scholarly journals PATH-26. INTEGRATED MOLECULAR AND CLINICAL ANALYSIS OF BRAF-MUTATED GLIOMA IN ADULTS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii169-ii170
Author(s):  
Karisa Schreck ◽  
Pinky Langat ◽  
Taibo Li ◽  
Wenya Linda Bi
Keyword(s):  
Class Ii ◽  
Class I ◽  
Response To Treatment ◽  
Cancer Center ◽  
Johns Hopkins Hospital ◽  
Low Grade ◽  
Braf Mutations ◽  
Who Grade ◽  
Grade Ii ◽  
Adult Glioma

Abstract INTRODUCTION BRAF mutations in glioma have been recognized as a significant driver of disease in pediatric low-grade glioma, but the implications of BRAF alterations on disease trajectory and response to treatment are unknown in adult glioma. Here, we characterize a multi-institutional cohort of adults with BRAF-altered glioma. METHODS We identified patients aged ≥ 18 years with glioma containing BRAF alteration on sequencing in multi-institutional cohorts (Dana-Farber/Brigham Cancer Center, Johns Hopkins Hospital, GENIE, TCGA). BRAF mutations were grouped into three previously-defined classes: I (RAS-independent/dimerization-independent), II (RAS-independent/dimerization-dependent), III (RAS-dependent/dimerization-dependent). RESULTS We identified 198 adults with BRAF-altered glioma (median age 42 years, range 18-85 years), including 17 WHO grade I, 33 grade II, 26 grade III, 114 grade IV, and 8 others. Glioblastoma (n=115) predominated, followed by grade II-III astrocytoma (n=31), pleomorphic xanthoastrocytoma (n=18), pilocytic astrocytoma (n=12), oligodendroglioma (n=7), or other glioma (n=15). Class I mutations (BRAFV600E) comprised 49% (n=97), class II mutations 4.5% (n=9) and class III mutations 4.5% (n=9). Rearrangements occurred in 9.6% (n=19), of which canonical fusions comprised 4% (n=8), occurring primarily in pilocytic astrocytomas; copy number gains affected 13% (n=26), and other alterations 19% (n=38). All pleomorphic xanthoastrocytomas and 43.5% of glioblastoma harbored BRAFV600E. Mutation of NF1, an inhibitor of RAS/ERK signaling, was significantly associated with class II/III BRAF mutations (64.3%) and not observed in BRAFV600E-altered glioma (0%, n=62; p< 0.0001). BRAFV600E was the sole alteration in a subset of glioma with class I mutations, while others harbored multiple genomic alterations. Among 45 patients with glioblastoma and detailed clinicopathologic data, 7 received RAF-targeted therapy, with variable clinical response. Overall survival was 26 months with BRAFV600E, 21 months with class II/III mutation, and 33 months with other BRAF-alteration. CONCLUSIONS This large cohort of BRAF-altered adult glioma demonstrates a broad range of alterations, with implications for treatment sensitivity and patient survival.

scholarly journals ECOA-10. Integrated genomic and clinical analysis of BRAF-mutated glioma in adults

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii3-ii3
Author(s):  
Pinky Langat ◽  
Taibo Li ◽  
Wenya Linda Bi ◽  
Karisa C Schreck
Keyword(s):  
Risk Stratification ◽  
Copy Number ◽  
Negative Regulator ◽  
Class I ◽  
Cancer Center ◽  
Johns Hopkins Hospital ◽  
Low Grade ◽  
Molecular Features ◽  
Significant Difference ◽  
Adult Glioma

Abstract BRAF alterations are recognized as a significant driver of disease in pediatric low-grade glioma (pLGG) but the implications of BRAF alterations on the natural history and response to treatment are unclear in adult glioma. We characterized the molecular and clinical features of a multi-institutional cohort of adults with BRAF-mutated gliomas. We identified patients with glioma containing BRAF alterations on sequencing in multi-institutional cohorts (Dana-Farber/Brigham Cancer Center, Johns Hopkins Hospital, GENIE, TCGA). BRAF alterations were grouped into previously defined classes: I (V600E; RAS-independent/dimerization-independent), II (RAS-independent/dimerization-dependent), III (RAS-dependent/dimerization-dependent) in addition to BRAF copy number gains, fusions, and other. We interrogated 289 BRAF-altered gliomas (199 patients >=18yrs, 90 patients <18yrs; range 0-85yrs), and observed histopathologic and molecular differences between BRAF-altered gliomas in adults versus pediatric patients. Amongst adults, the most common BRAF alterations were Class I followed by copy number gains, with glioblastoma (GBM) the most prevalent histology. In comparison, pediatric gliomas in our cohort frequently harbored Class I mutations followed by BRAF fusions, with primarily pilocytic astrocytoma and pLGG histologies. Principal component analysis and correlation analysis revealed molecular features associated with gliomas of different BRAF alterations and histologies, including mutation of NF1, a negative regulator of RAS, which was significantly associated with class II/III BRAF alterations (64.3%) and not observed in BRAFV600E-mutated gliomas (0%, n=62) (p<0.0001). Demographic and molecular features were evaluated for correlates for adult glioma risk stratification. Comparative survival analysis showed no significant difference between adult GBM harboring Class I compared to other BRAF alterations, whereas young adult age (18-35yrs) was associated with improved outcomes (p<0.05). Among 86 GBM patients with detailed clinicopathologic data, 7 received RAF-targeted therapy, with variable clinical response. This cohort of BRAF-altered adult gliomas demonstrates a broad range of molecular alterations with implications for treatment sensitivity and patient risk stratification.

scholarly journals RTID-05. INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF VORASIDENIB (AG-881) VS PLACEBO IN PATIENTS WITH RESIDUAL/RECURRENT GRADE II GLIOMA WITH AN ISOCITRATE DEHYDROGENASE 1/2 (IDH1/2) MUTATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii194-ii194
Author(s):  
Ingo Mellinghoff ◽  
Martin van den Bent ◽  
Jennifer Clarke ◽  
Elizabeth Maher ◽  
Katherine Peters ◽  
...  
Keyword(s):  
High Risk ◽  
Dose Escalation ◽  
Objective Response ◽  
Data Monitoring Committee ◽  
Progression Free Survival ◽  
High Risk Population ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival ◽  
Grade Ii

Abstract BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).

scholarly journals A 25-year retrospective, single center analysis of 343 WHO grade II/III glioma patients: implications for grading and temozolomide therapy

2021 ◽  
Author(s):  
Eike Steidl ◽  
Katharina Filipski ◽  
Pia S. Zeiner ◽  
Marlies Wagner ◽  
Emmanouil Fokas ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Molecular Markers ◽  
Treatment Time ◽  
Real Life ◽  
Patient Characteristics ◽  
Low Grade ◽  
Who Grade ◽  
Idh1 R132h ◽  
Treatment Data ◽  
Grade Ii

Abstract Purpose Classification and treatment of WHO grade II/III gliomas have dramatically changed. Implementing molecular markers into the WHO classification raised discussions about the significance of grading and clinical trials showed overall survival (OS) benefits for combined radiochemotherapy. As molecularly stratified treatment data outside clinical trials are scarce, we conducted this retrospective study. Methods We identified 343 patients (1995–2015) with newly diagnosed WHO grade II/III gliomas and analyzed molecular markers, patient characteristics, symptoms, histology, treatment, time to treatment failure (TTF) and OS. Results IDH-status was available for all patients (259 mutant, 84 IDH1-R132H-non-mutant). Molecular subclassification was possible in 173 tumors, resulting in diagnosis of 80 astrocytomas and 93 oligodendrogliomas. WHO grading remained significant for OS in astrocytomas/IDH1-R132H-non-mutant gliomas (p < 0.01) but not for oligodendroglioma (p = 0.27). Chemotherapy (and temozolomide in particular) showed inferior OS compared to radiotherapy in astrocytomas (median 6.1/12.1 years; p = 0.03) and oligodendrogliomas (median 13.2/not reached (n.r.) years; p = 0.03). While radiochemotherapy improved TTF in oligodendroglioma (median radiochemotherapy n.r./chemotherapy 3.8/radiotherapy 7.3 years; p < 0.001/ = 0.06; OS data immature) the effect, mainly in combination with temozolomide, was weaker in astrocytomas (median radiochemotherapy 6.7/chemotherapy 2.3/radiotherapy 2.0 years; p < 0.001/ = 0.11) and did not translate to improved OS (median 8.4 years). Conclusion This is one of the largest retrospective, real-life datasets reporting treatment and outcome in low-grade gliomas incorporating molecular markers. Current histologic grading features remain prognostic in astrocytomas while being insignificant in oligodendroglioma with interfering treatment effects. Chemotherapy (temozolomide) was less effective than radiotherapy in both astrocytomas and oligodendrogliomas while radiochemotherapy showed the highest TTF in oligodendrogliomas.

scholarly journals The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 808-814 ◽  
Author(s):  
Toral Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany Powell ◽  
Gustav Young-Min Cederquist ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
World Health ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Low Grade Gliomas ◽  
Grade Ii ◽  
The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

scholarly journals Prevalence of class I–III BRAF mutations among 114,662 cancer patients in a large genomic database

2020 ◽  
pp. 153537022095965
Author(s):  
Jeff Owsley ◽  
Matthew K Stein ◽  
Jason Porter ◽  
Gino K In ◽  
Mohamed Salem ◽  
...  
Keyword(s):  
Braf Mutation ◽  
Kinase Activity ◽  
Human Cancer ◽  
Class Ii ◽  
Class I ◽  
Clinical Activity ◽  
Class Iii ◽  
Braf Mutations ◽  
Comprehensive Genomic Profiling ◽  
Relative Prevalence

BRAF mutations are relatively common in many cancers, particularly melanoma, colorectal cancer, and thyroid cancer and to a lesser extent in lung cancer. These mutations can be targeted by BRAF and MEK inhibitors, which exhibit good clinical activity. There are conflicting reports of the various relative rates of BRAF Class I mutations (V600 locus), defined as those that exhibit extremely strong kinase activity by stimulating monomeric activation of BRAF, Class II, define as non-V600 mutations that activate BRAF to signal as a RAS-independent dimer, and Class III mutations, defined as “kinase-dead” with low kinase activity as compared to wild type BRAF. Prospective studies have largely focused on patients with tumors harboring Class I BRAF mutations (limited to the V600 locus) where response rates up to 70% with BRAF plus MEK inhibition have been demonstrated. We report on the relative prevalence of various types of BRAF mutations across human cancers in a cohort of 114,662 patients that received comprehensive genomic profiling using next-generation sequencing. Of these patients, 4517 (3.9%) a pathogenic or presumed pathogenic BRAF mutation (3.9%). Of these, 1271 were seen in melanoma, representing 39.7% of all melanomas sequenced, representing the highest rate in all tumors. Class I (V600) mutations were seen overall in 2841 patients (62.1% of BRAF mutations, 2.4% of total cancers). Class II mutations were seen in 746 tumors (16.5% of BRAF mutant, 0.7% of total), and Class III mutations were seen in 801 tumors (17.7% of BRAF, 0.7% of total). Knowledge of the relative prevalence of these types of mutations can aid in the development of agents that might better address non-V600 mutations in cancer. Impact statement These data represent the largest aggregation of BRAF mutations within a single clinical database to our knowledge. The relative proportions of both BRAF V600 mutations and non-V600 mutations are informative in all cancers and by malignancy, and can serve as a definitive gold-standard for BRAF mutation cancer incidence by malignancy. The rate of BRAF mutation in human cancer in a real-world large database is lower than previously reported likely representing testing more broadly across tumor types. The relative percentages of Class II and Class III BRAF mutations are higher than previously reported, representing almost 35% of BRAF mutations in cancer. These findings provide support for the development of effective treatments for non-V600 BRAF mutations in cancer.

scholarly journals The role of up-front radiation therapy for incompletely resected pediatric WHO grade II low-grade gliomas1

2006 ◽  
Vol 8 (2) ◽  
pp. 166-174 ◽  
Author(s):  
Kavita K. Mishra ◽  
Dev R. Puri ◽  
Brian T. Missett ◽  
Kathleen R. Lamborn ◽  
Michael D. Prados ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Low Grade ◽  
Who Grade ◽  
Grade Ii

Interstitial radiosurgery of low-grade gliomas

1995 ◽  
Vol 82 (3) ◽  
pp. 418-429 ◽  
Author(s):  
Friedrich W. Kreth ◽  
Michael Faist ◽  
Peter C. Warnke ◽  
Reinhard Roβner ◽  
Benedikt Volk ◽  
...  
Keyword(s):  
Ct Scan ◽  
Tumor Recurrence ◽  
Survival Rates ◽  
Low Grade ◽  
Who Grade ◽  
Content Type ◽  
Low Grade Gliomas ◽  
Interstitial Radiosurgery ◽  
Grade Ii ◽  
Fine Print

✓ The treatment of patients with low-grade gliomas remains a subject of controversy, especially with respect to new treatment modalities such as interstitial radiosurgery (brachytherapy), radiosurgery, and stereotactic radiotherapy. In a retrospective analysis conducted between 1979 and 1991, the authors studied the results of interstitial radiosurgery in 455 patients with low-grade gliomas (World Health Organization (WHO) Grade I + WHO Grade II) with regard to survival time, quality of life, the risk of malignant transformation, and the risk profile of the treatment concept. Interstitial radiosurgery with iodine-125 was performed using permanent (1979–1985) or temporary implants (after 1985) with low-dose rates (≤ 10 cGy/hr) and a reference dose of 60 to 100 Gy calculated to the outer rim of the tumor. The 5- and 10-year survival rates in patients with pilocytic astrocytomas (97 patients) were 84.9% and 83%, and in patients with WHO Grade II astrocytomas (250 patients) 61% and 51%, respectively. Five-year survival rates for patients with oligoastrocytomas (60 patients), oligodendrogliomas (27 patients), and gemistocytic astrocytomas (21 patients) were 49%, 50%, and 32%, respectively. In the group with WHO Grade II gliomas, young age and a good performance status were associated with a better prognosis. Unfavorable factors were midline shift, enhancement on computerized tomography (CT) scan, and tumor recurrence after previous radiotherapy or surgery. Tumor location had no influence on the prognosis (247 patients in this series had deep-seated tumors). Malignant transformation was the major cause of death. Important risk factors for malignancy were the patient's age, tumor enhancement in CT scan, and tumor recurrence after previous surgery or radiotherapy. Perioperative mortality was 0.9% and perioperative morbidity was 1.7%. Radiogenic complications were observed in 2.7% of all patients, most often in larger tumors and after using permanent implants. The authors conclude that interstitial radiosurgery represents a specific treatment modality for selected patients with unifocal circumscribed low-grade gliomas with a diameter of less than 4 cm in any location. The efficacy of this treatment lies in the same range as the best results after surgery and radiotherapy.

scholarly journals Systematic Review - Time To Malignant Transformation In Low Grade Gliomas: Predicting A Catastrophic Event With Clinical, Neuroimaging And Molecular Markers

2021 ◽  
Author(s):  
Zabina Satar ◽  
Gary Hotton ◽  
George Samandouras
Keyword(s):  
Malignant Transformation ◽  
Epileptic Seizures ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Invasive Treatment ◽  
Who Grade ◽  
Grade Ii ◽  
Cortical Involvement ◽  
Impaired Quality

Abstract Background Despite an initially indolent course, all WHO grade II, LGGs inevitably transform to malignant, WHO grades III and IV, without current curative options. Malignant transformation (MT) remains unpredictable with limited prognostic markers to steer timing of interventions. The aim of this study was to review and assign predictive value to specific clinical, molecular and radiological markers impacting MT, thereby justifying timely therapeutic interventions. Methods Searches of MEDLINE, Embase and Cochrane databases were conducted from inception to April 28, 2021 and outputs were analysed in accordance with PRISMA protocol. Results From an initial 5,032 articles, 31 articles were included, totalling 5,193 patients. Forty-three prognostic factors were registered to significantly impact MT. These were categorised as 7 clinical; 14 neuroimaging; 8 biological/molecular; 3 volumetric; 5 topological; 3 histological; and 3 treatment-related. Following analysis, 10 factors were highlighted: the pre-operative prognosticators were 1. presentation with epileptic seizures; 2. VDE &gt;8mm/year; 3. VDE &gt;4mm/year; 4. rCBV &gt;1.75; 5. PTV ≥5 cm (65ml); 6. PTV ≥100 ml; and 7. cortical involvement. The post-operative prognosticators were 1.IDH-wt; 2. TP53 mutation; and 3. temozolomide monotherapy. Conclusions The management of LGGs remains controversial, as conservative and invasive treatment may be associated with MT and impaired quality of life, respectively. Our review indicates that MT can be predicted by specific metrics in VDE, PTV and rCBV, alongside cortical involvement. Additionally, patients with IDH-wt tumours TP53 mutations, or receiving TMZ monotherapy are more likely to undergo MT. Our data may form the basis of a predictive scoring system.

scholarly journals Relationship between Histopathological Subtypes of Intracranial Astrocytoma Patients

2014 ◽  
Vol 27 (2) ◽  
pp. 87-93
Author(s):  
Fazle Mahmud ◽  
Haradhan Deb Nath ◽  
Kanak Kanti Barua ◽  
Afzal Hossain
Keyword(s):  
Age Groups ◽  
Low Grade ◽  
Age Group ◽  
Who Grade ◽  
Grade Ii ◽  
The Mean ◽  
The Relationship

Background : The study was carried out in the department of neurosurgery, BSMMU, Dhaka during the period of July 2003 to June 2005. Objective: This study was done to elucidate the relationship between age groups and histopathologicas subtypes in case of intracranial astrocytoma patients. For this purpose, a total number of 44 cases were studied. Results: The mean age of all the patients was 33.1 years (range:1-65 years). The highest incidence was found in the age group of 20 years or below group. Male were more commonly effected than female. WHO grade I astrocytoma was the commonest type. Mean age of low grade astrocytoma (WHO grade II) and glioblastoma were nearly similar to other studies, but the mean age of presentation of grade I astrocytomas patients was little late and for anaplastic actrocytoma a little early in comparison to other study. Conclusion: This showed subtype of astrocytoma has definitive relation to age. Bangladesh Journal of Neuroscience 2011; Vol. 27 (2) : 87-93 DOI: http://dx.doi.org/10.3329/bjn.v27i2.17575

scholarly journals Long-term outcome of stereotactic brachytherapy with temporary Iodine-125 seeds in patients with WHO grade II gliomas

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Juliana Watson ◽  
Alexander Romagna ◽  
Hendrik Ballhausen ◽  
Maximilian Niyazi ◽  
Stefanie Lietke ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Low Grade ◽  
Toxicity Profile ◽  
Who Grade ◽  
Low Grade Gliomas ◽  
Stereotactic Brachytherapy ◽  
Grade Ii ◽  
Iodine 125

Abstract Background This long-term retrospective analysis aimed to investigate the outcome and toxicity profile of stereotactic brachytherapy (SBT) in selected low-grade gliomas WHO grade II (LGGII) in a large patient series. Methods This analysis comprised 106 consecutive patients who received SBT with temporary Iodine-125 seeds for histologically verified LGGII at the University of Munich between March 1997 and July 2011. Investigation included clinical characteristics, technical aspects of SBT, the application of other treatments, outcome analyses including malignization rates, and prognostic factors with special focus on molecular biomarkers. Results For the entire study population, the 5- and 10-years overall survival (OS) rates were 79% and 62%, respectively, with a median follow-up of 115.9 months. No prognostic factors could be identified. Interstitial radiotherapy was applied in 51 cases as first-line treatment with a median number of two seeds (range 1–5), and a median total implanted activity of 21.8 mCi (range 4.2–43.4). The reference dose average was 54.0 Gy. Five- and ten-years OS and progression-free survival rates after SBT were 72% and 43%, and 40% and 23%, respectively, with a median follow-up of 86.7 months. The procedure-related mortality rate was zero, although an overall complication rate of 16% was registered. Patients with complications had a significantly larger tumor volume (p = 0.029). Conclusion SBT is a minimally invasive treatment modality with a favorable outcome and toxicity profile. It is both an alternative primary treatment method as well as an adjunct to open tumor resection in selected low-grade gliomas.

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