Browsing by Author "Shah, Mitesh"

Now showing 1 - 6 of 6
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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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    Posterior Interhemispheric Transfalcine Transprecuneus Approach for Microsurgical Resection of Peri-Atrial Lesions: Indications, Technique, and Outcomes
    (2015-10) Bohnstedt, Bradley N.; Kulwin, Charles; Shah, Mitesh; Cohen-Gadol, Aaron A.; Department of Neurological Surgery, IU School of Medicine
    OBJECT Surgical exposure of the peritrigonal or periatrial region has been challenging due to the depth of the region and overlying important functional cortices and white matter tracts. The authors demonstrate the operative feasibility of a contralateral posterior interhemispheric transfalcine transprecuneus approach (PITTA) to this region and present a series of patients treated via this operative route. METHODS Fourteen consecutive patients underwent the PITTA and were included in this study. Pre- and postoperative clinical and radiological data points were retrospectively collected. Complications and extent of resection were reviewed. RESULTS The mean age of patients at the time of surgery was 39 years (range 11–64 years). Six of the 14 patients were female. The mean duration of follow-up was 4.6 months (range 0.5–19.6 months). Pathology included 6 arteriovenous malformations, 4 gliomas, 2 meningiomas, 1 metastatic lesion, and 1 gray matter heterotopia. Based on the results shown on postoperative MRI, 1 lesion (7%) was intentionally subtotally resected, but ≥ 95% resection was achieved in all others (93%) and gross-total resection was accomplished in 7 (54%) of 13. One patient (7%) experienced a temporary approach-related complication. At last follow-up, 1 patient (7%) had died due to complications of his underlying malignancy unrelated to his cranial surgery, 2 (14%) demonstrated a Glasgow Outcome Scale (GOS) score of 4, and 11 (79%) manifested a GOS score of 5. CONCLUSIONS Based on this patient series, the contralateral PITTA potentially offers numerous advantages, including a wider, safer operative corridor, minimal need for ipsilateral brain manipulation, and better intraoperative navigation and working angles.
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    Preoperative Embolization With Fused CT Angiography and Tractography Facilitates Safe Resection of a Spetzler-Martin Grade IV Arteriovenous Malformation
    (Cureus, 2021-12-24) Weyhenmeyer, Jonathan; Ordaz, Josue D.; Gadol, Aaron Cohen; Shah, Mitesh; Neurological Surgery, School of Medicine
    Brain arteriovenous malformations (BAVMs) are high-flow vascular lesions that have a propensity to rupture resulting in high rates of morbidity and mortality. Microsurgical resection of BAVMs is the standard of care for high-risk, resectable lesions. Multiple imaging modalities aid in the surgical planning and resection of high-grade BAVMs, but all have hidden variables that would prove useful if available. We present a 20-year-old male with a ruptured BAVM with concern for the involvement of the corticospinal tract (CST) and basal ganglia. We describe the melding of computed tomography angiography (CTA) and diffusion tensor imaging (DTI) in addition to preoperative embolization to aid in the planning and resection of a lesion close to eloquent structures. Post-operative CTA and DTI showed a total resection of the lesion with retained CST white matter tracts, and the patient retained the functional ability of the contralateral limbs. The combination of CTA, brain DTI, and preoperative embolization provides a framework to improve the safety of resection of BAVMs that occur near eloquent brain networks.
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    Radt-42. Adjuvant Radiation Therapy for Subtotally Resected Cerebellar Liponeurocytoma
    (Oxford University Press, 2020-11) McClelland, Shearwood, III.; Gardner, Ulysses; Shah, Mitesh; Watson, Gordon; Shiue, Kevin; Radiation Oncology, School of Medicine
    Introduction: Classified as a benign glioneural tumor, cerebellar liponeurocytoma is a rare disease (fewer than 80 reported cases) and was upgraded from WHO grade I to grade II in 2007 due to its high recurrence rate. The authors report a case of definitive radiation therapy for recurrent subtotally resected cerebellar liponeurocytoma. Methods: An 80-year-old man having undergone seven resections for his left cerebellar liponeurocytoma without adjuvant therapy over the previous decade at outside institutions was referred for radiation therapy two months following his eighth resection, where gross total resection was limited by the lesion proximity to his brainstem resulting in a 2 cm residual left cerebellar lesion. Pathology revealed tumor cells strongly positive for synaptophysin and a Ki-67 labeling index < 1%. Due to the propensity of this disease to recur following resection, his entire resection cavity was treated with external beam radiation therapy (EBRT) to 46 Gy, followed by a 10 Gy boost to his residual disease yielding a total of 56 Gy to the residual disease. Results: Reimaging following the initial 46 Gy revealed the residual disease remained amenable (< 3 cm) to stereotactic radiosurgery (SRS), which was delivered via linear accelerator (10 Gy to the 80% isodose line) in a single fraction. Following EBRT + SRS, the patient responded well. At last follow-up, he has demonstrated no evidence of disease progression, brainstem-related morbidity or surgical incision-related morbidity. Conclusions: The first reported case of SRS treatment of cerebellar liponeurocytoma as the culmination of a coordinated definitive plan beginning with EBRT supports the applicability and feasibility of this treatment strategy following subtotal resection. This case indicates that a radiation treatment plan similar to that for central neurocytoma may be an optimal strategy, and suggests that adjuvant radiation therapy following operative resection of this rare disease may be underutilized.