Meningioma metastases: incidence and proposed screening paradigm.

OBJECTIVE: Extracranial meningioma metastases are uncommon, occurring in less than 1% of patients diagnosed with meningioma. Due to the rarity of meningioma metastases, patients are not routinely screened for distant disease. In this series, we report their experience with meningioma metastases and results of screening for metastases in select patients with recurrent meningiomas. METHODS: All patients undergoing resection or stereotactic radiosurgery for primary or recurrent meningioma from 2009 to 2017 at a single center were retrospectively reviewed to identify patients who were diagnosed with or underwent imaging to evaluate for systemic metastases. Imaging to evaluate for metastases was performed with CT scanning of the chest, abdomen, and pelvis or whole-body PET/CT using either FDG or 68Ga-DOTA-octreotate (DOTATATE) tracers in 28 patients. Indications for imaging were symptomatic lesions concerning for metastasis or asymptomatic screening in patients with greater than 2 recurrences being evaluated for additional treatment. RESULTS: Of 1193 patients treated for meningioma, 922 (77.3%) patients had confirmed or presumed WHO grade I tumors, 236 (19.8%) had grade II tumors, and 35 (2.9%) had grade III tumors. Mean follow-up was 4.3 years. A total of 207 patients experienced recurrences (17.4%), with a mean of 1.8 recurrences. Imaging for metastases was performed in 28 patients; 1 metastasis was grade I (3.6%), 16 were grade II (57.1%), and 11 were grade III (39.3%). Five patients (17.9%) underwent imaging because of symptomatic lesions. Of the 28 patients screened, 27 patients had prior recurrent meningioma (96.4%), with a median of 3 recurrences. On imaging, 10 patients had extracranial lesions suspicious for metastasis (35.7%). At biopsy, 8 were meningioma metastases, 1 was a nonmeningioma malignancy, and 1 patient was lost to follow-up prior to biopsy. Biopsy-confirmed metastases occurred in the liver (5), lung (3), mediastinum (1), and bone (1). The observed incidence of metastases was 0.67% (n = 8). Incidence increased to 2% of WHO grade II and 8.6% of grade III meningiomas. Using the proposed indications for screening, the number needed to screen to identify one patient with biopsy-confirmed malignancy was 3.83. CONCLUSIONS: Systemic imaging of patients with multiply recurrent meningioma or symptoms concerning for metastasis may identify extracranial metastases in a significant proportion of patients and can inform decision making for additional treatments.

Surgical Outcomes, Complications, and Management Strategies for Foramen Magnum Meningiomas.

Objectives Foramen magnum meningiomas (FMM) are complex lesions because of their proximity to the brain stem and posterior cerebrovasculature. The objective of this study is to report surgical outcomes and complications after resection of FMM. Methods A retrospective chart review was conducted on patients with FMM from 1998 to 2015. Univariate logistic regression and recursive partitioning analysis were used to identify risk factors associated with complications and extent of resection (EOR). Results We identified 28 patients with FMM. Median follow-up was 5.9 years. Tumors were World Health Organization grade I (92.9%) or grade II (7.1%). The vertebral artery was completely encased (25%), partially encased (11%), or not encased (64%). Median size was 11.9 cm 3 . EOR was gross total (39%) and subtotal (61%). The observed recurrence rate was 4% ( n = 1). There were 38 complications in 12 patients (43%), and 6 patients (21%) had complications requiring additional surgery. Complications included cerebrospinal fluid leak/hydrocephalus ( n = 7, 25%), weakness ( n = 4, 14%), numbness ( n = 4, 14%), and cranial nerve deficits: IX, X ( n = 4, 14%), XI ( n = 2, 7%), XII ( n = 5, 18%). Medical complications included pneumonia ( n = 1, 4%) and meningitis ( n = 1, 4%). Tumor volume greater than 14 cm 3 (odds ratio [OR] = 21.7, p = 0.0010), any vertebral artery encasement (OR 6.1, p = 0.0386), and subtotal resection (OR 6.4, p = 0.0398) were significantly associated with complications. Tumor volume greater than 14 cm 3 was also significantly associated with subtotal resection (OR 8.3, p = 0.0201). Conclusions Resection of FMM carries perioperative morbidity that increases with larger tumor size. Despite the morbidity, long-term recurrence-free survival is achievable with maximal safe resection and adjuvant radiation.

The Stability of Factors Influencing the Choice of Medical Specialty Among Medical Students and Postgraduate Radiology Trainees.

OBJECTIVE: To investigate whether general psychological motivating factors that guide career selection of a medical specialty differ over the course of medical school and to compare differences in motivating factors among students choosing "controllable" lifestyle specialties, students choosing "uncontrollable" lifestyle specialties, and a cohort of radiology residents. MATERIALS AND METHODS: An anonymous survey was distributed to first- through fourth-year medical students and radiology residents at a single institution. Participants were asked to select their top three of seven factors that most influenced their choice of medical specialty. Fourth-year students were asked to designate the specialty to which they had applied. RESULTS: The survey was distributed to 259 students and 47 radiology residents with a response rate of 93.8% (243 of 259) and 95.7% (45 of 47), respectively. The top three factors indicated by medical students were finding the daily work fulfilling, work-life balance, and interest in the subject. These top three factors were common to all medical student classes and did not differ between students choosing "controllable" versus "uncontrollable" fields. The factors uncommonly selected were similar personality to others in the field, attending income, competitiveness or prestige, and job market conditions. For radiology residents, the top three motivating factors were the same as for medical students. CONCLUSION: Three out of seven motivating factors were universally important to trainees, regardless of their stage of medical training or their selection of a controllable versus uncontrollable lifestyle specialty. These data suggest the variety of career choices made by students may not derive from differing underlying values.

Surgical outcomes after reoperation for recurrent skull base meningiomas.

OBJECTIVE: Skull base meningiomas are surgically challenging tumors due to the intricate skull base anatomy and the proximity of cranial nerves and critical cerebral vasculature. Many studies have reported outcomes after primary resection of skull base meningiomas; however, little is known about outcomes after reoperation for recurrent skull base meningiomas. Since reoperation is one treatment option for patients with recurrent meningioma, the authors sought to define the risk profile for reoperation of skull base meningiomas. METHODS: A retrospective review of 2120 patients who underwent resection of meningiomas between 1985 and 2016 was conducted. Clinical information was extracted from the medical records, radiology data, and pathology data. All records of patients with recurrent skull base meningiomas were reviewed. Demographic data, presenting symptoms, surgical management, outcomes, and complications data were collected. Kaplan-Meier analysis was used to evaluate survival after reoperation. Logistic regression was used to evaluate for risk factors associated with complications. RESULTS: Seventy-eight patients underwent 100 reoperations for recurrent skull base meningiomas. Seventeen patients had 2 reoperations, 3 had 3 reoperations, and 2 had 4 or more reoperations. The median age at diagnosis was 52 years, and 64% of patients were female. The median follow-up was 8.5 years. Presenting symptoms included cranial neuropathy, headache, seizure, proptosis, and weakness. The median time from initial resection to first reoperation was 4.4 years and 4.1 years from first to second reoperation. Seventy-two percent of tumors were WHO grade I, 22% were WHO grade II, and 6% were WHO grade III. The sphenoid wing was the most common location (31%), followed by cerebellopontine angle (14%), cavernous sinus (13%), olfactory groove (12%), tuberculum sellae (12%), and middle fossa floor (5%). Forty-four (54%) tumors were ≥ 3 cm in maximum diameter at the time of the first reoperation. In 100 reoperations, 60 complications occurred in 30 cases. Twenty of the 60 complications required surgical intervention (33%). Complications included hydrocephalus (12), CSF leak/pseudomeningocele (11), wound infection (9), postoperative hematoma (4), venous infarction (1), and pneumocephalus (1). Postoperative neurological deficits included new or worsened cranial nerve deficits (10) and hemiparesis (3). There were no perioperative deaths in this series. On multivariate analysis, posterior fossa location was significantly associated with complications (OR 3.45, p = 0.0472). The 1-, 2-, 5-, and 10-year overall survival rates according to Kaplan-Meier analysis after the first reoperation were 94%, 92%, 88%, and 76%, respectively. The median survival after the first reoperation was 17 years. CONCLUSIONS: Recurrent skull base meningiomas are surgically challenging tumors, and reoperation is associated with high morbidity and complication rates. Despite these cautionary data, repeat resection of recurrent skull base meningiomas in appropriately selected patients provides excellent long-term survival.

Advanced cataract learning experience in United States ophthalmology residency programs.

This study examined resident exposure to and competency in new techniques for cataract removal and intraocular lens (IOL) implantation. A questionnaire was sent to 116 United States ophthalmology program directors and completed by 71. In response to the questionnaire, program directors reported that 95.3% of their graduating seniors were competent to select and implant toric IOLs and 52.3% were competent to implant capsular tension rings (CTRs). Divide and conquer (56.6%) and stop and chop (25.4%) dominated phacoemulsification teaching. Femtosecond laser-assisted cataract surgery was performed by residents in 44.1% of programs. In 25.4%, residents observed but did not perform the procedure; in 35.6%, they received didactic-only training; and in 22.0%, they received no exposure. Most programs (73.2%) had virtual-reality simulators for cataract surgery, but wet-lab practice (91.1%), didactic training (82.1%), and watching videos (82.1%) were the primary curricular tools used to teach advanced technologies.

Metformin and trametinib have synergistic effects on cell viability and tumor growth in NRAS mutant cancer.

Attempts to directly block the mutant neuroblastoma rat sarcoma oncogene (NRAS) protein, a driving mutation in many cancer types, have been unsuccessful. Current treatments focus on inhibition of different components of NRAS' two main downstream cascades: PI3K/AKT/mTOR and MAPK. Here we test a novel dual therapy combination of metformin and trametinib on a panel of 16 NRAS mutant cell lines, including melanoma cells, melanoma cells with acquired trametinib resistance, lung cancer and neuroblastoma cells. We show that both of the main downstream cascades of NRAS can be blocked by this combination: metformin indirectly inhibits the PI3K/AKT/mTOR pathway and trametinib directly impedes the MAPK pathway. This dual therapy synergistically reduced cell viability in vitro and xenograft tumor growth in vivo. We conclude that metformin and trametinib combinations are effective in preclinical models and may be a possible option for treatment of NRAS mutant cancers.

Mutant NRASQ61 shares signaling similarities across various cancer types--potential implications for future therapies.

Oncogenic mutations in the Neuroblastoma Rat Sarcoma oncogene (NRAS) are frequent in melanoma, but are also found in several other cancer types, such as lung cancer, neuroblastoma and colon cancer. We designed our study to analyze changes in NRAS mutant tumor cells derived from malignancies other than melanoma. A variety of small molecule inhibitors as well as their combinations was tested in order to find beneficial inhibitory modalities in NRASQ61mutant lung cancer and neuroblastoma cell lines. Signaling changes after incubation with inhibitors were studied and compared to those found in NRAS mutant melanoma. All cell lines were most sensitive to inhibition in the MAPK pathway with the MEK inhibitor trametinib. MEK/AKT and MEK/CDK4,6 inhibitor combinations did not show any beneficial effects in vitro. However, we observed strong synergism combining MEK and PI3K/mTOR inhibitors in all cell lines. Our study provides evidence that NRAS mutant cancers share signaling similarities across different malignancies. We demonstrate that dual pathway inhibition of the MAPK and PI3K/AKT/mTOR pathway synergistically reduces cell viability in NRAS mutant cancers regardless of their tissue origin. Our results suggest that such inhibitor combinations may be a potential treatment option for non-melanoma tumors harboring activating NRAS mutations.