Browsing by Author "Payner, Troy"

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    Efficacy of pre-operative stereotactic radiosurgery followed by surgical resection and correlative radiobiological analysis for patients with 1-4 brain metastases: study protocol for a phase II trial
    (Biomed Central, 2018-12-20) Huff, Wei X.; Agrawal, Namita; Shapiro, Scott; Miller, James; Kulwin, Charles; Shah, Mitesh; Savage, Jesse J.; Payner, Troy; Vortmeyer, Alexander; Watson, Gordon; Dey, Mahua; Neurological Surgery, School of Medicine
    BACKGROUND: Stereotactic radiosurgery (SRS) has emerged as a common adjuvant modality used with surgery for resectable brain metastases (BMs). However, the optimal sequence of the multi-modality therapy has not been established. The goal of the study is to evaluate 6-month local control utilizing pre-operative SRS followed by surgical resection for patients with 1-4 brain metastases. METHODS: This prospective, single arm, phase II trial will recruit patients with up to 4 brain metastases and at least one resectable lesion. All lesions will be treated with SRS and symptomatic lesions will be resected within 1-4 days after SRS. Patients will be monitored for 6-month local control, in-brain progression free survival, distant in-brain failure, rate of leptomeningeal spread, radiation necrosis and overall survival. Additionally, we will also perform correlative radiobiological molecular studies to assess the effect of radiation dosing on the tumor tissue and clinical outcomes. We expect that pre-operative SRS to the gross tumor prior to surgical resection will improve local control and decrease leptomeningeal failure. DISCUSSION: Our study is the second prospective trial to investigate the efficacy of pre-operative SRS in the treatment of multiple BMs. In addition, the correlative molecular studies will be the first to investigate early response of BMs at a cellular and genetic level in response to radiation doses and potentially provide molecular prognostic markers for local control and overall survival.
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    Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure
    (Elsevier, 2024-03-27) Shireman, Jack M.; White, Quinn; Ni, Zijian; Mohanty, Chitrasen; Cai, Yujia; Zhao, Lei; Agrawal, Namita; Gonugunta, Nikita; Wang, Xiaohu; Mccarthy, Liam; Kasulabada, Varshitha; Pattnaik, Akshita; Ahmed, Atique U.; Miller, James; Kulwin, Charles; Cohen-Gadol, Aaron; Payner, Troy; Lin, Chih-Ta; Savage, Jesse J.; Lane, Brandon; Shiue, Kevin; Kamer, Aaron; Shah, Mitesh; Iyer, Gopal; Watson, Gordon; Kendziorski, Christina; Dey, Mahua; Radiation Oncology, School of Medicine
    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.
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    Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge
    (medRxiv, 2023-04-24) Shireman, Jack M.; White, Quinn; Agrawal, Namita; Ni, Zijian; Chen, Grace; Zhao, Lei; Gonugunta, Nikita; Wang, Xiaohu; Mccarthy, Liam; Kasulabada, Varshitha; Pattnaik, Akshita; Ahmed, Atique U.; Miller, James; Kulwin, Charles; Cohen-Gadol, Aaron; Payner, Troy; Lin, Chih-Ta; Savage, Jesse J.; Lane, Brandon; Shiue, Kevin; Kamer, Aaron; Shah, Mitesh; Iyer, Gopal; Watson, Gordon; Kendziorski, Christina; Dey, Mahua; Radiation Oncology, School of Medicine
    Stereotactic Radiosurgery (SRS) is one of the leading treatment modalities for oligo brain metastasis (BM), however no comprehensive genomic data assessing the effect of radiation on BM in humans exist. Leveraging a unique opportunity, as part of the clinical trial (NCT03398694), we collected post-SRS, delivered via Gamma-knife or LINAC, tumor samples from core and peripheral-edges of the resected tumor to characterize the genomic effects of overall SRS as well as the SRS delivery modality. Using these rare patient samples, we show that SRS results in significant genomic changes at DNA and RNA levels throughout the tumor. Mutations and expression profiles of peripheral tumor samples indicated interaction with surrounding brain tissue as well as elevated DNA damage repair. Central samples show GSEA enrichment for cellular apoptosis while peripheral samples carried an increase in tumor suppressor mutations. There are significant differences in the transcriptomic profile at the periphery between Gamma-knife vs LINAC.
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    Neurosurgical Management of Self-Inflicted Cranial Crossbow Injury
    (Elsevier, 2018-08) Kulwin, Charles G.; DeNardo, Andrew; Khairi, Saad; Payner, Troy; Neurological Surgery, School of Medicine
    Background Although gun-related penetrating traumatic brain injuries make up the majority of cranial missile injuries, low-velocity penetrating injuries present significant clinical difficulties that cannot necessarily be identically managed. Bow hunting is an increasingly popular pastime, and a crossbow allows a unique mechanism to cause a self-inflicted cranial injury with a large, low-velocity projectile. Historically, arrow removal is described in an operating room setting, which provides limited knowledge of the location of vascular injury in the setting of postremoval hemorrhage, and may represent an inefficient use of operating room availability. Case Description Two patients presented after self-inflicted cranial crossbow injuries. Both were neurologically salvageable. Initial assessment with computed tomography angiography allowed triage into likely or unlikely vascular injury. Arrow removal was performed in a radiology setting rather than in the operating room to allow immediate postremoval imaging to localize hemorrhage. While an operating room was on standby, neither patient required neurosurgical operative intervention. Both patients made a good recovery with no further injury caused by arrow removal. Conclusions We describe a novel approach to retained cranial arrow removal in a radiologic, rather than operative, setting and describe its relative benefits over traditional removal in the operating room.