Natural history of spinal cord metastasis from brain glioblastomas.

BACKGROUND AND OBJECTIVES: Spinal cord metastasis arising from an intracranial glioblastoma is a rare and late event during the natural course of the disease. These pathological entities remain poorly characterized. This study aimed to identify and investigate the timeline, clinical and imaging findings, and prognostic factors of spinal cord metastasis from a glioblastoma. METHODS: Consecutive histopathological cases of spinal cord metastasis from glioblastomas in adults entered in the French nationwide database between January 2004 and 2016 were screened. RESULTS: Overall, 14 adult patients with a brain glioblastoma (median age 55.2 years) and harboring a spinal cord metastasis were included. The median overall survival as 16.0 months (range, 9.8-22.2). The median spinal cord Metastasis Free Survival (time interval between the glioblastoma diagnosis and the spinal cord metastasis diagnosis) was 13.6 months (range, 0.0-27.9). The occurrence of a spinal cord metastasis diagnosis greatly impacted neurological status: 57.2% of patients were not ambulatory, which contributed to dramatically decreased Karnofsky Performance Status (KPS) scores (12/14, 85.7% with a KPS score ≤ 70). The median overall survival following spinal cord metastasis was 3.3 months (range, 1.3-5.3). Patients with a cerebral ventricle effraction during the initial brain surgery had a shorter spinal cord Metastasis Free Survival (6.6 vs 18.3 months, p = 0.023). Out of the 14 patients, eleven (78.6%) had a brain IDH-wildtype glioblastoma. CONCLUSIONS: Spinal cord metastasis from a brain IDH-wildtype glioblastoma has a poor prognosis. Spinal MRI can be proposed during the follow-up of glioblastoma patients especially those who have benefited from cerebral surgical resection with opening of the cerebral ventricles.

Surgical Site Infections after glioblastoma surgery: results of a multicentric retrospective study.

BACKGROUND: The effects of surgical site infections (SSI) after glioblastoma surgery on patient outcomes are understudied. The aim of this retrospective multicenter study was to evaluate the impact of SSI on the survival of glioblastoma patients. METHODS: Data from SSI cases after glioblastoma surgeries between 2009 and 2016 were collected from 14 French neurosurgical centers. Collected data included patient demographics, previous medical history, risk factors, details of the surgical procedure, radiotherapy/chemotherapy, infection characteristics, and infection management. Similar data were collected from gender- and age-paired control individuals. RESULTS: We used the medical records of 77 SSI patients and 58 control individuals. 13 were excluded. Our analyses included data from 64 SSI cases and 58 non-infected glioblastoma patients. Infections occurred after surgery for primary tumors in 38 cases (group I) and after surgery for a recurrent tumor in 26 cases (group II). Median survival was 381, 633, and 547 days in patients of group I, group II, and the control group, respectively. Patients in group I had significantly shorter survival compared to the other two groups (p < 0.05). The one-year survival rate of patients who developed infections after surgery for primary tumors was 50%. Additionally, we found that SSIs led to postoperative treatment discontinuation in 30% of the patients. DISCUSSION: Our findings highlighted the severity of SSIs after glioblastoma surgery, as they significantly affect patient survival. The establishment of preventive measures, as well as guidelines for the management of SSIs, is of high clinical importance.

Pre-surgical embolization of intracranial meningioma with Onyx: A safety and efficacy study.

BACKGROUND AND PURPOSE: Pre-surgical embolization of large intracranial meningioma has been demonstrated to decrease blood loss and to improve the resectability of the tumor. Few reports have evaluated the risk and benefits of using Onyx in this indication. The objective of our study was to assess the efficiency and safety of pre-surgical embolization in a consecutive series of intracranial meningioma using Onyx. MATERIALS AND METHODS: We conducted a retrospective study of consecutive patients treated from 2010 to 2018 with pre-surgical embolization with Onyx for intracranial histologically-proven meningioma. Safety was evaluated by a report of the complications related to the procedure while efficacy was assessed on angiographic and histopathologic criteria. RESULTS: Forty-four meningioma in 44 patients treated with pre-surgical embolization were included in this study. Proximal artery occlusion was obtained in 97.6% (41/42) of the cases and good intra-tumoral penetration was achieved in 75.6% (31/41). Embolic agent inside blood vessels was identified in 63.5% (28/44) of cases. Embolization-induced necrosis was present in 79.6% (35/44) of cases. Six complications have been encountered (13.6%); 3 were stated as minor complications (6.8%) and 3 as major occurring in case of trans-ophthalmic route (6.8%). CONCLUSIONS: The present work is to date the largest study to evaluate intracranial meningioma embolization using Onyx. Onyx's allowed good intra-tumoral penetration and proximal artery occlusion in most cases but carries a higher risk of complication in case of ophthalmic supply.

Analysis of CDKN2A gene alterations in recurrent and non-recurrent meningioma.

PURPOSE: Assessment of the risk of recurrence is essential to determine the therapeutic strategy of meningioma treatment. Many relapsing or aggressive meningiomas show elevated mitotic and/or Ki67 indices, reflecting cell cycle deregulation. As CDKN2A is a key tumor suppressor gene involved in cell cycle control, we investigated whether CDKN2A alterations may be involved in tumor recurrence. METHODS: We carried out a comparative analysis of 17 recurrent and 13 non-recurrent meningiomas. CDKN2A single nucleotide variations (SNVs), deletions, methylation status of the promotor, and p16 expression were investigated. Results were correlated with the recurrent or non-recurrent status and clinicopathological data. RESULTS: We identified a CDKN2A SNV (NM_000077, exon2, c.G442A, p.Ala148Thr) in five meningiomas that was significantly associated with recurrence (p = 0.03). This mutation, confirmed by Sanger sequencing and referenced in the COSMIC database in various cancers, has not been reported in meningioma. The presence of one of the three following CDKN2A alterations-p.(Ala148Thr) mutation, whole homozygous or heterozygous gene loss, or promotor methylation > 8%-was observed in 13 of the 17 relapsing meningiomas and was strongly associated with recurrence (p < 0.0001) and a Ki67 labeling index > 7% (p = 0.004). CONCLUSION: We report an undescribed p.(Ala148Thr) CDKN2A mutation in meningioma that was only present in relapsing tumors. In our series, CDKN2A gene alterations were only found in recurrent meningiomas. However, our results need to be evaluated on a larger series to ensure that these CDKN2A alterations can be used as biomarkers of recurrence in meningioma.

MRI predictive score of pial vascularization of supratentorial intracranial meningioma.

OBJECTIVE: Meningiomas are highly vascularized tumors which may recruit pial blood supply. Pial supply complicates tumor treatment in numerous ways. The objective of this study was to establish a reliable MRI-based diagnostic score to predict the existence of pial blood supply in supratentorial intracranial meningiomas and then correlate the score with clinical and surgical outcomes and histopathological findings. METHODS: We performed a retrospective analysis of supratentorial histologically proven meningiomas in our institution from 2010 to 2018. A score was built based on MRI criteria and correlated with digital subtraction angiography (DSA) pial vascularization assessment. The score was then validated on a second independent population recruited with the same modalities. RESULTS: Logistic regression identified four parameters related to pial blood supply which were used to build the score: skull base location, tumor size > 45 mm, peritumoral flow voids, and incomplete cerebrospinal fluid rim. The overall diagnostic performance in predicting pial blood supply was as follows: sensitivity 97.8%, specificity 76.9%, predictive positive value 88.2%, negative predictive value 95.2%, and accuracy 90.3%. Inter-reader agreement and Cohen's kappa were good, respectively, of 90.7% and 0.69. A high score was associated with aggressive meningioma (World Health Organization II-III) (p = 0.04) and with greater importance of pial supply relative to dural supply. CONCLUSIONS: We have identified a reliable way to use MRI to predict the existence of pial blood supply in supratentorial intracranial meningiomas. A higher score also predicted higher grade meningioma. KEY POINTS: • Accurate and reproducible MRI score composed of four items to predict the existence of pial blood supply in supratentorial meningioma. • High score is associated with high-grade meningioma (WHO II-III) but also with greater importance of pial supply relative to dural supply.

Comparative analysis of histopathological parameters, genome-wide copy number alterations, and variants in genes involved in cell cycle regulation in chordomas of the skull base and sacrum.

Chordomas are rare tumors of the axial skeleton that are refractory to conventional therapy. Few studies have compared the morphological and molecular characteristics of chordomas according to the skull base and sacral locations. Histopathological data and changes revealed by array comparative genomic hybridization (CGH) and next-generation sequencing (NGS) of cell cycle regulation genes were analyzed for 28 skull base (SBCs) and 15 sacral (SC) chordomas. All cases were conventional chordomas. SBCs were significantly more frequent in patients aged <40 years and SCs predominated in patients aged >60 years. Mitotic indices ≥2 mitoses/10 high-power fields were correlated with high degrees of nuclear atypia and Ki67 labeling indices ≥6%. We identified 321 genomic positions, and copy number variation losses were more frequent than gain. Moreover, we report a panel of 85 genetic variants of cell cycle genes and the presence of molecular clusters for chordoma as well in CGH as in NGS. These new data strengthen the view that the chordoma should not be considered as a single molecular entity.

Development of a Novel Orthotopic Primary Human Chordoma Xenograft Model: A Relevant Support for Future Research on Chordoma.

Chordomas are slow-growing rare malignant neoplasms. The aim of this study was to establish a primary model of chordoma in the lumbosacral orthotopic area, to compare the growth rate to the subcutaneous site, and to show that this new graft site optimizes tumor growth and bony invasion. Eleven chordoma samples were transplanted subcutaneously in the flank and/or in contact with the lumbosacral region and grown into nude mice. Engraftment rate was significantly more successful in the lumbosacral environment compared with the flank at P0. Two xenografts from 2 patients showed bone invasion. One tumor was maintained through multiple rounds of serial transplantation, creating a model for study. Histological and immunostaining analysis confirmed that tumor grafts recapitulated the primary tumor from which they were derived, consisting of a myxoid chordoma expressing brachyury, cytokeratin AE1, EMA, and VEGF. Clear destruction of the bone by the tumor cells could be demonstrated. Molecular studies revealed PIK3CA and PTEN mutations involved in PI3K signaling pathway and most of the frequently reported chromosomal alterations. We present a novel orthotopic primary xenograft model of chordoma implanted for the first time in the lumbosacral area showing bone invasion, PIK3CA, and PTEN mutations that will facilitate preclinical studies.