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.

The Impact of Extent of Ablation on Survival of Patients With Newly Diagnosed Glioblastoma Treated With Laser Interstitial Thermal Therapy

Neurosurgery 93:427–435, 2023

Upfront laser interstitial thermal therapy (LITT) can be used as part of the treatment paradigm in difficult-to-access newly diagnosed glioblastoma multiforme (ndGBM) cases. The extent of ablation, though, is not routinely quantified; thus, its specific effect on patients’ oncological outcomes is unclear.

OBJECTIVE: To methodically measure the extent of ablation in the cohort of patients with ndGBM and its effect, and other treatment-related parameters, on patients’ progression-free survival (PFS) and overall survival (OS).

METHODS: A retrospective study was conducted on 56 isocitrate dehydrogenase 1/2 wild-type patients with ndGBM treated with upfront LITT between 2011 and 2021. Patient data including demographics, oncological course, and LITTassociated parameters were analyzed.

RESULTS: Patient median age was 62.3 years (31-84), and the median follow-up duration was 11.4 months. As expected, the subgroup of patients receiving full chemoradiation was found to have the most beneficial PFS and OS (n = 34). Further analysis showed that 10 of them underwent near-total ablation and had a significantly improved PFS (10.3 months) and OS (22.7 months). Notably, 84% excess ablation was detected which was not related to a higher rate of neurological deficits. Tumor volume was also found to influence PFS and OS, but it was not possible to further corroborate this finding because of low numbers.

CONCLUSION: This study presents data analysis of the largest series of ndGBM treated with upfront LITT. Near-total ablation was shown to significantly benefit patients’ PFS and OS. Importantly, it was shown to be safe, even in cases of excess ablation and therefore could be considered when using this modality to treat ndGBM.

Impact of awake mapping on overall survival and extent of resection in patients with adult diffuse gliomas within or near eloquent areas

Acta Neurochirurgica (2022) 164:395–404

Awake craniotomy (AC) with intraoperative mapping is the best approach to preserve neurological function for glioma surgery in eloquent or near eloquent areas, but whether AC improves the extent of resection (EOR) and overall survival (OS) is controversial. This study aimed to compare the long-term clinical outcomes of glioma resection under AC with those under general anesthesia (GA).

Methods Data of 335 patients who underwent surgery with intraoperative magnetic resonance imaging for newly diagnosed gliomas of World Health Organization (WHO) grades II-IV between 2000 and 2013 were reviewed. EOR and OS were quantitatively compared between the AC and GA groups after 1:1 propensity score matching. The two groups were matched for age, preoperative Karnofsky performance status (KPS), tumor location, and pathology.

Results After propensity score matching, 91 pairs were obtained. The median EOR was 96.1% (interquartile range [IQR] 7.3) and 97.4% (IQR 14.4) in the AC and GA groups, respectively (p = 0.31). Median KPS score 3 months after surgery was 90 (IQR 20) in both groups (p = 0.384). The median survival times were 163.3 months (95% confidence interval [CI] 77.9–248.7) and 143.5 months (95% CI 94.4–192.7) in the AC and GA groups, respectively (p = 0.585).

Conclusion Even if the glioma was within or close to the eloquent area, AC was comparable with GA in terms of EOR and OS. In case of difficulties in randomizing patients with eloquent or near eloquent glioma, our propensity score-matched analysis provides retrospective evidence that AC can obtain EOR and OS equivalent to removing glioma under GA.

Surgery of Insular Diffuse Gliomas—Part 1: Transcortical Awake Resection Is Safe and Independently Improves Overall Survival

Neurosurgery 89:565–578, 2021

Insular diffuse glioma resection is at risk of vascular injury and of postoperative new neurocognitive deficits.

OBJECTIVE: To assess safety and efficacy of surgical management of insular diffuse gliomas.

METHODS: Observational, retrospective, single-institution cohort analysis (2005-2019) of 149 adult patients surgically treated for an insular diffuse glioma: transcortical awake resection with intraoperative functional mapping (awake resection subgroup, n = 61), transcortical asleep resection without functional mapping (asleep resection subgroup, n = 50), and stereotactic biopsy (biopsy subgroup, n = 38). All cases were histopathologically assessed according to the 2016World Health Organization classification and cIMPACTNOW update 3.

RESULTS: Following awake resection, 3/61 patients had permanent motor deficit, seizure control rates improved (89% vs 69% preoperatively, P = .034), and neurocognitive performance improved from 5% to 24% in tested domains, despite adjuvant oncological treatments. Resection rates were higher in the awake resection subgroup (median 94%) than in the asleep resection subgroup (median 46%; P < .001). There was more gross total resection (25% vs 12%) and less partial resection (34% vs 80%) in the awake resection subgroup than in the asleep resection subgroup (P< .001). Karnofsky Performance Status score <70 (adjusted hazard ratio [aHR] 2.74, P = .031), awake resection (aHR 0.21, P = .031), isocitrate dehydrogenase (IDH)-mutant grade 2 astrocytoma (aHR 5.17, P = .003), IDHmutant grade 3 astrocytoma (aHR 6.11, P < .001), IDH-mutant grade 4 astrocytoma (aHR 13.36, P = .008), and IDH-wild-type glioblastoma (aHR 21.84, P < .001) were independent predictors of overall survival.

CONCLUSION:Awake surgery preserving the brain connectivity is safe, allows larger resections for insular diffuse gliomas than asleep resection, and positively impacts overall survival.

Impact of facility type and volume in low-grade glioma outcomes

J Neurosurg 133:1313–1323, 2020

The object of this study was to investigate the impact of facility type (academic center [AC] vs non-AC) and facility volume (high-volume facility [HVF] vs low-volume facility [LVF]) on low-grade glioma (LGG) outcomes.

METHODS This retrospective cohort study included 5539 LGG patients (2004–2014) from the National Cancer Database. Patients were categorized by facility type and volume (non-AC vs AC, HVF vs LVF). An HVF was defined as the top 1% of facilities according to the number of annual cases. Outcomes included overall survival, treatment receipt, and postoperative outcomes. Kaplan-Meier and Cox proportional-hazards models were applied. The Heller explained relative risk was computed to assess the relative importance of each survival predictor.

RESULTS Significant survival advantages were observed at HVFs (HR 0.67, 95% CI 0.55–0.82, p < 0.001) and ACs (HR 0.84, 95% CI 0.73–0.97, p = 0.015), both prior to and after adjusting for all covariates. Tumor resection was 41% and 26% more likely to be performed at HVFs vs LVFs and ACs vs non-ACs, respectively. Chemotherapy was 40% and 88% more frequently to be utilized at HVFs vs LVFs and ACs vs non-ACs, respectively. Prolonged length of stay (LOS) was decreased by 42% and 24% at HVFs and ACs, respectively. After tumor histology, tumor pattern, and codeletion of 1p19q, facility type and surgical procedure were the most important contributors to survival variance. The main findings remained consistent using propensity score matching and multiple imputation.

CONCLUSIONS This study provides evidence of survival benefits among LGG patients treated at HVFs and ACs. An increased likelihood of undergoing resections, receiving adjuvant therapies, having shorter LOSs, and the multidisciplinary environment typically found at ACs and HVFs are important contributors to the authors’ finding.

A Prospective Cohort Study of Neural Progenitor Cell-Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed PatientsWith Glioblastoma

Neurosurgery 87:E31–E40, 2020

In treating glioblastoma, irradiation of the neural progenitor cell (NPC) niches is controversial. Lower hippocampal doses may limit neurocognitive toxicity, but higher doses to the subventricular zones (SVZ) may improve survival.

OBJECTIVE: To prospectively evaluate the impact of limiting radiation dose to the NPC niches on tumor progression, survival, and cognition in patients with glioblastoma.

METHODS: Patients with glioblastoma received resection followed by standard chemoradiation. Radiation dose to the NPC niches, including the bilateral hippocampi and SVZ, was minimized without compromising tumor coverage. The primary outcome was tumor progression in the spared NPC niches. Follow-up magnetic resonance imaging was obtained bimonthly. Neurocognitive testing was performed before treatment and at 6- and 12-mo follow-up. Cox regression evaluated predictors of overall and progressionfree survival. Linear regression evaluated predictors of neurocognitive decline. RESULTS: A total of 30 patients enrolled prospectively. The median age was 58 yr. Median mean doses to the hippocampi and SVZ were 49.1 and 41.8 gray (Gy) ipsilaterally, and 16.5 and 19.9 Gy contralaterally. Median times to death and tumor progression were 16.0 and 7.6 mo, and were not significantly different compared to a matched historical control. No patients experienced tumor progression in the spared NPC-containing regions. Overall survival was associated with neurocognitive function (P ≤ .03) but not dose to the NPC niches. Higher doses to the hippocampi and SVZ predicted greater decline in verbal memory (P ≤ .01).

CONCLUSION: In treating glioblastoma, limiting dose to the NPC niches may reduce cognitive toxicity while maintaining clinical outcomes. Further studies are needed to confirm these results.

 

Posterior fossa meningiomas: perioperative predictors of extent of resection, overall survival and progression-free survival

Acta Neurochirurgica (2019) 161:1003–1011

Posterior fossa meningiomas (PFMs) often represent surgical challenges due to their proximity to neurovascular structures. Factors predicting the extent of resection (EOR), overall survival (OS), and progression-free survival (PFS) were identified and integrated in a prediction tool to offer evidence-based personalized therapeutic strategies.

Methods All meningiomas managed surgically from 1990 to 2010 from a single-center were reviewed. A classification tree was created using the classification and regression tree recursive partitioning analysis that incorporated patient and tumor data available before surgery in order to predict the rates of gross total resection (GTR).

Results A total of 198 patients were identified (female-to-male ratio, 2.7; mean age, 59.1 years) and compared with 1271 supratentorial meningiomas (STMs) operated in the same institution during the same time period. GTR was achieved less often (59.6% versus 81.9%; p < 0.01) in PFMs than STMs. Preoperative neurological symptoms were predictive of higher Simpson grades (OR, 2.19 [1.05; 4.58]; p = 0.04). Age was associated with reduced OS (OR, 1.08 [1.04;1.12]; p < 0.001). A KPS ≥ 70 was associated with higher survival rates (OR, 2.70 [2.19;2.92]; p = 0.02). Higher WHO grades were associated with reduced OS (OR, 3.56 [1.02;12.47]; p = 0.05). The GTR rate varies from 80% in patients without a preoperative deficit to 40% patients with a preoperative deficit, younger than 60 years old, and with adjacent bone invasion.

Conclusions This study provides a classification tree of the predictors of EOR in PFMs, based upon preoperative demographic, clinical, and radiological variables. An evidence-based management protocol with estimated EORs may guide the decision making process in PFMs.

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.

Advanced MRI may complement histological diagnosis of lower grade gliomas and help in predicting survival

Advanced MRI may complement histological diagnosis of lower grade gliomas and help in predicting survival

J Neurooncol (2016) 126:279–288

MRI grading of grade II and III gliomas may have an important impact on treatment decisions. Occasionally, both conventional MRI (cMRI) and histology fail to clearly establish the tumour grade. Three cMRI features (no necrosis; no relevant oedema; absent or faint contrast enhancement) previously validated in 196 patients with supratentorial gliomas directed our selection of 68 suspected low-grade gliomas (LGG) that were also investigated by advanced MRI (aMRI), including perfusion weighted imaging (PWI), diffusion weighted imaging (DWI) and spectroscopy. All the gliomas had histopathological diagnoses.

Sensitivity and specificity of cMRI preoperative diagnosis were 78.5 and 38.5 %, respectively, and 85.7 and 53.8 % when aMRI was included, respectively. ROC analysis showed that cut-off values of 1.29 for maximum rCBV, 1.69 for minimum rADC, 2.1 for rCho/Cr ratio could differentiate between LGG and HGG with a sensitivity of 61.5, 53.8, and 53.8 % and a specificity of 54.7, 43 and 64.3 %, respectively. A significantly longer OS was observed in patients with a maximum rCBV\1.46 and minimum rADC[1.69 (80 vs 55 months, p = 0.01; 80 vs 51 months, p = 0.002, respectively). This result was also confirmed when cases were stratified according to pathology (LGG vs HGG). The ability of aMRI to differentiate between LGG and HGG and to predict survival improved as the number of aMRI techniques considered increased.

In a selected population of suspected LGG, classification by cMRI underestimated the actual fraction of HGG. aMRI slightly increased the diagnostic accuracy compared to histopathology. However, DWI and PWI were prognostic markers independent of histological grade.

Anaplastic astrocytomas: survival and prognostic factors in a surgical series

AA

Acta Neurochir (2014) 156:1053–1061

To study patient characteristics, prognostic factors and overall survival (OS) in a consecutive, surgical series of WHO grade III anaplastic astrocytomas (AA).

Methods Patients were identified from a prospective tumor database at Oslo University Hospital, Norway, and patients undergoing surgery for an AA from 2005–2012 were included. Patients’ medical charts were retrospectively reviewed for data collection.

Results A total of 99 adult patients with histologically verified AA were included. Median age was 52 years (20–81). Biopsy was conducted in 33 % and resection in 67 %. Adjuvant treatment with radiation therapy + temozolomide or radiation therapy only was given in 63 % and 26 %, respectively. The thirty-day mortality rate was 3 %. Median OS was 19 months (95 % CI 11–27 months). Age≥65 years, KPS<70, biopsy as opposed to resection, and no adjuvant treatment were confirmed negative prognostic factors in multivariate analysis. For patients undergoing resection, presence of postoperative contrast-enhanced tumor, not volume of residual tumor, had significant impact on OS in adjusted analysis.

Conclusions Median OS following surgery was 19 months, though much variable outcome was observed among subgroups of AA (95 % CI 11–27 months). Age ≥65 years, KPS<70, biopsy as opposed to resection, and no adjuvant treatment were confirmed negative prognostic factors for OS.

Biopsy versus resection in the management of malignant gliomas: a systematic review and meta-analysis

J Neurosurg 112:1020–1032, 2010. DOI: 10.3171/2009.7.JNS09758

The aim of this study was to answer the question whether quality of life and progression-free and overall survival are increased in adults with supratentorial malignant glioma who are treated with cytoreductive resection as compared with those who only undergo biopsy.

Methods. A literature search of the electronic databases MEDLINE, EMBASE, and CENTRAL was performed to identify relevant studies published before May 2008. Hand-searching of reference lists of the identified studies and relevant review articles was also performed. A study was considered eligible, regardless of study design (prospective or retrospective), if: 1) quality of life and/or progression-free and/or overall survival was compared among adult patients undergoing biopsy or resection, and 2) patient age and Karnofsky Performance Scale scores were not significantly different among the 2 groups compared.

Results. One randomized controlled trial and 4 retrospective studies (involving a total of 1111 patients) were found eligible for this systematic review. A meta-analysis of the eligible studies demonstrated a significant increase in overall survival in the patients treated with resection instead of biopsy (hazard ratio 0.61, 95% CI 0.52–0.71, p < 0.0001, fixed-effect model). Although statistical pooling was not feasible, the available data suggest that quality of life was increased in patients treated with resection rather than biopsy, while there did not seem to be any significant difference in progression-free survival between the 2 groups.

Conclusions. Based on the best available evidence, it appears that cytoreductive resection in adults with supratentorial malignant glioma is associated with improved overall survival as compared with biopsy. However, well designed prospective studies are needed for more solid conclusions to be drawn.

Biopsy versus resection in the management of malignant gliomas

DOI: 10.3171/2009.7.JNS09758

The aim of this study was to answer the question whether quality of life and progression-free and overall survival are increased in adults with supratentorial malignant glioma who are treated with cytoreductive resection as compared with those who only undergo biopsy.

Methods. A literature search of the electronic databases MEDLINE, EMBASE, and CENTRAL was performed to identify relevant studies published before May 2008. Hand-searching of reference lists of the identified studies and relevant review articles was also performed. A study was considered eligible, regardless of study design (prospective or retrospective), if: 1) quality of life and/or progression-free and/or overall survival was compared among adult patients undergoing biopsy or resection, and 2) patient age and Karnofsky Performance Scale scores were not significantly different among the 2 groups compared.

Results. One randomized controlled trial and 4 retrospective studies (involving a total of 1111 patients) were found eligible for this systematic review. A meta-analysis of the eligible studies demonstrated a significant increase in overall survival in the patients treated with resection instead of biopsy (hazard ratio 0.61, 95% CI 0.52–0.71, p <0.0001, fixed-effect model). Although statistical pooling was not feasible, the available data suggest that quality of life was increased in patients treated with resection rather than biopsy, while there did not seem to be any significant difference in progression-free survival between the 2 groups.

Conclusions. Based on the best available evidence, it appears that cytoreductive resection in adults with supratentorial malignant glioma is associated with improved overall survival as compared with biopsy. However, welldesigned prospective studies are needed for more solid conclusions to be drawn.