Several Molecular Markers Predict Clinical Outcomes After Surgical Resection of Anaplastic Astrocytoma. (16th November 2020)

• Record Type: Journal Article
• Authors: Baldassari, Michael P; Ye, Donald Yandong; Yudkoff, Clifford; Doermann, Allison; Henry, Tyler; Evans, James J; Andrews, David W; Farrell, Christopher J; Judy, Kevin D
• Is Part Of: Neurosurgery. Volume 67(2010)Supplement 1
• Publication Date: 2020-11-16
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1093/neuros/nyaa447_906
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract: INTRODUCTION: After surgical resection, anaplastic astrocytoma (AA) samples are routinely subjected to a standard panel of histopathological tests. Among these include proliferative index (Ki67%), isocitrate dehydrogenase 1 (IDH-1), O 6 -methylguanine DNA methyltransferase (MGMT), epidermal growth factor receptor (EGFR), glial fibrillary acidic protein (GFAP), tumor protein 53 (TP53), retinoblastoma 1 (RB1), and ATRX gene mutations. Their diagnostic utility is well-defined in the literature, but their prognostic relevance is not yet well-developed. METHODS: We analyzed a retrospective database of AA patients treated surgically between January 2012 and January 2019. We collected clinical characteristics and histological results from pathology reports. RESULTS: We identified 124 patients who had undergone surgical resection of AA. Mean age was 50.0 (SD 17.3, range 20 to 88). Ki67% was calculated by attending pathologists for 79.8% of all patients (99/124). Genetic marker results were available for all patients. Average Ki67% was 15.9 (Q1 = 5.2, Q2 = 9.9, Q3 = 19.0, Q4 = 85.0). Common mutations included IDH1 (46.0%), GFAP (37.9%), ATRX (35.5%), and TP53 (32.3%), while less common were EGFR (8.9%), MGMT (3.2%), and RB1 (1.6%). No mutations in PTEN gene were identified. Univariate analysis revealed Ki67% within the first quartile predicted lower risk of mortality ( P = .001). IDH1 mutation was associated with decreased lengths-of-stay ( P = .01), lower rates of 30-day readmission ( P = .046), and lower rates of overall mortality ( P = .001). Survival at 6 months, 1 year, 2 years, 3, years, and 5 years for first quartile Ki67 patients was 100.0%, 95.5%, 92.9%, 92.3%, and 66.7%, respectively. Likewise, survival at 6 months, 1 year, 2 years, 3, years and 5 years for IDH1 positive patients was 98.0%, 91.1%, 78.4%, 69.7%, and 29.4%, respectively. For IDH1 negative patients, these values were 78.4%, 67.3%, 45.2%, 27.0%, and 6.1%. No other prognostic associations were found among the molecular markers included in our study. CONCLUSION: Low Ki67% and positive IDH1 mutation confer the direct clinical benefit to AA patients in terms of mortality. IDH1 mutation specifically indicates shorter LOS and lower rates of 30-day readmission.