Browsing by Author "Kulwin, Charles"

Now showing 1 - 6 of 6
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    Diagnosis and evaluation of intracranial arteriovenous malformations
    (Wolters Kluwer, 2015-05-12) Conger, Andrew; Kulwin, Charles; Lawton, Michael T.; Cohen-Gadol, Aaron A.; Department of Neurological Surgery, IU School of Medicine
    BACKGROUND: Ideal management of intracranial arteriovenous malformations (AVMs) remains poorly defined. Decisions regarding management of AVMs are based on the expected natural history of the lesion and risk prediction for peritreatment morbidity. Microsurgical resection, stereotactic radiosurgery, and endovascular embolization alone or in combination are all viable treatment options, each with different risks. The authors attempt to clarify the existing literature's understanding of the natural history of intracranial AVMs, and risk-assessment grading scales for each of the three treatment modalities. METHODS: The authors conducted a literature review of the existing AVM natural history studies and studies that clarify the utility of existing grading scales available for the assessment of peritreatment risk for all three treatment modalities. RESULTS: The authors systematically outline the diagnosis and evaluation of patients with intracranial AVMs and clarify estimation of the expected natural history and predicted risk of treatment for intracranial AVMs. CONCLUSION: AVMs are a heterogenous pathology with three different options for treatment. Accurate assessment of risk of observation and risk of treatment is essential for achieving the best outcome for each patient.
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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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    Endovascular and microsurgical treatment of cerebral arteriovenous malformations: Current recommendations
    (Wolters Kluwer, 2015-03-19) Conger, Andrew; Kulwin, Charles; Lawton, Michael T.; Cohen-Gadol, Aaron A.; Department of Neurological Surgery, IU School of Medicine
    BACKGROUND: Cerebral arteriovenous malformations (AVMs) can be a heterogeneous pathological entity whose management requires a complex decision-making process due to the risks associated with their treatment and natural history. Despite the recently published conclusions of the aborted Randomized Trial of Brain Unruptured AVMs (ARUBA) trial, the authors of this article believe multimodality intervention in general and microsurgical resection in particular continue to play a major role in the management of carefully selected ruptured or unruptured AVMs. METHODS: The authors provide an overview of their methodology for endovascular intervention and microsurgical resection and share their technical nuances for successful embolization and microsurgical resection of AVMs with special emphasis on complication avoidance. RESULTS: The authors have achieved successful outcomes in embolization and resection of cerebral AVMs when using their methodology. CONCLUSIONS: These lesions are among the most technically difficult pathological entities handled by the cerebrovascular specialist, and an overview of technical concepts to help systematize this challenging and variable endeavor can improve the safety of their treatment.
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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.