and ongoing clinical trials of MTTs, including several tyrosine kinase inhibitors used as monotherapy or in combination, such as imatinib, sorafenib, dasatinib, and lapatinib, among others, as well as mammalian target of rapamycin inhibitors such as everolimus and rapamycin. They present their experience and other recent studies demonstrating vast benefits in advanced chordoma from ICIs. Additionally, they provide a brief overview of novel systemic strategies such as adoptive cell transfer (CAR-T and NK cells), oncolytic viruses, epigenetic targeting (KDM6, HDAC, and EZH2 inhibitors), and several promising preclinical studies with high translational potential. Finally, the authors present their institutional multidisciplinary protocol for the incorporation of systemic therapy for both newly diagnosed and recurrent chordomas based on molecular studies including upfront enrollment in MTT trials in patients with epidermal growth factor receptor upregulation or INI-1 deficiency or enrollment in ICI clinical trials for patients with high tumor mutational burden or high PD-L1 expression on tumor cells or in the tumor microenvironment.

Synchronous skull base and spinal metastases in a patient with treatment-resistant, high-grade serous adenocarcinoma of tubo-ovarian origin.

Brain metastases (BMs) arising from ovarian cancer remain rare. Spinal cord metastases are even rarer, accounting for just 0.4% of total metastatic spinal cord compressions. In this report, we describe a case of a woman in her 70s who developed sequential brain and spinal cord metastases during her treatment for high-grade serous ovarian cancer, without a germline or somatic BRCA mutation. Following completion of neoadjuvant chemotherapy, interval debulking surgery and adjuvant chemotherapy, relapsed disease was ultimately identified as a single BM, curiously mimicking an acoustic neuroma. Subsequently, spinal cord metastases rapidly developed. Throughout, multidisciplinary team meetings guided decisions on patient management. In this report, we highlight the rarity of such a presentation and discuss the possible role of disease pathophysiology, associated systemic anticancer therapy resistance, and treatment possibilities for both cerebral and spinal metastases.

Tumor Embolization via the Meningohypophyseal and Inferolateral Trunk in Patients with Skull Base Tumors Using the Distal Balloon Protection Technique.

BACKGROUND AND PURPOSE: Tumor embolization through the meningohypophyseal trunk and inferolateral trunk is known to be effective in skull base tumors; however, microcatheter cannulation into these arteries is difficult, and the number of cases that can be safely embolized is limited. In this study, we present a novel embolization procedure for the meningohypophyseal trunk and inferolateral trunk using the distal balloon protection technique and detail its clinical efficacy and complication risks. We developed this procedure to allow safe embolization in patients who cannot be adequately cannulated with microcatheters into these arteries. MATERIALS AND METHODS: Patients who underwent meningohypophyseal trunk or inferolateral trunk embolization using the distal balloon protection technique for skull base tumors at our institution between 2010 and 2023 were included. In this procedure, the ICA was temporarily occluded with a balloon at the ophthalmic artery bifurcation, the microcatheter was guided to the meningohypophyseal trunk or inferolateral trunk vicinity, and embolic particles were injected into the arteries. The balloon was deflated after the embolic particles that had refluxed into the ICA were aspirated. RESULTS: A total of 25 meningohypophyseal trunks and inferolateral trunks were embolized during 21 operations. Of these 25 arteries, only 9 (36.0%) were successfully cannulated with microcatheters. Nevertheless, effective embolization was achieved in all cases. Permanent complications occurred in only 1 case (4.8%) in which the central retinal artery was occluded during inferolateral trunk embolization, resulting in a visual field defect. No permanent complications resulting from the embolic cerebral infarction were observed. Of 16 cases that underwent MR imaging within a week after embolization, however, 11 (68.8%) demonstrated embolic cerebral infarctions. CONCLUSIONS: In patients with skull base tumors with meningohypophyseal trunk or inferolateral trunk feeders that cannot be catheterized directly, embolization using the distal balloon protection technique for tumor supply can be considered as a salvage technique.

Skull Base Tumors.

OBJECTIVE: This article reviews the presenting features, molecular characteristics, diagnosis, and management of selected skull base tumors, including meningiomas, vestibular schwannomas, pituitary neuroendocrine tumors, craniopharyngiomas, chordomas, ecchordosis physaliphora, chondrosarcomas, esthesioneuroblastomas, and paragangliomas. LATEST DEVELOPMENTS: Skull base tumors pose a management challenge given their complex location and, as a result, the tumors and treatment can result in significant morbidity. In most cases, surgery, radiation therapy, or both yield high rates of disease control, but the use of these therapies may be limited by the surgical accessibility of these tumors and their proximity to critical structures. The World Health Organization classification of pituitary neuroendocrine tumors was updated in 2022. Scientific advances have led to an enhanced understanding of the genetic drivers of many types of skull base tumors and have revealed several potentially targetable genetic alterations. This information is being leveraged in the design of ongoing clinical trials, with the hope of rendering these challenging tumors treatable through less invasive and morbid measures. ESSENTIAL POINTS: Tumors involving the skull base are heterogeneous and may arise from bony structures, cranial nerves, the meninges, the sinonasal tract, the pituitary gland, or embryonic tissues. Treatment often requires a multidisciplinary approach, with participation from radiation oncologists, medical oncologists, neuro-oncologists, and surgical specialists, including neurosurgeons, otolaryngologists, and head and neck surgeons. Treatment has largely centered around surgical resection, when feasible, and the use of first-line or salvage radiation therapy, with chemotherapy, targeted therapy, or both considered in selected settings. Our growing understanding of the molecular drivers of these diseases may facilitate future expansion of pharmacologic options to treat skull base tumors.

Tumor Embolization through Meningohypophyseal and Inferolateral Trunks is Safe and Effective.

BACKGROUND AND PURPOSE: Skull base tumors are commonly supplied by dural branches of the meningohypophyseal and inferolateral trunks. Embolization through these arteries is often avoided due to technical challenges and inherent risks; however, successful embolization can be a valuable surgical adjunct. We aimed to review the success and complications in our series of tumor embolizations through the meningohypophyseal and inferolateral trunks. MATERIALS AND METHODS: We performed a retrospective review of patients with tumor treated with preoperative embolization at our institution between 2010 and 2020. We reviewed the following data: patients' demographics, tumor characteristics, endovascular embolization variables, and surgical results including estimated blood loss, the need for transfusion, and operative time. RESULTS: Among 155 tumor embolization cases, we identified 14 patients in whom tumor embolization was performed using the meningohypophyseal (n = 13) or inferolateral (n = 4) trunk. In this group of patients, on average, 79% of tumors were embolized. No mortality or morbidity from the embolization procedure was observed in this subgroup of patients. The average estimated blood loss in the operation was 395 mL (range, 200-750 mL). None of the patients required a transfusion, and the average operative time was 7.3 hours. CONCLUSIONS: Some skull base tumors necessitate embolization through ICA branches such as the meningohypophyseal and inferolateral trunks. Our series demonstrates that an effective and safe embolization may be performed through these routes.

Embolization of Skull Base Meningiomas with Embosphere Microspheres: Factors Predicting Treatment Response and Evaluation of Complications.

OBJECTIVE: Preoperative embolization for intracranial meningiomas can cause tumor necrosis, reduce intraoperative blood loss, and facilitate surgery. This study aimed to evaluate the efficacy of tumor embolization using Embosphere microspheres for skull base meningiomas and analyze postembolization plain computed tomography (CT) and magnetic resonance imaging (MRI) scans to identify findings that could potentially predict treatment response. METHODS: Between April 2014 and April 2020, 80 patients with skull base meningiomas presenting at our medical center underwent embolization with Embosphere microspheres. The effects of tumor embolization were evaluated through a comparison of postembolization plain CT and contrast-enhanced MRI. RESULTS: A total of 143 vessels (102 of 108 external carotid artery branches and 41 of 65 internal carotid artery branches) from 80 skull base meningiomas were embolized with Embosphere microspheres. Microspheres 100-300 µm in size were used in 2 cases, microspheres 300-500 µm in size were used in 12 cases, and microspheres 500-700 µm in size were used in 66 cases. Postembolization contrast-enhanced MRI showed reductions in enhancing lesions within the tumor in 55 of 80 cases. Postembolization plain CT scans showed high-density lesions within the tumor in 41 of 55 cases. Thus, reductions in enhancing lesions on postembolization contrast-enhanced MRI were statistically significantly associated with the presence of high-density lesions on postembolization plain CT (P < 0.001). Embolization-related neurological complications occurred in 3 cases. CONCLUSIONS: Embosphere microspheres are user friendly and effective embolic materials for the embolization of skull base meningiomas. Postembolization contrast-enhanced MRI and plain CT findings may be useful for evaluating the effects of tumor embolization.

Benign bony tumors of the paranasal sinuses, orbit, and skull base.

Benign bony tumors of the skull base and paranasal sinuses are uncommon entities, with an overall higher incidence in males. Benign bony tumors may lead to local expansion with resultant mass effect of potentially critical structures. Some benign bony tumors may undergo malignant transformation. This article reviews the presentation and management of benign bone tumors of the skull base and paranasal sinuses with special consideration to involvement of the adjacent orbit, intracranial and critical neurovascular structures. This review covers tumor incidence, location, gross and histologic appearance as well as radiographic findings, treatment, and recurrence rates. Tumors discussed in this article include osteochondromas, osteomas, osteoid osteomas, aneurysmal bone cysts, fibrous dysplasia, giant cell tumors, cemento-ossifying fibroma, ameloblastic fibro-odontoma, ecchordosis physaliphora, chondromyxoid fibroma, primary chronic osteomyelitis, primary chronic osteomyelitis, osteochondromyxoma, and dense bone islands.

[Skull base metastases with cranial nerve deficits : Clinical profile of a severe disease]. / Schädelbasismetastasen mit Hirnnervenaffektionen : Klinischer Steckbrief einer schwerwiegenden Erkrankung.

BACKGROUND AND PURPOSE: Skull base metastases are a severe complication of various malignant tumors. If cranial nerves are involved even small lesions can cause significant symptoms. Specific clinical characteristics like neurological symptoms, associated primary tumors, prognosis and optimal treatment are poorly defined and are systematically described in this article. METHODS: In a monocentric retrospective study patients with skull base metastases and cranial nerve deficits who received treatment between 2006 and 2018 were analyzed concerning clinical characteristics at initial diagnosis, treatment and course of the disease. RESULTS: In this study 45 patients with skull base metastases and cranial nerve deficits were included. The most frequent primary tumors were prostate cancer (27%), breast cancer (22%) and multiple myeloma (16%). The most involved cranial nerves were trigeminal nerve (42%), oculomomotor nerve (33%) and facial nerve (27%). Of the patients 84% had additional bone metastases outside the skull base. Dural infiltration or meningeal carcinomatosis were each observed in 13% of the patients. After radiotherapy cranial nerve deficits remained stable in 61% of all cases and in 22% symptoms improved. Median overall survival from treatment was 8 months (range 0.4-51 months). Patients with dose-escalated radiotherapy appeared to live longer (16.4 months vs. 4.7 months). This effect persisted in a multivariate analysis including the Karnofsky index, number of metastases, primary tumor and radiation dose (HR 0.37, p = 0.02). CONCLUSION: Skull base metastases with cranial nerve deficits are complex diseases with poor prognosis. Precise diagnosis and treatment are required. Further research is needed to improve treatment.

Skull Base Tumors: Neuropathology and Clinical Implications.

Tumors that arise in and around the skull base comprise a wide range of common and rare entities. Recent studies have advanced our understanding of their pathogenesis, which in some cases, have significantly influenced clinical practice. The genotype of meningiomas is strongly associated with their phenotype, including histologic subtype and tumor location, and clinical outcome. A single molecular alteration, NAB2-STAT6 fusion, has redefined the category of solitary fibrous tumors to include the previous entity hemangiopericytomas. Schwannomas, both sporadic and familial, are characterized by near ubiquitous alterations in NF2 , with additional mutations in SMARCB1 or LZTR1 in schwannomatosis. In pituitary adenohypophyseal tumors, cell lineage transcription factors such as SF-1, T-PIT, and PIT-1 are now essential for classification, providing a more rigorous taxonomy for tumors that were previously considered null cell adenomas. The pituicyte lineage transcription factor TTF-1 defines neurohypophyseal tumors, which may represent a single nosological entity with a spectrum of morphologic manifestations (ie, granular cell tumor, pituicytoma, and spindle cell oncocytoma). Likewise, the notochord cell lineage transcription factor brachyury defines chordoma, discriminating them from chondrosarcomas. The identification of nonoverlapping genetic drivers of adamantinomatous craniopharyngiomas and papillary craniopharyngiomas indicates that these are distinct tumor entities and has led to successful targeted treatment of papillary craniopharyngiomas using BRAF and/or mitogen-activated protein kinase inhibitors. Similarly, dramatic therapeutic responses have been achieved in patients with Langerhans cell histiocytosis, both with BRAF -mutant and BRAF -wildtype tumors. Familiarity with the pathology of skull base tumors, their natural history, and molecular features is essential for optimizing patient care.

Determinants of Survival in Skull Base Osteosarcoma: A National Cancer Database Study.

OBJECTIVE: Skull base osteosarcoma is a rare and aggressive tumor that is most commonly treated with primary surgical resection and adjuvant chemoradiation. Using the National Cancer Database, we analyzed demographic and clinical prognosticators for overall survival (OS). METHODS: The National Cancer Database was queried for cases of histologically confirmed skull base osteosarcoma treated between 2004 and 2015, excluding patients receiving palliation or having <1 month of follow-up. A total of 314 patients treated with surgery alone (n = 82), surgery with adjuvant radiotherapy (n = 35), surgery with chemotherapy (n = 114), or trimodality therapy (n = 56) were identified. The χ2 test for categorical variables, Cox proportional hazards models, and Kaplan-Meier log-rank analysis were used to test associations with treatment, OS, and survival time. RESULTS: None of the studied demographic characteristics (age, sex, race, overall health) and socioeconomic factors (income and average regional education) were associated with OS (none P < 0.05). Treatment modalities also did not show a significant association with OS (none P < 0.05). Certain tumor characteristics showed an association with OS, with fibroblastic and Paget histologic subtypes (each P = 0.003), poorly differentiated tumor grade (P = 0.03), and tumor size >5 cm (P = 0.045) associated with poorer OS. CONCLUSIONS: Tumor histologic subtype, advanced tumor grade, and greater tumor size are predictors of worse OS in skull base osteosarcoma. No significant differences in OS were identified based on treatment modality, which warrants further investigation.

Midfacial Degloving Technique for Free Flap Reconstruction of Nasal and Anterior Skull Base Defects.

SUMMARY: Traditionally, surgical access for extirpation and reconstruction of midfacial tumors requires external incisions that can cause a myriad of complications, especially in irradiated patients. The modern midfacial degloving approach involves hidden, sublabial and intranasal incisions that provide reliable access for free flap reconstruction of nasal and maxillofacial tumors. Seven patients with a history of radiation therapy underwent free flap reconstruction of the midface. Five patients underwent the technique in a delayed manner, and the remaining two underwent reconstruction immediately at the time of resection. Five patients underwent free radial forearm fasciocutaneous free flaps and two underwent reconstruction with anterolateral thigh perforator flaps. Bone and/or rib cartilage grafting was used in all patients. All patients underwent successful free flap reconstruction of the midface without external incisions. The most common complication was postoperative infection requiring oral or intravenous antibiotics. No patients sustained loss of their grafts or hardware in the postoperative period. The midfacial degloving technique provides satisfactory exposure to the nasal cavity, midface, orbits, and skull base for free flap reconstruction, without disrupting the external soft tissue. The authors describe a novel use of the midfacial degloving technique to provide safe and reliable results with improved cosmetic outcome.

Outcomes and Patterns of Care in Adult Skull Base Chondrosarcoma Patients in the United States.

BACKGROUND: Chondrosarcomas of the skull base are rare intracranial tumors of chondroid origin. The rarity of these lesions has made it difficult to form a consensus on optimal treatment regimens. The aim of this study was to provide a comprehensive analysis of prognostic factors, treatment modalities, and survival outcomes in patients with chondrosarcoma of the skull base. METHODS: Patients with diagnosis codes for chondrosarcoma of the skull base were queried from the National Cancer Database for the years 2004-2016. Outcomes were investigated using Cox univariate and multivariate regression analyses, and survival curves were generated for comparative visualization. RESULTS: A total of 718 patients with chondrosarcoma of the skull base were identified. Mean overall survival (OS) in these patients was 10.7 years. Older age and presence of metastases were associated with worsened OS. Of patients, 83.3% received surgical intervention, and both partial resection and radical resection were associated with significantly improved OS (P < 0.001). Neither radiotherapy nor chemotherapy improved OS; however, patients who received proton-based radiation and patients who received high-dose radiation (≥6000 cGy) had significantly improved OS compared with patients who received traditional radiation. CONCLUSIONS: In the largest study to our knowledge of skull base chondrosarcoma to date, both partial resection and radical resection significantly improved OS, thus supporting the goal of maximal safe resection to preserve vital neurovascular structures without sacrificing outcome. In patients who received radiotherapy, proton-based modalities and high-dose radiation were associated with increased OS.

The role of a virtual telephone clinic in the follow-up management of lateral skull base tumours.

OBJECTIVE: The purpose of this article was to determine the impact of employing a telephone clinic for follow-up of patients with stable lateral skull-base tumours. METHOD: An analysis of 1515 patients in the national lateral skull-base service was performed, and 148 patients enrolled in the telephone clinic to date were identified. The length of time that patients waited for results of their follow-up scans and the travel distance saved by patients not having to attend the hospital for their results was determined. RESULTS: The mean time from scan to receiving results was 30.5 ± 32 days, 14 days sooner than in the face-to-face group (p = 0.0016). The average round-trip distance travelled by patients to the hospital for results of their scans was 256 ± 131 km. CONCLUSION: The telephone clinic led to a significant reduction in time until patients received their scan results and helped reduce travel distance and clinic numbers in traditional face-to-face clinics.

Clival chordoma in a young male patient: a case report.

Chordoma is a rare malignant tumor of the spine. We report the case of a 26-year-old man who presented with facial paralysis and upper limbs paresthesia. Cerebral CT-scan and cerebro-spinal MRI revealed a 58mm locally advanced middle clival mass with deviation of median cerebral structures. Endoscopic biopsy concluded to a chondroid chordoma. Skeletal survey and thoraco-abdomino-pelvic CT-scan were normal. Treatment consisted in complete surgical removal of the tumor followed by adjuvant radiotherapy. The patient is alive free of disease with a follow up of 12 months.

Management of Skull Base Metastases.

Autopsy studies suggest that skull base metastases are likely underrecognized in patients with cancer. Patients frequently present with one or a combination of skull base clinical syndromes that manifest as pain or cranial neuropathy. Once a skull base metastasis is suspected, establishing a histologic diagnosis, dedicated imaging, and restaging (if appropriate) are the first steps in management. A multidisciplinary approach should then be used to identify the optimal histology-based treatment strategy, taking into account the burden of systemic disease. Finally, definitive treatment may include one or a combination of surgical management, radiation therapy, or chemotherapy."

A narrative review of targeted therapy in meningioma, pituitary adenoma, and craniopharyngioma of the skull base.

Management of solid tumors involving the skull base are primarily managed with surgery and radiation, though proximity to important vascular and neuroanatomic structures often limit the extent of resection and permissible radiation dose. Meningiomas are the most common primary brain tumor in adults, and although the majority of skull base meningiomas are low-grade, their location in proximity to critical anatomical structures precludes aggressive surgical resection, and larger tumors are often resistant to radiation treatment. In patients with clinically aggressive, unresectable meningiomas, several molecular biomarkers of angiogenesis, as well as genetic mutations (SMO, AKT1, PIK3CA, KLF4, POLR2, SMARCE1, and TRAF7), have been shown to play a crucial role in the pathophysiology of these tumors. Pituitary adenomas are commonly slow growing tumors that are amenable to surgical resection, but tumors with higher Ki67 proliferative indices are associated with an increased risk of relapse and resistance to standard therapies. Chemotherapeutic agents and checkpoint inhibitors have been trialed, albeit with limited success, to treat these aggressive pituitary adenomas. Craniopharyngiomas are categorized as adamantinomatous and papillary subtypes, each with unique molecular mechanisms that drive pathogenesis of these tumors, and have introduced the possibility that targeted therapies may be developed for improved neurologic and endocrinological outcomes. Skull base tumors that exhibit recurrence despite surgical resection and radiation treatment pose a unique challenge, and systemic agents offer a non-invasive option of treating tumors that are refractory to conventional approaches. Recent insights into the molecular aberrations that elucidate the pathophysiology of these difficult-to-treat tumors have provided potential therapeutic targets for drug delivery. In this review, the authors discuss promising therapies and current knowledge gaps needed for the development of effective targeted agents for meningioma, pituitary adenoma, and craniopharyngioma.

Clivus Chordoma: Case Report and Current Considerations on Treatment Strategies.

Chordomas are the rare malignant bone lesions derived from the embryonic notochord. They are slow-growing tumors with a locally aggressive behavior. The clival chordomas are extradural, exophytic, and lytic lesions centered on the clivus, and are managed differently from those arising elsewhere because of the emphasis on preserving the neurological function. The gold standard for therapy is the complete resection followed by radiation therapy for a better local control of the tumor. This case report concerns a 20-year old girl with an incidental diagnosis of the clival chordoma, which was first treated via an endoscopic anterior approach to remove the exophytic portion of the tumor. The adjuvant radiation therapy was not feasible because of the macroscopic intradural residual tumor being at the level of jugular foramen. The girl was referred to our institute for the removal of the intradural residual tumor via a petro-occipital trans-sigmoid (POTS) approach followed by adjuvant proton beam therapy. The choice of the surgical approach depends on the size of the tumor, its location, and its anatomical distribution, but should also be balanced against the morbidity, considering the patient's age, and the feasibility of postoperative rehabilitation.

Endoscopic Endonasal Approaches for Anterior Skull Base Meningiomas.

Anterior skull base meningiomas are a diverse group of tumors that involve different locations. The role of the expanded endoscopic transnasal approach in the management of anterior cranial fossa meningiomas has significantly changed over the past 2 decades. Patient selection is paramount to benefit from the advantages of endoscopic transnasal surgery such as direct access to ventral skull base lesions avoiding brain and brainstem retraction, early de-vascularization, removal of bone infiltrated by tumor, near-field magnification, better surgical field illumination, and minimal manipulation of neurovascular structures. Here we discuss some of the main limitations and advantages of the endoscopic transnasal approach related to patient selection, including nuances of their management, discussing preoperative imaging and planning, the surgical approach, and future perspectives in the treatment of these tumors.