RTHP-05. CONTRIBUTION OF ATM MUTATION TO THE IMPROVED RADIO-SENSITIVITY: RETROSPECTIVE ANALYSIS USING NEXT-GENERATION SEQUENCING DATA. (11th November 2019)

• Record Type: Journal Article
• Authors: In Yoon, Hong; Kim, Nalee; Hoon Kim, Se; Hyung Moon, Ju; Kang, Seok-Gu; Suh, Chang-Ok; Hee Chang, Jong
• Is Part Of: Neuro-oncology. Volume 21(2019)Supplement 6
• Page Start: vi210
• Page End: vi211
• Publication Date: 2019-11-11
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noz175.878
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: PURPOSE/OBJECTIVES: To identify the association of somatic ATM mutation (mATM) with improved radiotherapy sensitivity, we retrospectively reviewed the next-generation sequencing (NGS) data from high grade glioma patients. MATERIALS/METHODS: This analysis includes 48 consecutive individuals diagnosed with high grade glioma (diffuse astrocytoma IDH-wild type n=2, anaplastic astrocytoma n=18, and glioblastoma n=28) between June 2017 and October 2018. Patients who underwent subtotal (n=30, 62.5%), partial (n=17, 35.4%) removal or biopsy (n=1, 2.1%) were included in this analysis for interpreting radio-sensitivity of residual tumor. We investigated mATM by NGS of FFPE specimens with a TruSight Tumor 170 (TST-170) cancer panel. RESULTS: Among 48 samples, mATM was detected in 17% of cases (n=8). There was no significant difference in patient or tumor characteristics. Among mATM patients, there were 5 patients with glioblastoma and 3 patients with anaplastic astrocytoma IDH-wildtype. Most mutation was missense mutation (n=7, 88%). Median variant allele frequency was 44.7% (Interquartile range, IQR, 10.5–59.9%). Median follow-up duration after radiotherapy was 11.4 (IQR, 8.0–15.8) months. Radiation-related change was observed in 34 patients (71%). Tumors with mATM were related to higher frequency of radiation-related change at 6 months than tumors without mATM, respectively (88% and 64%, p = 0.016). Cases with mATM exhibited significantly 1-year progression free survival (PFS, 100% vs. 54%, p = 0.036). On subgroup of IDH WT (n=39) known as poor prognostic molecular marker, patients with mATM showed significantly higher PFS than patients without mATM (p=0.016, 1yr PFS 100% vs 43%). On subgroup with sub-ventricular zone involvement (n=38) representative of aggressiveness, PFS of patients with mATM was significantly higher than others (p=0.026, 1yr PFS 100% vs 43.9%). CONCLUSIONS: Our results demonstrated that mATM is involved in radio-sensitivity with immediate radiologic change after radiation therapy followed by favorable radiologic response and clinical outcome beyond the aggressive nature of high grade glioma.