The impact of surgery in molecularly defined low-grade glioma: an integrated clinical, radiological, and molecular analysis

Wijnenga, Maarten M.J.; French, Pim J.; Dubbink, Hendrikus J.; Dinjens, Winand N.M.; Atmodimedjo, Peggy N.; Kros, Johan M.; Smits, Marion; Gahrmann, Renske; Rutten, Geert‐Jan; Verheul, Jeroen B; Fleischeuer, Ruth; Dirven, Clemens; Vincent, Arnaud; Bent, Martin J. van den

doi:10.1093/neuonc/nox176

Cited by 248 publications

(191 citation statements)

References 30 publications

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“…In addition, we observed that the EOR affected the survival outcome. As the treatment policy of our institution has been maximal safe surgical resection, the proportion of GTR was higher than that in other studies, which had a 4-15% GTR rates [12][13][14] . Consequently, we obtained relatively high survival rates in all three molecular subtypes as compared to those in other series.…”

Section: Discussionmentioning

confidence: 57%

“…As grade II gliomas and grade III gliomas share molecular-genetic markers that are stronger prognostic factors than histologic grade, WHO grade II and III gliomas are now categorized together as "lower-grade gliomas". IDH-wildtype tumors are clinically similar to glioblastoma and are called as the glioblastoma-like subtype 14 .…”

Section: Discussionmentioning

confidence: 99%

“…IDH1-mutant tumors have an additional survival benefit associated with maximal resection, but in IDH1-wildtype tumors, no survival benefit is observed in association with further resection of residual tumor. The impact of surgery in molecularly defined LGG was evaluated retrospectively by Wijnenga et al 14…”

Section: Discussionmentioning

confidence: 99%

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Extent of resection and molecular pathologic subtype are potent prognostic factors of adult WHO grade II glioma

Choi

Kim

Ahn

et al. 2020

Sci Rep

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We evaluated prognostic factors of adult low-grade glioma (LGG) according to the new 2016 WHO classification. Records of 153 patients diagnosed with WHO grade II LGG between 2003 and 2015 were retrospectively reviewed. Based on the 2016 WHO classification, 80 patients (52.3%) had diffuse astrocytoma, IDH-mutant; 45 (29.4%) had oligodendroglioma, IDH-mutant and 1p/19q-codeleted (ODG); and 28 (18.3%) had diffuse astrocytoma, IDH-wildtype. Gross total resection (GTR) was performed in 71 patients (46.4%), subtotal resection in 31 (20.3%), partial resection in 43 (28.1%), and biopsy in 8 (5.2%). One hundred two patients (66.7%) received postoperative radiotherapy. The 5-and 10-year progression-free survival (PFS) rates were 72.7% and 51.5%, respectively, and the 5and 10-year overall survival (OS) rates were 82.5% and 63.5%, respectively. GTR and IDH-mutant and/ or 1p/19q codeletion were favorable prognostic factors for PFS and OS. Patients with IDH-wildtype had significantly decreased OS. Among patients with ODG who underwent GTR, no recurrence was observed after radiotherapy. Patients who underwent non-GTR frequently experienced recurrence after radiotherapy (IDH-mutant: 47.6%, IDH-wildtype: 57.9%). In conclusion, molecular classification of LGG was of prognostic relevance, with IDH-wildtype patients having a particularly poor outcome, regardless of the treatment. Favorable results were observed in patients who underwent GTR. World Health Organization (WHO) grade II low-grade glioma (LGG) included astrocytoma, oligodendroglioma, and oligoastrocytoma 1. LGG has relatively favorable clinical outcomes and a slow progression without serious neurologic symptoms 2. With increasing evidence that molecular markers, such as isocitrate dehydrogenase (IDH) 1/2 gene mutation and chromosome 1p/19q codeletion, are more important than histologic subtype in the prediction of tumor response to treatment and prognosis, phenotypic and genotypic parameters have been integrated in the updated 2016 WHO classification of gliomas 3-6. As most previous studies about prognostic factors in LGG were based on the old histologic classification, the impact of prognostic factors in the different molecular subtypes remains to be determined. Although maximal safe resection followed by adjuvant radiotherapy (RT) and PCV (procarbazine, lomustine, and vincristine) or temozolomide for high-risk patients (≤40 year old or subtotal resection) 7 is the current standard of care, optimal treatment for each molecular subtype of LGG remains disputed. This study aimed to validate the molecular pathologic subtypes as prognostic factors. Also, we examine the impact of surgery and adjuvant RT on outcomes in molecularly defined LGG.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

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Extent of resection and molecular pathologic subtype are potent prognostic factors of adult WHO grade II glioma

Choi

Kim

Ahn

et al. 2020

Sci Rep

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“…Preoperative genotyping matters for several reasons: in IDH mut astrocytoma even small residual volumes of tumour reduce survival (19), however, molecular results are not usually available during surgery. Glioblastoma therapy is considered appropriate for WHO II-III IDH wt gliomas, consisting of maximum safe resection followed by radiotherapy and chemotherapy.…”

Section: Single Slice Analysis For Idh Typingmentioning

confidence: 99%

Filtration-histogram based magnetic resonance texture analysis (MRTA) for glioma IDH and 1p19q genotyping

Lewis

Ganeshan

Barnes

et al. 2019

European Journal of Radiology

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BackgroundTo determine if filtration-histogram based texture analysis (MRTA) of clinical MR imaging can non-invasively identify molecular subtypes of untreated gliomas.Methods Post Gadolinium T1-weighted (T1+Gad) images, T2-weighted (T2) images and apparent diffusion coefficient (ADC) maps of 97 gliomas (54=WHO II, 20=WHO III, 23=WHO IV) between 2010 and 2016 were studied. Whole-tumor segmentations were performed on a proprietary texture analysis research platform (TexRAD, Cambridge, UK) using the software's freehand drawing tool.MRTA commences with a filtration step, followed by quantification of texture using histogram texture parameters. Results were correlated using non-parametric statistics with a logistic regression model generated.Results T1+Gad performed best for IDH typing of glioblastoma (sensitivity 91.9%, specificity 100%, AUC 0.945) and ADC for non-Gadolinium-enhancing gliomas (sensitivity 85.7%, specificity 78.4%, AUC 0.877). T2 was moderately precise (sensitivity 83.1%, specificity 78.9%, AUC 0.821). Excellent results for IDH typing were achieved from a combination of the three sequences (sensitivity 90.5%, specificity 94.5%, AUC=0.98). For discriminating 1p19q genotypes, ADC produced the best results using unfiltered textures (sensitivity 80.6%, specificity 89.3%, AUC 0.811).Conclusion Preoperative glioma genotyping with MRTA appears valuable with potential for clinical translation. The optimal choice of texture parameters is influenced by sequence choice, tumour morphology and segmentation method.

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“…There is thus a pressing need to identify new systemic therapies [9][10][11]. The variety in overall survival and response to treatment in GBM is largely due to the high heterogeneity of GBM with a different distribution of aggressive biological traits across tumors, as well as within a single tumor [12][13][14]. To classify GBM cases according to this heterogeneity, different prognostic factors have been suggested for GBM, including age, performance status, specific molecular markers [e.g., MGMT methylation (O 6 -methylguanine-DNA methyl-transferase), mutation of IDH1, IDH2(isocitrate dehydrogenase) or TERT (telomerase reverse transcriptase), 1p19q codeletion, overexpression of EGFR (epidermal growth factor receptor)], the size of necrosis and the extent of resection (EOR) [15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

A Novel Comprehensive Clinical Stratification Model to Refine Prognosis of Glioblastoma Patients Undergoing Surgical Resection

Ius

Pignotti²,

Pepa

et al. 2020

Cancers

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Despite recent discoveries in genetics and molecular fields, glioblastoma (GBM) prognosis still remains unfavorable with less than 10% of patients alive 5 years after diagnosis. Numerous studies have focused on the research of biological biomarkers to stratify GBM patients. We addressed this issue in our study by using clinical/molecular and image data, which is generally available to Neurosurgical Departments in order to create a prognostic score that can be useful to stratify GBM patients undergoing surgical resection. By using the random forest approach [CART analysis (classification and regression tree)] on Survival time data of 465 cases, we developed a new prediction score resulting in 10 groups based on extent of resection (EOR), age, tumor volumetric features, intraoperative protocols and tumor molecular classes. The resulting tree was trimmed according to similarities in the relative hazard ratios amongst groups, giving rise to a 5-group classification tree. These 5 groups were different in terms of overall survival (OS) (p < 0.000). The score performance in predicting death was defined by a Harrell’s c-index of 0.79 (95% confidence interval [0.76–0.81]). The proposed score could be useful in a clinical setting to refine the prognosis of GBM patients after surgery and prior to postoperative treatment.

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The impact of surgery in molecularly defined low-grade glioma: an integrated clinical, radiological, and molecular analysis

Cited by 248 publications

References 30 publications

Extent of resection and molecular pathologic subtype are potent prognostic factors of adult WHO grade II glioma

Extent of resection and molecular pathologic subtype are potent prognostic factors of adult WHO grade II glioma

Filtration-histogram based magnetic resonance texture analysis (MRTA) for glioma IDH and 1p19q genotyping

A Novel Comprehensive Clinical Stratification Model to Refine Prognosis of Glioblastoma Patients Undergoing Surgical Resection

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