scholarly journals Prognostic value of preoperative inflammatory markers in patients with different molecular subgroups of WHO grade II and III diffuse gliomas

2019 ◽  
Author(s):  
Zengxin Qi ◽  
Jiajun Cai ◽  
Xiangda Meng ◽  
Shengyong Cai ◽  
Chao Tang ◽  
...  

Abstract Objective: To determine the prognostic implications of these immune indices in WHO Grade II & III gliomas and different molecular subgroups.Methods : Clinical data from 214 newly diagnosed WHO grade II and III diffuse glioma patients were studied retrospectively. Cut-off values were determined by X-tile software. IDH and TERT promotor mutations were detected by gene sequencing, and 1p19q co-deletion was estimated via fluorescence in situ hybridization.Results: NLR was verified to be an independent prognostic marker for OS in WHO grade II and III diffuse gliomas. NLR level was also associated with OS of IDH mutant subgroup, TERT promotor mutant subgroup, 1p19q intact subgroup and with PFS of 1p19q intact subgroup. LMR level was associated with OS of WHO grade II and III diffuse gliomas and TERT promotor mutant subgroup. dNLR was verified to be an independent prognostic marker for OS in TERT promotor wild-type subgroup, 1p19q intact subgroup, IDH mutant TERT promotor wild-type 1p19q intact subgroup and for PFS of 1p19q intact subgroup. dNLR was associated with OS of WHO grade II and III diffuse gliomas and IDH mutant subgroup. 1p19q co-deletion was correlated with low NLR. Conclusion: Preoperative NLR, LMR and dNLR levels were helpful to forecast prognosis in patients with WHO grade II and III gliomas and different genetic phenotypes.

2019 ◽  
Author(s):  
Zengxin Qi ◽  
Jiajun Cai ◽  
Xiangda Meng ◽  
Shengyong Cai ◽  
Chao Tang ◽  
...  

Abstract Background: To determine the prognostic implications of these immune indices in WHO Grade II & III gliomas and different molecular subgroups. Methods: Clinical data from 214 newly diagnosed WHO grade II and III diffuse glioma patients were studied retrospectively. Cut-off values were determined by X-tile software. IDH and TERT promotor mutations were detected by gene sequencing, and 1p19q codeletion was estimated via fluorescence in situ hybridization. Results: NLR was verified to be an independent prognostic marker for OS in WHO grade II and III diffuse gliomas. NLR level was also associated with OS of IDH mutant subgroup, TERT promotor mutant subgroup, 1p19q intact subgroup and with PFS of 1p19q intact subgroup. LMR level was associated with OS of WHO grade II and III diffuse gliomas and TERT promotor mutant subgroup. dNLR was verified to be an independent prognostic marker for OS in TERT promotor wild-type subgroup, 1p19q intact subgroup, IDH mutant TERT promotor wild-type 1p19q intact subgroup and for PFS of 1p19q intact subgroup. dNLR was associated with OS of WHO grade II and III diffuse gliomas and IDH mutant subgroup. 1p19q codeletion was correlated with low NLR.Conclusion: Preoperative NLR, LMR and dNLR levels were helpful to forecast prognosis in patients with WHO grade II and III gliomas and different genetic phenotypes.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii164-ii165
Author(s):  
Ashley Aaroe ◽  
Antonio Dono ◽  
Michael Youssef ◽  
Kristin Alfaro-Munoz ◽  
Shiao-Pei Weathers ◽  
...  

Abstract BACKGROUND WHO grade II and III IDH wild-type astrocytomas behave more aggressively than their IDH mutated counterparts. A subpopulation shares molecular features with the novel entity proposed in cIMPACT-NOW Update 3 “Diffuse astrocytic glioma, IDH wild-type, with molecular features of glioblastoma (GBM), WHO IV”. METHODS We performed a retrospective analysis of clinical and molecular features, management and survival of 134 adult patients treated for grade II and III IDH wild-type astrocytoma between 06/2012 and 12/2018 at MD Anderson Cancer Center (MDACC - 112) and UT Health Science Center at Houston (UTHSC - 22). All patients had IDH1 sequenced, all but 2 had IDH2 sequenced, and 73 had further next generation sequencing. RESULTS Median age at diagnosis was 53 (interquartile range 18-83). 82 patients (61%) were male. 31 patients were histologically diagnosed with grade II astrocytoma, 102 with grade III astrocytoma, and one with diffuse glioma (insufficient tissue to render histologic grade or perform sequencing). EGFR alterations were found in 31 patients and TERT promoter mutations in 22. 84 (63%) received concurrent chemoradiation and adjuvant temozolomide (grade II, n=9; grade III, n=74; NOS, n=1). PFS overall was 12.0 months (grade II = 17.9; grade III = 10.7). OS in patients treated with concurrent chemoradiation and adjuvant temozolomide was 17.1 months versus 17.7 in patients treated with sequential radiation and temozolomide (p = NS), and 10.6 in patients treated with RT alone or surveillance (p< 0.016). The highest 2-year OS was seen in grade II patients treated with concurrent chemoradiation and adjuvant temozolomide (60%). CONCLUSIONS WHO grade II and III IDHwt astrocytoma survival is similar to historical GBM cohorts. The proportion meeting molecular criteria for GBM is yet undefined. Groups who received chemotherapy may perform better than those who do not. Further analysis of MGMT methylation and other molecular factors is ongoing.


Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 808-814 ◽  
Author(s):  
Toral Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany Powell ◽  
Gustav Young-Min Cederquist ◽  
...  

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.


2018 ◽  
Vol 140 (1) ◽  
pp. 173-178 ◽  
Author(s):  
Julia Furtner ◽  
Anna S. Berghoff ◽  
Veronika Schöpf ◽  
Robert Reumann ◽  
Benjamin Pascher ◽  
...  

2019 ◽  
Vol 130 (4) ◽  
pp. 1289-1298 ◽  
Author(s):  
Gaëtan Poulen ◽  
Catherine Gozé ◽  
Valérie Rigau ◽  
Hugues Duffau

OBJECTIVEWorld Health Organization grade II gliomas are infiltrating tumors that inexorably progress to a higher grade of malignancy. However, the time to malignant transformation is quite unpredictable at the individual patient level. A wild-type isocitrate dehydrogenase (IDH-wt) molecular profile has been reported as a poor prognostic factor, with more rapid progression and a shorter survival compared with IDH-mutant tumors. Here, the oncological outcomes of a series of adult patients with IDH-wt, diffuse, WHO grade II astrocytomas (AII) who underwent resection without early adjuvant therapy were investigated.METHODSA retrospective review of patients extracted from a prospective database who underwent resection between 2007 and 2013 for histopathologically confirmed, IDH-wt, non–1p19q codeleted AII was performed. All patients had a minimum follow-up period of 2 years. Information regarding clinical, radiographic, and surgical results and survival were collected and analyzed.RESULTSThirty-one consecutive patients (18 men and 13 women, median age 39.6 years) were included in this study. The preoperative median tumor volume was 54 cm3 (range 3.5–180 cm3). The median growth rate, measured as the velocity of diametric expansion, was 2.45 mm/year. The median residual volume after surgery was 4.2 cm3 (range 0–30 cm3) with a median volumetric extent of resection of 93.97% (8 patients had a total or supratotal resection). No patient experienced permanent neurological deficits after surgery, and all patients resumed a normal life. No immediate postoperative chemotherapy or radiation therapy was given. The median clinical follow-up duration from diagnosis was 74 months (range 27–157 months). In this follow-up period, 18 patients received delayed chemotherapy and/or radiotherapy for tumor progression. Five patients (16%) died at a median time from radiological diagnosis of 3.5 years (range 2.6–4.5 years). Survival from diagnosis was 77.27% at 5 years. None of the 21 patients with a long-term follow-up greater than 5 years have died. There were no significant differences between the clinical, radiological, or molecular characteristics of the survivors relative to the patients who died.CONCLUSIONSHuge heterogeneity in the survival data for a subset of 31 patients with resected IDH-wt AII tumors was observed. These findings suggest that IDH mutation status alone is not sufficient to predict risk of malignant transformation and survival at the individual level. Therefore, the therapeutic management of AII tumors, in particular the decision to administer early adjuvant chemotherapy and/or radiation therapy following surgery, should not solely rely on routine molecular markers.


2021 ◽  
pp. 1-8
Author(s):  
Ramin A. Morshed ◽  
Anthony T. Lee ◽  
Elaina J. Wang ◽  
Jacob S. Young ◽  
Soonmee Cha ◽  
...  

OBJECTIVE The clinical outcomes for patients undergoing resection of diffuse glioma within the middle frontal gyrus (MFG) are understudied. Anatomically, the MFG is richly interconnected to known language areas, and nearby subcortical fibers are at risk during resection. The goal of this study was to determine the functional outcomes and intraoperative mapping results related to resection of MFG gliomas. Additionally, the study aimed to evaluate if subcortical tract disruption on imaging correlated with functional outcomes. METHODS The authors performed a retrospective review of 39 patients with WHO grade II–IV diffuse gliomas restricted to only the MFG and underlying subcortical region that were treated with resection and had no prior treatment. Intraoperative mapping results and postoperative neurological deficits by discharge and 90 days were assessed. Diffusion tensor imaging (DTI) tractography was used to assess subcortical tract integrity on pre- and postoperative imaging. RESULTS The mean age of the cohort was 37.9 years at surgery, and the median follow-up was 5.1 years. The mean extent of resection was 98.9% for the cohort. Of the 39 tumors, 24 were left sided (61.5%). Thirty-six patients (92.3%) underwent intraoperative mapping, with 59% of patients undergoing an awake craniotomy. No patients had positive cortical mapping sites overlying the tumor, and 12 patients (33.3%) had positive subcortical stimulation sites. By discharge, 8 patients had language dysfunction, and 5 patients had mild weakness. By 90 days, 2 patients (5.1%) had persistent mild hand weakness only. There were no persistent language deficits by 90 days. On univariate analysis, preoperative tumor size (p = 0.0001), positive subcortical mapping (p = 0.03), preoperative tumor invasion of neighboring subcortical tracts on DTI tractography (p = 0.0003), and resection cavity interruption of subcortical tracts on DTI tractography (p < 0.0001) were associated with an increased risk of having a postoperative deficit by discharge. There were no instances of complete subcortical tract transections in the cohort. CONCLUSIONS MFG diffuse gliomas may undergo extensive resection with minimal risk for long-term morbidity. Partial subcortical tract interruption may lead to transient but not permanent deficits. Subcortical mapping is essential to reduce permanent morbidity during resection of MFG tumors by avoiding complete transection of critical subcortical tracts.


2018 ◽  
Vol 129 (1) ◽  
pp. 35-47 ◽  
Author(s):  
Leland Rogers ◽  
Peixin Zhang ◽  
Michael A. Vogelbaum ◽  
Arie Perry ◽  
Lynn S. Ashby ◽  
...  

OBJECTIVEThis is the first clinical outcomes report of NRG Oncology RTOG 0539, detailing the primary endpoint, 3-year progression-free survival (PFS), compared with a predefined historical control for intermediate-risk meningioma, and secondarily evaluating overall survival (OS), local failure, and prospectively scored adverse events (AEs).METHODSNRG Oncology RTOG 0539 was a Phase II clinical trial allocating meningioma patients to 1 of 3 prognostic groups and management strategies according to WHO grade, recurrence status, and resection extent. For the intermediate-risk group (Group 2), eligible patients had either newly diagnosed WHO Grade II meningioma that had been treated with gross-total resection (GTR; Simpson Grades I–III) or recurrent WHO Grade I meningioma with any resection extent. Pathology and imaging were centrally reviewed. Patients were treated with radiation therapy (RT), either intensity modulated (IMRT) or 3D conformal (3DCRT), 54 Gy in 30 fractions. The RT target volume was defined as the tumor bed and any nodular enhancement (e.g., in patients with recurrent WHO Grade I tumors) with a minimum 8-mm and maximum 15-mm margin, depending on tumor location and setup reproducibility of the RT method. The primary endpoint was 3-year PFS. Results were compared with historical controls (3-year PFS: 70% following GTR alone and 90% with GTR + RT). AEs were scored using NCI Common Toxicity Criteria.RESULTSFifty-six patients enrolled in the intermediate-risk group, of whom 3 were ineligible and 1 did not receive RT. Of the 52 patients who received protocol therapy, 4 withdrew without a recurrence before 3 years leaving 48 patients evaluable for the primary endpoint, 3-year PFS, which was actuarially 93.8% (p = 0.0003). Within 3 years, 3 patients experienced events affecting PFS: 1 patient with a WHO Grade II tumor died of the disease, 1 patient with a WHO Grade II tumor had disease progression but remained alive, and 1 patient with recurrent WHO Grade I meningioma died of undetermined cause without tumor progression. The 3-year actuarial local failure rate was 4.1%, and the 3-year OS rate was 96%. After 3 years, progression occurred in 2 additional patients: 1 patient with recurrent WHO Grade I meningioma and 1 patient with WHO Grade II disease; both remain alive. Among 52 evaluable patients who received protocol treatment, 36 (69.2%) had WHO Grade II tumors and underwent GTR, and 16 (30.8%) had recurrent WHO Grade I tumors. There was no significant difference in PFS between these subgroups (p = 0.52, HR 0.56, 95% CI 0.09–3.35), validating their consolidation. Of the 52 evaluable patients, 44 (84.6%) received IMRT, and 50 (96.2%) were treated per protocol or with acceptable variation. AEs (definitely, probably, or possibly related to protocol treatment) were limited to Grade 1 or 2, with no reported Grade 3 events.CONCLUSIONSThis is the first clinical outcomes report from NRG Oncology RTOG 0539. Patients with intermediate-risk meningioma treated with RT had excellent 3-year PFS, with a low rate of local failure and a low risk of AEs. These results support the use of postoperative RT for newly diagnosed gross-totally resected WHO Grade II or recurrent WHO Grade I meningioma irrespective of resection extent. They also document minimal toxicity and high rates of tumor control with IMRT.Clinical trial registration no.: NCT00895622 (clinicaltrials.gov).


2018 ◽  
Vol 20 (11) ◽  
pp. 1505-1516 ◽  
Author(s):  
Lei Zhang ◽  
Liqun He ◽  
Roberta Lugano ◽  
Kenney Roodakker ◽  
Michael Bergqvist ◽  
...  

Abstract Background Vascular gene expression patterns in lower-grade gliomas (LGGs; diffuse World Health Organization [WHO] grades II–III gliomas) have not been thoroughly investigated. The aim of this study was to molecularly characterize LGG vessels and determine if tumor isocitrate dehydrogenase (IDH) mutation status affects vascular phenotype. Methods Gene expression was analyzed using an in-house dataset derived from microdissected vessels and total tumor samples from human glioma in combination with expression data from 289 LGG samples available in the database of The Cancer Genome Atlas. Vascular protein expression was examined by immunohistochemistry in human brain tumor tissue microarrays (TMAs) representing WHO grades II–IV gliomas and nonmalignant brain samples. Regulation of gene expression was examined in primary endothelial cells in vitro. Results Gene expression analysis of WHO grade II glioma indicated an intermediate stage of vascular abnormality, less severe than that of glioblastoma vessels but distinct from normal vessels. Enhanced expression of laminin subunit alpha 4 (LAMA4) and angiopoietin 2 (ANGPT2) in WHO grade II glioma was confirmed by staining of human TMAs. IDH wild-type LGGs displayed a specific angiogenic gene expression signature, including upregulation of ANGPT2 and serpin family H (SERPINH1), connected to enhanced endothelial cell migration and matrix remodeling. Transcription factor analysis indicated increased transforming growth factor beta (TGFβ) and hypoxia signaling in IDH wild-type LGGs. A subset of genes specifically induced in IDH wild-type LGG vessels was upregulated by stimulation of endothelial cells with TGFβ2, vascular endothelial growth factor, or cobalt chloride in vitro. Conclusion IDH wild-type LGG vessels are molecularly distinct from the vasculature of IDH-mutated LGGs. TGFβ and hypoxia-related signaling pathways may be potential targets for anti-angiogenic therapy of IDH wild-type LGG.


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii90-iii90
Author(s):  
A E Danyeli ◽  
C B Akyerli ◽  
A Dinçer ◽  
E Coşgun ◽  
U Abacıoğlu ◽  
...  

Abstract BACKGROUND Although the word “glioblastoma” still denotes a grade-IV pathology, basic molecular studies have clearly indicated that a significant proportion of lower-grade gliomas harbor genetic alterations typical of glioblastomas. Based on these findings cIMPACT-NOW update 3 has defined an entity called the “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. A TERT-promoter mutation is one of these typical molecular markers of glioblastomas. In this study we analyzed IDH-wild type, TERT-mutant diffuse gliomas of different pathological grades to look for differences in demographic, clinical and survival characteristics. MATERIAL AND METHODS 147 adult hemispheric diffuse-gliomas with wild-type IDH1/2 and mutant TERT-promoter (C228T or C250T) were retrospectively analyzed. Primary thalamic, cerebellar brainstem or spinal cases were excluded. 126 (86%), 16(11%) and 5(3%) patients were WHO grade IV, III and II respectively. After surgical treatment or stereotactic biopsy all patients underwent chemoradiation. Median follow-up was 16mo (1–110). Tumors of different grades were compared for age, gender, multifocality, gliomatosis pattern, Ki-67 index, progression-free survival and overall-survival. RESULTS Mean age at presentation for grade II, III and IV were comparable (58.1, 58 and 58.1; ANOVA, p=0.72). There was a slight male predominance in both lower-grades and WHO-grade IV (M:F ratios 1.625 and 1.74). Mean Ki-67 index was significantly higher in higher grades (0.06, 0.14 and 0.25 for grades II, III and IV; ANOVA, p=0.001). Multifocality was comparable (chi-sq, p=1) in lower-grades (3/21; 14.3%) vs. WHO-grade IV (18/126; 14.3%). Gliomatosis pattern was comparable (chi-sq, p=0.095) in lower-grades (2/21; 9.5%) vs. (3/126; 2.3%). Median recurrence free survival (RFS) was 16 months (0–63) in lower-grades and 8months (1–50) in WHO-grade IV. PFS was significantly different between 3 WHO-grades (Log rank, p=0.007) and also between lower-grades and WHO-grade IV (Log rank, p=0.002). Median overall survival was 26 months(2–110) in lower-grades and 15mo(1–91) in WHO-grade IV. OS was significantly different between 3 WHO-grades (Log rank, p=0.014) and also between lower-grades and WHO-grade IV (Log rank, p=0.007). CONCLUSION Increasing pathological grades of hemispheric “IDH-wild type, TERT-mutant diffuse gliomas” have similar demographic and clinical characteristics but incrasing proliferation indices, decrasing progression free survival and shorter overall survival. The findings may be suggesitve of different grades of one common tumor entity.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii149-ii149
Author(s):  
Lazaros Lazaridis ◽  
Sied Kebir ◽  
Manuel Weber ◽  
Teresa Schmidt ◽  
Kathy Keyvani ◽  
...  

Abstract BACKGROUND Advanced imaging techniques entered the field of neurooncology. In this analysis we compare the diagnostic potential of 18F-fluorethyltyrosine (FET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) in their potential to preoperatively predict certain glioma subtypes. AIMS Goal of this analysis ist the evaluation of FET PET and MRS regarding the preoperative prediction of glioma subtypes. METHODS We analyzed 33 patients with histopathologically confirmed newly diagnosed glioma. The patients received FET PET and MRS during one single preoperative diagnostic session. According to the molecular portfolio patients were subdivided in IDH wildtype glioblastoma patients (GBM), IDH wildtype WHO grade II/III glioma patients (Astro_IDHwt), IDH mutant WHO grade II/III glioma patients without 1p/19q codeletion (Astro_IDHmut) and with 1p/19q codeletion (ODG). Mean and maximum tumor-to-brain ratio (TBRmean and TBRmax), N-acetylaspartate, choline and creatine peaks were correlated with postoperative tumor diagnosis. To gain generalizable implications we subdivided the study cohort into a development and validation subcohort. A support vector machine model was fitted to the development subcohort and evaluated on the validation subcohort. Receiver operating characteristic curve served to assess model performance. RESULTS GBM patients had highest TBRmax and TBRmean values (mean: 3.5 and 3.8) and the ODG patients showed the second highest TBRmax and TBRmean values (mean: 2.6 and 3). The distribution of MRS markers exhibited to clear trend. The performance of glioma subtyping was comparatively low for the TBR values (AUC: 0.68) and even lower for the MRS markers (AUC: 0.60). These results are in line with preliminary investigations performed by our institute for the comparison of 11C-methionine PET with MRS in preoperative glioma subtyping. CONCLUSIONS FET PET and MRS bear limited potential in glioma subgrouping. However, FET PET appears to be slightly superior. Investigation in a larger cohort is required to draw definite conclusions.


Sign in / Sign up

Export Citation Format

Share Document