Evidence-Based Optimization of Post-Treatment Surveillance for Skull Base Chordomas Based on Local and Distant Disease Progression.

BACKGROUND: There are no guidelines regarding post-treatment surveillance specific to skull base chordomas. OBJECTIVE: To determine an optimal imaging surveillance schedule to detect both local and distant metastatic skull base chordoma recurrences. METHODS: A retrospective review of 91 patients who underwent treatment for skull base chordoma between 1993 and 2017 was conducted. Time to and location of local and distant recurrence(s) were cataloged. Existing chordoma surveillance recommendations (National Comprehensive Cancer Network [NCCN], London and South East Sarcoma Network [LSESN], European Society for Medical Oncology [ESMO], Chordoma Global Consensus Group [CGCG]) were applied to our cohort to compare the number of recurrent patients and months of undiagnosed tumor growth between surveillances. These findings were used to inform the creation of a revised imaging surveillance protocol (MD Anderson Cancer Center Chordoma Imaging Protocol [MDACC-CIP]), presented here. RESULTS: Thirty-four patients with 79 local/systemic recurrences met inclusion criteria. Mean age at diagnosis and follow-up time were 45 yr and 79 mo, respectively. The MDACC-CIP imaging protocol significantly reduced the time to diagnosis of recurrence compared with the LSESN and CGCG/ESMO imaging protocols for surveillance of local disease with a cumulative/average of 576/16.9 (LSESN), 336/9.8 (CGCG), and 170/5.0 (MDACC-CIP) months of undetected growth, respectively. The NCCN and MDACC-CIP guidelines for distant metastatic surveillance identified a cumulative/average of 65/6.5 and 51/5.1 mo of undetected growth, respectively, and were not significantly different. CONCLUSION: The MDACC-CIP for skull base chordoma accounts for recurrence trends unique to this disease, including a higher rate of leptomeningeal spread than sacrococcygeal primaries, resulting in improved sensitivity and prompt diagnosis.

Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design.

INTRODUCTION: Surgery and radiation therapy are the standard treatment options for meningiomas, but these treatments are not always feasible. Expression profiling was performed to determine the presence of therapeutic actionable biomarkers for prioritization and selection of agents. METHODS: Meningiomas (n = 115) were profiled using a variety of strategies including next-generation sequencing (592-gene panel: n = 14; 47-gene panel: n = 94), immunohistochemistry (n = 8-110), and fluorescent and chromogenic in situ hybridization (n = 5-70) to determine mutational and expression status. RESULTS: The median age of patients in the cohort was 60 years, with a range spanning 6-90 years; 52% were female. The most frequently expressed protein markers were EGFR (93%; n = 44), followed by PTEN (77%; n = 110), BCRP (75%; n = 8), MRP1 (65%, n = 23), PGP (62%; n = 84), and MGMT (55%; n = 97). The most frequent mutation among all meningioma grades occurred in the NF2 gene at 85% (11/13). Recurring mutations in SMO and AKT1 were also occasionally detected. PD-L1 was expressed in 25% of grade III cases (2/8) but not in grade I or II tumors. PD-1 + T cells were present in 46% (24/52) of meningiomas. TOP2A and thymidylate synthase expression increased with grade (I = 5%, II = 22%, III = 62% and I = 5%, II = 23%, III = 47%, respectively), whereas progesterone receptor expression decreased with grade (I = 79%, II = 41%, III = 29%). CONCLUSION: If predicated on tumor expression, our data suggest that therapeutics directed toward NF2 and TOP2A could be considered for most meningioma patients.

Multimodality Management of Recurrent Skull Base Chordomas: Factors Impacting Tumor Control and Disease-Specific Survival.

BACKGROUND: Limited data exist to guide the management of recurrent chordomas arising in the skull base. OBJECTIVE: To determine factors affecting tumor control rates and disease-specific survival (DSS) in recurrent disease. METHODS: A retrospective review was performed of 29 patients with 55 recurrences treated at our institution. Tumor and treatment factors were assessed for impact on freedom from progression (FFP; primary outcome) and DSS (secondary outcome). RESULTS: Postradiotherapy disease failure was much more difficult to manage vs progression after surgery alone (15.9 vs 41.4 mo, P = .094). Distant metastases and, specifically, leptomeningeal disease at presentation were associated with poorer DSS and FFP (P < .05). For local progression after surgery alone, repeat resection (P < .05) improved median FFP. With postradiotherapy local failure, repeat resection did not confer any benefit (13.5 vs 17.6 mo, P > .05), while a trend towards improved FFP was seen with stereotactic radiosurgery (28.3 vs 16.2 mo, P = .233). For distant metastases, site-directed therapy (surgery or radiation) allowed for site control (P < .05) but did not affect FFP or DSS. Presentation with early progression <6 mo from previous treatment portended significantly worse DSS (19.3 vs 77.6 mo, P < .05). CONCLUSION: There is a need for treatment of recurrent disease to be tailored to the pattern of tumor recurrence and previously received treatments. Postradiotherapy progression poses particular challenges given the apparent limited role of repeat resection alone. Stereotactic radiosurgery may have a role in this setting. While patients with systemic metastases appear to respond well to site-directed therapy, those with leptomeningeal disease have a dismal prognosis.

Impact of early access to multidisciplinary care on treatment outcomes in patients with skull base chordoma.

OBJECTIVE: To determine if early access to multidisciplinary surgical care affects outcomes in patients with skull base chordoma. METHOD: A retrospective chart review of prospectively collected data was performed on 51 patients treated from 1993 to 2014. The cohort was divided into those presenting (1) for initial management (ID, n = 21) or (2) with persistent/progressive disease after prior biopsy/surgery (PD, n = 30) outside of a multidisciplinary setting. The impact of initial surgical management in a multidisciplinary center on progression-free survival (PFS) was assessed with Kaplan-Meier and log-rank analyses. RESULTS: Mean follow-up, median PFS, median overall survival (OS), and 10-year OS for the entire cohort was 70 months, 47 months, 159 months, and 19%, respectively. Initial management in a multidisciplinary center resulted in a significant improvement in PFS versus initial surgery with or without radiotherapy (XRT) outside of this setting (64 vs 25 months, p = 0.035). Initial surgical resection outside of a multidisciplinary setting increased the risk of recurrence/progression on univariate (HR, 2.276; p = 0.022) and multivariate analysis (HR, 2.831; p = 0.006), respectively. CONCLUSIONS: The results from this study emphasize the impact that coordinated multidisciplinary surgical care has on patient outcomes for chordomas of the clivus. Biopsy followed by attempted radical resection at a dedicated center does not affect PFS and, therefore, represents a reasonable first step in management for patients presenting outside of multidisciplinary setting.

Progesterone-only contraception is associated with a shorter progression-free survival in premenopausal women with WHO Grade I meningioma.

The hormonally active nature of intracranial meningioma has prompted research examining the risk of tumorigenesis in patients using hormonal contraception. Studies exploring estrogen-only and estrogen/progesterone combination contraceptives have failed to demonstrate a consistent increased risk of meningioma. By contrast, the few trials examining progesterone-only contraceptives have shown higher odds ratios for risk of meningioma. With progesterone-only contraception on the rise, the risk of tumor recurrence with these specific medications warrants closer study. We sought to determine whether progesterone-only contraception increases recurrence rate and decreases progression-free survival in pre-menopausal women with surgically resected WHO Grade I meningioma. Comparative analysis of 67 pre-menopausal women taking hormone-based contraceptives (progesterone-only medication, n = 21; estrogen-only or estrogen/progesterone combination medication, n = 46) who underwent surgical resection of WHO Grade I intracranial meningioma was performed. Differences in demographics, degree of resection, adjuvant therapy and time to recurrence were compared between the two groups. Compared to patients taking combination or estrogen-only contraception, those taking progesterone-only contraception demonstrated a greater recurrence rate (33.3 vs. 19.6%) with a reduced time to recurrence (18 vs. 32 months, p = 0.038) despite a significantly shorter follow-up (p = 0.014). There were no significant demographic or treatment related differences. The results from this study suggest that exogenous progesterone-only medications may represent a specific contraceptive subgroup that should be avoided in patients with meningioma.

Expanding the endoscopic transpterygoid corridor to the petroclival region: anatomical study and volumetric comparative analysis.

OBJECTIVE The endoscopic endonasal transmaxillary transpterygoid (TMTP) approach has been the gateway for lateral skull base exposure. Removal of the cartilaginous eustachian tube (ET) and lateral mobilization of the internal carotid artery (ICA) are technically demanding adjunctive steps that are used to access the petroclival region. The gained expansion of the deep working corridor provided by these maneuvers has yet to be quantified. METHODS The TMTP approach with cartilaginous ET removal and ICA mobilization was performed in 5 adult cadaveric heads (10 sides). Accessible portions of the petrous apex were drilled during the following 3 stages: 1) before ET removal, 2) after ET removal but before ICA mobilization, and 3) after ET removal and ICA repositioning. Resection volumes were calculated using 3D reconstructions generated from thin-slice CT scans obtained before and after each step of the dissection. RESULTS The average petrous temporal bone resection volumes at each stage were 0.21 cm3, 0.71 cm3, and 1.32 cm3 (p < 0.05, paired t-test). Without ET removal, inferior and superior access to the petrous apex was limited. Furthermore, without ICA mobilization, drilling was confined to the inferior two-thirds of the petrous apex. After mobilization, the resection was extended superiorly through the upper extent of the petrous apex. CONCLUSIONS The transpterygoid corridor to the petroclival region is maximally expanded by the resection of the cartilaginous ET and mobilization of the paraclival ICA. These added maneuvers expanded the deep window almost 6 times and provided more lateral access to the petroclival region with a maximum volume of 1.5 cm3. This may result in the ability to resect small-to-moderate sized intradural petroclival lesions up to that volume. Larger lesions may better be approached through an open transcranial approach.

Spheno-Orbital Meningiomas: A 16-Year Surgical Experience.

OBJECTIVE: To examine the efficacy of spheno-orbital meningioma (SOM) resection aimed at symptomatic improvement, rather than gross total resection, followed by radiation therapy for recurrence. METHODS: A retrospective review of all patients having undergone resection between 2000 and 2016 was performed. Demographics, operative details, postoperative outcomes, recurrence rates, and radiation treatment plans were analyzed. Statistical analysis was performed to assess for factors affecting recurrence (Fisher exact and Student t test), changes in exophthalmos index (EI) (Student t test), and progression-free survival (Kaplan-Meier and log rank). RESULTS: Twenty-five patients were included; 92% of participants were women. Mean age was 51 years. World Health Organization grades were I (n = 21) and II (n = 4). Simpson grades were I (n = 14), II (n = 3), and IV (n = 8). Mean follow-up time was 44.8 months. Proptosis was significantly improved at the 3- to 6-month postoperative visit (mean ΔEI, 0.15; P < 0.05) and at last follow-up (mean ΔEI, 0.13; P < 0.05). Visual acuity was either improved or stable in 18 of 19 patients. There were 12 recurrences; mean time to recurrence was 21.8 months. Increased recurrence rate was significantly associated with younger age. Eight patients received fractionated radiation at time of recurrence. To date, all treated patients are progression free. CONCLUSIONS: Among this cohort, surgery provided a lasting improvement in proptosis and improved or stabilized visual deficits. Surgery followed by radiation at recurrence provided excellent tumor control and lends credence to the growing body of literature demonstrating effective control of subtotally resected skull base meningiomas.

Unilateral endonasal transcribriform approach with septal transposition for olfactory groove meningioma: can olfaction be preserved?

BACKGROUND: Loss of olfaction has been considered inevitable in endoscopic endonasal resection of olfactory groove meningiomas. Olfaction preservation may be feasible through an endonasal unilateral transcribriform approach, with the option for expansion using septal transposition and contralateral preservation of the olfactory apparatus. METHODS: An expanded unilateral endonasal transcribriform approach with septal transposition was performed in five cadaver heads. The approach was applied in a surgical case of a 24 × 26-mm olfactory groove meningioma originating from the right cribriform plate with partially intact olfaction. RESULTS: The surgical approach offered adequate exposure to the anterior skull base bilaterally. The nasal/septal mucosa was preserved on the contralateral side. Gross total resection of the meningioma was achieved with the successful preservation of the contralateral olfactory apparatus and preoperative olfaction. Six months later, the left nasal cavity showed no disruption of the mucosal lining and the right side was at the appropriate stage of healing for a harvested nasoseptal flap. One year later, the preoperative olfactory function was intact and favorably viewed by the patient. Objective testing of olfaction showed microsomia. CONCLUSIONS: Olfaction preservation may be feasible in the endoscopic endonasal resection of a unilateral olfactory groove meningioma through a unilateral transcribriform approach with septal transposition and preservation of the contralateral olfactory apparatus.

Transposition of the paraclival carotid artery: a novel concept of self-retaining vascular retraction during endoscopic endonasal skull base surgery technical report.

BACKGROUND: Fixed retraction of the internal carotid artery (ICA) has previously been described for use during transcranial microscopic surgery. We report the novel use of a self-retaining microvascular retractor for static repositioning and protection of the ICA during expanded endonasal endoscopic approaches to the paramedian skull base. METHODS: The transmaxillary, transpterygoid approach was performed in five cadaver heads (ten sides). The self-retaining microvascular retractor was used to laterally reposition the pterygopalatine fossa contents during exposure of the pterygoid base/plates and the paraclival ICA to expose the petrous apex. Maximum ICA retraction distance was measured in the x-axis for all ten sides. RESULTS: The average horizontal distance of ICA retraction measured at the mid-paraclival segment for all ten sides was 4.75 mm. In all cases, the carotid artery was repositioned without injury to the vessel or disruption of the surrounding neurovascular structures. CONCLUSIONS: Static repositioning of the ICA and other delicate neurovascular structures was effectively performed during endonasal, endoscopic cadaveric surgery of the skull base and has potential merits in live patients.

Invasive Giant Cell Tumor of the Lateral Skull Base: A Systematic Review, Meta-Analysis, and Case Illustration.

BACKGROUND: The current literature regarding cranial giant cell tumor (GCT) management includes scattered case reports and small case series. We present a comprehensive literature review and meta-analysis on this subject, along with a case report describing our management of a patient with temporal GCT. METHODS: A systematic literature review of all reports on GCTs of the skull was performed, followed by a meta-analysis examining the effect of radiation and degree of resection on tumor recurrence. RESULTS: Fifty-nine abstracts published between 1945 and 2015, reporting 110 cases of GCT, were reviewed. After exclusions were applied, 31 reports, covering 67 patients, were selected for meta-analysis. Average patient age was 33.7 years, and the male:female ratio was roughly 1:1. Tumor locations were temporal in 37 patients, sphenoid in 20 patients, occipital in 6 patients, frontal in 2 patients, and the temporomandibular joint in 2 patients. Treatments were surgery plus radiation in 25 patients, surgery alone in 41 patients, and radiation alone in 1 patient. In the 66 patients who underwent surgery, the degree of resection was gross total resection (GTR) in 34 patients, subtotal resection (STR) in 31 patients, and not recorded in 1 patient. The mean follow-up time was 36 months. Recurrence occurred in 8.8% of patients in the GTR group and in 32.3% of those in the STR group (odds ratio, 0.203; 95% confidence interval, 0.033-0.937; P = 0.018). The odds ratio for STR alone compared with STR plus radiation was 14.01 (P = 0.0038). CONCLUSION: GCTs of the skull commonly affect young adults, with an equal sex distribution, and are most often centered in temporal bone. GTR is associated with the lowest recurrence rate and should be the goal of treatment. If GTR cannot be achieved, the combination of STR and radiation results in a similar recurrence rate. With the advent of denosumab, there is now a role for chemotherapy in the treatment of GCTs.

Damage-control neurosurgery: Packing to halt relentless intracranial bleeding.

BACKGROUND: The objective of this study was to review the efficacy of intracranial packing as a means of tamponade for life-threatening intraoperative hemorrhage that was refractory to more common techniques for achieving hemostasis. METHODS: Neuroimaging and hospital records were reviewed for the seven adult patients who had experienced life-threateningly severe hemorrhage during intracranial surgery and in whom packing was used to control the bleeding. All packing was left in place at the time of closure and was removed when the patient's condition was considered safe for a second operation. RESULTS: Hemorrhage was successfully halted in all seven patients, and all survived their operations. Six were discharged from the hospital, but one patient with severe parenchymal injury from trauma and multiple medical comorbidities died on postoperative Day 2 after supportive care was withdrawn. Four had an improved Glasgow Outcome Scale (GOS) score at the time of last follow-up, and two of these improved from dependent to independent living. There were no postoperative intracranial or wound infections. CONCLUSION: Intracranial packing to tamponade severe intracranial hemorrhage can be a lifesaving neurosurgical maneuver. LEVEL OF EVIDENCE: Therapeutic study, level V.

Unilateral Tailored Fronto-Orbital Approach for Giant Olfactory Groove Meningiomas: Technical Nuances.

OBJECTIVE: Giant olfactory groove meningiomas (maximum diameter ≥6 cm) remain a surgical challenge. Historically, extensive anterior and antero-lateral approaches have been the primary approaches for removal of such large tumors with limitations and morbidity pertaining to each approach. Herein, the authors describe a minimally invasive, unilateral, tailored fronto-orbital approach for resection of these complex lesions with an emphasis on preservation of the anterior cerebral arteries and olfactory nerves. METHODS: A 4-stage approach using neuronavigation is performed: 1) predefined corridor, 2) identification of the ipsilateral anterior cerebral artery, 3) postdefined corridor, and 4) tumor base. The details of this approach are described below in a stepwise fashion and supplemented by a sample of 3 cases utilizing this technique. RESULTS: In the 3 representative cases in which this technique was used, gross total resection was achieved without injury to any of the adjacent neurovascular structures. Significant sellar extension can be resected through a second stage endoscopic endonasal approach. CONCLUSION: Giant olfactory groove meningiomas (≥6 cm) can be safely and completely resected with this 4-stage, unilateral fronto-orbital technique. Furthermore, early identification and preservation of the adjacent critical neurovascular structures can be achieved. This technique avoids the inherent limitations and morbidity associated with the more classic pterional and bifrontal approaches respectively while minimizing normal tissue disruption.

Breach of Posterior Wall of Frontal Sinus: Management with Preservation of the Sinus.

OBJECTIVE: To analyze outcomes after the management of mild (<1 mm) and moderately severe (>1 mm and <5 mm) breaches of the posterior wall of the frontal sinus with a goal of maintaining or restoring the functional status of the sinus. METHODS: A retrospective analysis of prospectively accrued data was performed on patients with mild and moderately severe breaches of the posterior wall of their frontal sinus who were managed with the intent to preserve the frontal sinus. Data on presenting features, pathology, details on breaches of the posterior wall, management, outcome, and complications were collected from medical records and neuroimages. RESULTS: Forty-two cases met inclusion criteria. Diagnostic categories included trauma in 34 cases, infection in 3, and other categories in another 5 cases. Five presented with cerebrospinal fluid rhinorrhea, and 26 had radiographic evidence of obstruction of a nasofrontal duct at time of presentation. Fifteen patients were managed without surgical intervention, and 27 underwent surgery. No complications occurred in the patients managed without surgery and 4 postoperative cerebrospinal leaks that were managed successfully with a period of drainage occurred in the surgical group. No patient developed meningitis or mucocele. CONCLUSIONS: Many patients with mild to moderately severe breaches of the posterior wall of the frontal sinus can be managed safely and effectively by techniques that preserve the anatomy and function of the frontal sinus.