The applicability of established clinical and histopathological risk factors for tumor recurrence during long-term postoperative care in meningioma patients

Risk factors to predict late-onset tumor recurrence in meningioma patients are urgently needed to schedule control intervals during long-term follow-up. We therefore analyzed the value of established risk factors for postoperative meningioma recurrence for the prediction of long-term prognosis. Correlations of clinical and histopathological variables with tumor relapse after 3, 5, and 10 years following microsurgery were analyzed in uni- and multivariate analyses, and compared to findings in the entire cohort. In the entire cohort (N = 1218), skull base location (HR: 1.51, 95%CI 1.05–2.16; p = .026), Simpson ≥ IV resections (HR: 2.41, 95%CI 1.52–3.84; p < .001), high-grade histology (HR: 3.70, 95%CI 2.50–5.47; p < .001), and male gender (HR: 1.46, 95%CI 1.01–2.11; p = .042) were independent risk factors for recurrence. Skull base location (HR: 1.92, 95%CI 1.17–3.17; p = .010 and HR: 2.02, 95%CI 1.04–3.95; p = .038) and high-grade histology (HR: 1.87, 95%CI 1.04–3.38; p = .038 and HR: 2.29, 95%CI 1.07–4.01; p = .034) but not subtotal resection (HR: 1.53, 95%CI .68–3.45; p = .303 and HR: 1.75, 95%CI .52–5.96; p = .369) remained correlated with recurrence after a recurrence-free follow-up of ≥ 3 and ≥ 5 years, respectively. Postoperative tumor volume was related with recurrence in general (p < .001) but not beyond a follow-up of ≥ 3 years (p > .05). In 147 patients with a follow-up of ≥ 10 years, ten recurrences occurred and were not correlated with any of the analyzed variables. Skull base tumor location and high-grade histology but not the extent of resection should be considered when scheduling the long-term follow-up after meningioma surgery. Recurrences ≥ 10 years after surgery are rare, and predictors are lacking.

DDRE-43. SCREENING OF FDA-APPROVED COMPOUNDS FOR THE TREATMENT OF CHORDOMA, WITH IN VIVO VALIDATION USING THREE DIFFERENT XENOGRAFT MODELS, IDENTIFIES BRIGATINIB AS A POTENTIAL TREATMENT

BACKGROUND Chordoma is a rare malignant tumor with poor surgical control and no existing pharmacotherapies. Therefore, these tumors require additional research into novel therapeutics for their treatment. METHODS In this study we created a high-throughput drug screen and culture system to evaluate the efficacy of existing FDA-approved compounds in 10 chordoma cell lines and primary tumors. The cell lines were graciously donated by the Chordoma Foundation. Primary tumors were collected from our operating room. In vivo validation using three separate chordoma xenograft models was also performed through the Chordoma Foundation. One model was a primary clival pediatric tumor, the second was a metastatic sacral tumor, and the third model was a recurrent skull base tumor. RESULTS Using a 127 FDA-approved compound library, we screened 6 donated chordoma cell lines and 4 tumors resected from our institution. 5 of the chordomas were primary, 3 were recurrent, and 2 were metastatic. 6 chordoma were located in the sacrum, three were located in the mobile spine, and one was located in the clivus. Five tumors came from female patients and five came from male patients. After a single 72-hour 1um dose of brigatinib, the average tumor viability in our drug screen was reduced to 81.5% +/-9.5SD (p=1.61x10-13). In the in vivo studies, brigatinib achieved a full response in the metastatic sacral chordoma xenograft model (TGI=100%, p&lt; 0.0001), a partial response in the recurrent skull base xenograft model (TGI=54%, p=0.3048), and no response in the primary clival pediatric xenograft model (TGI = 0%, p &gt;0.9). CONCLUSIONS Brigatinib may be a viable treatment option for recurrent and metastatic chordomas.

3D Printing-Assisted Skull Base Tumor Surgeries: An Institutional Experience

Three-dimensional (3D) printing technology in neurosurgery has gained popularity nowadays. Skull base contains many major neurovascular structures in a confined space, along with anatomical variations making surgical approaches to this region challenging. 3D-printed model of skull base tumors consists of the patient's bony skull base, actual tumor dimensions, and surrounding major neurovascular structures. We included a total number of five patients with skull base tumors (one case of planum sphenoidale meningioma, two cases of sellar tumor with suprasellar extension, and two cases of cerebellopontine angle tumor) and 3D-printed tumor model of each of them. These models were used for preoperative simulation and served as very true to life training tool. These help in increasing the efficacy of the surgeon, improves surgical safety and ergonomics. They were also used for patient counselling, educating about the disease, the surgical procedure, and associated risks.

Oscillopsia following orbitotomy for intracranial tumor resection

Background: Oscillopsia is a visual phenomenon in which an individual perceives that their environment is moving when it is in fact stationary. In this report, we describe two patients with pulsatile oscillopsia following orbitocranial approaches for skull base meningioma resection. Case Description: Two patients, both 42-year-old women, underwent orbitocranial approaches for resection of a right sphenoid wing (Patient 1) and left cavernous sinus (Patient 2) meningioma. Patient 1 underwent uncomplicated resection and was discharged home without neurologic or visual complaints; she presented 8 days later with pulsatile oscillopsia. This was managed expectantly, and MRA revealed no evidence of vascular pathology. She has not required intervention as of most recent follow-up. Patient 2 developed trochlear and trigeminal nerve palsies following resection and developed pulsatile oscillopsia 4 months postoperatively. After patching and corrective lens application, the patient’s symptoms had improved by 26 months postoperatively. Conclusion: Oscillopsia is a potential complication following skull base tumor resection about which patients should be aware. Patients may improve with conservative management alone, although the literature describes repair of orbital defects for ocular pulsations in traumatic and with some developmental conditions.

Atypical Evolution of Meningiomatosis After Discontinuation of Cyproterone Acetate: Clinical Cases and Histomolecular Characterization.

Purpose Long-term use of cyproterone acetate (CPA) is associated with an increased risk of developing an intracranial meningioma. Discontinuation of CPA most often induce stabilization or regression of the tumor. The exact mechanism of regression is unknown as well as the reason why some meningiomas are still growing after CPA discontinuation.We are reporting four patients with multiple meningiomas, showing opposite tumor evolutions after stopping the CPA highlighting the underlying histologic and genetic features.MethodsPatients presenting several meningiomaswith opposite evolutions following the discontinuation of CPA were identified. The clinical and radiological data’s were reviewed. A retrospective volumetric analysis of the meningiomas was performed. All the growing meningiomas were operated. Each tumor was characterized histopathologically and by molecular and genetic analyses.ResultsFour female withmultiple meningiomas and opposite tumor volume evolution after CPA discontinuation were identified. The histopathological results found fibroblastic meningiomas for tumorsgrowinglocated in the convexity and a morefibrousmeningioma in the skull-base tumor which decreased. Meningothelial and transitional meningiomaswere found in two skull-base growing meningiomas.The molecular characterization found twoNF2-mutations among the 4 growing meningiomas. In one patient who presented both patterns, the shrinking skull-basetumor harbored a PIK3CA-mutation whereas the growing tumor, a NF2-mutation.ConclusionTo our knowledge, this is the first report of such an atypical tumor evolution of CPA-associated meningiomatosis after CPA discontinuation in the same patient. Underlying biological mechanisms explaining this observationespecially, the close relationship between mutational landscapes and the meningeal embryologyin CPA-related meningiomasrequire further research.

GIANT BENIGN SCHWANNOMA OF THE ANTERIOR BASE OF THE SKULL WITH SINONASAL AND PHARYNGEAL EXTENSION

Introduction: Schwannomas are tumors developed from Schwann cells present in the peripheral nerve sheaths. Their development both extra and intracranial is extremely rare. Observation: We report the case of a 36-year-old man who consulted for sinonasal syndrome evolving over the past ten years in which explorations found a large benign schwannoma of the anterior base of the skull with sinonasal and pharyngeal extension. The excision was performed externally by Moure and Sébileau with ENT and neurosurgery collaboration. The suites were simple. Discussion: The present observation again raises the question of the exact origin of developing sinonasal and endocranial schwannomas. The origin of the lesion and our management conditions were discussed. Conclusion: as for other authors, schwannoma should be considered in the diagnosis of skull base tumors. External surgery for extensive forms and ENT and neurosurgery collaboration help to minimize the risk of complications. Keywords: schwannoma; sinonasal schwannoma; skull base tumor.

Primary Dural Repair Using Titanium Microclips Following Lateral Skull Base Surgery

Objective Standard techniques for primary dural repair following lateral skull base surgery are both technically challenging and time consuming without the potential for primary dural repair. Inadequate closure may result in postoperative cerebrospinal fluid (CSF) leak infectious sequalae. Traditional methods of dural repair rely on secondary obliteration of the CSF fistula. We hypothesized that the use of nonpenetrating titanium microclips may serve as a useful adjunct in primary dural repair or the establishment of an immobile repair layer following lateral skull base surgery. Methods Here, we report a novel technique for primary dural repair using nonpenetrating titanium microclips as an adjunct to standard techniques in a series of six patients with lateral skull base pathologies. Results A total of six consecutive lateral skull base tumor patients with titanium microclip dural reconstruction were included in our case series. Lateral skull base pathologies represented in this group included two jugular foramen schwannomas, one vestibular schwannoma, one petroclival meningioma, one glomus jugulare paraganglioma, and one jugular foramen chordoid meningioma. Conclusion To our knowledge, this is the first report on the use of microclips in repairing dural defects following lateral skull base surgery. Surgical outcomes for this small case series suggest that dural repair of the later skull base with nonpenetrating titanium microclips is a useful adjunct in dural repair following lateral skull base surgery.