Minimally invasive keyhole approach for supramaximal frontal glioma resections: technical note.

OBJECTIVE: The authors aimed to review the frontal lobe's surgical anatomy, describe their keyhole frontal lobectomy technique, and analyze the surgical results. METHODS: Patients with newly diagnosed frontal gliomas treated using a keyhole approach with supramaximal resection (SMR) from 2016 to 2022 were retrospectively reviewed. Surgeries were performed on patients asleep and awake. A human donor head was dissected to demonstrate the surgical anatomy. Kaplan-Meier curves were used for survival analysis. RESULTS: Of the 790 craniotomies performed during the study period, those in 47 patients met our inclusion criteria. The minimally invasive approach involved four steps: 1) debulking the frontal pole; 2) subpial dissection identifying the sphenoid ridge, olfactory nerve, and optic nerve; 3) medial dissection to expose the falx cerebri and interhemispheric structures; and 4) posterior dissection guided by motor mapping, avoiding crossing the inferior plane defined by the corpus callosum. A fifth step could be added for nondominant lesions by resecting the inferior frontal gyrus. Perioperative complications were recorded in 5 cases (10.6%). The average hospital length of stay was 3.3 days. High-grade gliomas had a median progression-free survival of 14.8 months and overall survival of 23.9 months. CONCLUSIONS: Keyhole approaches enabled successful SMR of frontal gliomas without added risks. Robust anatomical knowledge and meticulous surgical technique are paramount for obtaining successful resections.

Chat-GPT on brain tumors: An examination of Artificial Intelligence/Machine Learning's ability to provide diagnoses and treatment plans for example neuro-oncology cases.

OBJECTIVE: Assess the capabilities of ChatGPT-3.5 and 4 to provide accurate diagnoses, treatment options, and treatment plans for brain tumors in example neuro-oncology cases. METHODS: ChatGPT-3.5 and 4 were provided with twenty example neuro-oncology cases of brain tumors, all selected from medical textbooks. The artificial intelligence programs were asked to give a diagnosis, treatment option, and treatment plan for each of these twenty example cases. Team members first determined in which cases ChatGPT-3.5 and 4 provided the correct diagnosis or treatment plan. Twenty neurosurgeons from the researchers' institution then independently rated the diagnoses, treatment options, and treatment plans provided by both artificial intelligence programs for each of the twenty example cases, on a scale of one to ten, with ten being the highest score. To determine whether the difference between the scores of ChatGPT-3.5 and 4 was statistically significant, a paired t-test was conducted for the average scores given to the programs for each example case. RESULTS: In the initial analysis of correct responses, ChatGPT-4 had an accuracy of 85% for its diagnoses of example brain tumors and an accuracy of 75% for its provided treatment plans, while ChatGPT-3.5 only had an accuracy of 65% and 10%, respectively. The average scores given by the twenty independent neurosurgeons to ChatGPT-4 for its accuracy of diagnosis, provided treatment options, and provided treatment plan were 8.3, 8.4, and 8.5 out of 10, respectively, while ChatGPT-3.5's average scores for these categories of assessment were 5.9, 5.7, and 5.7. These differences in average score are statistically significant on a paired t-test, with a p-value of less than 0.001 for each difference. CONCLUSIONS: ChatGPT-4 demonstrates great promise as a diagnostic tool for brain tumors in neuro-oncology, as attested to by the program's performance in this study and its assessment by surveyed neurosurgeon reviewers.

The Learning Curve and Clinical Outcomes With 250 Laser Ablations for Brain Tumors: A Pathway to Experience.

BACKGROUND AND OBJECTIVES: Laser interstitial thermal therapy (LITT) has gained popularity as a minimally invasive technique for treating brain tumors. Despite its proven safety profile, LITT is not yet widely available, and there is a lack of data on the learning curve required to achieve proficiency. This study analyzes a 250-patient cohort of laser-ablated tumors to describe changes in patient selection and clinical outcomes over time and experience, with the aim of providing insight into the learning curve for incorporating LITT into a neuro-oncology program and identifying a cutoff point that distinguishes novice from expert performance. METHODS: We retrospectively reviewed 250 patients with brain tumor who underwent LITT between 2013 and 2022. Demographic and clinical data were analyzed. Kaplan Meier curves were used for survival analysis. Operative time was evaluated using exponential curve-fit regression analysis to identify when consistent improvement began. RESULTS: The patients were divided into quartiles (Q) based on their date of surgery. Mean tumor volume increased over time (Q1 = 5.7 and Q4 = 11.9 cm3, P = .004), and newly diagnosed lesions were more frequently ablated (P = .0001). Mean operative time (Q1 v Q4 = 322.3 v 204.6 min, P < .0001) and neurosurgical readmission rate (Q1 v Q4 = 7.8% v 0%, P = .03) were reduced over time. The exponential curve-fit analysis showed a sustained decay in operative time after case #74. The extent of ablation (P = .69), the recurrence (P = .11), and the postoperative complication rate (P = .78) did not vary over time. CONCLUSION: After treating 74 patients, a downward trend in the operative time is observed. Patient selection is broadened as experience increases.

Predictors of clinical and structural outcomes after surgery for spinal nerve sheath tumor resection: a retrospective analysis.

OBJECTIVE: Resection of spinal nerve sheath tumors (SNSTs) typically necessitates laminectomy, often with facetectomy, for adequate exposure of tumor. While removal of bone affords a greater operative window and extent of resection, it places the patient at greater risk for spinal instability. Although studies have identified risk factors for fusion at the time of tumor resection, there has yet to be a study assessing long-term stability following SNST resection. In this study, the authors sought to identify preoperative and operative risk factors that predispose to long-term spinal instability and investigate clinical variables associated with greater risk for subsequent fusion in the time following initial SNST resection. METHODS: An institutional registry of spinal surgeries was queried at a single institution over a 20-year period. Demographic, clinical, and operative variables were recorded retrospectively and investigated for predictive value of several postoperative sequelae. RESULTS: A total of 122 SNST cases among 112 patients were included. At a mean follow-up time of 27.7 months, patients with a history of neurofibromatosis type 2 (NF2) (p = 0.014) and those who had undergone a laminectomy of ≥ 4 levels at the time of initial SNST resection (p = 0.028) were more likely to present with some degree of structural abnormality or neurological deficit following their initial surgery. The presence of facetectomy, degree of laminectomy, and level of spinal surgery were not found to be predictors of future instability. Ultimately, there was no significant predictor for true spinal instability following index surgery without fusion. A secondary analysis showed that an entirely extradural location (p = 0.044) and facetectomy at index surgery (p = 0.012) were predictive of fusion being performed at the time of tumor resection. Four of the 112 patients required fusion after their index SNST resection, 3 of whom underwent fusion for instability at the level of the index surgery. No variables were identified as predictive for future instrumentation. CONCLUSIONS: Ultimately, the authors conclude that resection of SNSTs does not always necessitate fusion, and good outcomes can be obtained with motion-preserving techniques and minimizing facetectomy when possible. Patients with a history of NF2 and those with SNSTs that required ≥ 4-level laminectomy were more likely to exhibit some degree of structural abnormality and/or neurological deficit localized to the index level defined as either new or worsening spinal instability and/or new or worsening neurological deficit at last follow-up; however, no variable was found to be predictive of true spinal instability. Furthermore, a complete facetectomy at initial SNST resection and entirely extradural tumor location were noted to be associated with fusion at index surgery. Lastly, the authors were unable to identify a clinical predictor for future instrumentation.

Exploring the Landscape of Machine Learning Applications in Neurosurgery: A Bibliometric Analysis and Narrative Review of Trends and Future Directions.

BACKGROUND: The field of neurosurgery has consistently represented an area of innovation and integration of technology since its inception. As such, machine learning (ML) has found its way into applications within neurosurgery relatively rapidly. Through this bibliometric review and cluster analysis, we seek to identify trends and emerging applications of ML within neurosurgery. METHODS: A bibliometric analysis was carried out in the Web of Science database on publications from January 2000 to March 2023. The full data set of the 200 most cited publications including title, author information, journal, citation count, keywords, and abstracts for each publication was evaluated in CiteSpace. CiteSpace was used to elucidate publication characteristics, trends, and topic clusters via collaborate network analysis using the Kamada-Kawai algorithm. RESULTS: The 25 most cited titles were included in our analysis. Harvard University and its affiliates represented the top institution, contributing nearly 25% of publications in the literature. WORLD NEUROSURGERY was the journal with the highest net citation count of 747 (29%). Collaborative network analysis generated 12 unique clusters, the largest of which was machine learning, followed by feature importance and deep brain stimulation. CONCLUSION: This review highlights the most impactful articles pertaining to ML in the field of neurosurgery. ML has been applied into several sub-specialties within neurosurgery to optimize patient care, with special attention to outcome predictors, patient selection, and surgical decision making.

Same-day discharge after craniotomy for brain tumor resection: enhancing patient selection through a prognostic scoring system.

OBJECTIVE: Neurosurgery, among other surgical fields, is amid a shift in patient management with enhanced recovery and same-day discharge (SDD) protocols slowly becoming more popular and feasible. While such protocols reduce the risk of nosocomial complications and improve patient satisfaction, appropriate patient selection remains an area of debate. The authors aimed to better quantify selection criteria through a prospective follow-up study of patients undergoing brain tumor resection with SDD. METHODS: Three arms of analysis were carried out. First, clinical data of SDD patients were prospectively collected between August 2021 and August 2022. In parallel, a retrospective analysis of patients who qualified for SDD but were excluded at surgeon clinical discretion over the same period was performed. Third, a comparative analysis of the pilot and follow-up studies was done from which a clinical scoring system for patient selection was derived. RESULTS: Over the duration of the study, 31 of 334 patients were selected for SDD while 59 qualified for SDD by previously defined criteria but were not selected at the surgeon's discretion. There was no difference in outcomes between the two groups, and there were no postoperative complications among the SDD group within 30 days of surgery. Preoperative clinical characteristics found to be significantly different between the two cohorts (left-sided lesion, extra-axial pathology, prior treatment of brain tumor, and tumor volume ≤ 11.75 cm3) were included in a predictive scoring system for successful SDD. The scoring system was found to significantly predict high or low likelihood for successful SDD when tested on the mixed prospective cohort. CONCLUSIONS: This study provides a straightforward clinical scoring system for appropriate selection of candidates for SDD after craniotomy for brain tumor resection. This clinical tool aims to aid clinicians in appropriate admission course selection and builds on the growing literature surrounding same-day and outpatient cranial neurosurgery.

Bilateral Laser Interstitial Thermal Therapy for Butterfly Gliomas Compared With Needle Biopsy: A Preliminary Survival Study.

BACKGROUND AND OBJECTIVES: Bilateral/butterfly glioblastoma (bGBM) has a poor prognosis. Resection of these tumors is limited due to severe comorbidities that arise from surgical procedures. Laser interstitial thermal therapy (LITT) offers a minimally invasive cytoreductive therapy for deep-seated tumors such as bGBM. The objective of this study was to evaluate the safety of bilateral LITT in patients with bGBM. METHODS: Medical records of all consecutive patients diagnosed with bGBM by a single surgeon at a single institution from January 2014 to August 2022 were reviewed. Clinical, safety, and radiographic volumetric data were obtained. In addition, an exploratory analysis of survival was performed. RESULTS: A total of 25 patients were included; 14 underwent biopsy only, and 11 underwent biopsy + LITT (7 underwent bilateral and 4 underwent unilateral LITT). No (0%) intraoperative or postoperative complications were recorded in the treatment group. Tumor volume negatively correlated with extent of treatment (r 2 = 0.44, P = .027). The median progression-free survival was 2.8 months in the biopsy-only group and 5.5 months in the biopsy + LITT group ( P = .026). The median overall survival was 4.3 months in the biopsy-only group and 10.3 months in the biopsy + LITT group ( P = .035). CONCLUSION: Bilateral LITT for bGBM can be safely performed and shows early improvement of the progression-free survival and long-term survival outcomes of these patients.

Two-stage radiosurgery for large brain metastases: a systematic review and meta-analysis of clinical outcomes.

OBJECTIVE: Brain metastases (BMs) are the most common intracranial tumors. In several cases, they present as large masses, which are related to a worse prognosis and more complex therapeutic alternatives. Staged radiosurgery is reported to achieve local control with minimal radiation-related adverse events in BMs. However, no methodological consensus has been achieved in its use for large brain metastases (LBMs; > 2 cm). Therefore, the authors aimed to determine the effectiveness and safety of 2-stage Gamma Knife radiosurgery (GKRS) for LBMs, in order to optimize patients' postoperative course. METHODS: A systematic review of available literature was run in PubMed/MEDLINE, Scopus, Web of Science, Cochrane (OvidSP), and Google Scholar for works published up to December 14, 2022. Nonrandomized clinical trials, case series, and cohort studies were included. The risk of bias was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) and Joanna Briggs Institute tools. Pooled mean difference and rates estimates were calculated by a random-effects model meta-analysis. The degree of heterogeneity was expressed using the I2 statistic. A subgroup analysis was performed. Ultimately, the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment. RESULTS: Fourteen studies met the eligibility criteria (cohorts, case series, and nonrandomized clinical trials), including 958 patients. A total pooled mean volume reduction of 6.27 cm3 (95% CI 5.67-6.88 cm3) and 54.36% (95% CI 39.92%-68.79%) after 2-stage GKRS was reported. Pooled rates of complete response (44.63%; 95% CI 26.50%-64.31%), neurological mortality (16.19%; 95% CI 7.68%-30.98%), and all-cause mortality (47.92%; 95% CI 28.04%-68.49%) were calculated. Overall certainty of evidence ranged from very low to moderate. CONCLUSIONS: Two-stage GKRS is an effective and safe approach for the treatment of LBMs. Nevertheless, the lack of available literature and the weak methodological approaches used determine a low to very low certainty of evidence and cannot provide robust evidence to recommend this intervention. Therefore, it is necessary to conduct higher-quality primary studies.

Surgical management of brain metastasis from ovarian cancer: a systematic review and case series.

OBJECTIVE: Ovarian cancer is a rare origin of brain metastasis (BM), with an incidence of only 1%-3%. Consequently, the literature is sparse, and no treatment consensus guideline is available for ovarian BM. The authors conducted a systematic review of ovarian BM and performed a combined pooled cohort survival analysis with their case series. METHODS: A systematic review of PubMed, Scopus, and Web of Science consistent with PRISMA guidelines along with an institutional retrospective chart review was conducted. Inclusion criteria for the systematic review included patients with confirmed BM and primary ovarian cancer, reported perioperative complications and outcomes, differentiated histology, and explicitly reported individual patient data. Reviews, commentaries, technical notes, and articles without English-language translations were excluded. The Newcastle-Ottawa Quality Assessment Scale was used independently by the first and second authors to assess the quality of each article. The authors performed univariate and multivariate analyses of several survival prognostic factors. Kaplan-Meier curves were generated for significant prognostic factors in the univariate analysis. RESULTS: A total of 48 patients with individual data across 34 studies and 8 patients from the authors' institution were included. All patients (n = 56) underwent resection for BM; 83.9% received adjuvant radiotherapy following surgery and 41.1% of patients received adjuvant chemotherapy. The median progression-free survival was 12 months (range 2-43 months). The median overall survival was 9 months (range 1-49 months). On univariate analysis, a single BM and no extracranial metastasis conferred a survival benefit, while clear cell carcinoma as the primary histology corresponded to worsened OS. Multivariable analysis showed that age > 50 years (p = 0.002) and > 1 BM (p < 0.001) were risk factors for poor prognosis. Protective factors included the addition of the following multimodal adjuvant therapy with surgery: radiotherapy (p = 0.002), chemotherapy and radiotherapy (p = 0.005), and stereotactic radiosurgery (p = 0.002). CONCLUSIONS: Although the scarcity of published individual patient data hinders the determination of optimal management, the authors' analysis highlights that multimodal therapies, a single cranial lesion, and age < 50 years are associated with increased survival for patients with ovarian BMs.

Towards the definition of progressive disease in brain metastasis treated with laser ablation: an evidence-based study.

PURPOSE: The postoperative period after laser interstitial thermal therapy (LITT) is marked by a temporary increase in volume, which can impact the accuracy of radiographic assessment. The current criteria for progressive disease (PD) suggest that a 20% increase in size of brain metastasis (BM) assessed in 6-12 weeks intervals should be considered as local progression (LP). However, there is no agreement on how LP should be defined in this context. In this study, we aimed to statistically analyze which tumor volume variations were associated with LP. METHODS: We analyzed 40 BM that underwent LITT between 2013 and 2022. For this study, LP was defined following radiographic features. A ROC curve was generated to evaluate volume change as a predictor of LP and find the optimal cutoff point. A logistic regression analysis and Kaplan Meier curves were performed to assess the impact of various clinical variables on LP. RESULTS: Out of 40 lesions, 12 (30%) had LP. An increase in volume of 25.6% from baseline within 120-180 days after LITT presented a 70% sensitivity and 88.9% specificity for predicting LP (AUC: 0.78, p = 0.041). The multivariate analysis showed a 25% increase in volume between 120 and 180 days as a negative predictive factor (p = 0.02). Volumetric changes within 60-90 days after LITT did not predict LP (AUC: 0.57; p = 0.61). CONCLUSION: Volume changes within the first 120 days after the procedure are not independent indicators of LP of metastatic brain lesions treated with LITT.

Nitric oxide synthase inhibitors as potential therapeutic agents for gliomas: A systematic review.

INTRODUCTION: Gliomas represent the most prevalent form of brain tumors, among which glioblastomas are the most malignant subtype. Despite advances in comprehending their biology and treatment strategies, median survival remains disappointingly low. Inflammatory processes involving nitric oxide (NO), critically contribute to glioma formation. The inducible isoform of NO synthase (iNOS) is highly overexpressed in gliomas and has been linked to resistance against temozolomide (TMZ) treatment, neoplastic transformation, and modulation of immune response. While both in vitro and in vivo studies showed the potential of iNOS inhibitors as effective treatments for gliomas, no clinical trials on gliomas have been published. This review aims to summarize the available evidence regarding iNOS as a target for glioma treatment, focusing on clinically relevant data. METHODS: Following PRISMA guidelines, we conducted a systematic review by searching PubMed/Medline, and Embase databases in May 2023. We included studies that investigated the impact of NOS inhibitors on glioma cells using L-NMMA, CM544, PBN, 1400W or l-NAME either alone or combined with TMZ. We extracted data on the NOS inhibitor used, subtype, study setting, animal model or cell lines employed, obtained results, and safety profile. Our inclusion criteria encompassed original articles in English or Spanish, studies with an untreated control group, and a primary outcome focused on the biological effects on glioma cells. RESULTS: Out of 871 articles screened from the aforementioned databases, 37 reports were assessed for eligibility. After excluding studies that did not utilize glioma cells or address the designated outcome, 11 original articles satisfied the inclusion and exclusion criteria. Although no NOS inhibitor has been tested in a published clinical trial, three inhibitors have been evaluated using in vivo models of intracranial gliomas. l-NAME, 1400W, and CM544 were tested in vitro. Co-administration of l-NAME, or CM544 with TMZ showed superior results in vitro compared to individual agent testing. CONCLUSION: Glioblastomas remain a challenging therapeutic target. iNOS inhibitors exhibit substantial potential as treatment options for oncologic lesions, and they have demonstrated a safe toxicity profile in humans for other pathological conditions. Research endeavors should be focused on investigating their potential effects on brain tumors.

Development of an enhanced recovery protocol after laser ablation surgery protocol: a preliminary analysis.

Background: Enhanced recovery after surgery (ERAS) programs are a model of care that aim to improve patient outcomes, reduce complications, and facilitate recovery while reducing healthcare-associated costs and admission length. While such programs have been developed in other surgical subspecialties, there have yet to be guidelines published specifically for laser interstitial thermal therapy (LITT). Here we describe the first multidisciplinary ERAS preliminary protocol for LITT for the treatment of brain tumors. Methods: Between the years 2013 and 2021, 184 adult patients consecutively treated with LITT at our single institution were retrospectively analyzed. During this time, a series of pre, intra, and postoperative adjustments were made to the admission course and surgical/anesthesia workflow with the goal of improving recovery and admission length. Results: The mean age at surgery was 60.7 years with a median preoperative Karnofsky performance score of 90 ± 13. Lesions were most commonly metastases (50%) and high-grade gliomas (37%). The mean length of stay was 2.4 days, with the average patient being discharged 1.2 days after surgery. There was an overall readmission rate of 8.7% with a LITT-specific readmission rate of 2.2%. Three of 184 patients required repeat intervention in the perioperative period, and there was one perioperative mortality. Conclusions: This preliminary study shows the proposed LITT ERAS protocol to be a safe means of discharging patients on postoperative day 1 while preserving outcomes. Although future prospective work is needed to validate this protocol, results show the ERAS approach to be promising for LITT.

Frontal lobe low-grade tumors seizure outcome: a pooled analysis of clinical predictors.

OBJECTIVE: Seizures present in 50-90 % of cases with low-grade brain tumors. Frontal lobe epilepsy is associated with dismal seizure outcomes compared to temporal lobe epilepsy. Our objective is to conduct a systematic review, report our case series, and perform a pooled analysis of clinical predictors of seizure outcomes in frontal lobe low-grade brain tumors. METHODS: Searches of five electronic databases from January 1990 to June 2022 were reviewed following PRISMA guidelines. Individual patient data was extracted from 22 articles that fit the inclusion criteria. A single-surgeon case series from our institution was also retrospectively reviewed and analyzed through a pooled cohort of 127 surgically treated patients with frontal lobe low-grade brain tumors. RESULTS: The mean age at surgery was 30.8 years, with 50.4 % of patients diagnosed as oligodendrogliomas. The majority of patients (81.1 %) were seizure-free after surgery (Engel I). On the multivariate analysis, gross total resection (GTR) (OR = 8.77, 95 % CI: 1.99-47.91, p = 0.006) and awake resection (OR = 9.94, 95 % CI: 1.93-87.81, p = 0.015) were associated with seizure-free outcome. A Kaplan-Meier curve showed that the probability of seizure freedom fell to 92.6 % at 3 months, and to 85.5 % at 27.3 months after surgery. CONCLUSION: Epilepsy from tumor origin demands a balance between oncological management and epilepsy cure. Our pooled analysis suggests that GTR and awake resections are positive predictive factors for an Engel I at more than 6 months follow-up. To validate these findings, a longer-term follow-up and larger cohorts are needed.

Newly Diagnosed Adult Basal Ganglia Gliomas Treated With Laser Interstitial Thermal Therapy: A Comparative Cohort With Needle Biopsy.

BACKGROUND: Few cytoreductive surgical tools are available for newly diagnosed basal ganglia gliomas. Current reports showed high associated morbidity and mortality. Given their deep localization, laser interstitial thermal therapy (LITT) is still a rare indication. Moreover, few reports account for which of the available options have better outcomes. OBJECTIVE: To retrospectively analyze our experience with LITT and compare its safety, feasibility, and efficacy with needle biopsy for the management of adult basal ganglia gliomas. METHODS: Twenty-two patients with gliomas from the midline (e.g. thalamus and lenticular nucleus) managed with either LITT/biopsy or needle biopsy from 2015 to 2021 were included. Records regarding location, diagnosis, Karnofsky Performance Score, length of hospital stay, preoperative lesion and ablation volume, perioperative complications, and data of adjuvant treatment were collected. Overall survival was evaluated with Kaplan-Meier analysis. RESULTS: Seven patients had LITT, and 15 underwent biopsy. The overall mean age was 60.9 years (25-82 years). The average tumor volume in the former was 16.99 cm 3 and 17.65 cm 3 in the latter. No postsurgical complications were found in the LITT group, and 1 patient had a postsurgical hemorrhage after biopsy. The mean overall survival was 20.28 ± 9.63 months in the LITT group, which was greater but not statistically significant than in the biopsy group (13.85 ± 4.48 months; P = .78). CONCLUSION: Our results show that laser ablation may be both feasible and safe in adult basal ganglia gliomas. Given the lack of safe cytoreductive treatment options, LITT should be considered as a valid choice for these patients.

Algoritmo para el diagnóstico integrado de los gliomas 2021. Nuestra experiencia / Algorithm for the integrated diagnosis of gliomas 2021. Our experience

Resumen La aplicación de las diferentes técnicas moleculares para el diagnóstico de los gliomas según la clasificación de la OMS, sigue sin estar al alcance de todos en nuestro país. Nuestro objetivo fue describir el protocolo diagnóstico desarrollado en función de los recursos disponibles, conforme con la clasificación vigente (2021). También, describir el perfil epidemiológico de los gliomas diagnosticados entre 2018-2021 en el Instituto Roffo y contrastarlo con la literatura. Se evaluó la mutación en IDH1-R132H, ATRX, el estado del 1p19q, CDKN2A, EGFR y del p53. Se incluyeron 94 pacientes, 53.2% fueron masculinos, con una edad promedio de 50.9 años. El diagnóstico más frecuente fue el de GB IDH1-no mutado (63.8%). Considerando únicamente a los gliomas grado 2 y 3, el astrocitoma difuso IDH1-Mutado/ATRX-Mutado/p53-sobreexpresado, grado 2 (11.7%) fue el más frecuente. En cuanto a su localización, el 67% de los tumores se ubicaron en el telencéfalo neocortical: 24.5% del total en el lóbulo frontal. En el 95.7% de los casos se arribó a un diagnóstico integrado concluyente siguiendo el algoritmo propuesto. Las características epidemiológicas coinciden con lo publicado en la literatura. La biología molecular nos permitió diferenciar nítidamente enfermedades que suponíamos emparentadas desde un punto de vista histológico, pero que observando su historia natural, su genética y su respuesta a tratamientos instaurados eran tumores distintos, aunque todos fueran llamados "gliomas". Los estándares internacionales no conciben su diagnóstico sin la biología molecular. No es aceptable que se siga diagnosticando únicamente con estándares histológicos. El algoritmo propuesto podría ser una alternativa viable y confiable.

Abstract The utilization of the different molecular techniques for the diagnosis of gliomas according to the WHO classification is still not available to everyone in our country. Our objective was to describe the diagnostic algorithm devel oped based on available resources, in accordance with the current classification (2021). Also, to describe the epidemiological profile of gliomas diagnosed between 2018-2021 at the Roffo Institute and compare it with the international literature. IDH1-R132H and ATRX mutation, as well as 1p19q status, CDKN2A, EGFR, and p53 were evaluated. 94 patients were included, 53.2% were male, with a mean age of 50.9 years. The most frequent diagnosis was GB IDH1-wild type (63.8%). Considering only grade 2 and 3 gliomas, diffuse astrocytoma IDH1- Mutated / ATRX-Mutated / p53-overexpressed, grade 2 (11.7%) was the most frequent diagnosis. Regarding their location, 67% of the tumors were located in the neocortical telencephalon: 24.5% of the total in the frontal lobe. In 95.7% of cases, a conclusive integrated diagnosis was reached following the proposed algorithm. The epidemiological characteristics coincide with what has been published in the literature. Molecular biology allowed us to clearly differentiate pathologies that we assumed were related from a histological point of view, but which, observing their natural history, their genetics and their response to established treatments were different tumors, although they were all called "gliomas". International standards do not conceive CNS tumor diagnosis without molecular biology. It is not acceptable to continue to diagnose only with histological standards. The proposed algorithm could be a viable and reliable alternative.

[Algorithm for the integrated diagnosis of gliomas 2021. Our experience]. / Algoritmo para el diagnóstico integrado de los gliomas 2021. Nuestra experiencia.

The utilization of the different molecular techniques for the diagnosis of gliomas according to the WHO classification is still not available to everyone in our country. Our objective was to describe the diagnostic algorithm developed based on available resources, in accordance with the current classification (2021). Also, to describe the epidemiological profile of gliomas diagnosed between 2018-2021 at the Roffo Institute and compare it with the international literature. IDH1-R132H and ATRX mutation, as well as 1p19q status, CDKN2A, EGFR, and p53 were evaluated. 94 patients were included, 53.2% were male, with a mean age of 50.9 years. The most frequent diagnosis was GB IDH1-wild type (63.8%). Considering only grade 2 and 3 gliomas, diffuse astrocytoma IDH1-Mutated / ATRX-Mutated / p53-overexpressed, grade 2 (11.7%) was the most frequent diagnosis. Regarding their location, 67% of the tumors were located in the neocortical telencephalon: 24.5% of the total in the frontal lobe. In 95.7% of cases, a conclusive integrated diagnosis was reached following the proposed algorithm. The epidemiological characteristics coincide with what has been published in the literature. Molecular biology allowed us to clearly differentiate pathologies that we assumed were related from a histological point of view, but which, observing their natural history, their genetics and their response to established treatments were different tumors, although they were all called "gliomas". International standards do not conceive CNS tumor diagnosis without molecular biology. It is not acceptable to continue to diagnose only with histological standards. The proposed algorithm could be a viable and reliable alternative.

La aplicación de las diferentes técnicas moleculares para el diagnóstico de los gliomas según la clasificación de la OMS, sigue sin estar al alcance de todos en nuestro país. Nuestro objetivo fue describir el protocolo diagnóstico desarrollado en función de los recursos disponibles, conforme con la clasificación vigente (2021). También, describir el perfil epidemiológico de los gliomas diagnosticados entre 2018-2021 en el Instituto Roffo y contrastarlo con la literatura. Se evaluó la mutación en IDH1-R132H, ATRX, el estado del 1p19q, CDKN2A, EGFR y del p53. Se incluyeron 94 pacientes, 53.2% fueron masculinos, con una edad promedio de 50.9 años. El diagnóstico más frecuente fue el de GB IDH1-no mutado (63.8%). Considerando únicamente a los gliomas grado 2 y 3, el astrocitoma difuso IDH1-Mutado/ATRX-Mutado/p53-sobreexpresado, grado 2 (11.7%) fue el más frecuente. En cuanto a su localización, el 67% de los tumores se ubicaron en el telencéfalo neocortical: 24.5% del total en el lóbulo frontal. En el 95.7% de los casos se arribó a un diagnóstico integrado concluyente siguiendo el algoritmo propuesto. Las características epidemiológicas coinciden con lo publicado en la literatura. La biología molecular nos permitió diferenciar nítidamente enfermedades que suponíamos emparentadas desde un punto de vista histológico, pero que observando su historia natural, su genética y su respuesta a tratamientos instaurados eran tumores distintos, aunque todos fueran llamados "gliomas". Los estándares internacionales no conciben su diagnóstico sin la biología molecular. No es aceptable que se siga diagnosticando únicamente con estándares histológicos. El algoritmo propuesto podría ser una alternativa viable y confiable.

Effects of time to chemoradiation on high-grade gliomas from the Buenos Aires Metropolitan Area.

High-Grade Gliomas (HGG) are the most frequent brain tumor in adults. The gold standard of clinical care recommends beginning chemoradiation within 6 weeks of surgery. Disparities in access to healthcare in Argentina are notorious, often leading to treatment delays. We conducted this retrospective study to evaluate if time to chemoradiation after surgery is correlated with progression-free survival (PFS). Our study included clinical cases with a histological diagnosis of Glioblastoma (GBM), Anaplastic Astrocytoma (AA) or High-Grade Glioma (HGG) in patients over 18 years of age from 2014 to 2020. We collected data on clinical presentation, type of resection, time to surgery, time to chemoradiation, location within the Buenos Aires Metropolitan Area (BAMA) and type of health insurance. We found 63 patients that fit our inclusion criteria, including 26 (41.3%) females and 37 (58.7%) males. Their median age was 54 years old (19-86). Maximal safe resection was achieved in 49.2% (n = 31) of the patients, incomplete resection in 34.9% (n = 22) and the other 15.9% (n = 10) received a biopsy, but no resection. The type of health care insurance was almost evenly divided, with 55.6% (n = 35) of the patients having public vs. 44.4% (n = 28) having private health insurance. Median time to chemoradiation after surgery was 8 (CI 6.68-9.9) weeks for the global population. When we ordered the patients PFS by time to chemoradiation we found that there was a statistically significant effect of time to chemoradiation on patient PFS. Patients had a PFS of 10 months (p = 0.014) (CI 6.89-13.10) when they received chemoradiation <5 weeks vs a PFS of 7 months (CI 4.93-9.06) when they received chemoradiation between 5 to 8 weeks and a PFS of 4 months (CI 3.76-4.26 HR 2.18 p = 0.006) when they received chemoradiation >8 weeks after surgery. Also, our univariate and multivariate analysis found that temporal lobe location (p = 0.03), GMB histology (p = 0.02) and biopsy as surgical intervention (p = 0.02) all had a statistically significant effect on patient PFS. Thus, time to chemoradiation is an important factor in patient PFS. Our data show that although an increase in HGG severity contributes to a decrease in patient PFS, there is also a large effect of time to chemoradiation. Our results suggest that we can improve patient PFS by making access to healthcare in Buenos Aires more equitable by reducing the average time to chemoradiation following tumor resection.