Huge heterogeneity in survival in a subset of adult patients with resected, wild-type isocitrate dehydrogenase status, WHO grade II astrocytomas

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.

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Frequent Diagnostic Under-Grading in Isocitrate Dehydrogenase Wild-Type Gliomas due to Small Pathological Tissue Samples

Neurosurgery ◽

10.1093/neuros/nyy433 ◽

2018 ◽

Vol 85 (5) ◽

pp. 689-694 ◽

Cited By ~ 3

Author(s):

Marielena Gutt-Will ◽

Michael Murek ◽

Christa Schwarz ◽

Ekkehard Hewer ◽

Sonja Vulcu ◽

...

Keyword(s):

Sample Size ◽

Isocitrate Dehydrogenase ◽

Permutation Test ◽

World Health ◽

Wild Type ◽

Sample Sizes ◽

Who Grade ◽

Tissue Samples ◽

Significant Difference ◽

Grade Ii

Abstract BACKGROUND In contrast to isocitrate dehydrogenase (IDH) mutation analysis, which is homogenous within a given tumor, diagnostic errors in histological analysis following the 2016 World Health Organization (WHO) classification could be due to small samples because of histological heterogeneity. OBJECTIVE To assess whether the sample size sent to histopathology influences the tumor grading in IDH wild-type gliomas. METHODS Histologically diagnosed WHO grade, sample volume, and preoperative tumor volume data of 111 patients aged who received resection of IDHwt gliomas between January 2007 and December 2015 at our hospital were evaluated. The differences between absolute and relative pathological sample sizes stratified by WHO grade were conducted using One-Way-Permutation-Test. RESULTS With a mean sample size of 10.9 cc, 83.8% of patients were histologically diagnosed as WHO grade IV, while 16.2% of patients with a mean sample size of 2.62 cc were diagnosed as WHO grade II/III. One-Way-Permutation-Test showed a significant difference between absolute tissue samples stratified by WHO grade (P = .0374). The distribution of preoperative tumor volumes with WHO grade IV vs WHO grade II/III showed no significant difference (P = .8587). Of all tumors with a sample size >10 cc 100% were pathologically diagnosed as WHO grade IV and those with sample size >5 cc 93.5% were diagnosed as WHO grade IV. CONCLUSION Small sample sizes are associated with a higher risk of under-estimating malignancy in histological grading in IDHwt gliomas. This study suggests a standard minimum sample size (>5cc) in every resection. Modalities of adjuvant treatment for IDHwt, WHO grade II/III gliomas need to reflect a prognosis that is only marginally better than of a glioblastoma.

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

Neurosurgery ◽

10.1093/neuros/nyx265 ◽

2017 ◽

Vol 82 (6) ◽

pp. 808-814 ◽

Cited By ~ 20

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.

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Stereotactic radiation treatment for recurrent nonbenign meningiomas

Journal of Neurosurgery ◽

10.3171/jns.2007.106.5.846 ◽

2007 ◽

Vol 106 (5) ◽

pp. 846-854 ◽

Cited By ~ 48

Author(s):

Carlos A. Mattozo ◽

Antonio A. F. De Salles ◽

Ivan A. Klement ◽

Alessandra Gorgulho ◽

David McArthur ◽

...

Keyword(s):

Radiation Treatment ◽

Progression Free Survival ◽

Malignant Progression ◽

World Health ◽

Who Grade ◽

Stereotactic Radiation ◽

Grade Ii ◽

Health Organization ◽

Grade Iii

Object The authors analyzed the results of stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for the treatment of recurrent meningiomas that were described at initial resection as showing aggressive, atypical, or malignant features (nonbenign). Methods Twenty-five patients who underwent SRS and/or SRT for nonbenign meningiomas between December 1992 and August 2004 were included. Thirteen of these patients underwent treatment for multiple primary or recurrent lesions. In all, 52 tumors were treated. All histological sections were reviewed and reclassified according to World Health Organization (WHO) 2000 guidelines as benign (Grade I), atypical (Grade II), or anaplastic (Grade III) meningiomas. The median follow-up period was 42 months. Seventeen (68%) of the cases were reclassified as follows: WHO Grade I (five cases), Grade II (11 cases), and Grade III (one case). Malignant progression occurred in eight cases (32%) during the follow-up period; these cases were considered as a separate group. The 3-year progression-free survival (PFS) rates for the Grades I, II, and III, and malignant progression groups were 100, 83, 0, and 11%, respectively (p < 0.001). In the Grade II group, the 3-year PFS rates for patients treated with SRS and SRT were 100 and 33%, respectively (p = 0.1). After initial treatment, 22 new tumors required treatment using SRS or SRT; 17 (77%) of them occurred inside the original resection cavity. Symptomatic edema developed in one patient (4%). Conclusions Stereotactic radiation treatment provided effective local control of “aggressive” Grade I and Grade II meningiomas, whereas Grade III lesions were associated with poor outcome. The outcome of cases in the malignant progression group was intermediate between that of the Grade II and Grade III groups, with the lesions showing a tendency toward malignancy.

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Seizure response to temozolomide chemotherapy in patients with WHO grade II oligodendroglioma: a single-institution descriptive study

Neuro-Oncology Practice ◽

10.1093/nop/npy029 ◽

2018 ◽

Vol 6 (3) ◽

pp. 203-208 ◽

Cited By ~ 1

Author(s):

Aya Haggiagi ◽

Edward K Avila

Keyword(s):

Disease Progression ◽

Seizure Frequency ◽

World Health ◽

Low Grade ◽

Inclusion Criteria ◽

Who Grade ◽

Seizure Reduction ◽

Grade Ii ◽

Health Organization

Abstract Background Tumor-related epilepsy (TRE) is common in patients with low-grade oligodendrogliomas. TRE is difficult to control despite multiple antiepileptic drugs (AEDs) in up to 30% of patients. Chemotherapy has been used for treatment to avoid potential radiotherapy-related neurotoxicity. This study evaluates the effect of temozolomide on seizure frequency in a homogeneous group with World Health Organization (WHO) grade II oligodendrogliomas. Methods A retrospective analysis was conducted of adult patients with WHO grade II oligodendrogliomas and TRE followed at Memorial Sloan Kettering between 2005 and 2015 who were treated with temozolomide alone either as initial treatment or for disease progression. All had seizures 3 months prior to starting temozolomide. Seizure frequency was reviewed every 2 cycles and at the end of temozolomide treatment. Seizure reduction of ≥50% compared to baseline was defined as improvement. Results Thirty-nine individuals met inclusion criteria. Median follow-up since starting temozolomide was 6 years (0.8-13 years). Reduction in seizure frequency occurred in 35 patients (89.7%). Improvement was independent of AED regimen adjustments or prior antitumor treatment in 16 (41%); of these, AED dosage was successfully reduced or completely eliminated in 10 (25.6%). Twenty-five patients (64.1%) remained on a stable AED regimen. The majority (n = 32, 82%) had radiographically stable disease, 5 (12.8%) had objective radiographic response, and 2 (5.2%) had disease progression. Conclusions Temozolomide may result in reduced seizure frequency, and permit discontinuation of AEDs in patients with WHO II oligodendroglioma. Improvement was observed irrespective of objective tumor response on MRI, emphasizing the importance of incorporating seizure control in assessing response to tumor-directed therapy.

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Preoperative Serum Lactate Dehydrogenase Level Predicts Progression and Prognosis in Patients with Glioma

10.21203/rs.3.rs-133034/v1 ◽

2021 ◽

Author(s):

Xiao-Yong Chen ◽

Jin-Yuan Chen ◽

Lue-Ming Cai ◽

Jia-Fang Chen ◽

Zan-Yi Wu ◽

...

Keyword(s):

Lactate Dehydrogenase ◽

Serum Lactate ◽

World Health ◽

Serum Lactate Dehydrogenase ◽

Who Grade ◽

Preoperative Serum ◽

Grade Ii ◽

Cox Analysis ◽

Grade Iii

Abstract Background: To evaluate the value of serum Lactate Dehydrogenase (LDH) level in predicting recurrence and the overall survival (OS) of glioma patients.Methods: A total number of 216 patients with glioma in our institution were retrospectively recruited to analyze the relationship between preoperative serum LDH level and prognosis.Results: Overall, the average age of patients was 43.58±17.22 years old; 53.7% (116 of 216) of the enrolled patients were male. Multivariate analysis revealed that serum LDH level (odds ratio [OR]=0.97, 95% confidence interval [CI]=0.96-0.98, P<0.001) and World Health Organization (WHO) grade (grade II: OR=19.64, 95%CI=5.56-69.35, P<0.001; grade III: OR=19.50, 95%CI=7.08-53.73, P<0.001; grade IV: OR=15.23, 95%CI=4.94-46.97, P<0.001) were significant and independent of 1-year Progression-free survival (PFS) after adjusting for confounders. The predictive performance of serum LDH level was represented with area under curve (AUC) = 0.741, 95%CI=0.677-0.798. Multivariate Cox analysis revealed that LDH level (hazard ratio [HR]=2.56, 95%CI=1.59-4.15, P<0.001) and WHO grade (grade II: HR=4.58, 95%CI=0.56-37.23, P=0.155; grade III: HR=16.35, 95%CI=2.16-123.80, P=0.007; grade IV: HR=42.13, 95%CI=5.83-304.47, P<0.001) remained associated with survival at 2-year follow-up. At 3-year follow-up, lymphocyte count (HR=0.68, 95%CI=0.51-0.91, P=0.008), LDH level (HR=2.21, 95%CI=1.40-3.49, P=0.001), and WHO grade (grade II: HR=1.44, 95%CI=0.44-4.68, P=0.543; grade III: HR=4.99, 95%CI=1.68-14.87, P=0.004; grade IV: HR=16.96, 95%CI=6.13-46.93, P<0.001) remained associated with survival in multivariate Cox analysis.Conclusion: Our study demonstrated that preoperative serum LDH level could serve as a reliable indicator for predicting prognosis of glioma patients. Further multicenter studies are still required to verify our findings.

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Clinical, Morphological, and Molecular Study of Diffuse WHO Grade II and III Astrocytomas: A Retrospective Analysis from a Single Tertiary Care Institute

Indian Journal of Medical and Paediatric Oncology ◽

10.1055/s-0041-1741061 ◽

2021 ◽

Vol 42 (06) ◽

pp. 569-576

Author(s):

Ramya Lakshmi Veduruvada ◽

Megha S. Uppin ◽

Meher Lakshmi Konatam ◽

Rajesh Alugolu ◽

Vamsi Krishna Yeramneni ◽

...

Keyword(s):

World Health ◽

Survival Duration ◽

Diffuse Astrocytoma ◽

Wild Type ◽

Immunohistochemical Expression ◽

Who Grade ◽

Genetic Characteristics ◽

Integrated Diagnosis ◽

Idh Mutations ◽

Grade Ii

Abstract Introduction Astrocytomas are the most common gliomas, classified on the basis of grade and IDH mutation status according to the World Health Organization (WHO) 2016 update. IDH mutations are seen in 70 to 80% of diffuse grade II and III astrocytomas and are associated with better outcome. They serve as predictive biomarker in IDH-targeted therapies such as small-molecule inhibitors or vaccines. Objective The aim of this study was to analyze the clinical, morphological, immunohistochemical, and molecular genetic characteristics of diffuse astrocytoma (DA: grades II and III). The IDH mutant and wild-type tumors are compared and contrasted with survival analysis on follow-up. Materials and Methods This was a retrospective study conducted on surgically resected tumor specimens. The hematoxylin and eosin-stained slides were examined for histologic features. Immunohistochemistry (IHC) was performed using IDH1R132H, ATRX, p53, and Ki67. All cases of negative immunohistochemical expression of IDH1R132H were subjected to IDH1 mutation analysis by Sanger sequencing. Overall survival was estimated by the Kaplan-Meier method using the log-rank (Mantel–Cox) test. Results The study included 51 cases of DA in the age of 17 to 66 years, mean ± standard deviation was 35.5 ± 9.7 years, and male:female ratio was 2:1.The IDH1R132H cytoplasmic immunopositivity was seen in 36 cases (70.5%), of which 63.6% were of grade II and 72.5% were of grade III. ATRX showed loss of expression in 50 cases (98%), and p53 showed diffuse strong immunohistochemical expression in all the cases of IDH mutant tumors. The difference in the age at presentation for IDH mutant (32.5 years) and wild type tumors (38 years) was statistically significant. Median survival was 55.3 months and 22.2 months in of IDH mutant and wild type cases, respectively. Conclusion IHC and sequencing for IDH mutations is helpful in making an integrated diagnosis and classifying definite molecular subgroups of astrocytic tumors. Mutations in IDH core-elate with survival. IDH mutant tumors showed longer survival duration and are good prognostic indicators.

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Multicentric Registry Study on Epidemiological and Biological Disease Profile as Well as Clinical Outcome in Patients with Low-Grade Gliomas: The LoG-Glio Project

Journal of Neurological Surgery Part A Central European Neurosurgery ◽

10.1055/s-0039-1693650 ◽

2019 ◽

Vol 81 (01) ◽

pp. 048-057 ◽

Cited By ~ 1

Author(s):

Andrej Pala ◽

Minou Nadji-Ohl ◽

Katharina Faust ◽

Stefan Rückriegel ◽

Constantin Roder ◽

...

Keyword(s):

Surgical Management ◽

Adjuvant Treatment ◽

Low Grade ◽

Inclusion Criteria ◽

Wild Type ◽

Who Grade ◽

Low Grade Gliomas ◽

Grade Ii ◽

Multicenter Registry

Abstract Background World Health Organization (WHO) grade II low-grade gliomas (LGGs) in adults are rare, and patients' mean overall survival (OS) is relatively long. Epidemiological data on factors influencing tumor genesis and progression are scarce, and prospective data on surgical management are still lacking. Because of the molecular heterogeneity of LGG, a comprehensive molecular characterization is required for any clinical and epidemiological research. Further, a detailed radiologic assessment is needed as the only established objective criterion for progressive disease. Both radiologic and molecular assessments have to be standardized to produce comparable data. The aim of the registry is to improve the evidence for surgical management of LGG patients by establishing a multicenter registry with a strong surgical and clinical focus including mandatory biobanking. Methods The LoG-Glio project is a prospective national observational multicenter registry that began on November 1, 2015. Inclusion criteria encompass all patients > 18 years of age with a radiologic suspicion of LGG. Patients with severe neurologic or psychiatric disorders that may interfere with their informed consent or if there is no possibility for further follow-up are excluded. Diagnosis of glioblastoma WHO grade IV isocitrate dehydrogenase (IDH) wild type leads to a secondary exclusion of patients. In addition to demographic data, results of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, add-on for patients with brain tumors, and National Health Institute Stroke Scale before and after surgery and during regular follow-ups are collected. At each time point a detailed recording of surgical and adjuvant treatment is performed. Radiologic assessment involves three-dimensional (3D) acquisition of T1, fluid-attenuated inversion recovery, and T2 sequences. For the final evaluation, a central detailed neuropathologic and molecular assessment of tumor samples and a radiologic evaluation of imaging sets are part of the study protocol. Results We report the first 100 consecutively registered patients for LoG-Glio. Three patients dropped out due to loss of follow-up. Of the remaining recruited patients, 8 were classified as wait and scan; 89 had surgery. Using the inclusion criteria described previously, 70 patients had an IDH-mutated glioma, 10 had miscellaneous rare LGGs, and 8 patients had an IDH wild-type WHO grade II or III glioma. Conclusion The LoG-Glio registry has been successfully implemented. Applied selection criteria result in an appropriately balanced patient cohort. Short-term outcome data on epidemiology as well as the influence of current surgical techniques and adjuvant treatment on patient outcomes are expected. In the long run, the aim of the registry is to validate the new molecular-based WHO classification and the influence of the extent of resection on progression-free survival and OS. The registry provides an open platform for future research projects benefiting patients with LGG.

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Clinical Outcomes of Recurrent Intracranial Meningiomas Treated with Proton Beam Reirradiation

International Journal of Particle Therapy ◽

10.14338/ijpt-18-00045.1 ◽

2019 ◽

Vol 5 (4) ◽

pp. 11-22 ◽

Cited By ~ 3

Author(s):

Brandon S. Imber ◽

Brian Neal ◽

Dana L. Casey ◽

Heba Darwish ◽

Andrew L. Lin ◽

...

Keyword(s):

Radiation Therapy ◽

Proton Beam ◽

Proportional Hazards ◽

Progression Free Survival ◽

World Health ◽

Clinical Predictors ◽

Beam Radiation ◽

Who Grade ◽

Health Organization

Abstract Purpose: Recurrent meningiomas remain therapeutically challenging, often progressive despite multimodality salvage. There are limited data guiding reirradiation (reRT), and proton beam radiation therapy (PBRT) offers a potential advantage owing to lower integral brain dose. Patients and Methods: We retrospectively conducted a review of 16 patients who received PBRT reRT for recurrent meningiomas. Kaplan-Meier and proportional hazards were used to determine post-PBRT progression-free survival (PFS) and overall survival (OS) and to evaluate clinical predictors. Results: At diagnosis, 7 (44%), 8 (50%), and 1 (6%) patient had World Health Organization (WHO) grade I, II and III tumors, respectively. All received prior radiation therapy (RT) to a median of 54 Gy (range 13-65.5). Median time to PBRT reRT after prior RT was 5.8 years (range 0.7-18.7). Median PBRT dose was 60 Gy(RBE) (range 30-66.6), and median planning tumor volume (PTV) was 76 cm3 (range 8-249). Median follow-up was 18.8 months. At last follow-up, 7 intracranial recurrences (44%) and 3 disease-related deaths (19%) were found. Median cohort PFS was 22.6 months, with 1- and 2-year PFS of 80% and 43%, respectively. Median OS was not achieved, with 1- and 2-year OS of 94% and 73%; all deaths were felt to be related to meningioma. Patients with initially grade I tumors had improved PFS versus higher grade (Hazard Ratio, HR = 0.23, P = .03) with 1- and 2-year PFS estimates of 100% versus 71% and 75% versus 29%, respectively. Longer interval between prior RT and PBRT also predicted improved PFS (P = .03) and OS (P = .049). Overall late grade 3+ toxicity rate was 31%. Two patients (13%) developed radionecrosis at 6 and 16 months after PBRT; only 1 was symptomatic. Conclusions: This is the first series specifically analyzing PBRT alone as a reRT strategy for recurrent meningioma. We report fair intracranial control with low rates of radionecrosis at 1 year after reRT. However, strategies to achieve durable outcomes are needed, particularly for high-grade tumors.

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Pre-operative Neurocognitive Function Was More Susceptible to Decline in Isocitrate Dehydrogenase Wild-Type Subgroups of Lower-Grade Glioma Patients

Frontiers in Neurology ◽

10.3389/fneur.2020.591615 ◽

2020 ◽

Vol 11 ◽

Author(s):

Zhe Zhang ◽

Zeping Jin ◽

Xiaojie Yang ◽

Liang Zhang ◽

Yang Zhang ◽

...

Keyword(s):

Working Memory ◽

Isocitrate Dehydrogenase ◽

Neurocognitive Function ◽

World Health ◽

Lower Grade ◽

Wild Type ◽

Molecular Subgroups ◽

Lower Grade Glioma ◽

Grade Ii ◽

Grade Iii

Background: Neuropsychological deficits frequently occur in diffuse lower-grade glioma (DLGG) patients, but their relationship with molecular subgroups based on the 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) is unclear.Methods: All patients enrolled for this study were divided into different subgroups according to the molecular-integrated 2016 CNS WHO and morphology-centric 2007 CNS WHO to compare their neurocognitive function (NCF) dysfunction. Univariate and multivariate analyses were used to assess the independent factors for NCF decline. The performance of NCF changes for discrimination of IDH and 1p19q status was evaluated by receiver operating characteristic (ROC).Results: There was no significant difference in the clinical characteristics among the molecular and morphologic subgroups. In the molecular subgroups, significant differences in NCF alterations were found in terms of attention function, working memory and executive function in grade II glioma patients; in addition to these changes in NCF, memory function and abstract thinking were also significantly different in grade III glioma patients. The pairwise comparison further confirmed that patients with astrocytoma (A)/anaplastic astrocytoma (AA) with isocitrate dehydrogenase wild-type (IDHwt) glioma were more susceptible to severe cognitive decline in terms of the NCF performance described above. For the morphologic subgroups, only working memory was significantly different in grade III glioma patients. The distribution proportion was significantly different among each subgroup of DLGG (grade II, P = 0.001; grade III, P = 0.002). The proportion of extensive NCF decline (≥5 tests) was 4, 12, and 50% in the IDH mutant oligodendroglioma (IDHm-O), IDHm-A, and IDHwt-A subgroups, and this proportion was 33, 60, and 93% in the IDHm-AO, IDHm-AA, and IDHwt-AA subgroups, respectively. In multivariate regression analysis, molecular types were independent factors for NCF alterations after adjusted the factors of tumor and demographics (p < 0.05). ROC curves suggested combined NCF tests model showed an advantage in the differentiation of IDH status.Conclusions: NCF alteration is closely related to molecular-integrated subgroups with varying degrees and frequencies in DLGG. Patients with IDHwt gliomas are more susceptible to suffer from severe and extensive NCF decline than other subgroups.

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