Determinants of survival after re-resection for recurrent glioblastoma: a meta-analysis

Acta Neurochirurgica (2026) 168:11

This systematic review and meta-analysis examines prognostic factors affecting survival after re-resection for recurrent glioblastoma, synthesizing data from 30 studies (1,741 pooled patients). Key findings identify gross total resection and MGMT promoter methylation as strong positive predictors, while age and low preoperative KPS associate with poorer outcomes; adjuvant therapies and time to re-resection showed inconsistent effects.

The paper details search methods, risk-of-bias assessment, statistical approaches, sensitivity analyses for IDH status, and study heterogeneity limitations. Conclusions emphasize patient selection for re-resection based on functional status and molecular markers and call for prospective, standardized trials and individual-patient data analyses to refine management of recurrent glioblastoma.

Gross Total Resection (GTR): Achieving GTR at re-resection for recurrent glioblastoma is significantly associated with improved survival compared to subtotal resection (pooled HR ~0.52–0.70, p < 0.001).

MGMT Promoter Methylation: Patients with methylated MGMT promoter status at recurrence have significantly better survival following re-resection (multivariate HR = 0.45, 95% CI: 0.27–0.76, p < 0.01).

Preoperative Karnofsky Performance Status (KPS): A KPS score <70 before re-resection is strongly associated with poorer survival outcomes (HR = 2.25, 95% CI: 1.59–3.19, p < 0.001).

Age: Older age is modestly associated with worse survival after re-resection, but the effect size is small (HR = 1.02, 95% CI: 1.01–1.03, p < 0.001); age alone should not preclude aggressive treatment.

Adjuvant Chemotherapy and Radiotherapy: No significant survival benefit was found for adjuvant chemotherapy (HR = 0.69, p = 0.33), radiotherapy (HR = 0.62, p = 0.50), or combined chemoradiotherapy after re-resection.

Time to Re-resection: Longer time intervals between initial surgery and re-resection did not show a statistically significant association with improved survival (HR = 0.69, p = 0.16).

Personalized Approach: Selection for re-resection should prioritize patients with good performance status, favorable tumor characteristics, and methylated MGMT promoter, with GTR as a key goal.

Evidence Limitations: Most included studies were retrospective with heterogeneity in definitions and reporting; high-quality prospective trials are needed to refine prognostic assessments and treatment strategies.

Functional status in long-term survivors after mapping-guided surgery for diffuse low-grade glioma

J Neurosurg 144:139–150, 2026

This clinical study reports long-term functional outcomes in 103 consecutive patients with diffuse low-grade glioma who underwent mapping-guided resections and were followed for at least 15 years. Key findings include high overall survival (83.5%), mean postoperative KPS of 94.8, and 90% return-to-work rate, with low permanent neurological morbidity across 205 resections.

Comparative analysis shows patients who sustained employment had smaller pre/postoperative tumor volumes, greater extent of resection (including more supratotal resections), and less exposure to radiotherapy. The data support early maximal safe resection and postponement of radiotherapy to preserve long-term functional status and professional activity.

Functional Preservation: Long-term survivors of diffuse low-grade glioma (LGG) surgery had high rates of preserved functional status, with 90.7% of surviving patients maintaining a Karnofsky Performance Scale (KPS) score ≥ 80 after an average of 18.2 years follow-up.

Return to Work: 90% of patients were able to return to work after mapping-guided resection, and maintaining professional activity was strongly associated with higher preoperative KPS and greater extent of resection (EOR).

Extent of Resection (EOR): Greater EOR, particularly supratotal or total resections, correlated with better long-term functional outcomes and higher rates of continued employment.

Radiation Therapy Impact: Early or any radiotherapy (RT) was linked to lower rates of return to work and a reduced proportion of patients with KPS ≥ 80 at last follow-up, while chemotherapy did not show this negative association.

Timing of Surgery: Early surgery at diagnosis, especially in patients with higher KPS and smaller tumor volume, increased the chance for maximal resection and long-term preservation of functional status.

Low Neurological Morbidity: Permanent postoperative neurological deficits were rare (1.5% after 205 resections), supporting the safety of maximal resection with intraoperative mapping.

Malignant Transformation: The risk of malignant transformation was lower in patients with greater EOR and those who continued to work, suggesting oncological benefit from radical resection.

Adjuvant Therapy Strategy: A wait-and-watch strategy after maximal safe resection, postponing adjuvant treatments unless necessary, helped preserve long-term quality of life and autonomy.

Awake surgery for IDH-mutant grade 2 glioma involving the corpus callosum: long-term onco-functional results after callosectomy in 157 consecutive patients

J Neurosurg 143:1280–1289, 2025

This clinical study reports outcomes from 157 consecutive patients with IDH‑mutant grade 2 gliomas infiltrating the corpus callosum who underwent connectome-guided awake surgery with callosectomy. It summarizes surgical technique, extent of resection, complication rates, return-to-work statistics, histology, adjuvant treatments, reoperations, and long-term overall survival.

Comparative analysis contrasts complete (total/supratotal) versus incomplete resections, showing higher extent of resection, greater reoperation potential, and longer median overall survival when callosal tumor was fully removed, while preserved function and a 96.8% return-to-work rate underline favorable onco-functional balance.

Is FLAIRectomy Directly Correlated with Prolonged Survival in Glioblastoma? A Prospective National Multicenter Study on Correlation Between Extent of Tumor Resection and Clinical Outcome

Neurosurgery 97:489–500, 2025

This multicenter prospective study shows that the extent of FLAIRectomy (resection of FLAIR-positive areas) in glioblastoma is a stronger predictor of survival than traditional resection, with higher EOFR significantly improving progression-free and overall survival, especially in IDH-mutant tumors, without increasing neurological complications.

• FLAIRectomy, or resection of FLAIR-MRI hyperintense regions beyond the contrast-enhancing tumor, was studied in a prospective multicenter cohort of 150 glioblastoma patients.

• A higher extent of FLAIR resection (EOFR) was associated with significantly improved overall survival (OS) and progression-free survival (PFS), more so than resection of contrast-enhancing tumor alone.

• Each 1% increase in EOFR correlated with a 6.8% reduction in mortality risk for IDH-wildtype and 12.1% for IDH-mutant tumors.

• Mean OS was 28.4 months and mean PFS was 16.3 months in the study cohort.

• IDH1 mutation status was also associated with longer survival, but EOFR remained an independent predictor after adjustment.

• AI analysis confirmed that patients with higher EOFR clustered with longer survival.

• Neurological safety was addressed with intraoperative neuromonitoring and careful planning; permanent deficits occurred in 9/150 patients.

• The study concludes that FLAIR-based supramarginal resection may be a more reliable predictor of survival in glioblastoma than conventional imaging-guided resection.

Outcomes After Definitive Surgery for Spinal and Sacral Chordoma in 101 Patients Over 20 Years

Neurosurgery 96:494–504, 2025

Study Objective: Investigate postoperative outcomes of spinal chordoma surgery over 20 years.

Patient Cohort: 101 patients, average follow-up of 6.0 ± 4.2 years.

Recurrence and Mortality: 24.8% recurrence, 9.9% mortality.

Risk Factors: Tumors ≥100 cm³ and mobile spine chordomas linked to worse outcomes.

Neoadjuvant Radiotherapy: Associated with improved local recurrence-free survival (LRFS).

Age Impact: Patients ≥65 years at surgery have a higher mortality risk.

Surgical Outcomes: Pain decreased post-surgery, sensory deficits and weakness remained static.

Functional Outcomes: 39% of patients pain-free long-term, no significant change in sensory deficits.

Surgical Complications: 65.3% experienced complications; 32.7% required reoperation.

Radiotherapy Advances: Newer modalities like stereotactic photon therapy show promising LRFS rates.

Study Design: Retrospective review from 2003-2023 at a quaternary spinal oncology center.

Data Analysis: Multivariable Cox regression used to identify predictors of LRFS and OS.

Surgical Approach: Enneking Appropriate surgery preferred for better outcomes.

Clinical Predictors of Overall Survival in Very Elderly Patients With Glioblastoma: A National Cancer Database Multivariable Analysis

Neurosurgery 96:373–385, 2025

• Study Focus: The study analyzes clinical predictors of overall survival in very elderly patients (aged 80 and older) with glioblastoma, using data from the National Cancer Database.

• Patient Demographics: It includes 578 very elderly patients and 2836 elderly patients (aged 65-79), highlighting differences in insurance status and treatment patterns.

• Treatment Patterns: Very elderly patients are less likely to receive gross total resection (GTR), radiotherapy (RT), or chemotherapy (CT) compared to younger elderly counterparts, despite these treatments improving overall survival.

• Survival Outcomes: GTR, RT, and CT are associated with improved survival in very elderly patients, suggesting aggressive treatment may benefit selected patients.

• Statistical Methods: The study employs multivariable regression analysis and Cox proportional-hazards models to assess the effects of age and treatment on survival.

• Key Findings: Aggressive treatment approaches, including GTR, RT, and CT, should be considered for very elderly patients, aligning with patient and family goals.

• Limitations: The study acknowledges limitations in meeting the Cox proportional hazard assumption and suggests further research on quality of life post-treatment.

• Conclusion: The study supports offering standard multimodal treatment protocols for glioblastoma to patients aged 65 and older, enhancing external validity across the U.S.

Awake Versus Asleep Craniotomy for Patients With Eloquent Glioma: A Systematic Review and Meta-Analysis

Neurosurgery 94:38–52, 2024

Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the resection of gliomas in the eloquent regions. METHODS: MEDLINE and PubMed were searched from inception to December 13, 2022. Primary outcomes were the extent of resection (EOR), overall survival (month), progression-free survival (month), and rates of neurological deficit, Karnofsky performance score, and seizure freedom at the 3-month follow-up. Secondary outcomes were duration of operation (minute) and length of hospital stay (LOS) (day).

RESULTS: Fifteen studies yielded 2032 patients, from which 800 (39.4%) and 1232 (60.6%) underwent awake and asleep craniotomy, respectively. The meta-analysis concluded that the awake group had greater EOR (mean difference [MD]= MD= 8.52 [4.28, 12.76], P < .00001), overall survival (MD = 2.86 months [1.35, 4.37], P = .0002), progression-free survival (MD = 5.69 months [0.75, 10.64], P = .02), 3-month postoperative Karnofsky performance score (MD = 13.59 [11.08, 16.09], P < .00001), and 3-month postoperative seizure freedom (odds ratio = 8.72 [3.39, 22.39], P < .00001). Furthermore, the awake group had lower 3-month postoperative neurological deficit (odds ratio = 0.47 [0.28, 0.78], P = .004) and shorter LOS (MD = -2.99 days [-5.09, -0.88], P = .005). In addition, the duration of operation was similar between the groups (MD = 37.88 minutes [-34.09, 109.86], P = .30).

CONCLUSION: Awake craniotomy for gliomas in the eloquent regions benefits EOR, survival, postoperative neurofunctional outcomes, and LOS. When feasible, the authors recommend awake craniotomy for surgical resection of gliomas in the eloquent regions.

Surgical, functional, and oncological considerations regarding awake resection for giant diffuse lower-grade glioma of more than 100 cm3

J Neurosurg 139:934–943, 2023

Surgery for giant diffuse lower-grade gliomas (LGGs) is challenging, and very few data have been reported on this topic in the literature. In this article, the authors investigated surgical, functional, and oncological aspects in patients who underwent awake resection for large LGGs with a volume > 100 cm3.

METHODS The authors retrospectively reviewed a consecutive cohort of patients who underwent surgery in an awake condition for an LGG (WHO grade 2 with possible foci of grade 3 transformation) with a volume > 100 cm3.

RESULTS A total of 108 patients were included, with a mean age of 36.1 ± 8.5 years. The mean presurgical LGG volume was 136.7 ± 34.5 cm3. In all but 2 patients a disconnection resective surgery up to functional boundaries was possible thanks to active patient collaboration during the awake period. At 3 months of follow-up, all but 1 patient had a normal neurological examination, with a mean Karnofsky Performance Status (KPS) score of 89.8 ± 10.36. In all patients with preoperative epilepsy, there was postoperative control or significant reduction of seizure events. Moreover, 85.1% of patients returned to work. The mean extent of resection (EOR) was 88.9% ± 7.0%, with a mean residual tumor volume (RTV) of 16.3 ± 12.0 cm3 (median RTV 15 cm3). Pathological examination revealed 73 grade 2 gliomas (67.6%; 26 oligodendrogliomas and 47 astrocytomas) and 35 gliomas with foci of grade 3 (32.4%; 19 oligodendrogliomas and 16 astrocytomas). During the postoperative period, 93.6% of patients underwent adjuvant chemotherapy with a median interval between surgery and first chemotherapy of 14 months (IQR 2–26 months), and 55% of patients had radiotherapy with a median interval of 38.5 months (IQR 18–59.8 months). At the last follow-up, 69.7% of patients were still alive with a median follow-up of 62 months (IQR 36–99 months). Overall survival (OS) rates at 1, 5, and 10 years were 100% (95% CI 0.99–1), 80% (95% CI 0.72–0.9), and 58% (95% CI 0.45–0.73), respectively. The median OS was 138 months. In multivariable Cox regression analysis, RTV was established as the only independent prognostic factor for survival.

CONCLUSIONS With the application of rigorous surgical methodology based on functional-guided resection, resection of giant LGGs (volume > 100 cm3) can be reproducibly achieved during surgery with patients under awake mapping with both favorable functional results (< 1% permanent neurological worsening) and favorable long-term oncological outcomes (median OS > 11 years, with a more significant benefit when the RTV is < 15 cm3).

Management strategies in clival and craniovertebral junction chordomas: a 29-year experience

J Neurosurg 138:1640–1652, 2023

Chordomas represent one of the most challenging subsets of skull base and craniovertebral junction (CVJ) tumors to treat. Despite extensive resection followed by proton-beam radiation therapy, the recurrence rate remains high, highlighting the importance of developing efficient treatment strategies. In this study, the authors present their experience in treating clival and CVJ chordomas over a 29-year period.

METHODS The authors conducted a retrospective study of clival and CVJ chordomas that were surgically treated at their institution from 1991 to 2020. This study focuses on three aspects of the management of these tumors: the factors influencing the extent of resection (EOR), the predictors of survival, and the outcomes of the endoscopic endonasal approaches (EEAs) compared with open approaches (OAs).

RESULTS A total of 265 surgical procedures were performed in 210 patients, including 123 OAs (46.4%) and 142 EEAs (53.6%). Tumors that had an intradural extension (p = 0.03), brainstem contact (p = 0.005), cavernous sinus extension (p = 0.004), major artery encasement (p = 0.01), petrous apex extension (p = 0.003), or high volume (p = 0.0003) were significantly associated with a lower EOR. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 52.1% and 75.1%, respectively. Gross-total resection and Ki-67 labeling index < 6% were considered to be independent prognostic factors of longer PFS (p = 0.0005 and p = 0.003, respectively) and OS (p = 0.02 and p = 0.03, respectively). Postoperative radiation therapy correlated independently with a longer PFS (p = 0.006). Previous surgical treatment was associated with a lower EOR (p = 0.01) and a higher rate of CSF leakage after EEAs (p = 0.02) but did not have significantly lower PFS and OS compared with primary surgery. Previously radiation therapy correlated with a worse outcome, with lower PFS and OS (p = 0.001 and p = 0.007, respectively). EEAs were more frequently used in patients with upper and middle clival tumors (p = 0.002 and p < 0.0001, respectively), had a better rate of EOR (p = 0.003), and had a lower risk of de novo neurological deficit (p < 0.0001) compared with OAs. The overall rate of postoperative CSF leakage after EEAs was 14.8%.

CONCLUSIONS This large study showed that gross-total resection should be attempted in a multidisciplinary skull base center before providing radiation therapy. EEAs should be considered as the gold-standard approach for upper/middle clival lesions based on the satisfactory surgical outcome, but OAs remain important tools for large complex chordomas.

The impact of multiple lesions on progression-free survival of meningiomas: a 10-year multicenter experience

J Neurosurg 137:9–17, 2022

Multiple meningiomas (MMs) occur in as many as 18% of patients with meningioma, and data on progression- free survival (PFS) are scarce. The objective of this study was to explore the influence of the number of lesions and clinical characteristics on PFS in patients with WHO grade I meningiomas.

METHODS The authors retrospectively reviewed the records of all adults diagnosed with a meningioma at their three main sites from January 2009 to May 2020. Progression was considered the time from diagnosis until radiographic growth of the originally resected meningioma. A secondary analysis was performed to evaluate the time of diagnosis until the time to second intervention (TTSI). Univariable and multivariable analyses were conducted to assess whether the number of lesions or any associated variables (age, sex, race, radiation treatment, tumor location, and extent of resection) had a significant impact on PFS and TTSI.

RESULTS Eight hundred thirty-eight patients were included. Use of a log-rank test to evaluate PFS and TTSI between a single and multiple lesions showed a significantly shorter progression for MM (p < 0.001 and p < 0.001, respectively). Multivariable Cox regression analysis showed significantly inferior PFS on MM compared to a single lesion (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.392–3.677, p = 0.001) and a significantly inferior TTSI for patients with MM when compared to patients with a single meningioma (HR 2.377, 95% CI 1.617–3.494, p = 0.001). By testing the number of meningiomas as a continuous variable, PFS was significantly inferior for each additional meningioma (HR 1.350, 95% CI 1.074–1.698, p = 0.010) and TTSI was significantly inferior as well (HR 1.428, 95% CI 1.189–1.716, p < 0.001). African American patients had an inferior PFS when compared to non-Hispanic White patients (HR 3.472, 95% CI 1.083–11.129, p = 0.036).

CONCLUSIONS The PFS of meningiomas appears to be influenced by the number of lesions present. Patients with MM also appear to be more prone to undergoing a second intervention for progressive disease. Hence, a closer follow-up may be warranted in patients who present with multiple lesions. These results show a decreased PFS for each additional lesion present, as well as a shorter PFS for MM compared to a single lesion. When assessing associated risk factors, African American patients showed an inferior PFS, whereas older age and adjuvant therapy with radiation showed an improved PFS.

 

Extending the multistage surgical strategy for recurrent initially low-grade gliomas: functional and oncological outcomes in 31 consecutive patients who underwent a third resection under awake mapping

J Neurosurg 136:1035–1044, 2022

Maximal safe resection is the first treatment in diffuse low-grade glioma (DLGG). Due to frequent tumor recurrence, a second surgery has already been reported, with favorable results. This study assesses the feasibility and functional and oncological outcomes of a third surgery in recurrent DLGG.

METHODS Patients with DLGG who underwent a third functional-based resection using awake mapping were consecutively selected. They were classified into group 1 in cases of slow tumor regrowth or group 2 if a radiological enhancement occurred during follow-up. All data regarding clinicoradiological features, histomolecular results, oncological treatment, and survival were collected.

RESULTS Thirty-one patients were included, with a median age of 32 years. There were 20 astrocytomas and 11 oligodendrogliomas in these patients. Twenty-one patients had medical oncological treatment before the third surgery, consisting of chemotherapy in 19 cases and radiotherapy in 8 cases. No neurological deficit persisted after the third resection except mild missing words in 1 patient, with 84.6% of the patients returning to work. The median follow-up duration was 13.1 ± 3.4 years since diagnosis, and 3.1 ± 2.9 years since the third surgery. The survival rates at 7 and 10 years were 100% and 89.7%, respectively, with an estimated median overall survival of 17.8 years since diagnosis. A comparison between the groups showed that the Karnofsky Performance Scale score dropped below 80 earlier in group 2 (14.3 vs 17.1 years, p = 0.01). Median residual tumor volume at the third surgery was smaller (2.8 vs 14.4 cm 3 , p = 0.003) with a greater extent of resection (89% vs 70%, p = 0.003) in group 1.

CONCLUSIONS This is the first consecutive series showing evidence that, in select patients with progressive DLGG, a third functional-based surgery can be achieved using awake mapping with low neurological risk and a high rate of total resection, especially when reoperation is performed before malignant transformation.

Influence of supramarginal resection on survival outcomes after gross-total resection of IDH–wild-type glioblastoma

J Neurosurg 136:1–8, 2022

The authors’ goal was to use a multicenter, observational cohort study to determine whether supramarginal resection (SMR) of FLAIR-hyperintense tumor beyond the contrast-enhanced (CE) area influences the overall survival (OS) of patients with isocitrate dehydrogenase–wild-type (IDH-wt) glioblastoma after gross-total resection (GTR).

METHODS The medical records of 888 patients aged ≥ 18 years who underwent resection of GBM between January 2011 and December 2017 were reviewed. Volumetric measurements of the CE tumor and surrounding FLAIR-hyperintense tumor were performed, clinical variables were obtained, and associations with OS were analyzed.

RESULTS In total, 101 patients with newly diagnosed IDH-wt GBM who underwent GTR of the CE tumor met the inclusion criteria. In multivariate analysis, age ≥ 65 years (HR 1.97; 95% CI 1.01–2.56; p < 0.001) and contact with the lateral ventricles (HR 1.59; 95% CI 1.13–1.78; p = 0.025) were associated with shorter OS, but preoperative Karnofsky Performance Status ≥ 70 (HR 0.47; 95% CI 0.27–0.89; p = 0.006), MGMT promotor methylation (HR 0.63; 95% CI 0.52–0.99; p = 0.044), and increased percentage of SMR (HR 0.99; 95% CI 0.98–0.99; p = 0.02) were associated with longer OS. Finally, 20% SMR was the minimum percentage associated with beneficial OS (HR 0.56; 95% CI 0.35–0.89; p = 0.01), but > 60% SMR had no significant influence (HR 0.74; 95% CI 0.45–1.21; p = 0.234).

CONCLUSIONS SMR is associated with improved OS in patients with IDH-wt GBM who undergo GTR of CE tumor. At least 20% SMR of the CE tumor was associated with beneficial OS, but greater than 60% SMR had no significant influence on OS.

Is There a Role for Surgical Resection of Multifocal Glioblastoma? A Retrospective Analysis of 100 Patients

Neurosurgery 89:1042–1051, 2021

Glioblastoma with multiple localizations (mGBMs) can be defined as multifocal, where enhancing lesions present a connection visible on magnetic resonance imaging fluid-attenuated inversion recovery imaging, or multicentric, in the absence of a clear dissemination pathway.

OBJECTIVE: To evaluate the role of the extent of resection (EOR) in the treatment of mGBMs and its correlation with overall survival (OS) and progression free survival (PFS).

METHODS: One hundred patients with mGBMs were treated at our Institution between 2009 and 2019. Clinical, radiological, and follow-up datawere collected. EOR of the contrastenhancing part of lesions was classified as gross total resection (GTR, absence of tumor remnant), subtotal resection (STR, residual tumor < 30% of the initial mass), partial resection (PR, residual tumor>30% of the initialmass), and needle or open biopsy (residual tumor > 75% of the initial mass).

RESULTS: Approximately 15% of patients underwent GTR, 14% STR, 32% PR, and 39% biopsy. Median OS was 17 mo for GTR, 11 mo for STR, 7 mo for PR, and 5 mo for biopsy. Greater EOR was associated with a significantly longer OS than biopsy. GTR and STR were associated with a longer PFS in Kaplan-Meier survival analyses. After adjusting for age, Karnofsky performance status (KPS), number of lesions, and adjunctive therapy in multivariable Cox regression analyses, GTR, STR, and PR were still associated with OS, but only GTR remained associated with PFS.

CONCLUSION: Our study suggests that EOR may positively influence survival of patients with mGBM. Surgical resection can be a reasonable option when performance and access to adjuvant treatment can be preserved.

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.

Tumor Growth Rate as a New Predictor of Progression-Free Survival After Chordoma Surgery

Neurosurgery 89:291–299, 2021

Currently, different postoperative predictors of chordoma recurrence have been identified. Tumor growth rate (TGR) is an image-based calculation that provides quantitative information of tumor’s volume changing over time and has been shown to predict progression-free survival (PFS) in other tumor types.

OBJECTIVE: To explore the usefulness of TGR as a new preoperative radiological marker for chordoma recurrence.

METHODS: A retrospective single-institution study was carried out including patients reflecting these criteria: confirmed diagnosis of chordoma on pathological analysis, no history of previous radiation, and at least 2 preoperative thin-slice magnetic resonance images available to measure TGR. TGR was calculated for all patients, showing the percentage change in tumor size over 1 mo.

RESULTS: A total of 32 patients were retained for analysis. Patients with a TGR ≥ 10.12%/m had a statistically significantly lower mean PFS (P<.0001). TGR≥10.12%/m (odds ratio=26, P=.001) was observed more frequently in recurrent chordoma. In a subgroup analysis, we found that the association of Ki-67 labeling index≥6% and TGR≥10.12%/m was correlated with recurrence (P = .0008).

CONCLUSION: TGR may be considered as a preoperative radiological indicator of tumor proliferation and seems to preoperatively identify more aggressive tumors with a higher tendency to recur. Our findings suggest that the therapeutic strategy and clinical radiological follow-up of patients with chordoma can be adapted also according to this new parameter.

Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN): 12-Month Outcomes and Quality of Life After Brain Tumor Ablation

Neurosurgery 87:E338–E346, 2020

Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN) is an ongoing multicenter prospective NeuroBlate (Monteris Medical) LITT (laser interstitial thermal therapy) registry collecting real-world outcomes and quality- of-life (QoL) data.

OBJECTIVE: To compare 12-mo outcomes from all subjects undergoing LITT for intracranial tumors/neoplasms.

METHODS: Demographics, intraprocedural data, adverse events, QoL, hospitalizations, health economics, and survival data are collected; standard data management and monitoring occur.

RESULTS: A total of 14 centers enrolled 223 subjects; the median follow-up was 223 d. There were 119 (53.4%) females and 104 (46.6%) males. The median age was 54.3 yr (range 3-86) and 72.6% had at least 1 baseline comorbidity. The median baseline Karnofsky Performance Score (KPS) was 90. Of the ablated tumors, 131 were primary and 92 were metastatic. Most patients with primary tumors had high-grade gliomas (80.9%). Patients with metastatic cancer had recurrence (50.6%) or radiation necrosis (40%). The median postprocedure hospital stay was 33.4 h (12.7-733.4). The 1-yr estimated survival rate was 73%, and this was not impacted by disease etiology. Patient-reported QoL as assessed by the Functional Assessment of Cancer Therapy-Brain was stabilized postprocedure. KPS declined by an average of 5.7 to 10.5 points postprocedure; however, 50.5% had stabilized/improved KPS at 6 mo. There were no significant differences in KPS or QoL between patients with metastatic vs primary tumors.

CONCLUSION: Results from the ongoing LAANTERN registry demonstrate that LITT stabi- lizes and improves QoL from baseline levels in a malignant brain tumor patient population with high rates of comorbidities. Overall survival was better than anticipated for a real- world registry and comparative to published literature.

Efficacy and safety of gamma knife radiosurgery for posterior cranial fossa meningioma

Neurosurgical Review (2020) 43:1089–1099

The management of posterior cranial fossa meningioma [PCFM] is challenging and many neurosurgeons advise gamma knife radiosurgery [GKRS] as a modality for its upfront or adjuvant treatment. Due to the varying radiosurgical response based on lesion location, tumor biology, and radiation dosage, we performed a pioneer attempt in doing a systematic review analyzing the treatment efficacy and safety profile of GKRS for PCFM based on current literature.

A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] guidelines. A thorough literature search was conducted on PubMed, Web of science, and Cochrane data base; articles were selected systematically based on PRISMA protocol, reviewed completely, and relevant data was summarized and discussed.

A total of 18 publications pertaining to GKRS for PCFM were included with a pooled sample size of 2131 patients. The median pre-GKRS tumor volume ranged from 2.28 to 10.5 cm [3]. Primary GKRS was administered in 61.1% of the pooled study cohorts, adjuvant treatment in 32.9%, and salvage therapy in 6.5% patients. Majority of the meningiomas were WHO grade 1 tumors (99.7%). The pooled mean marginal dose in the studies was 13.6 Gy (range 12–15.2 Gy) while the mean of maximum doses was 28.6 Gy (range 25–35 Gy). Most studies report an excellent radiosurgical outcome including the tumor control rate and the progression-free survival [PFS] of over 90%. The tumor control, PFS, and adverse radiation effect [ARE] rates in author’s series were 92.3%, 91%, and 9.6%, respectively. The favorable radiosurgical outcome depends on multiple factors such as small tumor volume, absence of previous radiotherapy, tumor location, elderly patients, female gender, longer time from symptom onset, and decreasing maximal dose.

GKRS as primary or adjuvant treatment modality needs to be considered as a promising management strategy for PCFM in selected patients in view of the growing evidence of high tumor control rate, improved neurological functions, and low incidence of ARE. The use of multiple isocenters, 3-D image planning, and limit GKRS treatment to tumors less than 3.5 cm help to avoid complications and achieve the best results. The treatment decisions in PCFM cases must be tailored and should consider the factors such as radiological profile, symptom severity, performance level, and patient preference for a good outcome.

To treat or not to treat? A retrospective multicenter assessment of survival in patients with IDH-mutant low-grade glioma based on adjuvant treatment

J Neurosurg 133:273–280, 2020

The level of evidence for adjuvant treatment of diffuse WHO grade II glioma (low-grade glioma, LGG) is low. In so-called “high-risk” patients most centers currently apply an early aggressive adjuvant treatment after surgery. The aim of this assessment was to compare progression-free survival (PFS) and overall survival (OS) in patients receiving radiation therapy (RT) alone, chemotherapy (CT) alone, or a combined/consecutive RT+CT, with patients receiving no primary adjuvant treatment after surgery.

METHODS Based on a retrospective multicenter cohort of 288 patients (≥ 18 years old) with diffuse WHO grade II gliomas, a subgroup analysis of patients with a confirmed isocitrate dehydrogenase (IDH) mutation was performed. The influence of primary adjuvant treatment after surgery on PFS and OS was assessed using Kaplan-Meier estimates and multivariate Cox regression models, including age (≥ 40 years), complete tumor resection (CTR), recurrent surgery, and astrocytoma versus oligodendroglioma.

RESULTS One hundred forty-four patients matched the inclusion criteria. Forty patients (27.8%) received adjuvant treatment. The median follow-up duration was 6 years (95% confidence interval 4.8–6.3 years). The median overall PFS was 3.9 years and OS 16.1 years. PFS and OS were significantly longer without adjuvant treatment (p = 0.003). A significant difference in favor of no adjuvant therapy was observed even in high-risk patients (age ≥ 40 years or residual tumor, 3.9 vs 3.1 years, p = 0.025). In the multivariate model (controlled for age, CTR, oligodendroglial diagnosis, and recurrent surgery), patients who received no adjuvant therapy showed a significantly positive influence on PFS (p = 0.030) and OS (p = 0.009) compared to any other adjuvant treatment regimen. This effect was most pronounced if RT+CT was applied (p = 0.004, hazard ratio [HR] 2.7 for PFS, and p = 0.001, HR 20.2 for OS). CTR was independently associated with longer PFS (p = 0.019). Age ≥ 40 years, histopathological diagnosis, and recurrence did not achieve statistical significance.

CONCLUSIONS In this series of IDH-mutated LGGs, adjuvant treatment with RT, CT with temozolomide (TMZ), or the combination of both showed no significant advantage in terms of PFS and OS. Even in high-risk patients, the authors observed a similar significantly negative impact of adjuvant treatment on PFS and OS. These results underscore the importance of a CTR in LGG. Whether patients ≥ 40 years old should receive adjuvant treatment despite a CTR should be a matter of debate. A potential tumor dedifferentiation by administration of early TMZ, RT, or RT+CT in IDH-mutated LGG should be considered. However, these data are limited by the retrospective study design and the potentially heterogeneous indication for adjuvant treatment.

 

An Online Calculator for the Prediction of Survival in Glioblastoma Patients Using Classical Statistics and Machine Learning

Neurosurgery, Volume 86, Issue 2, February 2020, Pages E184–E192

Although survival statistics in patients with glioblastoma multiforme (GBM) are well-defined at the group level, predicting individual patient survival remains challenging because of significant variation within strata.

OBJECTIVE: To compare statistical and machine learning algorithms in their ability to predict survival in GBM patients and deploy the best performing model as an online survival calculator.

METHODS: Patients undergoing an operation for a histopathologically confirmed GBM were extracted from the Surveillance Epidemiology and End Results (SEER) database (2005-2015) and split into a training and hold-out test set in an 80/20 ratio. Fifteen statistical and machine learning algorithms were trained based on 13 demographic, socioeconomic, clinical, and radiographic features to predict overall survival, 1-yr survival status, and compute personalized survival curves.

RESULTS: In total, 20 821 patients met our inclusion criteria. The accelerated failure time model demonstrated superior performance in terms of discrimination (concordance index = 0.70), calibration, interpretability, predictive applicability, and computational efficiency compared to Cox proportional hazards regression and other machine learning algorithms. This model was deployed through a free, publicly available software interface (https://cnoc-bwh.shinyapps.io/gbmsurvivalpredictor/).

CONCLUSION: The development and deployment of survival prediction tools require a multimodal assessment rather than a single metric comparison. This study provides a framework for the development of prediction tools in cancer patients, as well as an online survival calculator for patients with GBM. Future efforts should improve the interpretability, predictive applicability, and computational efficiency of existing machine learning algorithms, increase the granularity of population-based registries, and externally validate the proposed prediction tool.

Comparative Analysis of Subventricular Zone Glioblastoma Contact and Ventricular Entry During Resection in Predicting Dissemination, Hydrocephalus, and Survival

Neurosurgery, Volume 85, Issue 5, November 2019, Pages E924–E932

Ventricular entry during glioblastoma resection and tumor contact with the subventricular zone (SVZ) have both been shown to associate with development of hydrocephalus, leptomeningeal dissemination, distant parenchymal recurrence, and decreased survival. However, prior studies did not analyze these variables together in a single-patient population; therefore, it is unknown which is an independent predictor of these outcomes.

OBJECTIVE: To conduct a comparative outcome analysis of surgical ventricular entry and SVZ contact by glioblastoma in a retrospective cohort of 232 patients.

METHODS: Outcomes studied included hydrocephalus, leptomeningeal dissemination, distant tumor recurrences, and progression-free (PFS) and overall (OS) survival. The Cox proportional regression analyses were adjusted for age at diagnosis, preoperative Karnofsky performance status score, extent of resection, temozolomide and radiation treatments, and tumor molecular status (specifically, IDH1/2 mutation and MGMT promoter methylation).

RESULTS: Surgical ventricular entry, SVZ-contacting glioblastoma, hydrocephalus, leptomeningeal dissemination, and distant recurrences were observed in 85 (36.6%), 114 (49.1%), 19 (8.2%), 78 (33.6%), and 59 (25.4%) patients, respectively. Multivariate, adjusted analysis revealed SVZ tumor contact—but not ventricular entry—associated with hydrocephalus (hazard ratio, HR, 4.20 [1.13-15.7], P = .03), leptomeningeal dissemination (HR 1.93 [1.14-3.28], P = .01), PFS (HR 2.10 [1.53-2.88], P < .001), and OS (HR 1.90 [1.35-2.67], P < .001). Distant recurrences were not associated with either. No interaction between the 2 variables was statistically noted.

CONCLUSION: SVZ contact by glioblastoma was independently associated with the development of hydrocephalus, leptomeningeal dissemination, and decreased survival. SVZ tumor contact was associated with ventricular entry during surgical resections, which did not independently correlate with these outcomes.