Clinical outcomes of solitary fibrous tumors and hemangiopericytomas and risk factors related to recurrence and survival based on the 2021 WHO classification of central nervous system tumors

J Neurosurg 140:69–79, 2024

OBJECTIVE The authors aimed to explore the clinical outcomes and risk factors related to recurrence of and survival from solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) that were reclassified according to the 2021 WHO classification of central nervous system (CNS) tumors.

METHODS The authors retrospectively collected and analyzed the clinical and pathological data of SFTs and HPCs recorded from January 2007 to December 2021. Two neuropathologists reassessed pathological slides and regraded specimens on the basis of the 2021 WHO classification. The prognostic factors related to progression-free survival (PFS) and overall survival (OS) were statistically assessed with univariate and multivariate Cox regression analyses.

RESULTS A total of 146 patients (74 men and 72 women, mean ± SD [range] age 46.1 ± 14.3 [3–78] years) were reviewed, and 86, 35, and 25 patients were reclassified as having grade 1, 2, and 3 SFTs on the basis of the 2021 WHO classification, respectively. The median PFS and OS of the patients with WHO grade 1 SFT were 105 months and 199 months after initial diagnosis; for patients with WHO grade 2 SFT, 77 months and 145 months; and for patients with WHO grade 3 SFT, 44 months and 112 months, respectively. Of the entire cohort, 61 patients experienced local recurrence and 31 died, of whom 27 (87.1%) died of SFT and relevant complications. Ten patients had extracranial metastasis. In multivariate Cox regression analysis, subtotal resection (STR) (HR 4.648, 95% CI 2.601–8.304, p < 0.001), tumor located in the parasagittal or parafalx region (HR 2.105, 95% CI 1.099–4.033, p = 0.025), tumor in the vertebrae (HR 3.352, 95% CI 1.228–9.148, p = 0.018), WHO grade 2 SFT (HR 2.579, 95% CI 1.343–4.953, p = 0.004), and WHO grade 3 SFT (HR 5.814, 95% CI 2.887–11.712, p < 0.001) were significantly associated with shortened PFS, whereas STR (HR 3.217, 95% CI 1.435–7.210, p = 0.005) and WHO grade 3 SFT (HR 3.433, 95% CI 1.324–8.901, p = 0.011) were significantly associated with shortened OS. In univariate analyses, patients who received adjuvant radiotherapy (RT) after STR had longer PFS than patients who did not receive RT.

CONCLUSIONS The 2021 WHO classification of CNS tumors better predicted malignancy with different pathological grades, and in particular WHO grade 3 SFT had worse prognosis. Gross-total resection (GTR) can significantly prolong PFS and OS and should serve as the most important treatment method. Adjuvant RT was helpful for patients who underwent STR but not for patients who underwent GTR.

Predictors of Progression-Free Survival in Patients With Spinal Intramedullary Ependymoma: A Multicenter Retrospective Study by the Neurospinal Society of Japan

Neurosurgery 93:1046–1056, 2023

Ependymoma is the most common spinal intramedullary tumor. Although clinical outcomes have been described in the literature, most of the reports were based on limited numbers of cases or been confined to institutional experience. The objective of this study was to analyze more detailed characteristics of spinal intramedullary ependymoma (SIE) and provide clinical factors associated with progression-free survival (PFS).

METHODS: This retrospective observational multicenter study included consecutive patients with SIE in the cervical or thoracic spine treated surgically at a total of 58 institutions between 2009 and 2020. The results of pathological diagnosis at each institute were confirmed, and patients with myxopapillary ependymoma, subependymoma, or unverified histopathology were strictly excluded from this study. Outcome measures included surgical data, surgery-related complications, postoperative systemic adverse events, postoperative adjuvant treatment, postoperative functional condition, and presence of recurrence.

RESULTS: This study included 324 cases of World Health Organization grade II (96.4%) and 12 cases of World Health Organization grade III (3.6%). Gross total resection (GTR) was achieved in 76.5% of cases. Radiation therapy (RT) was applied after surgery in 16 cases (4.8%), all of which received local RT and 5 of which underwent chemotherapy in combination. Functional outcomes were significantly affected by preoperative neurological symptoms, tumor location, extent of tumor resection, and recurrence. Multivariate regression analysis suggested that limited extent of tumor resection or recurrence resulted in poor functional outcomes. Multiple comparisons among the groups undergoing GTR, subtotal resection and biopsy, or partial resection of the tumor showed that the probability of PFS differed significantly between GTR and other extents of resection.

CONCLUSION: When GTR can be safely obtained in the surgery for SIE, functional maintenance and longer PFScan be expected.


Management of cavernous sinus meningiomas: Consensus statement on behalf of the EANS skull base section

Brain and Spine 2 (2022) 100864

The evolution of cavernous sinus meningiomas (CSMs) might be unpredictable and the efficacy of their treatments is challenging due to their indolent evolution, variations and fluctuations of symptoms, heterogeneity of classifications and lack of randomized controlled trials. Here, a dedicated task force provides a consensus statement on the overall management of CSMs. Research question: To determine the best overall management of CSMs, depending on their clinical presentation, size, and evolution as well as patient characteristics.

Material and methods: Using the PRISMA 2020 guidelines, we included literature from January 2000 to December 2020. A total of 400 abstracts and 77 titles were kept for full-paper screening.

Results: The task force formulated 8 recommendations (Level C evidence). CSMs should be managed by a highly specialized multidisciplinary team. The initial evaluation of patients includes clinical, ophthalmological, endocrinological and radiological assessment. Treatment of CSM should involve experienced skull-base neurosurgeons or neuro-radiosurgeons, radiation oncologists, radiologists, ophthalmologists, and endocrinologists.

Discussion and conclusion: Radiosurgery is preferred as first-line treatment in small, enclosed, pauci-symptomatic lesions/in elderly patients, while large CSMs not amenable to resection or WHO grade II-III are candidates for radiotherapy. Microsurgery is an option in aggressive/rapidly progressing lesions in young patients presenting with oculomotor/visual/endocrinological impairment. Whenever surgery is offered, open cranial approaches are the current standard. There is limited experience reported about endoscopic endonasal approach for CSMs and the main indication is decompression of the cavernous sinus to improve symptoms. Whenever surgery is indicated, the current trend is to offer decompression followed by radiosurgery.

Experience with awake throughout craniotomy in tumour surgery

Acta Neurochirurgica (2020) 162:3055–3065

Awake craniotomy is the standard of care in surgery of tumours located in eloquent parts of the brain. However, high variability is recorded in multiple parameters, including anaesthetic techniques, mapping paradigms and technology adjuncts. The current study is focused primarily on patients’ level of consciousness, surgical technique, and experience based on a cohort of 50 consecutive cases undergoing awake throughout craniotomy (ATC).

Methods Data was collected prospectively for 46 patients undergoing 50 operations over 14-month period, by the senior author, including demographics, extent of resection (EOR), adverse intraoperative events, surgical morbidity, surgery duration, levels of O2 saturation and brain oedema. A prospective, patient experience questionnaire was delivered to 38 patients.

Results The ATC technique was well tolerated in all patients. Once TCI stopped, all patients were immediately assessable for mapping. Despite > 75% of cases being considered inoperable/high risk, gross total resection (GTR) was achieved in 68% patients and subtotal resection in 20%. The average duration of surgery was 220 min with no episodes of hypoxia. Early and late severe deficits recorded in 12% and 2%, respectively. No stimulation-induced seizures or failed ATCs were recorded. Patient-recorded data showed absent/minimal pain during (1) clamp placement in 95.6% of patients; (2) drilling in 94.7% of patients; (3) surgery in 78.9% of patients. Post-operatively, 92.3% of patients reported willingness to repeat the ATC, if necessary.

Conclusions The current ATC paradigm allows immediate brain mapping, maximising patient comfort during selfpositioning. Despite the cohort of challenging tumour location, satisfactory EOR was achieved with acceptable morbidity and no adverse intraoperative events.

Prognostic Importance of Age, Tumor Location, and Tumor Grade in Grade II Astrocytomas

World Neurosurg. (2019) 121:e411-e418

Previous work in anaplastic astrocytoma (AA) demonstrated that the survival benefit from gross total resection (GTR) is modified by age and tumor location. Here, we determined the influence of age and tumor location on survival benefit from GTR in diffuse astrocytoma (DA).

METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database (1999-2010). We used Kaplan- Meier curves and Cox survival models to determine the survival benefit from GTR in populations stratified by age and tumor location. We determined the prevalence of the mutated isocitrate dehydrogenase (mIDH) using The Cancer Genome Atlas (TCGA).

RESULTS: We identified 1980 patients with DA. For frontal DAs, GTR resulted in improved survival relative to subtotal resection in all ages (age ≤50 years hazard ratio [HR], 0.56; P [ 0.002; age >50 years HR, 0.41; P < 0.001). For nonfrontal DAs, only patients ≤50 years experienced improved survival with GTR (age ≤50 years HR, 0.55; P [ 0.002; age >50 years HR, 0.78; P [ 0.114). For patients ≤50 years with frontal tumors, survival was comparable between DA and AA after GTR (75% survival DA: 80 months, AA: 89 months, P [ 0.973). In TCGA, these tumors were nearly uniformly mIDH (DA: 98%; AA: 90%, P [ 0.11). However, for patients ≤50 years with nonfrontal tumors, there was a survival difference after GTR (75% survival DA: 80 months, AA: 30 months, P [ 0.001) despite comparable mIDH prevalence (DA: 82%, AA: 75%, P [ 0.49).

CONCLUSIONS: Age and tumor location modify the survival benefit derived from GTR in DA. Survival patterns in SEER imperfectly correlated with mIDH prevalence in TCGA, suggesting that tumor grade and mIDH status convey nonredundant prognostic information in select clinical contexts

Quality of Life in Patients with Vestibular Schwannomas Following Gross Total or Less than Gross Total Microsurgical Resection: Should We be Taking the Entire Tumor Out?

Neurosurgery 82:541–547, 2018

The goal of microsurgical removal of a vestibular schwannoma is to completely remove the tumor, to provide long-term durable cure. In many cases, less than gross total resection (GTR) is performed to preserve neurological, and especially facial nerve function.

OBJECTIVE: To analyze long-term quality of life (QoL) in a cohort of patients who received either GTR or less than GTR.

METHODS: Patients operated for vestibular schwannoma less than 3.0 cm in posterior fossa diameter at 1 of 2 international tertiary care centers were surveyed using generic and disease-specific QoL instruments.

RESULTS: A total of 143 patients were analyzed. GTR was performed in 122, and 21 underwent less than GTR. QoL was assessed at a mean of 7.7 yr after surgery (interquartile range: 5.7-9.6). Patients who underwent GTR had smaller tumors; otherwise, there were no baseline differences between groups. Patients who underwent GTR, after multivariable adjustment for baseline features and facial nerve and hearing outcomes, reported statistically significantly better Short Form Health Survey-36 (SF-36) physical and mental scores, Patient-Reported Outcomes Measurement Information System (PROMIS-10) physical and mental scores, and Penn Acoustic NeuromaQuality of Life (PANQOL) facial, energy, general health, and total scores compared to patients receiving less than GTR.

CONCLUSION: GTR is associated with better QoL using the general QoL measures SF-36 and PROMIS-10 and the disease-specific PANQOL, even after controlling for baseline and outcome differences. This is especially significant in the assessment of mental health, indicating there may indeed be a psychological advantage to the patient that translates to overall well-being to have the entire tumor removed if microsurgical resection is undertaken.


Low-grade Glioma Surgery in Intraoperative Magnetic Resonance Imaging

Hypnosis for Awake Surgery of Low-grade Gliomas

Neurosurgery 78:775–786, 2016

The ideal treatment strategy for low-grade gliomas (LGGs) is a controversial topic. Additionally, only smaller single-center series dealing with the concept of intraoperative magnetic resonance imaging (iMRI) have been published.

OBJECTIVE: To investigate determinants for patient outcome and progression-freesurvival (PFS) after iMRI-guided surgery for LGGs in a multicenter retrospective study initiated by the German Study Group for Intraoperative Magnetic Resonance Imaging.

METHODS: A retrospective consecutive assessment of patients treated for LGGs (World Health Organization grade II) with iMRI-guided resection at 6 neurosurgical centers was performed. Eloquent location, extent of resection, first-line adjuvant treatment, neurophysiological monitoring, awake brain surgery, intraoperative ultrasound, and fieldstrength of iMRI were analyzed, as well as progression-free survival (PFS), new permanent neurological deficits, and complications. Multivariate binary logistic and Cox regression models were calculated to evaluate determinants of PFS, gross total resection (GTR), and adjuvant treatment.

RESULTS: A total of 288 patients met the inclusion criteria. On multivariate analysis, GTR significantly increased PFS (hazard ratio, 0.44; P < .01), whereas “failed” GTR did not differ significantly from intended subtotal-resection. Combined radiochemotherapy as adjuvant therapy was a negative prognostic factor (hazard ratio: 2.84, P < .01). Field strength of iMRI was not associated with PFS. In the binary logistic regression model, use of high-field iMRI (odds ratio: 0.51, P < .01) was positively and eloquent location (odds ratio: 1.99, P < .01) was negatively associated with GTR. GTR was not associated with increased rates of new permanent neurological deficits.

CONCLUSION: GTR was an independent positive prognostic factor for PFS in LGG surgery. Patients with accidentally left tumor remnants showed a similar prognosis compared with patients harboring only partially resectable tumors. Use of high-field iMRI was significantly associated with GTR. However, the field strength of iMRI did not affect PFS.

Gross Total Resection Rates in Contemporary Glioblastoma Surgery: Results of an Institutional Protocol Combining 5-Aminolevulinic Acid Intraoperative Fluorescence Imaging and Brain Mapping

Neurosurgery 71:927–936, 2012

Complete resection of contrast-enhancing tumor has been recognized as an important prognostic factor in patients with glioblastoma and is a primary goal of surgery. Various intraoperative technologies have recently been introduced to improve glioma surgery.

OBJECTIVE: To evaluate the impact of using 5-aminolevulinic acid and intraoperative mapping and monitoring on the rate of complete resection of enhancing tumor (CRET), gross total resection (GTR), and new neurological deficits as part of an institutional protocol.

METHODS: One hundred three consecutive patients underwent resection of glioblastoma from August 2008 to November 2010. Eligibility for CRET was based on the initial magnetic resonance imaging assessed by 2 reviewers. The primary end point was the number of patients with CRET and GTR. Secondary end points were volume of residual contrast-enhancing tissue and new postoperative neurological deficits. RESULTS: Fifty-three patients were eligible for GTR/CRET (n = 43 newly diagnosed glioblastoma, n = 10 recurrent); 13 additional patients received surgery for GTR/CRET-ineligible glioblastoma. GTR was achieved in 96% of patients (n = 51, no residual enhancement . 0.175 cm3); CRET was achieved in 89% (n = 47, no residual enhancement). Postoperatively, 2 patients experienced worsening of preoperative hemianopia, 1 patient had a new mild hemiparesis, and another patient sustained sensory deficits.

CONCLUSION: Using 5-aminolevulinic acid imaging and intraoperative mapping/ monitoring together leads to a high rate of CRET and an increased rate of GTR compared with the literature without increasing the rate of permanent morbidity. The combination of safety and resection-enhancing intraoperative technologies was likely to be the major drivers for this high rate of CRET/GTR.

Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience

J Neurooncol (2011) 102:105–113.DOI 10.1007/s11060-010-0296-4

We analyzed the efficacy and applicability of surgery guided by 5-aminolevulinic acid (ALA) fluorescence in consecutive patients with glioblastoma multiforme (GBM).

Thirty-six patients with GBM were operated on using ALA fluorescence. Resections were performed using the fluorescent light to assess the right plane of dissection. In each case, biopsies with different fluorescent quality were taken from the tumor center, from the edges, and from the surrounding tissue. These samples were analyzed separately with hematoxylin–eosin examination and immunostaining against Ki67. Tumor volume was quantified with pre- and postoperative volumetric magnetic resonance imaging.

Strong fluorescence identified solid tumor with 100% positive predictive value. Invaded tissue beyond the solid tumor mass was identified by vague fluorescence with 97% positive predictive value and 66% negative predictive value, measured against hematoxylin–eosin examination. All the contrast-enhancing volume was resected in 83.3% of the patients, all patients had resection over 98% of the volume and mean volume resected was 99.8%. One month after surgery there was no mortality, and new or increased neurological morbidity was 8.2%.

The fluorescence induced by 5-aminolevulinic can help to achieve near total resection of enhancing tumor volume in most surgical cases of GBM. It is possible during surgery to obtain separate samples of the infiltrating cells from the tumor border.