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

ABSTRACT: 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 5- and 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.

SUBMITTER: Choi J

PROVIDER: S-EPMC7005814 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Choi Jinhyun J Kim Se Hoon SH Ahn Sung Soo SS Choi Hye Jin HJ Yoon Hong In HI Cho Jae Ho JH Roh Tae Hoon TH Kang Seok-Gu SG Chang Jong Hee JH Suh Chang-Ok CO

Scientific reports 20200207 1

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 (4 ...[more]

PMID: 32034238

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Project description:OBJECTIVE:While the effect of increased extent of resection (EOR) on survival in diffuse infiltrating low-grade glioma (LGG) patients is well established, there is still uncertainty about the influence of the new WHO molecular subtypes. The authors designed a retrospective analysis to assess the interplay between EOR and molecular classes. METHODS:The authors retrospectively reviewed the records of 326 patients treated surgically for hemispheric WHO grade II LGG at Brigham and Women's Hospital and Massachusetts General Hospital (2000-2017). EOR was calculated volumetrically and Cox proportional hazards models were built to assess for predictive factors of overall survival (OS), progression-free survival (PFS), and malignant progression-free survival (MPFS). RESULTS:There were 43 deaths (13.2%; median follow-up 5.4 years) among 326 LGG patients. Median preoperative tumor volume was 31.2 cm3 (IQR 12.9-66.0), and median postoperative residual tumor volume was 5.8 cm3 (IQR 1.1-20.5). On multivariable Cox regression, increasing postoperative volume was associated with worse OS (HR 1.02 per cm3; 95% CI 1.00-1.03; p = 0.016), PFS (HR 1.01 per cm3; 95% CI 1.00-1.02; p = 0.001), and MPFS (HR 1.01 per cm3; 95% CI 1.00-1.02; p = 0.035). This result was more pronounced in the worse prognosis subtypes of IDH-mutant and IDH-wildtype astrocytoma, for which differences in survival manifested in cases with residual tumor volume of only 1 cm3. In oligodendroglioma patients, postoperative residuals impacted survival when exceeding 8 cm3. Other significant predictors of OS were age at diagnosis, IDH-mutant and IDH-wildtype astrocytoma classes, adjuvant radiotherapy, and increasing preoperative volume. CONCLUSIONS:The results corroborate the role of EOR in survival and malignant transformation across all molecular subtypes of diffuse LGG. IDH-mutant and IDH-wildtype astrocytomas are affected even by minimal postoperative residuals and patients could potentially benefit from a more aggressive surgical approach.

Project description:Due to the extremely intrinsic heterogeneity among glioma patients, the outcomes of these patients are tremendously different. Therefore, the exploitation of novel biomarker classification of glioma is vitally important for deep insight into the essence and predicting the prognosis of glioma. We aim to analyze the correlation between TP73 mRNA expression, DNA methylated alteration and the prognosis of WHO grade II/III glioma, utilizing bioinformatics to evaluate its significance as a risk-factor in predicting the prognosis of these glioma patients. The analysis found that TP73 expression was positively correlated with the grade of glioma, and showed a strong correlation with glioma molecular classification, which revealed significantly higher TP73 expression in IDH-wildtype than in IDH-mutant subtype of WHO grade II/III glioma. Cox regression analysis indicated that high expression of TP73 shared an independent high-risk factor impacting the prognosis of WHO grade II/III glioma. We discovered 8 DNA promoter methylation sites with prognostic significance, which were negatively associated with TP73 expression, and positively associated with beneficial overall survival (OS) and progression-free survival (PFS). Integrating with four independent glioma datasets, subsequent Meta-analysis verified that low expression of TP73 was closely related to favorable OS, especially in IDH-mutant subtype. Moreover, we found that 1p/19qCodel /TP73low subgroup shared the most favorable OS, 1p/19qNon-codel /TP73high subgroup suffered the worst OS. Meanwhile, the enrichment analysis of TP73-related differential mRNAs demonstrated that TP73 aberration in WHO grade II/III glioma might be closely related to cell cycle and P53 signaling pathways. Finally, TP73 expression of 53 glioma specimens was measured by qRT-PCR, which was consistent with the previous analytical result, and TP73 high-expression subgroup suffered worse PFS than TP73 low-expression subgroup. In summary, our funding supports that TP73 gene can perform as a reliable biomarker to evaluate the survival outcome of patients diagnosed with WHO grade II/III glioma.

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

Publications

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

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