iScience (Apr 2024)
Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure
- Jack M. Shireman,
- Quinn White,
- Zijian Ni,
- Chitrasen Mohanty,
- Yujia Cai,
- Lei Zhao,
- Namita Agrawal,
- Nikita Gonugunta,
- Xiaohu Wang,
- Liam Mccarthy,
- Varshitha Kasulabada,
- Akshita Pattnaik,
- Atique U. Ahmed,
- James Miller,
- Charles Kulwin,
- Aaron Cohen-Gadol,
- Troy Payner,
- Chih-Ta Lin,
- Jesse J. Savage,
- Brandon Lane,
- Kevin Shiue,
- Aaron Kamer,
- Mitesh Shah,
- Gopal Iyer,
- Gordon Watson,
- Christina Kendziorski,
- Mahua Dey
Affiliations
- Jack M. Shireman
- Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Quinn White
- Department of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Zijian Ni
- Department of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Chitrasen Mohanty
- Department of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Yujia Cai
- Department of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Lei Zhao
- Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Namita Agrawal
- Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA
- Nikita Gonugunta
- Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Xiaohu Wang
- Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Liam Mccarthy
- Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Varshitha Kasulabada
- Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Akshita Pattnaik
- Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Atique U. Ahmed
- Department of Neurological Surgery, Northwestern University, Chicago, IL, USA
- James Miller
- Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
- Charles Kulwin
- Goodman Campbell Brain and Spine Neurological Surgery, Indianapolis, IN, USA
- Aaron Cohen-Gadol
- Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
- Troy Payner
- Goodman Campbell Brain and Spine Neurological Surgery, Indianapolis, IN, USA
- Chih-Ta Lin
- Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
- Jesse J. Savage
- Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
- Brandon Lane
- Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
- Kevin Shiue
- Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA
- Aaron Kamer
- Department of Clinical Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA
- Mitesh Shah
- Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
- Gopal Iyer
- Department of Human Oncology, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Gordon Watson
- Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA
- Christina Kendziorski
- Department of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
- Mahua Dey
- Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA; Corresponding author
- Journal volume & issue
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Vol. 27,
no. 4
p. 109601
Abstract
Summary: Stereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis on resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in human, biological evidence of differential effects of SRS across BM’s.
