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 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.

Venous Thromboembolism (VTE) in Patients (pts.) with Monoclonal Gammopathy of Undetermined Significance (MGUS)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5340-5340
Author(s):  
Alaa A Muslimani ◽  
Fadi Bailony ◽  
Madappa Kundranda ◽  
Timothy Spiro ◽  
Asif Chaudhry ◽  
...  
Keyword(s):  
Risk Factors ◽  
General Population ◽  
Risk Stratification ◽  
Cleveland Clinic ◽  
Risk Groups ◽  
Cancer Center ◽  
Intermediate Risk ◽  
Risk Stratification Model ◽  
Significant Difference

Abstract Introduction: MGUS is considered to be a pre-malignant condition, and previous studies have reported VTE as a marker for a subsequent malignancy. We conducted a retrospective study to evaluate the incidence of VTE among MGUS patients (pts) and to correlate this incidence with different risk groups for developing malignancy in MGUS pts. Methods: The complete medical records of all MGUS pts at Cleveland Clinic Cancer Center at Fairview hospital from Jun/2005–Jun/2008 were retrospectively reviewed. Of 237 pts diagnosed with MGUS, 112 pts (65 males, 47 females) were eligible for our study. These pts were divided into 2 risk groups: low risk (LR)/low-intermediate risk (LIR) group (78 pts.) and high intermediate risk (HIR)/high risk (HR) group (34 pts) based on the Risk Stratification Model using three adverse risk factors; serum M-protein level ≥ 3 gm/dL, non-IgG MGUS, and an abnormal kappa/lambda free light chain ratio. Only pts with ≥ 12 months follow up were included. Exclusion criteria included a personal history of inherited thrombophilia, previous episode of VTE or anticoagulant treatment, thrombocytosis, malignancy, and renal impairment. Risk factors (RF) for VTE were identified in each pt and categorized into four groups: no RF, 0; one RF, 1; two RF, 2; and > 2 RF, >2. RF included > 48 hours of immobilization, surgery in the past 3 months, current hospitalization at the time of VTE occurrence, oral contraceptive use, and congestive heart failure. Objectives: To compare the proportion of pts with MGUS who developed VTE to the proportion of pts in the general population who developed VTE. To compare VTE incidence between the two risk groups. Results: During the study period, 9 pts with MGUS experienced VTE. In the general population, the incidence of VTE is 117/100,000 persons/year (from literature). Therefore, the proportion of pts in the general population over 3 years was 117/100000 × 3 =0.0035. The proportion of VTE in MGUS pts, adjusted for 3 years, of 0.080 is significantly higher than that for the general population (p<0.001). Comparison of VTE incidence between the two risk groups, while adjusting for the number of risk factors, showed no difference (Cox Proportional Model, p=0.38). There is no significant difference in the risk of VTE among different levels of risk factors (p=0.96). The Kaplan-Meier estimates of the proportions of pts free of VTE at 24 months are 0.96 and 0.93 for the LR/LIR and HIR/HR groups, respectively. Conclusions: MGUS is associated with a significantly higher rate of VTE compared to the general population. Despite many studies indicating VTE as a marker for subsequent malignancy, we did not find a difference in the incidence of VTE among the various risk factor groups. Any suggestive signs of VTE in pts with MGUS should be promptly evaluated and treatment initiated as soon as possible. Since the number of pts is small and the period of follow-up relatively short, a prospective cohort study is needed to verify our results. Table?: Comparison of event rate: VTE Po p-value Total number of pts Risk stratification model (pts) Groups (pts) VTE Proportion Note: Po is the VTE proportion for the general population over a 3-year time period. 112 LR (38) LR/LIR (78) (5) LIR (40) 0.080 0.0035 <0.001 HIR (26) HIR/HR (34) (4) HR (8)

High Resolution Array-Based Analysis in Marginal Zone Lymphomas and Lymphoplasmacytic Lymphomas Identified Disease-Specific Patterns of Chromosome Abnormalities

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 621-621 ◽  
Author(s):  
Esteban Braggio ◽  
Ellen Remstein ◽  
Wee Joo J Chng ◽  
Gaofeng Huang ◽  
Michael Barrett ◽  
...  
Keyword(s):  
High Resolution ◽  
B Cell ◽  
Copy Number ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Negative Regulator ◽  
Low Grade ◽  
B Cell Lymphomas ◽  
Disease Specific

Abstract Marginal zone B-cell lymphomas (MZL) represent a sub-group of indolent B-cell lymphomas, normally localized in the “marginal zone” of the secondary lymphoid follicles. Depending on the site of involvement, three distinct sub-types have been identified: extra nodal MZL of MALT type, splenic MZL (SMZL), and nodal MZL (NMZL). MALT lymphoma is the most frequent of the MZL subtypes, representing 70% of MZL and 7% to 8% of non-Hodgkin lymphomas. SMZL and NMZL comprise the remaining 20% and 10% of MZL, respectively, and account for less than 1% of NHL. The relative rarity of these lymphomas and difficulty in distinguishing them from other low-grade B-cell lymphoma subtypes like lymphoplasmacytic lymphomas (LPL), making therapeutic decisions difficult. The aim of this study was to perform a comprehensive high-resolution study to identify distinctive molecular markers in MZL and LPL, which would help to better define these lymphomas at genomic level and distinguish them from other types of low-grade B-cell lymphoma. We analyzed 119 patients, including 22 pulmonary MALT (pMALT), 20 non-pulmonary MALT (npMALT), 34 SMZL, 21 NMZL and 22 LPL (8 Waldenström’s Macroglobulinemia and 14 non-WM) cases. Human Agilent 244A platform was used by array-based comparative genomic hybridization (aCGH) analysis. Overall, 93% of patients have an altered genome. LPL had the highest amount of copy number abnormalities (median of 7.5 per patient; average of 11.7; range: 0–44), followed by npMALT (6.5; 7.6; 0–33), NMZL (5; 8.3; 0–31), SMZL (4; 7.1; 0–56) and pMALT (3.5; 4.3; 1–11). When the overall size of the abnormalities was considered, LPL was also the most affected disease with an average size of 245.15Mb included in copy number changes per patient, followed by NMZL (188.6Mb), npMALT (187.2Mb), SMZL (126.4Mb) and pMALT (109Mb). Deletions were more commonly observed than amplifications but the affected area was significantly smaller (average of 55.2Mb and 118.6Mb included in deletions and amplifications per genome, respectively). Partial or total gains of chromosome 3 and 18 were recurrently identified in all the entities, being the most common abnormalities in npMALT (60% and 50%, respectively) and pMALT (27% each). Trisomy 12 was also ubiquitously observed, ranging from 24% of NMZL to 9% of pMALT. Deletions in 6q were commonly identified in LPL (55%), npMALT (35%) and, in a less extent, in SMZL (12%) and NMZL (5%), but not in pMALT. Biallelic and focal monoallelic deletions at 6q23 clearly delineate a minimal deleted region (MDR) that includes TNFAIP3 as being the target gene of the abnormality. Deletions on 7q were found in SMZL and npMALT, thus delineating two MDR. Interstitial 11q deletions were found in LPL, NMZL and SMZL, but not in MALT. Chromosome 13 abnormalities were monosomies in NMZL and interstitial 13q14 deletions in LPL and SMZL, comprising MIRN15A and MIRN16-1 in the MDR. Partial X chromosome gains were common to all the entities but involving different areas: Xq27.3–q28 gains were recurrent events in LPL and NMZL, but not in SMZL and MALT, which were characterized by p arm gains or trisomies. Finally, some recurrent abnormalities were exclusive of specific entities: 1p deletions and 1q gains were only common in NMZL; a focal 2p gain including BCL11A and REL was found in npMALT and partial 8q gains were only identified in LPL. Trisomy 4 was only identified in the subgroup of LPL with WM, but not in the remaining LPL cases or in the remaining diseases. In this study we made a compendium of chromosomal abnormalities present in a group of related diseases, in which the molecular basis remains poorly defined. Using this high-resolution approach we were able to establish recurrent and disease-specific patterns of abnormalities and minimal deleted/amplified regions were redefined. Furthermore, TNFAIP3, a negative regulator of the NF-kB pathway, has been identified as being a commonly affected gene in MALT, LPL and NMZL, highlighting its potential role in pathogenesis.

Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 336-336 ◽  
Author(s):  
Nilay M Gandhi ◽  
Alexander S Baras ◽  
Enrico Munari ◽  
Sheila Faraj ◽  
Leonardo O Reis ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Clinical Stage ◽  
Pathologic Response ◽  
Johns Hopkins Hospital ◽  
Tree Model ◽  
Cancer Specific Survival ◽  
Nccn Guidelines ◽  
Molecular Features ◽  
Significant Difference ◽  
Muscle Invasive

336 Background: To evaluate gemcitabine-cisplatin (GC) neoadjuvant chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) and identify clinical parameters associated with pR. Methods: We studied 150 consecutive cases of MIBC that received GC NAC followed by open RC (2000-2013). A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index (JHH-DI) to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance. Results: No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non-muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma (p=0.99). NAC pR (≤pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, p<0.01) and decreased nodal positivity rates (0% vs. 41.3%, p<0.01) compared to non-responders (≥pT2). Clinicopathologic outcomes were inferior in NAC pathologic non-responders (pNR) compared to the entire RC-only treated cohort. A lower pNR rate was seen in patients tolerating sufficient dosing of NAC as stratified by the JHH-DI (p=0.049), congruent with NCCN guidelines. A multivariate decision tree model demonstrated age ≤60 years and clinical stage cT2 as significant of NAC response (p<0.05). Conclusions: Pathologic non-responders fare worse than patients proceeding directly to RC alone. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify patients most likely to benefit from GC NAC.

scholarly journals Genomic analysis of primary and recurrent gliomas reveals clinical outcome related molecular features

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Longbo Zhang ◽  
Zhiqiang Liu ◽  
Jin Li ◽  
Tianxiang Huang ◽  
Ying Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Copy Number ◽  
Disease Free Survival ◽  
Genomic Analysis ◽  
Predictive Biomarkers ◽  
Recurrent Gliomas ◽  
Molecular Features ◽  
Significant Difference ◽  
Number Variation ◽  
Cell Cycle Pathway

Abstract Tremendous efforts have been made to explore biomarkers for classification and grading on gliomas. The goal of this study was to identify more molecular features that are associated with clinical outcomes by comparing the genomic profiles of primary and recurrent gliomas and determine potential recurrence leading factors that are significantly enriched in relapse tumors. Hybrid capture based next generation sequencing (NGS) analysis was performed on 64 primary and 17 recurrent glioma biopsies. Copy number variation (CNV) was more frequent in recurrent tumors and CDKN2A/B loss was significantly enriched. In addition, overall mutations in cell cycle pathway are more common in relapse tumors. The patterns of gene sets, including IDH1/TERT and IDH1/TP53 exhibited significant difference between the groups. Survival analysis uncovered the worse disease-free survival (DFS) and overall survival (OS) associated with altered copy number and excessive activation of CELL CYCLE pathway. High Tumor Mutation Burden (TMB) was also a biomarker with great potential for poor prognosis. The assessment of genomic characteristics in primary versus recurrent gliomas aids the discovery of potential predictive biomarkers. The prognostic value of TMB in gliomas was raised for the first time.

scholarly journals Hypomethylating Agent/Venetoclax Versus Intensive Chemotherapy in Relapsed or Refractory Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2322-2322
Author(s):  
Omer Hassan Jamy ◽  
Sarah Worth ◽  
Sravanti Rangaraju ◽  
Kimo Bachiashvili ◽  
Pankit Vachhani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Stratification ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
High Dose ◽  
University Of Alabama ◽  
Significant Difference ◽  
Acute Myeloid

Abstract Background: Patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) have limited treatment options. Outside of clinical trials and in the absence of a targetable mutation, there is no consensus on an optimal treatment regimen. Venetoclax (Ven), combined with hypomethylating agents (HMA) such as azacitadine (Aza) or decitabine (Dec), is approved as frontline treatment for elderly or unfit patients with AML. HMA/Ven is also being used frequently in the salvage setting. However, outcomes of HMA/Ven compared to IC for patients with r/r AML are largely unknown. Methods: We conducted a retrospective study to compare outcomes of adult patients (&gt;18y) with r/r AML treated with either HMA/Ven or IC at the University of Alabama at Birmingham. Patients treated with HMA/Ven were matched in a 1:1 ratio to patients receiving IC following a hierarchal algorithm based on age, ELN risk stratification, time to relapse (primary refractory/&lt;6m vs. ≥6m) and line of therapy. Treatment with HMA consisted of either Aza 75mg/m 2 for 7 days or Dec 20mg/m 2 for 5 days. Venetoclax was administered at an effective dose of 400mg daily for 21-28 days per cycle (dose adjusted for concomitant azole use). Results: There were 74 patients included in the analysis (HMA/Ven=37, IC=37). The baseline characteristics (Table 1) were well balanced with the exception of increased bone marrow blast percentage in the IC arm (59% vs. 39%, p=0.03). The median age of the IC and HMA/Ven groups was 56y (24-72y) and 63y (22-75y), respectively (p=0.06). Regimens in the IC arm included FLAG (n=16, 43%), FLAG-ida (n=11, 30%), CLAG-M (n=5, 14%), 7+3 (n=3, 8%), HiDAC (n=1, 2.5%) and MEC (n=1, 2.5%). In the HMA/Ven arm, 21 patients (57%) received Aza and 16 (43%) received Dec. The rate of complete remission (CR) was higher for IC (49% vs. 24%, p=0.02) whereas rate of CR with incomplete count recovery (CRi) was higher for HMA/Ven (35% vs. 8%, p=0.001) (Table 2). There was no difference in composite CR (CR+CRi) rates between the two arms (IC 57% vs. 59% HMA/Ven, p=0.8). Additionally, there was no difference in rate of refractory disease (27% vs. 27%, p=0.9) or 30-day mortality (IC 13% vs 11% HMA/Ven, p=0.6) between the two arms. More patients in the IC arm (41%), compared to the HMA/Ven (19%) arm proceeded to allogeneic stem cell transplantation (allo-sct) (p=0.04). The median overall survival (mOS) for the IC arm was 16m, compared to 8m for the HMA/Ven arm (p=0.1) (Figure 1). The mOS for patients with primary refractory/&lt;6m relapse from remission was 10m for IC and 6m for HMA/Ven (p=0.4). The mOS for patients refractory to one cycle of intensive induction (7+3 in approximately 90% cases in both arms) was 20m for the IC arm and 5m for the HMA/Ven arm (p=0.03) (Figure 2). The mOS for patients relapsing ≥6m from remission was 15m for IC and 9m for HMA/Ven (p=0.5). There was no difference in survival based on age, ELN risk stratification or cytogenetics. Conclusion: Overall, there appears to be no significant difference in outcomes between IC and HMA/Ven for patients with r/r AML. Higher CR rates as well as ability to proceed to allo-sct are observed with IC. For patients refractory to the first cycle of intensive induction chemotherapy, a significant survival benefit was observed in those receiving IC compared to HMA/Ven. A second round of induction, preferably with a high-dose cytarabine based regimen, may provide better long term outcomes for these patients. Figure 1 Figure 1. Disclosures Vachhani: CTI BioPharma Corp: Consultancy; Abbvie: Consultancy; Agios: Consultancy; Blueprint Medicines: Consultancy; Pfizer: Consultancy; Seattle Genetics: Research Funding; Astellas Pharma: Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham: Current Employment; Jazz Pharmaceuticals: Consultancy.

METODE PEMBELAJARAN SAS UNTUK MENINGKATKAN KETERAMPILAN MEMBACA SISWA KELAS I SD NEGERI 021 SITORAJO KARI KECAMATAN KUANTAN TENGAH KABUPATEN KUANTAN SINGINGI

2018 ◽  
Vol 2 (5) ◽  
pp. 659
Author(s):  
Emgusnadi Emgusnadi
Keyword(s):  
Learning Outcomes ◽  
Reading Skills ◽  
Class I ◽  
Low Grade ◽  
Observation Data ◽  
School Students ◽  
Class 1 ◽  
Reading Study ◽  
Student Observation ◽  
Daily Test

Reading learning in the low grade class 1, which is often done in the early stages of learning which is calledpreliminary reading, has been done in various ways so that students read smoothly, but the numbers of studentswho cannot read in grade 1 are high. Therefore, researchers conducted research to improve reading skills ingrade 1 elementary school students by using the SAS learning method. . The research class study is improvementstudying process to solve problem that can be happen by a teacher in the class. Data on gain after research toteacher activity in cycle I meeting 1 with percentage 58%, meeting 2 with percentage 70,5%, in cycle II meeting3 percentage in the amount of 84%, and meeting 4 percentage obtained 97%. The student observation data inthis research obtained percentage in cycle I meeting 1 in the amount 51,5%, meeting 2 in the amount 66,5%, inthe cycle II meeting 3 in the amount 89%, and inthe meeting 4 obtained percentage in the amount 94% this isprove if the student activity is rise experience. Data increase learning outcomes in the class I SDN 021 SitorajoKari kecamatan Kuantan Tengah in the data early obtained average 60,5, in the daily test 1 obtained average inthe amount 74, and in the daily test 2 obtained average in the amount 83 this prove using the method of SAS theefective reading study used in class I.

Associations between clinical outcome and tractography based on navigated transcranial magnetic stimulation in patients with language-eloquent brain lesions

2020 ◽  
Vol 132 (4) ◽  
pp. 1033-1042 ◽  
Author(s):  
Nico Sollmann ◽  
Alessia Fratini ◽  
Haosu Zhang ◽  
Claus Zimmer ◽  
Bernhard Meyer ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Brain Tumors ◽  
Risk Stratification ◽  
Magnetic Stimulation ◽  
Diffusion Tensor ◽  
Tumor Resection ◽  
Navigated Transcranial Magnetic Stimulation ◽  
Language Mapping ◽  
Significant Difference ◽  
Related Pathway

OBJECTIVENavigated transcranial magnetic stimulation (nTMS) in combination with diffusion tensor imaging fiber tracking (DTI FT) is increasingly used to locate subcortical language-related pathways. The aim of this study was to establish nTMS-based DTI FT for preoperative risk stratification by evaluating associations between lesion-to-tract distances (LTDs) and aphasia and by determining a cut-off LTD value to prevent surgery-related permanent aphasia.METHODSFifty patients with left-hemispheric, language-eloquent brain tumors underwent preoperative nTMS language mapping and nTMS-based DTI FT, followed by tumor resection. nTMS-based DTI FT was performed with a predefined fractional anisotropy (FA) of 0.10, 0.15, 50% of the individual FA threshold (FAT), and 75% FAT (minimum fiber length [FL]: 100 mm). The arcuate fascicle (AF), superior longitudinal fascicle (SLF), inferior longitudinal fascicle (ILF), uncinate fascicle (UC), and frontooccipital fascicle (FoF) were identified in nTMS-based tractography, and minimum LTDs were measured between the lesion and the AF and between the lesion and the closest other subcortical language-related pathway (SLF, ILF, UC, or FoF). LTDs were then associated with the level of aphasia (no/transient or permanent surgery-related aphasia, according to follow-up examinations).RESULTSA significant difference in LTDs was observed between patients with no or only surgery-related transient impairment and those who developed surgery-related permanent aphasia with regard to the AF (FA = 0.10, p = 0.0321; FA = 0.15, p = 0.0143; FA = 50% FAT, p = 0.0106) as well as the closest other subcortical language-related pathway (FA = 0.10, p = 0.0182; FA = 0.15, p = 0.0200; FA = 50% FAT, p = 0.0077). Patients with surgery-related permanent aphasia showed the lowest LTDs in relation to these tracts. Thus, LTDs of ≥ 8 mm (AF) and ≥ 11 mm (SLF, ILF, UC, or FoF) were determined as cut-off values for surgery-related permanent aphasia.CONCLUSIONSnTMS-based DTI FT of subcortical language-related pathways seems suitable for risk stratification and prediction in patients suffering from language-eloquent brain tumors. Thus, the current role of nTMS-based DTI FT might be expanded, going beyond the level of being a mere tool for surgical planning and resection guidance.

scholarly journals PATH-19. MOLECULAR, HISTOLOGIC AND CLINICAL CHARACTERISTICS OF OLIGODENDROGLIOMAS: A MULTI-INSTITUTIONAL RETROSPECTIVE STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii168-ii168
Author(s):  
Antonio Dono ◽  
Kristin Alfaro-Munoz ◽  
Yuanqing Yan ◽  
Carlos Lopez-Garcia ◽  
Zaid Soomro ◽  
...  
Keyword(s):  
Health Science ◽  
Cancer Center ◽  
Subtotal Resection ◽  
Adjuvant Radiation ◽  
Science Center ◽  
Who Grade ◽  
Pik3ca Mutations ◽  
Increased Risk ◽  
Significant Difference ◽  
Grade 3

Abstract In the 2016 WHO classification of CNS tumors, oligodendrogliomas are molecularly defined by IDH1 or IDH2 mutations and 1p/19q co-deletion. Some reports suggest that PI3K pathway alterations may confer increased risk of progression and poor prognosis in oligodendroglioma. However, factors that influence prognosis in molecularly defined oligodendroglioma (mOGD) have not been thoroughly studied. Also, the benefits of adjuvant radiation and temozolomide in mOGDs remain to be determined. 107 mOGDs diagnosed between 2008-2018 at the University of Texas Health Science Center at Houston (n= 39) and MD Anderson Cancer Center (n= 68) were included. A retrospective review of the demographic, clinical, histologic, molecular, and outcomes were performed. Median age at diagnosis was 37 years and 61 (57%) patients were male. There were 64 (60%) WHO Grade 2 and 43 (40%) WHO Grade 3 tumors. Ninety-five (88.8%) tumors were IDH1-mutant and 12 (11.2%) were IDH2-mutant. Eighty-two (77%) patients were stratified as high-risk: older than 40-years and/or subtotal resection (RTOG 9802). Gross-total resection was achieved in 47 (45%) patients. Treatment strategies included observation (n= 15), temozolomide (n= 11), radiation (n= 13), radiation with temozolomide (n= 62) and other (n= 6). Our results show a benefit of temozolomide vs. observation in progression-free survival (PFS). However, no benefit in PFS or overall survival (OS) was observed when comparing radiation vs. radiation with temozolomide. PIK3CA mutations were detected in 15 (14%) cases, and patients with PIK3CA-mutant mOGDs showed worse OS (10.7-years vs 15.1-years, p= 0.009). Patients with WHO Grade 3 tumors had shorter PFS but no significant difference in OS was observed compared to grade 2. Our findings suggest that mOGDs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS in temozolomide treated patients, adjuvant treatment with radiation or the combination of both, showed no significant advantage in terms of OS.

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