Long-term follow up of patients with WHO grade 2 oligodendroglioma.

PURPOSE: Since the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival. METHODS: All adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival. RESULTS: 126 patients diagnosed between 1998 and 2016 were identified. The median follow-up was 12.0 years, and the median survival was 17.8 years (95% CI 16.0-19.6). Factors associated with shorter survival in multivariable analysis were age (HR 1.05 per year; CI 1.02-1.08, p < 0.001), tumor diameter (HR 1.05 per millimeter; CI 1.02-1.08, p < 0.001) and poor preoperative functional status (KPS < 80) (HR 4.47; CI 1.70-11.78, p = 0.002). In our material, surgical strategy was not associated with survival. CONCLUSION: Individuals with molecularly defined oligodendrogliomas demonstrate long survival, also in a population-based setting. This is important to consider for optimal timing of therapies that may cause long-term side effects. Advanced age, large tumors and poor function before surgery are predictors of shorter survival.

Learning Curve Analysis and Adverse Events After Implementation of Neurosurgical Laser Ablation Treatment: A Population-Based Single-Institution Consecutive Series.

OBJECTIVE AND METHODS: We conducted a retrospective review of the first 30 patients treated with stereotactic laser ablation (SLA) at our institution since the introduction of the technique in September 2019. We aimed to analyze our initial results and potential learning curve by investigating precision and lesion coverage and assessing the frequency and nature of adverse events according to the Landriel-Ibanez classification for neurosurgical complications. RESULTS: Indications were de novo gliomas (23%), recurrent gliomas (57%), and epileptogenic foci (20%). There was a trend toward improvement of lesion coverage and target deviation, and a statistically significant improvement in entry point deviation, over time. Four patients (13.3%) experienced a new neurological deficit, where three patients had transient and one patient had permanent deficits, respectively. Our results show a learning curve on precision measures over the first 30 cases. Based on our results the technique can safely be implemented at centers with experience in stereotaxy.

Laser interstitial thermal therapy using the Leksell Stereotactic System and a diagnostic MRI suite: how I do it.

BACKGROUND: Laser interstitial thermal therapy (LITT) is a stereotactic neurosurgical procedure used to treat neoplastic and epileptogenic lesions in the brain. A variety of advanced technological instruments such as frameless navigation systems, robotics, and intraoperative MRI are often described in this context, although the surgical procedure can also be performed using a standard stereotactic setup and a diagnostic MRI suite. METHODS: We report on our experience and a surgical technique using a Leksell stereotactic frame and a diagnostic MRI suite to perform LITT. CONCLUSION: LITT can be safely performed using the Leksell frame and a diagnostic MRI suite, making the technique available even to neuro-oncology centers without advanced technological setup.

[Epilepsy surgery seems underutilized in Sweden]. / Epilepsikirurgin är underutny­­ttjad ­ fler bör hänvisas till utredning.

Epilepsy surgery should be considered for individuals with drug-resistant focal epilepsy. The pre-surgical evaluation is highly multi-disciplinary and performed by a team consisting of neurologists, neurophysiologists, neurosurgeons, neuroradiologists, neuropsychologists, biomedical scientists, speech-language pathologists and nursing staff. The evaluation comprises of a meticulous medical history with focus on seizure semiology, a 3 Tesla MRI, ictal video-EEG, neuropsychological evaluation and sometimes also MEG, nTMS, fMRI, PET or SISCOM/ictal SPECT. Occasionally, invasive monitoring with intracranial electrodes is necessary. Surgical options in treatment of epilepsy range from open resections of epileptogenic areas to focal ablations and neurostimulation. There is evidence of epilepsy surgery being an effective treatment in carefully selected cases. Epilepsy surgery seems underutilized in Sweden and referrals for epilepsy surgery work-up need to increase.

Standardized reporting of adverse events and functional status from the first 5 years of awake surgery for gliomas: a population-based single-institution consecutive series.

OBJECTIVE: To report our experience and investigate frequencies of adverse events and functional status from the first 5 years of performing awake surgery for gliomas in a single-center population-based setting. METHODS: We conducted a review of all patients with a glioma treated with awake surgery during the first 5 years following introduction of awake surgery at our center (February 2015 to February 2020). We assessed functional and radiological outcome, with adverse events classified according to the Landriel-Ibanez classification for neurosurgical complications, while neurological deficits were further subdivided into transient vs permanent. We sought to analyze our initial results and learning curve, as well as compare our results with literature. RESULTS: Forty-two patients were included. The median age was 38 years (range 18-66) and 13 (31%) were female. The indication for awake surgery was a presumed glioma in or near an eloquent area. The overall 30-day complication rate was 25 (59%), with 19 (45%) grade I complications, 3 (7%) grade II complications, and 3 (7%) grade III complications. Fifteen patients (36%) experienced transient neurological deficits, and 11 (26%) permanent neurological deficits. At 3-month follow-up, the Karnofsky Performance Score was 80 or higher for the entire cohort. The median extent of resection was 87%, with GTR achieved in 11 (26%). In search of potential learning curve difficulties, patients were divided into the 21 patients treated first (Early Group) versus the remaining 21 patients treated later (Late Group); no statistically significant difference in operating time, amount of tumor removed, or incidence of long-term postoperative neurological deficit was identified between groups. No awake surgery was aborted due to seizures. Comparison to the literature was limited by the diverse and unsystematic way in which previous studies have reported adverse events after awake craniotomy for gliomas. CONCLUSION: We provide a standardized report of adverse events and functional status following awake surgery for glioma during a single-center 5-year learning period, with similar rates of severe adverse events and functional outcome compared to literature without concerns of substantial learning curve difficulties. However, this comparison was flawed by non-standardized reporting of complications, highlighting a demand for more standardized reporting of adverse events after awake craniotomies.

Variations in the management of diffuse low-grade gliomas-A Scandinavian multicenter study.

BACKGROUND: Early extensive surgery is a cornerstone in treatment of diffuse low-grade gliomas (DLGGs), and an additional survival benefit has been demonstrated from early radiochemotherapy in selected "high-risk" patients. Still, there are a number of controversies related to DLGG management. The objective of this multicenter population-based cohort study was to explore potential variations in diagnostic work-up and treatment between treating centers in 2 Scandinavian countries with similar public health care systems. METHODS: Patients screened for inclusion underwent primary surgery of a histopathologically verified diffuse WHO grade II glioma in the time period 2012 through 2017. Clinical and radiological data were collected from medical records and locally conducted research projects, whereupon differences between countries and inter-hospital variations were explored. RESULTS: A total of 642 patients were included (male:female ratio 1:4), and annual age-standardized incidence rates were 0.9 and 0.8 per 100 000 in Norway and Sweden, respectively. Considerable inter-hospital variations were observed in preoperative work-up, tumor diagnostics, surgical strategies, techniques for intraoperative guidance, as well as choice and timing of adjuvant therapy. CONCLUSIONS: Despite geographical population-based case selection, similar health care organizations, and existing guidelines, there were considerable variations in DLGG management. While some can be attributed to differences in clinical implementation of current scientific knowledge, some of the observed inter-hospital variations reflect controversies related to diagnostics and treatment. Quantification of these disparities renders possible identification of treatment patterns associated with better or worse outcomes and may thus represent a step toward more uniform evidence-based care.

Lower-Grade Gliomas: An Epidemiological Voxel-Based Analysis of Location and Proximity to Eloquent Regions.

BACKGROUND: Glioma is the most common intra-axial tumor, and its location relative to critical areas of the brain is important for treatment decision-making. Studies often report tumor location based on anatomical taxonomy alone since the estimation of eloquent regions requires considerable knowledge of functional neuroanatomy and is, to some degree, a subjective measure. An unbiased and reproducible method to determine tumor location and eloquence is desirable, both for clinical use and for research purposes. OBJECTIVE: To report on a voxel-based method for assessing anatomical distribution and proximity to eloquent regions in diffuse lower-grade gliomas (World Health Organization grades 2 and 3). METHODS: A multi-institutional population-based dataset of adult patients (≥18 years) histologically diagnosed with lower-grade glioma was analyzed. Tumor segmentations were registered to a standardized space where two anatomical atlases were used to perform a voxel-based comparison of the proximity of segmentations to brain regions of traditional clinical interest. RESULTS: Exploring the differences between patients with oligodendrogliomas, isocitrate dehydrogenase (IDH) mutated astrocytomas, and patients with IDH wild-type astrocytomas, we found that the latter were older, more often had lower Karnofsky performance status, and that these tumors were more often found in the proximity of eloquent regions. Eloquent regions are found slightly more frequently in the proximity of IDH-mutated astrocytomas compared to oligodendrogliomas. The regions included in our voxel-based definition of eloquence showed a high degree of association with performing biopsy compared to resection. CONCLUSION: We present a simple, robust, unbiased, and clinically relevant method for assessing tumor location and eloquence in lower-grade gliomas.

[Laser ablation of brain tumors now available in the Nordic countries]. / Laserablation kan användas vid intrakraniella lesioner.

Laser Interstitial Thermal Therapy (LITT) is used to treat patients with intracranial lesions such as epileptogenic foci, radiation necrosis, cavernomas and brain tumors in the United States. The approval for this treatment in Europe has first been granted in 2018, with the first treatment(s) in the Nordic countries - in the form of 3 brain tumor patients - performed at the Karolinska University Hospital in 2019. In this article we briefly describe our initial experience in the context of current literature.

[Thermal ablation of brain tumours].

The diagnosis of a malignant brain tumour is often associated with a poor prognosis. Current treatment is surgical resection followed by radio-chemotherapy. Surgical resection is most favourable in relation to survival time. Unfortunately, many patients are not suitable for surgical resection, due to inoperable tumour location or the patients' poor state. Minimally invasive thermal ablation may pose an interesting new treatment alternative. In this review, we describe the evolution, the underlying physiology and the clinical applications of cryo- and laser-induced thermal therapy of primary and secondary brain tumours.

High-level language outcomes three and twelve months after awake surgery in low grade glioma and cavernoma patients.

OBJECTIVE: Knowledge about the long-term outcome of high-level language ability in awake surgery patients with low-grade gliomas or cavernomas in language eloquent regions is limited, particularly regarding subtle changes in high-level language abilities. PATIENTS AND METHODS: The study group consisted of 27 patients with LGG or cavernoma which involved language eloquent regions in the left hemisphere. A comprehensive assessment battery was used to target subtle changes in overall high-level language ability as well as in language sub skills. Assessments were made preoperatively and at 3 and 12 months postoperatively. RESULTS: The results showed that overall high-level language ability had not decreased significantly at group level at 3 or 12 months postoperatively. The proportion of patients with a decline of 5 percent or more at follow up 3 and 12 months were 13% and 9% respectively. There was a marked decline in semantic fluency (animals and verbs) at 3 and 12 months postoperatively. Phonemic fluency, while not significantly reduced at three months, improved markedly in the interval between 3 and 12 months. At 12 months, the only significant decline relative to preoperative scores were seen in semantic fluency for animals and verbs. Verbal cognitive speed did not decline significantly postoperatively but approximately 40% of the patients had a decline of 5% or more at 12 months. CONCLUSIONS: Overall high-level language ability was not significantly affected postoperatively at 3 and 12 months in LGG and cavernoma awake surgery patients. Semantic word fluency had deteriorated postoperatively at 3 and 12 months follow-up. Taken together our results indicate a decline in processing speed of verbal material postoperatively in the patient group.

Biopsy and Ablation of H3K27 Glioma Using Skull-Mounted Smartframe Device: Technical Case Report.

BACKGROUND: Clearpoint Smartframe is a magnetic resonance imaging-compatible stereotactic system often used to perform magnetic resonance imaging-guided biopsies. The system is typically mounted on the scalp through screws that pierce the skin and penetrate the outer table of the cranium. However, the frame can also be configured to be mounted directly onto the skull. CASE DESCRIPTION: Here, we describe the clinical context well suited for a skull-mount Clearpoint Smartframe surgery. The patient suffered from a subcentimeter right parafourth ventricular contrast-enhancing lesion with hydrocephalus and underwent a right suboccipital needle biopsy followed by an occipital ventriculoperitoneal shunt. Although the hydrocephalus resolved with the ventriculoperitoneal shunt, the biopsy sample proved nondiagnostic. The patient underwent a second procedure during which the Clearpoint Smartframe was mounted onto the skull through space dissected free during the previous surgery. Diagnostic biopsy (H3K27 glioma) was performed followed by stereotactic laser ablation of the lesion. CONCLUSIONS: We describe a case in which the skull mount Clearpoint Smartframe was used to biopsy and ablate a midline H3K27 glioma.

Stereotactic Brain Biopsy in Eloquent Areas Assisted by Navigated Transcranial Magnetic Stimulation: a Technical Case Report.

BACKGROUND AND IMPORTANCE: Stereotactic brain biopsy (SB) is an important part of the neurosurgical armamentarium, with the possibility of achieving histopathological diagnosis in otherwise inaccessible lesions of the brain. Nevertheless, the procedure is not without the risk of morbidity, which is especially true for lesions in eloquent parts of the brain, where even a minor adverse event can result in significant deficits. Navigated transcranial magnetic stimulation (nTMS) is widely used to chart lesions in eloquent areas, successfully guiding maximal safe resection, while its potential role in aiding with the planning of a stereotactic biopsy is so far unexplored. CLINICAL PRESENTATION: Magnetic resonance imaging of a 67-yr-old woman presenting with dysphasia revealed a noncontrast enhancing left-sided lesion in the frontal and parietal pars opercularis. Due to the location of the lesion, nTMS was used to chart both primary motor and language cortex, utilizing this information to plan a safe SB trajectory and sampling area according to the initial work-up recommendations from the multidisciplinary neuro-oncology board. The SB was uneventful, with histology revealing a ganglioglioma, WHO I. The patient was discharged the following day, having declined to proceed with tumor resection (awake surgery) due to the non-negligible risk of morbidity. Upon 1- and 3-mo follow-up, she showed no signs of any procedure-related deficits. CONCLUSION: nTMS can be implemented to aid with the planning of a stereotactic biopsy procedure in eloquent areas of the brain, and should be considered part of the neurosurgical armamentarium.