Prognostic significance of MRI contrast enhancement in newly diagnosed glioblastoma, IDH-wildtype according to WHO 2021 classification.

BACKGROUND AND OBJECTIVES: Contrast enhancement in glioblastoma, IDH-wildtype is common but not systematic. In the era of the WHO 2021 Classification of CNS Tumors, the prognostic impact of a contrast enhancement and the pattern of contrast enhancement is not clearly elucidated. METHODS: We performed an observational, retrospective, single-centre cohort study at a tertiary neurosurgical oncology centre (January 2006 - December 2022). We screened adult patients with a newly-diagnosed glioblastoma, IDH-wildtype in order to assess the prognosis role of the contrast enhancement and the pattern of contrast enhancement. RESULTS: We included 1149 glioblastomas, IDH-wildtype: 26 (2.3%) had a no contrast enhancement, 45 (4.0%) had a faint and patchy contrast enhancement, 118 (10.5%) had a nodular contrast enhancement, and 960 (85.5%) had a ring-like contrast enhancement. Overall survival was longer in non-contrast enhanced glioblastomas (26.7 months) than in contrast enhanced glioblastomas (10.9 months) (p < 0.001). In contrast enhanced glioblastomas, a ring-like pattern was associated with shorter overall survival than in faint and patchy and nodular patterns (10.0 months versus 13.0 months, respectively) (p = 0.033). Whatever the presence of a contrast enhancement and the pattern of contrast enhancement, surgical resection was an independent predictor of longer overall survival, while age ≥ 70 years, preoperative KPS score < 70, tumour volume ≥ 30cm3, and postoperative residual contrast enhancement were independent predictors of shorter overall survival. CONCLUSION: A contrast enhancement is present in the majority (97.7%) of glioblastomas, IDH-wildtype and, regardless of the pattern, is associated with a shorter overall survival. The ring-like pattern of contrast enhancement is typical in glioblastomas, IDH-wildtype (85.5%) and remains an independent predictor of shorter overall survival compared to other patterns (faint and patchy and nodular).

Impact of frailty on survival glioblastoma, IDH-wildtype patients.

PURPOSE: Frailty increases the risk of mortality among patients. We studied the prognostic significance of frailty using the modified 5-item frailty index (5-mFI) in patients harboring a newly diagnosed supratentorial glioblastoma, IDH-wildtype. METHODS: We retrospectively reviewed records of patients surgical treated at a single neurosurgical institution at the standard radiochemotherapy era (January 2006 - December 2021). Inclusion criteria were: age ≥ 18, newly diagnosed glioblastoma, IDH-wildtype, supratentorial location, available data to assess the 5-mFI index. RESULTS: A total of 694 adult patients were included. The median overall survival was longer in the non-frail subgroup (5-mFI < 2, n = 538 patients; 14.3 months, 95%CI 12.5-16.0) than in the frail subgroup (5-mFI ≥ 2, n = 156 patients; 4.7 months, 95%CI 4.0-6.5 months; p < 0.001). 5-mFI ≥ 2 (adjusted Hazard Ratio (aHR) 1.31; 95%CI 1.07-1.61; p = 0.009) was an independent predictor of a shorter overall survival while age ≤ 60 years (aHR 0.78; 95%CI 0.66-0.93; p = 0.007), KPS score ≥ 70 (aHR 0.71; 95%CI 0.58-0.87; p = 0.001), unilateral location (aHR 0.67; 95%CI 0.52-0.87; p = 0.002), total removal (aHR 0.54; 95%CI 0.44-0.64; p < 0.0001), and standard radiochemotherapy protocol (aHR 0.32; 95%CI 0.26-0.38; p < 0.0001) were independent predictors of a longer overall survival. Frailty remained an independent predictor of overall survival within the subgroup of patients undergoing a first-line oncological treatment after surgery (n = 549) and within the subgroup of patients who benefited from a total removal plus adjuvant standard radiochemotherapy (n = 209). CONCLUSION: In newly diagnosed supratentorial glioblastoma, IDH-wildtype patients treated at the standard combined radiochemotherapy era, frailty, defined using a 5-mFI score ≥ 2 was an independent predictor of overall survival.

Carmustine wafer implantation for supratentorial glioblastomas, IDH-wildtype in "extreme" neurosurgical conditions.

We assessed the feasibility of Carmustine wafer implantation in "extreme" conditions (i.e. patients > 80 years and Karnofsky Performance Status score < 50) and of implantation ≥ 12 Carmustine wafers in adult patients harbouring a newly diagnosed supratentorial glioblastoma, IDH-wildtype. We performed an observational, retrospective single-centre cohort study at a tertiary surgical neuro-oncological centre between January 2006 and December 2021. Four hundred eighty patients who benefited from a surgical resection at first-line treatment were included. We showed that Carmustine wafer implantation in patients > 80 years, in patients with a Karnofsky performance status score < 50, and that implantation ≥ 12 Carmustine wafers (1) did not increase overall postoperative complication rates, (2) did not affect the completion of standard radiochemotherapy protocol, (3) did not worsen the postoperative Karnofsky Performance Status scores, and (4) did not significantly affect the time to oncological treatment. We showed that the implantation of ≥ 12 Carmustine wafers improved progression-free survival (31.0 versus 10.0 months, p = 0.025) and overall survival (39.0 versus 16.5 months, p = 0.041) without increasing postoperative complication rates. Carmustine wafer implantation during the surgical resection of a newly diagnosed supratentorial glioblastoma, IDH-wildtype is safe and efficient in patients > 80 years and in patients with preoperative Karnofsky Performance Status score < 50. The number of Carmustine wafers should be adapted (up to 16 in our experience) to the resection cavity to improve survival without increasing postoperative overall complication rates.

Predictors of postoperative epidural hematomas after custom-made porous hydroxyapatite cranioplasty: a single-center experience of 194 consecutive cases.

Cranioplasty is important for improving cosmesis and functional recovery after decompressive craniectomy. We assessed the incidence and predictors of post-cranioplasty epidural hematomas requiring surgical evacuation. A single-institution, retrospective study enrolled 194 consecutive patients who underwent a cranioplasty using custom-made hydroxyapatite between February 2008 and April 2022. Variables associated with postoperative epidural hematoma requiring surgical evacuation at the p < 0.1 level in unadjusted analysis were entered into multivariable analyses. Nine patients (4.6%) experienced postoperative epidural hematomas requiring evacuation, with time interval between craniectomy and cranioplasty <6 months (adjusted odds ratio (aOR), 20.75, p = 0.047), cranioplasty-to-bone shift > half of the bone thickness (aOR, 17.53, p = 0.008), >10 mm difference between pre-cranioplasty and post-cranioplasty midline brain shift contralateral to the cranioplasty (aOR, 17.26, p < 0.001), and non-resorbable duraplasty (aOR, 17.43, p = 0.011) identified as independent predictors. Seventeen patients (8.8%) experienced post-cranioplasty hydrocephalus requiring shunt placement. Twenty-six patients (13.4%) experienced postoperative infection. Sixteen patients (8.2%) had postoperative epileptic seizures. The identification of independent predictors of post-cranioplasty epidural hematomas requiring surgical evacuation will help identify at-risk patients, guide prophylactic care, and reduce morbidity of this common and important procedure.

Meningioma in patients exposed to progestin drugs: results from a real-life screening program.

PURPOSE: To report the results of systematic meningioma screening program implemented by French authorities in patients exposed to progestin therapies (cyproterone (CPA), nomegestrol (NA), and chlormadinone (CMA) acetate). METHODS: We conducted a prospective monocentric study on patients who, between September 2018 and April 2021, underwent standardized MRI (injection of gadolinium, then a T2 axial FLAIR and a 3D-T1 gradient-echo sequence) for meningioma screening. RESULTS: Of the 210 included patients, 15 (7.1%) had at least one meningioma; seven (7/15, 47%) had multiple meningiomas. Meningiomas were more frequent in older patients and after exposure to CPA (13/103, 13%) compared to NA (1/22, 4%) or CMA (1/85, 1%; P = 0.005). After CPA exposure, meningiomas were associated with longer treatment duration (median = 20 vs 7 years, P = 0.001) and higher cumulative dose (median = 91 g vs. 62 g, P = 0.014). Similarly, their multiplicity was associated with higher dose of CPA (median = 244 g vs 61 g, P = 0.027). Most meningiomas were ≤ 1 cm3 (44/58, 76%) and were convexity meningiomas (36/58, 62%). At diagnosis, patients were non-symptomatic, and all were managed conservatively. Among 14 patients with meningioma who stopped progestin exposure, meningioma burden decreased in 11 (79%) cases with no case of progression during MR follow-up. CONCLUSION: Systematic MR screening in progestin-exposed patients uncovers small and multiple meningiomas, which can be managed conservatively, decreasing in size after progestin discontinuation. The high rate of meningiomas after CPA exposure reinforces the need for systematic screening. For NA and CMA, further studies are needed to identify patients most likely to benefit from screening.

Accuracy and safety of 101 consecutives neurosurgical procedures for newly diagnosed central nervous system lymphomas: a single-institution experience.

INTRODUCTION: Brain surgery is required to ascertain the diagnosis of central nervous system lymphoma. We assessed the diagnostic yield and safety of the surgical procedures, the predictors of postoperative morbidity, and of overall survival. METHODS: Observational single-institution retrospective cohort study (1992-2020) of 101 consecutive adult patients who underwent stereotactic biopsy, open biopsy, or resection for a newly diagnosed central nervous system lymphoma. RESULTS: The diagnostic yield was 100% despite preoperative steroid administration in 48/101 cases (47.5%). A preoperative Karnofsky Performance Status score less than 70 (p = 0.006) was an independent predictor of a new postoperative focal neurological deficit (7/101 cases, 6.9%). A previous history of hematological malignancy (p = 0.049), age 65 years or more (p = 0.031), and new postoperative neurological deficit (p < 0.001) were independent predictors of a Karnofsky Performance Status score decrease 20 points or more postoperatively (13/101 cases, 12.9%). A previous history of hematological malignancy (p = 0.034), and preoperative Karnofsky Performance Status score less than 70 (p = 0.024) were independent predictors of postoperative hemorrhage (13/101 cases, 12.9%). A preoperative Karnofsky Performance Status score less than 70 (p = 0.019), and a previous history of hematological malignancy (p = 0.014) were independent predictors of death during hospital stay (8/101 cases, 7.9%). In the 82 immunocompetent patients harboring a primary central nervous system lymphoma, age 65 years or more (p = 0.044), and time to hematological treatment more than 21 days (p = 0.008), were independent predictors of a shorter overall survival. A dedicated hematological treatment (p < 0.001) was an independent predictor of a longer overall survival. CONCLUSION: Brain biopsy is feasible with low morbidity for central nervous system lymphomas. Postoperatively, patients should be promptly referred for hematological treatment initiation.

Discriminating surgical bed cysts from bacterial brain abscesses after Carmustine wafer implantation in newly diagnosed IDH-wildtype glioblastomas.

Carmustine wafers can be implanted in the surgical bed of high-grade gliomas, which can induce surgical bed cyst formation, leading to clinically relevant mass effect. An observational retrospective monocentric study was conducted including 122 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent a surgical resection with Carmustine wafer implantation as first line treatment (2005-2018). Twenty-two patients (18.0%) developed a postoperative contrast-enhancing cyst within the surgical bed: 16 surgical bed cysts and six bacterial abscesses. All patients with a surgical bed cyst were managed conservatively, all resolved on imaging follow-up, and no patient stopped the radiochemotherapy. Independent risk factors of formation of a postoperative surgical bed cyst were age ≥ 60 years (p = 0.019), number of Carmustine wafers implanted ≥ 8 (p = 0.040), and partial resection (p = 0.025). Compared to surgical bed cysts, the occurrence of a postoperative bacterial abscess requiring surgical management was associated more frequently with a shorter time to diagnosis from surgery (p = 0.009), new neurological deficit (p < 0.001), fever (p < 0.001), residual air in the cyst (p = 0.018), a cyst diameter greater than that of the initial tumor (p = 0.027), and increased mass effect and brain edema compared to early postoperative MRI (p = 0.024). Contrast enhancement (p = 0.473) and diffusion signal abnormalities (p = 0.471) did not differ between postoperative bacterial abscesses and surgical bed cysts. Clinical and imaging findings help discriminate between surgical bed cysts and bacterial abscesses following Carmustine wafer implantation. Surgical bed cysts can be managed conservatively. Individual risk factors will help tailor their steroid therapy and imaging follow-up.

Evolution of the neurosurgical management of progestin-associated meningiomas: a 23-year single-center experience.

PURPOSE: The improving knowledge of interactions between meningiomas and progestin refines the management of this specific condition. We assessed the changes over time of the management of progestin-associated meningiomas. METHODS: We retrospectively studied consecutive adult patients who had at least one meningioma in the context of progestin intake (October 1995-October 2018) in a tertiary adult Neurosurgical Center. RESULTS: 71 adult women with 125 progestin-associated meningiomas were included. The number of progestin-associated meningioma patients increased over time (0.5/year before 2008, 22.0/year after 2017). Progestin treatment was an approved indication in 27.0%. A mean of 1.7 ± 1.2 meningiomas were discovered per patient (median 1, range 1-6). Surgery was performed on 36 (28.8%) meningiomas and the histopathologic grading was WHO grade 1 in 61.1% and grade 2 in 38.9%. The conservative management of meningiomas increased over time (33.3% before 2008, 64.3% after 2017) and progestin treatment withdrawal increased over time (16.7% before 2008, 95.2% after 2017). Treatment withdrawal varied depending on the progestin derivative used (88.9% with cyproterone acetate, 84.6% with chlormadinone acetate, 28.6% with nomegestrol acetate, 66.7% with progestin derivative combination). The main reason for therapeutic management of meningiomas was the presence of clinical signs. Among the 54 meningiomas managed conservatively for which the progestin had been discontinued, MRI follow-up demonstrated a regression in 29.6%, a stability in 68.5%, and an ongoing growth in 1.9% of cases. CONCLUSIONS: Conservative management, including progestin treatment discontinuation, has grown over time with promising results in terms of efficacy and safety.

Is function-based resection using intraoperative awake brain mapping feasible and safe for solitary brain metastases within eloquent areas?

To assess feasibility and safety of function-based resection under awake conditions for solitary brain metastasis patients. Retrospective, observational, single-institution case-control study (2014-2019). Inclusion criteria are adult patients, solitary brain metastasis, supratentorial location within eloquent areas, and function-based awake resection. Case matching (1:1) criteria between metastasis group and control group (high-grade gliomas) are sex, tumor location, tumor volume, preoperative Karnofsky Performance Status score, age, and educational level. Twenty patients were included. Intraoperatively, all patients were cooperative; no obstacles precluded the procedure from being performed. A positive functional mapping was achieved at both cortical and subcortical levels, allowing for a function-based resection in all patients. The case-matched analysis showed that intraoperative and postoperative events were similar, except for a shorter duration of the surgery (p<0.001) and of the awake phase (p<0.001) in the metastasis group. A total resection was performed in 18 cases (90%, including 10 supramarginal resections), and a partial resection was performed in two cases (10%). At three months postoperative months, none of the patients had worsening of their neurological condition or uncontrolled seizures, three patients had an improvement in their seizure control, and seven patients had a Karnofsky Performance Status score increase ≥10 points. Function-based resection under awake conditions preserving the brain connectivity is feasible and safe in the specific population of solitary brain metastasis patients and allows for high resection rates within eloquent brain areas while preserving the overall and neurological condition of the patients. Awake craniotomy should be considered to optimize outcomes in brain metastases in eloquent areas.

How I do it: trans-cortical approach for insular diffuse glioma.

BACKGROUND: The function-based resection using trans-cortical approach for removing insular diffuse glioma shares a positive benefit-to-risk ratio with a low rate of permanent morbidity. METHOD: The technique requires intraoperative functional brain mapping to be performed under awake condition using direct electrical stimulations at both cortical and subcortical levels to identify brain connectivity supporting neurocognition. CONCLUSION: The trans-cortical approach is a safe and efficient technique to remove insular diffuse glioma. Intraoperative functional brain mapping under awake condition allows preserving brain connectivity and tailoring the resection. Great care must be taken in preventing vascular damages, and particularly the lenticulostriate arteries.

MRI Atlas of IDH Wild-Type Supratentorial Glioblastoma: Probabilistic Maps of Phenotype, Management, and Outcomes.

Background Tumor location is a main prognostic parameter in patients with glioblastoma. Probabilistic MRI-based brain atlases specifying the probability of tumor location associated with important demographic, clinical, histomolecular, and management data are lacking for isocitrate dehydrogenase (IDH) wild-type glioblastomas. Purpose To correlate glioblastoma location with clinical phenotype, surgical management, and outcomes by using a probabilistic analysis in a three-dimensional (3D) MRI-based atlas. Materials and Methods This retrospective study included all adults surgically treated for newly diagnosed IDH wild-type supratentorial glioblastoma in a tertiary adult surgical neuro-oncology center (2006-2016). Semiautomated tumor segmentation and spatial normalization procedures to build a 3D MRI-based atlas were validated. The authors performed probabilistic analyses by using voxel-based lesion symptom mapping technology. The Liebermeister test was used for binary data, and the generalized linear model was used for continuous data. Results A total of 392 patients (mean age, 61 years ± 13; 233 men) were evaluated. The authors identified the preferential location of glioblastomas according to subventricular zone, age, sex, clinical presentation, revised Radiation Therapy Oncology Group-Recursive Partitioning Analysis class, Karnofsky performance status, O6-methylguanine DNA methyltransferase promoter methylation status, surgical management, and survival. The superficial location distant from the eloquent area was more likely associated with a preserved functional status at diagnosis (348 of 392 patients [89%], P < .05), a large surgical resection (173 of 392 patients [44%], P < .05), and prolonged overall survival (163 of 334 patients [49%], P < .05). In contrast, deep location and location within eloquent brain areas were more likely associated with an impaired functional status at diagnosis (44 of 392 patients [11%], P < .05), a neurologic deficit (282 of 392 patients [72%], P < .05), treatment with biopsy only (183 of 392 patients [47%], P < .05), and shortened overall survival (171 of 334 patients [51%], P < .05). Conclusion The authors identified the preferential location of isocitrate dehydrogenase wild-type glioblastomas according to parameters of interest and provided an image-based integration of multimodal information impacting survival results. This suggests the role of glioblastoma location as a surrogate and multimodal parameter integrating several known prognostic factors. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Huang in this issue.

Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model.

We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0-86) and 8.0 months (mean, 8.5; range, 0-56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03-2.08]; p = 0.032), RTOG-RPA V-VI classes (aHR, 1.38; 95% CI [1.11-1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10-5.72]; p < 0.001), while independent predictors of longer overall survival from progression included surgical resection (aHR, 0.57; 95% CI [0.44-0.73]; p < 0.001) and chemotherapy (aHR, 0.41; 95% CI [0.31-0.55]; p < 0.001). Single-tree recursive partitioning identified KPS at progression, surgical resection at progression, chemotherapy at progression, and RTOG-RPA class at histopathological diagnosis, as main survival predictors in the training set, yielding four risk categories highly predictive of overall survival from progression both in training (p < 0.0001) and validation (p < 0.0001) sets. Both random forest approaches identified KPS at progression as the most important survival predictor. Age, KPS at progression, RTOG-RPA classes, surgical resection at progression and chemotherapy at progression are prognostic for survival in recurrent glioblastomas and should inform the treatment decisions.

Extent of resection and Carmustine wafer implantation safely improve survival in patients with a newly diagnosed glioblastoma: a single center experience of the current practice.

For newly diagnosed glioblastomas treated with resection in association with the standard combined chemoradiotherapy, the impact of Carmustine wafer implantation remains debated regarding postoperative infections, quality of life, and feasibility of adjuvant oncological treatments. To assess together safety, tolerance and efficacy of Carmustine wafer implantation and of extent of resection for glioblastoma patients in real-life experience. Observational retrospective monocentric study including 340 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent surgical resection with (n = 123) or without (n = 217) Carmustine wafer implantation as first-line oncological treatment. Carmustine wafer implantation and extent of resection did not significantly increase postoperative complications, including postoperative infections (p = 0.269, and p = 0.446, respectively). Carmustine wafer implantation and extent of resection did not significantly increase adverse events during adjuvant oncological therapies (p = 0.968, and p = 0.571, respectively). Carmustine wafer implantation did not significantly alter the early postoperative Karnofsky performance status (p = 0.402) or the Karnofsky performance status after oncological treatment (p = 0.636) but a subtotal or total surgical resection significantly improved those scores (p < 0.001, and p < 0.001, respectively). Carmustine wafer implantation, subtotal and total resection, and standard combined chemoradiotherapy were independently associated with longer event-free survival (adjusted Hazard Ratio (aHR), 0.74 [95% CI 0.55-0.99], p = 0.043; aHR, 0.70 [95% CI 0.54-0.91], p = 0.009; aHR, 0.40 [95% CI 0.29-0.55], p < 0.001, respectively) and with longer overall survival (aHR, 0.69 [95% CI 0.49-0.96], p = 0.029; aHR, 0.52 [95% CI 0.38-0.70], p < 0.001; aHR, 0.58 [95% CI 0.42-0.81], p = 0.002, respectively). Carmustine wafer implantation in combination with maximal resection, followed by standard combined chemoradiotherapy is safe, efficient, and well-tolerated in newly diagnosed supratentorial glioblastomas in adults.

Recurrent glioblastomas in the elderly after maximal first-line treatment: does preserved overall condition warrant a maximal second-line treatment?

A growing literature supports maximal safe resection followed by standard combined chemoradiotherapy (i.e. maximal first-line therapy) for selected elderly glioblastoma patients. To assess the prognostic factors from recurrence in elderly glioblastoma patients treated by maximal safe resection followed by standard combined chemoradiotherapy as first-line therapy. Multicentric retrospective analysis comparing the prognosis and optimal oncological management of recurrent glioblastomas between 660 adult patients aged of < 70 years (standard group) and 117 patients aged of ≥70 years (elderly group) harboring a supratentorial glioblastoma treated by maximal first-line therapy. From recurrence, both groups did not significantly differ regarding Karnofsky performance status (KPS) (p = 0.482). Oncological treatments from recurrence significantly differed: patients of the elderly group received less frequently oncological treatment from recurrence (p < 0.001), including surgical resection (p < 0.001), Bevacizumab therapy (p < 0.001), and second line chemotherapy other than Temozolomide (p < 0.001). In multivariate analysis, Age ≥70 years was not an independent predictor of overall survival from recurrence (p = 0.602), RTOG-RPA classes 5-6 (p = 0.050) and KPS at recurrence <70 (p < 0.001), available in all cases, were independent significant predictors of shorter overall survival from recurrence. Initial removal of ≥ 90% of enhancing tumor (p = 0.004), initial completion of the standard combined chemoradiotherapy (p = 0.007), oncological treatment from recurrence (p < 0.001), and particularly surgical resection (p < 0.001), Temozolomide (p = 0.046), and Bevacizumab therapy (p = 0.041) were all significant independent predictors of longer overall survival from recurrence. Elderly patients had substandard care from recurrence whereas age did not impact overall survival from recurrence contrary to KPS at recurrence <70. Treatment options from recurrence should include repeat surgery, second line chemotherapy and anti-angiogenic agents.

Epileptic seizures in anaplastic gangliogliomas.

AIM: Prevalence and predictors of epileptic seizures are unknown in the malignant variant of ganglioglioma. METHODS: In a retrospective exploratory dataset of 18 supratentorial anaplastic World Health Organization grade III gangliogliomas, we studied: (i) the prevalence and predictors of epileptic seizures at diagnosis; (ii) the evolution of seizures during tumor evolution; (iii) seizure control rates and predictors of epilepsy control after oncological treatments. RESULTS: Epileptic seizures prevalence progresses throughout the natural course of anaplastic gangliogliomas: 44% at imaging discovery, 67% at histopathological diagnosis, 69% following oncological treatment, 86% at tumor progression, and 100% at the end-of-life phase. The medical control of seizures and their refractory status worsened during the tumor's natural course: 25% of uncontrolled seizures at histopathological diagnosis, 40% following oncological treatment, 45.5% at tumor progression, and 45.5% at the end-of-life phase. Predictors of seizures at diagnosis appeared related to the tumor location (i.e. temporal and/or cortical involvement). Prognostic parameters of seizure control after first-line oncological treatment were temporal tumor location, eosinophilic granular bodies, TP53 mutation, and extent of resection. Prognostic parameters of seizure control at tumor progression were a history of epileptic seizures at diagnosis, seizure control after first-line oncological treatment, eosinophilic granular bodies, and TP53 mutation. CONCLUSION: Epileptic seizures are frequently observed in anaplastic gangliogliomas and both prevalence and medically refractory status worsen during the tumor's natural course. Both oncological and antiepileptic treatments should be employed to improve the control of epileptic seizures and the quality of life of patients harboring an anaplastic ganglioglioma.

Epileptic seizures in diffuse low-grade gliomas in adults.

Diffuse low-grade gliomas are highly epileptogenic brain tumours. We aimed to explore the natural course of epileptic seizures, their predictors and the prognostic significance of their occurrence in adult patients harbouring a diffuse low-grade glioma. An observational retrospective multicentre study examined 1509 patients with diffuse low-grade gliomas to identify mutual interactions between tumour characteristics, tumour course and epileptic seizures. At diagnosis, 89.9% of patients had epileptic seizures. Male gender (P = 0.003) and tumour location within functional areas (P = 0.001) were independent predictors of a history of epileptic seizures at diagnosis. Tumour volume, growth velocity, cortical location, histopathological subtype or molecular markers did not significantly affect epileptic seizure occurrence probability. Prolonged history of epileptic seizures (P < 0.001), insular location (P = 0.003) and tumour location close to functional areas (P = 0.038) were independent predictors of uncontrolled epileptic seizures at diagnosis. Occurrence of epileptic seizures (P < 0.001), parietal (P = 0.029) and insular (P = 0.002) locations were independent predictors of uncontrolled epileptic seizures after oncological treatment. Patient age (P < 0.001), subtotal (P = 0.007) and total (P < 0.001) resections were independent predictors of total epileptic seizure control after oncological treatment. History of epileptic seizures at diagnosis and total surgical resection were independently associated with increased malignant progression-free (P < 0.001 and P < 0.001) and overall (P < 0.001 and P = 0.016) survivals. Epileptic seizures are independently associated with diffuse low-grade glioma prognosis. Patients diagnosed with epileptic seizures and those with complete and early surgical resections have better oncological outcomes. Early and maximal surgical resection is thus required for diffuse low-grade gliomas, both for oncological and epileptological purposes.

Combining intraoperative carmustine wafers and Stupp regimen in multimodal first-line treatment of primary glioblastomas.

BACKGROUND: The study investigated if intraoperative use of carmustine wafers, particularly in combination with Stupp regimen, is a viable and safe first-line treatment option of glioblastomas. METHODS: Eighty-three consecutive adult patients (50 men; mean age 60 years) with newly diagnosed supratentorial primary glioblastomas that underwent surgical resection with intraoperative carmustine wafers implantation (n = 7.1 ± 1.7) were retrospectively studied. RESULTS: The median overall survival (OS) was 15.8 months with 56 patients dying over the course of the study. There was no significant association between the number of implanted carmustine wafers and complication rates (four surgical site infections, one death). The OS was significantly longer in Stupp regimen patients (19.5 months) as compared with patients with other postoperative treatments (13 months; p = 0.002). In addition patients with eight or more implanted carmustine wafers survived longer (24.5 months) than patients with seven or less implanted wafers (13 months; p = 0.021). Finally, regardless of the number of carmustine wafers, median OS was significantly longer in patients with a subtotal or total resection (21.5 months) than in patients with a partial resection (13 months; p = 0.011). CONCLUSIONS: The intraoperative use of carmustine wafers in combination with Stupp regimen is a viable first-line treatment option of glioblastomas. The prognostic value of this treatment association should be evaluated in a multicenter trial, ideally in a randomized and placebo-controlled one.

Use of MR signal intensity variations to highlight structures at risk along brain biopsy trajectories.

OBJECTIVE: Postoperative intracerebral hemorrhages are significant complications following brain stereotactic biopsy. They can derive from anatomical structure (sulci, vessels) damage that is missed during stereotactic trajectory planning. In this study, the authors investigated the ability to detect contact between structures at risk and stereotactic trajectories using signal analysis from MRI obtained during clinical practice, with the aim to propose a visual tool to highlight areas with anatomical structures at risk of damage along the biopsy trajectory. METHODS: The authors retrospectively analyzed actual stereotactic trajectories using intraoperative imaging (intraoperative 2D radiographs in the exploratory data set and intraoperative 3D scans in the confirmatory data set). The MR signal variation along each biopsy trajectory was matched with the patient's anatomy. RESULTS: In the exploratory data set (n = 154 patients), 32 contacts between the actual biopsy trajectory and an anatomical structure at risk were identified along 28 (18.2%) biopsy trajectories, corresponding to 8 preventable intracerebral hemorrhages. Variations of the mean derivative of the MR signal intensity were significantly different between trajectories with and without contact (the pathological threshold of the mean derivative of the MR signal intensity was defined as ± 0.030 arbitrary units; p < 0.0001), with a sensitivity of 89.3% and specificity of 74.6% to detect a contact. In the confirmatory data set (n = 73 patients), the sensitivity and specificity of the 0.030 threshold to detect a contact between the actual stereotactic trajectory and an anatomical structure at risk were 81.3% and 68.4%, respectively. CONCLUSIONS: Variations of the mean derivative of the MR signal intensity can be converted into a green/red color code along the planned biopsy trajectory to highlight anatomical structures at risk, which can help neurosurgeons during the surgical planning of stereotactic procedures.

Presentation and Management of Cerebral Venous Sinus Thrombosis After Supratentorial Craniotomy.

BACKGROUND AND OBJECTIVES: Cerebral venous sinus thrombosis (CVST) after supratentorial craniotomy is a poorly studied complication, for which there are no management guidelines. This study assessed the incidence, associated risk factors, and management of postoperative CVST after awake craniotomy. METHODS: This is an observational, retrospective, monocentric analysis of patients who underwent a supratentorial awake craniotomy. Postoperative CVST was defined as a flow defect on the postoperative contrast-enhanced 3D T1-weighted sequence and/or as a T2* hypointensity within the sinus. RESULTS: In 401 supratentorial awake craniotomies (87.3% of diffuse glioma), the incidence of postoperative CVST was 4.0% (95% CI 2.5-6.4): 14/16 thromboses located in the superior sagittal sinus and 12/16 located in the transverse sinus. A venous sinus was exposed during craniotomy in 45.4% of cases, and no intraoperative injury to a cerebral venous sinus was reported. All thromboses were asymptomatic, and only two cases were diagnosed at the time of the first postoperative imaging (0.5%). Postoperative complications, early postoperative Karnofsky Performance Status score, and duration of hospital stay did not significantly differ between patients with and without postoperative CVST. Adjusted independent risk factors of postoperative CVST were female sex (adjusted Odds Ratio 4.00, 95% CI 1.24-12.91, P = .021) and a lesion ≤1 cm to a venous sinus (adjusted Odds Ratio 10.58, 95% CI 2.93-38.20, P < .001). All patients received standard prophylactic-dose anticoagulant therapy, and none received treatment-dose anticoagulant therapy. No thrombosis-related adverse event was reported. All thromboses presented spontaneous sinus recanalization radiologically at a mean of 89 ± 41 days (range, 7-171). CONCLUSION: CVST after supratentorial awake craniotomy is a rare event with satisfactory clinical outcomes and spontaneous sinus recanalization under conservative management without treatment-dose anticoagulant therapy. These findings are comforting to neurosurgeons confronted with postoperative MRI reports suggesting CVST.

Efficacy and Safety of Carmustine Wafer Implantation After Ventricular Opening in Glioblastomas, Isocitrate Dehydrogenase-Wildtype, in Adults.

BACKGROUND AND OBJECTIVES: We assessed the impact of ventricular opening on postoperative complications and survival of carmustine wafer implantation during surgery of newly diagnosed supratentorial glioblastomas, isocitrate dehydrogenase (IDH)-wildtype in adults. METHODS: We performed an observational, retrospective, single-center cohort study at a tertiary surgical neuro-oncological center between January 2006 and December 2021. RESULTS: One hundred ninety-four patients who benefited from a first-line surgical resection with carmustine wafer implantation were included. Seventy patients (36.1%) had a ventricular opening. We showed that ventricular opening (1) did not increase overall postoperative complication rates (P = .201); (2) did not worsen the early postoperative Karnofsky Performance Status score (P = .068); (3) did not increase the time interval from surgery to adjuvant oncological treatment (P = .458); (4) did not affect the completion of the standard radiochemotherapy protocol (P = .164); (5) did not affect progression-free survival (P = .059); and (6) did not affect overall survival (P = .142). CONCLUSION: In this study, ventricular opening during first-line surgical resection did not affect the survival and postoperative complications after use of carmustine wafer implantation in adult patients with a newly diagnosed supratentorial glioblastoma, IDH-wildtype. This warrants a prospective and multicentric study to clearly assess the impact of the ventricular opening after carmustine wafer implantation in glioblastoma, IDH-wildtype.