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MO_16_2878 - Cancer Genetic Markers According to Radiotherapeutic Response in Patients with Glioblastoma - Radiogenomic Approach for Precision Medicine

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Cancer Genetic Markers According to Radiotherapeutic Response in Patients with Glioblastoma - Radiogenomic Approach for Precision Medicine
K. Yang1, S. W. Jung2, H. M. Shin2, D. H. Lim1, D. H. Nam2,3, and S. T. Kim4; 1Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South), 2Institute for Refractory Cancer Research, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea, Republic of (South), 3Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South), 4Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South)

Purpose/Objective(s): To find genetic markers associated with response to radiotherapy (RT) in glioblastoma (GM) patients.

Materials/Methods: From Jan 2009 to Dec 2016, 161 patients with newly diagnosed IDH-wild type GM were treated with surgery and adjuvant concurrent chemoradiotherapy (CCRT) with the Stupp’s regimen at one institution, and proceeded genomic analyses with surgical specimens. Of the patients, 49 patients with clinically measurable disease on postoperative MRI were analyzed. Response evaluation to RT was based on Response Assessment in Neuro-Oncology (RANO) criteria and MRI at the time of 3 or 4 months after the end of CCRT was compared with baseline MRI. To identify pseudo-progression, we checked further follow-up MRI and clinical events including re-operation, additional RT or gamma knife surgery, and change of treatment for the next 3 months, which was regarded as true progression. To compare the genomic characteristics between patients with progression or non-responder group (NR-group) and non-progression or responder group (R-group) after RT, we performed genomic analyses with whole-exome sequencing, RNA sequencing and targeted-exome panel. The Fisher test to compare mutations and copy number alterations and the single-sample Gene Set Enrichment Analysis (GSEA) score to interpret gene expression were used.

Results: The median age was 57 years (range 22-82) and surgical extension was subtotal resection for all 49 patients. RT responses were complete response (CR) or partial response (PR), stable disease (SD), and progressive disease (PD) in 7 (14.3%), 15 (30.6%), and 27 patients (55.1%), respectively. After further evaluation for 3 months, 7 of 27 patients (25.9%) with PD were pseudoprogression. Median follow-up period was 15 months (range 2-46) and 90% of patients experienced intracranial PD, eventually. One-year progression-free survival (PFS) and overall survival (OS) rate were 25.8% and 69.6%, respectively. With RANO response, 1-year PFS for patients with CR / PR / SD or R-group and PD or NR-group were 43.2% and 12.5% (p = 0.013), and OS were 74.2% and 65.5% (p = 0.349), respectively. After adjusting pseudoprogression from NR-group, 1-year PFS for R- and NR-group were 45.4% and 0 (p < 0.001), and OS were 81.1% and 52.5% (p = 0.046), respectively. With genomic analyses, NR-group had more CDKN2A and EGFR mutations with statistical significance and TP53 mutations seemed more frequent in R-group without statistical significance. In GSEA, immune-related gene sets were enriched in NR-group, and in contrast, some gene sets related with cell cycle were enriched in R-group.

Conclusion: RT response evaluation with RANO criteria was related with disease progression despite of pseudo-progression, and this study showed the possibility of difference in genetic signatures according to RT response. To suggest molecular based strategies including RT and provide successful precision medicine for GM patients, therefore, further studies with larger patient number should be followed.

Author Disclosure: K. Yang: None. D. Lim: None.

Kyungmi Yang, MD

Biography:
I am Kyungmi Yang, MD, a radiation oncologist at AJOU University Medical Center, Suwon, Korea.
For my medical education, I completed the resident course in the department of Radiation Oncology at Samsung Medical Center, Korea. Before that, I graduated the medical school of the Chung-Ang University, Seoul, Korea in Feb, 2014, and completed the internship at Samsung Medical center in Feb, 2015. Previously, I recieved BS and MS degrees of Industrial Engineering at KAIST, Daejun, Korea and had work experience of marketing for 5 years.


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