Recurrence patterns after maximal surgical resection and postoperative radiotherapy in anaplastic gliomas according to the new 2016 WHO classification

Im, Jung Ho; Hong, Jong Chul; Kim, Se Hoon; Choi, Ji Sun; Chang, Jong Hee; Cho, Jaeho; Suh, Chang Ok

doi:10.1038/s41598-017-19014-1

Cited by 28 publications

(20 citation statements)

References 32 publications

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“…Although only one-fourth of patients received adjuvant chemotherapy, the 10-year OS rate of ODG patients was 96%, likely because of the high rate of GTR (53%) and because all 21 patients with non-GTR received RT. As compared with the IDHmt group, survival outcomes in the IDHwt group were poor, similar to those in patients with anaplastic astrocytoma, IDH-wildtype (5-year OS: 47.5%) and worse than those in patients with anaplastic astrocytoma, IDH-mutant (5-year OS: 71.6%) in our previous study 8 . 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".…”

Section: Discussionsupporting

confidence: 65%

“…For earlier cases, paraffin blocks of tissue taken at the time of surgery were obtained and used for retrospective examination. We examined IDH1 mutations using the Ventana Bench Mark XT autostainer (Ventana Medical System, Inc., Tucson, AZ, USA) according to the protocol as described at our previous report 8 . The anti-human IDH1 R132H mouse monoclonal antibody was used (Clone H09L, 1:80 dilution; Dianova, Hamburg, Germany).…”

Section: Molecular Pathologic Parameters and Surgical Resection Assesmentioning

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: Discussionsupporting

confidence: 65%

Section: Molecular Pathologic Parameters and Surgical Resection Assesmentioning

confidence: 99%

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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“…Though IDH wild-type grade II-III astrocytomas are rare, making up only 21.6% of patients, 25 their prognosis is poor with an overall survival of 31.8 vs 63.8 months for those with IDH mutant tumors (comparison made among TERT promoter wild type individuals). 26 The mutation status of gliomas is also associated with effects on the immune landscape of the tumor microenvironment, suggesting an impact on TAM protein expression in patient tumors. 27 A comparison of cores from IDH wild type and mutant tumors from our grade II-III TMA showed a slight increase in percentage of CD163 expressing cells in the IDH wild-type population (Figure 1E).…”

Section: Resultsmentioning

confidence: 99%

Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma

et al. 2018

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Efforts to reduce immunosuppression in the solid tumor microenvironment by blocking the recruitment or polarization of tumor associated macrophages (TAM), or myeloid derived suppressor cells (MDSCs), have gained momentum in recent years. Expanding our knowledge of the immune cell types, cytokines, or recruitment factors that are associated with high-grade disease, both within the tumor and in circulation, is critical to identifying novel targets for immunotherapy. Furthermore, a better understanding of how therapeutic regimens, such as Dexamethasone (Dex), chemotherapy, and radiation, impact these factors will facilitate the design of therapies that can be targeted to the appropriate populations and retain efficacy when administered in combination with standard of care regimens. Here we perform quantitative analysis of tissue microarrays made of samples taken from grades I-III astrocytoma and glioblastoma (GBM, grade IV astrocytoma) to evaluate infiltration of myeloid markers CD163, CD68, CD33, and S100A9. Serum, flow cytometric, and Nanostring analysis allowed us to further elucidate the impact of Dex treatment on systemic biomarkers, circulating cells, and functional markers within tumor tissue. We found that common myeloid markers were elevated in Dex-treated grade I astrocytoma and GBM compared to non-neoplastic brain tissue and grade II-III astrocytomas. Cell frequencies in these samples differed significantly from those in Dex-naïve patients in a pattern that depended on tumor grade. In contrast, observed changes in serum chemokines or circulating monocytes were independent of disease state and were due to Dex treatment alone. Furthermore, these changes seen in blood were often not reflected within the tumor tissue.Conclusions: Our findings highlight the importance of considering perioperative treatment as well as disease grade when assessing novel therapeutic targets or biomarkers of disease.

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“…With postoperative MRI, both the resection cavity and residual tumor were included in the gross tumor volume. The clinical target volume was delineated to include the peritumoral edema with a 1- or 1.5-cm margin on T2-weighted fluid-attenuated inversion recovery postoperative MRI, and a median total dose of 49.5 Gy (IQR: 48.0–51.0) in 30 fractions was then applied to the clinical target volume [ 14 , 15 ]. Following the treatment strategy followed at our institution, there was no difference in the dose prescription of the protocol according to pathology: all patients were treated with intensity-modulated RT using Tomotherapy (Hi-Art TomoTherapy; Accuray, Sunnyvale, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

ATM mutations improve radio-sensitivity in wild-type isocitrate dehydrogenase-associated high-grade glioma: retrospective analysis using next-generation sequencing data

Kim

Kang

et al. 2020

Radiat Oncol

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Background: To identify the association between somatic ataxia-telangiectasia mutated (ATM) mutations and improved radio-sensitivity, we retrospectively reviewed next-generation sequencing data from patients diagnosed with isocitrate dehydrogenase (IDH)-wildtype high-grade glioma. Methods: We included 39 individuals with (IDH)-wildtype high-grade glioma (diffuse astrocytoma n = 2, anaplastic astrocytoma n = 10, and glioblastoma n = 27) not subjected to gross tumor resection and undergoing radiation therapy with a median total dose of 60 Gy in 30 fractions. The mutational status of the ATM gene was obtained through next-generation sequencing using a TruSight Tumor 170 cancer panel. Disease progression was defined according to the Response Assessment in Neuro-Oncology (RANO) criteria as well as neurologic and clinical findings. Results: Among the 39 samples, ATM mutations (ATM mut(+)) were detected in 26% of cases (n = 10). No significant differences were observed in the characteristics of the patients or tumors. Among the 10 patients in the ATM mut(+) group, there were 6 patients with glioblastoma and 4 patients with anaplastic astrocytoma. Most mutations were missense mutations (n = 8, 80%). With a median follow-up of 16.5 mo (interquartile range, 11.4-19.8), ATM mut(+) exhibited 1-year in-field control of 100% compared with 44.1% in the ATM mut(−) group (p = 0.002). There was no difference in the out-field control rate or overall survival between the two groups (p = 0.861 and p = 0.247, respectively).

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Recurrence patterns after maximal surgical resection and postoperative radiotherapy in anaplastic gliomas according to the new 2016 WHO classification

Cited by 28 publications

References 32 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

Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma

ATM mutations improve radio-sensitivity in wild-type isocitrate dehydrogenase-associated high-grade glioma: retrospective analysis using next-generation sequencing data

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