David Jaehyun Park

All Publications

• Spinal metastases of pineal region glioblastoma with primitive neuroectodermal features highlighting the importance of molecular diagnoses: illustrative case. Journal of neurosurgery. Case lessons Shah, A., Marianayagam, N. J., Zamarud, A., Park, D. J., Persad, A. R., Soltys, S. G., Chang, S. D., Veeravagu, A. 2023; 6 (20)

  Abstract

  Glioblastoma (GBM) is the most common primary brain tumor with poor patient prognosis. Spinal leptomeningeal metastasis has been rarely reported, with long intervals between the initial discovery of the primary tumor in the brain and eventual spine metastasis.Here, the authors present the case of a 51-year-old male presenting with 7 days of severe headache, nausea, and vomiting. Magnetic resonance imaging of the brain and spine demonstrated a contrast-enhancing mass in the pineal region, along with spinal metastases to T8, T12, and L5. Initial frozen-section diagnosis led to the treatment strategy for medulloblastoma, but further molecular analysis revealed characteristics of isocitrate dehydrogenase-wild type, grade 4 GBM.Glioblastoma has the potential to show metastatic spread at the time of diagnosis. Spinal imaging should be considered in patients with clinical suspicion of leptomeningeal spread. Furthermore, molecular analysis should be confirmed following pathological diagnosis to fine-tune treatment strategies.

  View details for DOI 10.3171/CASE23536

  View details for PubMedID 37956418

• The outcome of central nervous system hemangioblastomas in Von Hippel-Lindau (VHL) disease treated with belzutifan: a single-institution retrospective experience. Journal of neuro-oncology Zamarud, A., Marianayagam, N. J., Park, D. J., Yener, U., Yoo, K. H., Meola, A., Chang, S. D. 2023

  Abstract

  Belzutifan is a Hypoxia Inducible Factor 2-alpha inhibitor approved in 2021 by the FDA for the treatment of renal cell carcinoma (RCC) in patients with Von-Hippel Landau (VHL) disease. These patients can also present with central nervous system (CNS) hemangioblastomas (HBs). We aim to study the effectiveness and adverse effects of belzutifan for CNS HBs, by reporting our preliminary institutional experience.We present a series of VHL patients with CNS HBs undergoing treatment with belzutifan for RCC. All the included patients met the RECIST inclusion criteria. The clinical and radiological outcome measures included: Objective response rate (ORR), time-to-response (TTR), adverse events (AE), and patient response. Patient response was classified as partial response (PR), complete response (CR), progressive disease (PD), or stable disease (SD).Seven patients with 25 HBs were included in our study. A belzutifan dose of 120 mg/day PO was administered for a median of 13 months (range 10-17). Median follow up time was 15 months (range 10-24). An ORR of 71% was observed. The median TTR was 5 months (range: 1-10). None of the patients showed CR, while 5 patients (71.4%) showed PR and 2 (28.5%) showed SD. Among patients with SD the maximum tumor response was 20% [increase/decrease] of the lesion diameter. All the patients experienced decreased hemoglobin concentration, fatigue, and dizziness. None of the patients experienced severe anemia (grade 3-4 CTCAE).Belzutifan appears to be an effective and safe treatment for CNS hemangioblastoma in VHL patients. Further clinical trials to assess the long-term effectiveness of the medication are required.

  View details for DOI 10.1007/s11060-023-04496-z

  View details for PubMedID 37955759

  View details for PubMedCentralID 5573741

• Stereotactic Radiosurgery for Cranial and Spinal Hemangioblastomas: A Single-Institution Retrospective Series. Neurosurgery Yoo, K. H., Park, D. J., Marianayagam, N. J., Gu, X., Pollom, E. L., Soltys, S. G., Chang, S. D., Meola, A. 2023

  Abstract

  Stereotactic radiosurgery (SRS) has been an attractive treatment modality for both cranial and spinal hemangioblastomas, especially for multiple lesions commonly associated with von Hippel-Lindau (VHL) disease. This study aims to provide the largest long-term analysis of treatment efficacy and adverse effects of SRS for cranial and spinal hemangioblastomas at a single institution.We evaluated the clinical and radiological outcomes of patients with hemangioblastomas treated with CyberKnife SRS at our institute from 1998 to 2022. The follow-up data were available for 135 hemangioblastomas in 35 patients. Twenty-eight patients had 123 hemangioblastomas associated with VHL, and 7 had 12 sporadic hemangioblastomas. The median age was 36 years, and the median tumor volume accounted for 0.4 cc. The SRS was administered with the median single-fraction equivalent dose of 18 Gy to the 77% median isodose line.At a median follow-up of 57 months (range: 3-260), only 20 (16.2%) of the VHL-associated and 1 (8.3%) sporadic hemangioblastomas progressed. The 5-year local tumor control rate was 91.3% for all hemangioblastomas, 91.7% among the sporadic lesions, and 92.9% in patients with VHL. SRS improved tumor-associated symptoms of 98 (74.8%) of 131 symptomatic hemangioblastomas, including headache, neck pain, dizziness, visual disturbances, dysesthesia, ataxia, motor impairment, seizures, and dysphagia. Two patients developed radiation necrosis (5.7%), and 1 of them required surgical resection.SRS is a safe and effective treatment option for patients with hemangioblastomas in critical locations, such as the brainstem, cervicomedullary junction, and spinal cord, and in patients with multiple hemangioblastomas associated with VHL disease.

  View details for DOI 10.1227/neu.0000000000002728

  View details for PubMedID 37967154

• Practical Guideline for Prevention of Patchy Hair Loss following CyberKnife Stereotactic Radiosurgery for Calvarial or Scalp Tumors: Retrospective Analysis of a Single Institution Experience. Stereotactic and functional neurosurgery Park, D. J., Marianayagam, N. J., Yener, U., Tayag, A., Ustrzynski, L., Emrich, S. C., Pollom, E., Soltys, S., Meola, A., Chang, S. D. 2023: 1-7

  Abstract

  Patchy alopecia is a common adverse effect of stereotactic radiosurgery (SRS) on the calvarium and/or scalp, yet no guidelines exist for its prevention. This study aims to investigate the incidence and outcomes of patchy alopecia following SRS for patients with calvarial or scalp lesions and establish preventive guidelines.The study included 20 patients who underwent CyberKnife SRS for calvarial or scalp lesions, resulting in a total of 30 treated lesions. SRS was administered as a single fraction for 8 lesions and hypofractionated for 22 lesions. The median SRS target volume was 9.85 cc (range: 0.81-110.7 cc), and the median prescription dose was 27 Gy (range: 16-40 Gy), delivered in 1-5 fractions (median: 3). The median follow-up was 15 months.Among the 30 treated lesions, 11 led to patchy alopecia, while 19 did not. All cases of alopecia resolved within 12 months, and no patients experienced other adverse radiation effects. Lesions resulting in alopecia exhibited significantly higher biologically effective dose (BED) and single-fraction equivalent dose (SFED) on the overlying scalp compared to those without alopecia. Patients with BED and SFED exceeding 60 Gy and 20 Gy, respectively, were 9.3 times more likely to experience patchy alopecia than those with lower doses. The 1-year local tumor control rate for the treated lesions was 93.3%. Chemotherapy was administered for 26 lesions, with 11 lesions receiving radiosensitizing agents. However, no statistically significant difference was found.In summary, SRS is a safe and effective treatment for patients with calvarial/scalp masses regarding patchy alopecia near the treated area. Limiting the BED under 60 Gy and SFED under 20 Gy for the overlying scalp can help prevent patchy alopecia during SRS treatment of the calvarial/scalp mass. Clinicians can use this information to inform patients about the risk of alopecia and the contributing factors.

  View details for DOI 10.1159/000533555

  View details for PubMedID 37699370

• Stereotactic Radiosurgery for Medically Refractory Trigeminal Neuralgia Secondary to Stroke: A Systematic Review and Clinical Case Presentation. World neurosurgery Zamarud, A., Park, D. J., Ung, T. H., McCleary, T. L., Yoo, K. H., Soltys, S. G., Lim, M., Chang, S. D., Meola, A. 2023

  View details for DOI 10.1016/j.wneu.2023.08.092

  View details for PubMedID 37640262

• Optimizing the synergy between stereotactic radiosurgery and immunotherapy for brain metastases. Frontiers in oncology Yoo, K. H., Park, D. J., Choi, J. H., Marianayagam, N. J., Lim, M., Meola, A., Chang, S. D. 2023; 13: 1223599

  Abstract

  Solid tumors metastasizing to the brain are a frequent occurrence with an estimated incidence of approximately 30% of all cases. The longstanding conventional standard of care comprises surgical resection and whole-brain radiotherapy (WBRT); however, this approach is associated with limited long-term survival and local control outcomes. Consequently, stereotactic radiosurgery (SRS) has emerged as a potential alternative approach. The primary aim of SRS has been to improve long-term control rates. Nevertheless, rare observations of abscopal or out-of-field effects have sparked interest in the potential to elicit antitumor immunity via the administration of high-dose radiation. The blood-brain barrier (BBB) has traditionally posed a significant challenge to the efficacy of systemic therapy in managing intracranial metastasis. However, recent insights into the immune-brain interface and the development of immunotherapeutic agents have shown promise in preclinical and early-phase clinical trials. Researchers have investigated combining immunotherapy with SRS to enhance treatment outcomes in patients with brain metastasis. The combination approach aims to optimize long-term control and overall survival (OS) outcomes by leveraging the synergistic effects of both therapies. Initial findings have been encouraging in the management of various intracranial metastases, while further studies are required to determine the optimal order of administration, radiation doses, and fractionation regimens that have the potential for the best tumor response. Currently, several clinical trials are underway to assess the safety and efficacy of administering immunotherapeutic agents concurrently or consecutively with SRS. In this review, we conduct a comprehensive analysis of the advantages and drawbacks of integrating immunotherapy into conventional SRS protocols for the treatment of intracranial metastasis.

  View details for DOI 10.3389/fonc.2023.1223599

  View details for PubMedID 37637032

  View details for PubMedCentralID PMC10456862

• Stereotactic Radiosurgery for Contrast-Enhancing Satellite Nodules in Recurrent Glioblastoma: A Rare Case Series From a Single Institution. Cureus Park, D. J., Persad, A. R., Yoo, K. H., Marianayagam, N. J., Yener, U., Tayag, A., Ustrzynski, L., Emrich, S. C., Chuang, C., Pollom, E., Soltys, S. G., Meola, A., Chang, S. D. 2023; 15 (8): e44455

  Abstract

  Introduction Glioblastoma (GBM) is the most common malignant adult brain tumor and is invariably fatal. The standard treatment for GBM involves resection where possible, followed by chemoradiation per Stupp's protocol. We frequently use stereotactic radiosurgery (SRS) as a single-fraction treatment for small (volume ≤ 1cc) nodular recurrent GBM to the contrast-enhancing target on T1 MRI scan. In this paper, we aimed to evaluate the safety and efficacy of SRS for patients with contrast-enhancing satellite nodules in recurrent GBM. Methods This retrospective study analyzed the clinical and radiological outcomes of five patients who underwent CyberKnife (Accuray Inc., Sunnyvale, California) SRS at the institute between 2013 and 2022. Results From 96 patients receiving SRS for GBM, five (four males, one female; median age 53) had nine distinct new satellite lesions on MRI, separate from their primary tumor beds. Those nine lesions were treated with a median margin dose of 20 Gy in a single fraction. The three-, six, and 12-month local tumor control rates were 77.8%, 66.7%, and 26.7%, respectively. Median progression-free survival (PFS) was seven months, median overall survival following SRS was 10 months, and median overall survival (OS) was 35 months. Interestingly, the only lesion that did not show radiological progression was separate from the T2-fluid attenuated inversion recovery (FLAIR) signal of the main tumor. Conclusion Our SRS treatment outcomes for recurrent GBM satellite lesions are consistent with existing findings. However, in a unique case, a satellite nodule distinct from the primary tumor's T2-FLAIR signal and treated with an enlarged target volume showed promising control until the patient's demise. This observation suggests potential research avenues, given the limited strategies for 'multicentric' GBM lesions.

  View details for DOI 10.7759/cureus.44455

  View details for PubMedID 37664337

  View details for PubMedCentralID PMC10470661

• Stereotactic radiosurgery for distant brain metastases secondary to esthesioneuroblastoma: a single-institution series. Neurosurgical focus Zamarud, A., Yener, U., Yoo, K. H., Park, D. J., Marianayagam, N. J., Ho, Q. A., Pollom, E., Soltys, S., Wang, L., Chang, S. D., Meola, A. 2023; 55 (2): E6

  Abstract

  Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare, malignant tumor of neuroectodermal origin that arises from the olfactory neuroepithelium. In this study the authors present the first series in the literature on distant brain metastases (BMs) secondary to ENB that were treated with stereotactic radiosurgery (SRS), to evaluate the safety and effectiveness of SRS for this indication.A retrospective analysis of clinical and radiological outcomes of patients with ENB who underwent CyberKnife (CK) SRS at a single center was conducted. The clinical and radiological outcomes of patients, including progression-free survival, overall survival, and local tumor control (LTC) were reported.Between 2003 and 2022, 32 distant BMs in 8 patients were treated with CK SRS at Stanford University. The median patient age at BM diagnosis was 62 years (range 47-75 years). Among 32 lesions, 2 (6%) had previously been treated with surgery, whereas for all other lesions (30 [94%]), CK SRS was used as their primary treatment modality. The median target volume was 1.5 cm3 (range 0.09-21.54 cm3). CK SRS was delivered by a median marginal dose of 23 Gy (range 15-30 Gy) and a median of 3 fractions (range 1-5 fractions) to a median isodose line of 77% (range 70%-88%). The median biologically effective dose was 48 Gy (range 21-99.9 Gy) and the median follow-up was 30 months (range 3-95 months). The LTC at 1-, 2-, and 3-year follow-up was 86%, 65%, and 50%, respectively. The median progression-free survival and overall survival were 29 months (range 11-79 months) and 51 months (range 15-79 months), respectively. None of the patients presented adverse radiation effects.In the authors' experience, SRS provided excellent LTC without any adverse radiation effects for BMs secondary to ENB.

  View details for DOI 10.3171/2023.5.FOCUS23216

  View details for PubMedID 37527675

• Stereotactic radiosurgery for sarcoma metastases to the brain: a single-institution experience. Neurosurgical focus Zamarud, A., Park, D. J., Dadey, D. Y., Yoo, K. H., Marianayagam, N. J., Yener, U., Szalkowski, G. A., Pollom, E., Soltys, S., Chang, S. D., Meola, A. 2023; 55 (2): E7

  Abstract

  Brain metastases (BMs) secondary to sarcoma are rare, and their incidence ranges from 1% to 8% of all bone and soft tissue sarcomas. Although stereotactic radiosurgery (SRS) is widely used for BMs, only a few papers have reported on SRS for sarcoma metastasizing to the brain. The purpose of this study was to evaluate the safety and effectiveness of SRS for sarcoma BM.The authors retrospectively reviewed the clinical and radiological outcomes of patients with BM secondary to histopathologically confirmed sarcoma treated with SRS, either as primary treatment or as adjuvant therapy after surgery, at their institution between January 2005 and September 2022. They also compared the outcomes of patients with hemorrhagic lesions and of those without.Twenty-three patients (9 females) with 150 BMs secondary to sarcoma were treated with CyberKnife SRS. Median age at the time of treatment was 48.22 years (range 4-76 years). The most common primary tumor sites were the heart, lungs, uterus, upper extremities, chest wall, and head and neck. The median Karnofsky Performance Status on presentation was 73.28 (range 40-100). Eight patients underwent SRS as a primary treatment and 15 as adjuvant therapy to the resection cavity. The median tumor volume was 24.1 cm3 (range 0.1-150.3 cm3), the median marginal dose was 24 Gy (range 18-30 Gy) delivered in a median of 1 fraction (range 1-5) to a median isodose line of 76%. The median follow-up was 8 months (range 2-40 months). Median progression-free survival and overall survival were 5.3 months (range 0.4-32 months) and 8.2 months (range 0.1-40), respectively. The 3-, 6-, and 12-month local tumor control (LTC) rates for all lesions were respectively 78%, 52%, and 30%. There were no radiation-induced adverse effects. LTC at the 3-, 6-, and 12-month follow-ups was better in patients without hemorrhagic lesions (100%, 70%, and 40%, respectively) than in those with hemorrhagic lesions (68%, 38%, and 23%, respectively).SRS, both as a primary treatment and as adjuvant therapy to the resection cavity after surgery, is a safe and relatively effective treatment modality for sarcoma BMs. Nonhemorrhagic lesions show better LTC than hemorrhagic lesions. Larger studies aiming to validate these results are encouraged.

  View details for DOI 10.3171/2023.5.FOCUS23168

  View details for PubMedID 37527671

• CyberKnife radiosurgery for treatment of residual or recurrent Grade 1 choroid plexus papilloma: A single institution experience. World neurosurgery Zhang, M., Park, D. J., Marianayagam, N. J., Yener, U., Soltys, S. G., Pollom, E., Chang, S. D., Meola, A. 2023

  Abstract

  Choroid plexus papillomas (CPP) are rare intraventricular brain tumors derived from the epithelium of the choroid plexus. Gross total resection has traditionally been considered curative, but residual tumor or recurrence remains possible. SRS has become particularly more important strategy for subtotally resectied and recurrent tumors. The evidence-based rationale of SRS treatment for residual or recurrent CPP in adult patients is still lacking due to its rarity.We retrospectively reviewed histopathologically confirmed cases of residual or recurrent CPP treated with SRS at our institute in the adult population between 2005 and 2022. Three patients, with five lesions, were identified with a median age of 63 years. Patients presented initially with hydrocephalus-related symptoms, although ventriculomegaly was noted only in one patient radiographically. The tumor locations were most common in 4th ventricle or along foramen of Luschka. Treatment was delivered in a single fraction in 4 lesions and in 3 fractions in 1 patient. The median follow-up was 26 months.The local tumor control rate for the lesions was 80%. One patient developed a new lesion outside the SRS field, and one lesion developed progression without need for subsequent treatment. There were no significant shrinkage of the lesions radiographically. None of the patients revealed radiation-related adverse events. No patients required surgical management after SRS treatment at our institution. Based on the literature review, our case series was the second largest retrospective series from a single institution on SRS for recurrent or residual CPP.SRS for patients with recurrent or residual CPP was a safe and effective treatment modality in this case series. Larger studies are encouraged to validate the role of SRS in the treatment of recurrent or residual CPP.

  View details for DOI 10.1016/j.wneu.2023.07.003

  View details for PubMedID 37423336

• Cyberknife Radiosurgery for Synovial Sarcoma Metastasizing to the Spine: Illustrative Case Reports. Cureus Zamarud, A., Park, D. J., Haider, G., Chang, S. D., Meola, A. 2023; 15 (4): e37087

  Abstract

  Synovial sarcoma (SS) is a rare and aggressive type of soft tissue sarcoma that commonly affects young adults. Metastasis in the spine is a rare complication, and the management of these lesions is challenging. Radiosurgery is an increasingly popular treatment option for spinal metastasis due to its ability to deliver high doses of radiation to the target volume with minimal exposure to surrounding healthy tissues. In this paper, we present two cases of SS with spinal metastasis that were treated with CyberKnife radiosurgery (CKRS). The first case was a 52-year-old female with a history of multiple thoracotomies and lobectomies for lung metastases, who was diagnosed with T6-T8 and T4 spinal metastasis. The second case was a 53-year-old female with Down syndrome, who was diagnosed with T12-L1 spinal metastasis. Both patients experienced an improvement in their symptoms following CKRS treatment and showed stable or decreasing lesion sizes on follow-up imaging. The progression-free survival (PFS) in the first case was 37 months and overall survival (OS) was 79 months. In the second case, the PFS was 12 months and OS was 18 months. These cases highlight the potential benefits of CKRS as a treatment option for SS with spinal metastasis and support its use in the management of this challenging condition.

  View details for DOI 10.7759/cureus.37087

  View details for PubMedID 37168194

  View details for PubMedCentralID PMC10166278

• Using 68Ga-DOTATATE PET for Postoperative Radiosurgery and Radiotherapy Planning in Patients With Meningioma: A Case Series. Neurosurgery Hintz, E. B., Park, D. J., Ma, D., Viswanatha, S. D., Rini, J. N., Schulder, M., Goenka, A. 2023

  Abstract

  For patients with either an incompletely resected meningioma or recurrence after surgery, stereotactic radiosurgery is frequently used. MRI is typically used for stereotactic radiosurgery targeting, but differentiating tumor growth from postoperative change can be challenging. 68Ga-DOTATATE, a positron emission tomography (PET) radiotracer targeting the somatostatin receptor type 2, has been shown to be a reliable meningioma biomarker.To evaluate the impact of 68Ga-DOTATATE on treatment planning in patients who had previously undergone meningioma resection.We present a consecutive case series of 12 patients with pathology-proven meningioma who received a 68Ga-DOTATATE PET between April 2019 and April 2021. Treatment planning was performed first using MRI. DOTATATE-PET images were then used to assess accurate tumor identification.Ten patients had WHO Grade 2 meningioma, and 2 patients had Grade 1 tumor. Eight patients had recurrent meningiomas, and 4 patients had newly diagnosed disease. Overall, 68Ga-DOTATATE PET scans altered previously formulated treatment plans in 5 of 12 patients. In addition, 9 of 12 patients had disease foci not appreciated on MRI.In this series, incorporating 68Ga-DOTATATE PET imaging had clinical utility for most patients in whom it was used. It proved particularly adept in demonstrating intraosseous meningiomas, differentiating recurrence from postoperative changes, and identifying subcentimeter disease foci. It is an imaging modality that our center will continue to use as a means of improving postoperative treatment plans after the surgical resection of meningiomas.

  View details for DOI 10.1227/neu.0000000000002377

  View details for PubMedID 36722951

• Stereotactic radiosurgery for localized cranial Langerhans cell histiocytosis: A single institution experience and review of literature. World neurosurgery Park, D. J., Marianayagam, N. J., Yener, U., Wang, L., Soltys, S. G., Pollom, E., Chang, S. D., Meola, A. 2023

  Abstract

  Langerhans cell histiocytosis (LCH) is a rare idiopathic disease characterized by the clonal proliferation of Langerhans histiocytes in various parts of the body and capable of leading to organ damage and tumor formation. Reports of cranial LCH in the adult population are extremely rare. Although surgery remains the preferred option for localized LCH lesions, the role of stereotactic radiosurgery (SRS) is emerging as well.To retrospectively review a rare case series to determine the safety and effectiveness of SRS for patients with localized cranial LCH.We retrospectively reviewed histopathologically confirmed cases of localized cranial LCH treated with SRS at our institute in the adult population between January 2005 and September 2022. Five patients were identified with a median age of 34 years (19-54 years). The tumor location was in the pituitary stalk in three patients, the orbit in one patient, and the parietal skull in one patient. The median target volume was 2.8 cc (range: 0.37-6.11). Treatment was delivered in a single fraction in 4 patients (median margin dose of 8 Gy (range: 7-10 Gy) and in 3 fractions (22.5 Gy) in 1 patient. The median follow-up was 12 years (range: 4-17). None of the patients required craniotomy for tumor debulking before or after SRS.The local tumor control rate for the lesions was 100%. All three patients with LCH in the pituitary stalk had diabetes insipidus at the initial presentation and developed panhypopituitarism after SRS. Diabetes insipidus was not improved after SRS. The other two patients presented no adverse radiation effects. Based on the literature review, our case series was the largest retrospective series on SRS for localized cranial LCH, with the longest median follow-up.SRS for patients with localized cranial LCH was a safe and effective treatment modality in this case series. Larger studies are encouraged to validate the role of SRS in the treatment of localized cranial LCH.

  View details for DOI 10.1016/j.wneu.2023.01.053

  View details for PubMedID 36681322

• Cyberknife Radiosurgery for Synovial Sarcoma Metastasizing to the Spine Cureus Zamarud, A., Park, D. J., Haider, G., Chang, S. D., Meola, A. 2023; 15 (4)

  View details for DOI 10.7759/cureus.37087

• Papillary craniopharyngioma in a patient following resection of nonfunctioning pituitary adenoma: illustrative case. Journal of neurosurgery. Case lessons Park, D. J., Mishra, A., Golub, D., Li, J. Y., Black, K. S., Schulder, M. 2021; 1 (2): CASE2063

  Abstract

  Although craniopharyngioma and pituitary adenoma are common tumors of the sellar or suprasellar region, the development of papillary craniopharyngioma in the same sellar region after resection of a nonfunctioning pituitary adenoma has not been reported.Here the authors report the first case of craniopharyngioma that developed long after resection of a pituitary adenoma. A 66-year-old male patient underwent endoscopic transsphenoidal resection for a large sellar mass, which histopathologically confirmed the diagnosis of a pituitary adenoma. He had an excellent recovery after surgery. For several years, he had no clinical or imaging evidence of tumor recurrence and then was lost to follow-up. Seven years after the initial surgery, the patient returned with a one-month history of visual field defects, and imaging confirmed a heterogeneous, cystic suprasellar mass. Endoscopic transsphenoidal resection of the tumor was performed, and histological examination showed it to be a papillary craniopharyngioma.Neurosurgeons should be aware that after pituitary adenoma resection, a recurrent mass could be a craniopharyngioma, with implications for very different management recommendations.

  View details for DOI 10.3171/CASE2063

  View details for PubMedID 35854932

  View details for PubMedCentralID PMC9241323

• Cystic Brain Metastases Managed With Reservoir Placement and Stereotactic Radiosurgery Neurosurgery Open Park, D. J., Unadkat, P., Goenka, A., Schulder, M. 2021; 2 (4): 1-10

  View details for DOI 10.1093/neuopn/okab028

• Stearoyl CoA Desaturase Is Essential for Regulation of Endoplasmic Reticulum Homeostasis and Tumor Growth in Glioblastoma Cancer Stem Cells STEM CELL REPORTS Pinkham, K., Park, D., Hashemiaghdam, A., Kirov, A. B., Adam, I., Rosiak, K., da Hora, C. C., Teng, J., Cheah, P., Carvalho, L., Ganguli-Indra, G., Kelly, A., Indra, A. K., Badr, C. E. 2019; 12 (4): 712-727

  Abstract

  Inherent plasticity and various survival cues allow glioblastoma stem-like cells (GSCs) to survive and proliferate under intrinsic and extrinsic stress conditions. Here, we report that GSCs depend on the adaptive activation of ER stress and subsequent activation of lipogenesis and particularly stearoyl CoA desaturase (SCD1), which promotes ER homeostasis, cytoprotection, and tumor initiation. Pharmacological targeting of SCD1 is particularly toxic due to the accumulation of saturated fatty acids, which exacerbates ER stress, triggers apoptosis, impairs RAD51-mediated DNA repair, and achieves a remarkable therapeutic outcome with 25%-100% cure rate in xenograft mouse models. Mechanistically, divergent cell fates under varying levels of ER stress are primarily controlled by the ER sensor IRE1, which either promotes SCD1 transcriptional activation or converts to apoptotic signaling when SCD1 activity is impaired. Taken together, the dependence of GSCs on fatty acid desaturation presents an exploitable vulnerability to target glioblastoma.

  View details for DOI 10.1016/j.stemcr.2019.02.012

  View details for Web of Science ID 000463364400007

  View details for PubMedID 30930246

  View details for PubMedCentralID PMC6450460

• Virus vector-mediated genetic modification of brain tumor stromal cells after intravenous delivery JOURNAL OF NEURO-ONCOLOGY Volak, A., LeRoy, S. G., Natasan, J., Park, D. J., Cheah, P., Maus, A., Fitzpatrick, Z., Hudry, E., Pinkham, K., Gandhi, S., Hyman, B. T., Mu, D., Guhasarkar, D., Stemmer-Rachamimov, A. O., Sena-Esteves, M., Badr, C. E., Maguire, C. A. 2018; 139 (2): 293-305

  Abstract

  The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively. Delivery of transgenes encoding secreted, anti-tumor proteins to tumor stromal cells may provide a more stable and localized reservoir of therapy as they are more differentiated than fast-dividing tumor cells. Reactive astrocytes and tumor-associated macrophage/microglia (TAMs) are stromal cells that comprise a large portion of the tumor mass and are associated with tumorigenesis. In mouse models of GBM, we used IV delivery of exosome-associated AAV vectors driving green fluorescent protein expression by specific promoters (NF-κB-responsive promoter and a truncated glial fibrillary acidic protein promoter), to obtain targeted transduction of TAMs and reactive astrocytes, respectively, while avoiding transgene expression in the periphery. We used our approach to express the potent, yet toxic anti-tumor cytokine, interferon beta, in tumor stroma of a mouse model of GBM, and achieved a modest, yet significant enhancement in survival compared to controls. Noninvasive genetic modification of tumor microenvironment represents a promising approach for therapy against cancers. Additionally, the vectors described here may facilitate basic research in the study of tumor stromal cells in situ.

  View details for DOI 10.1007/s11060-018-2889-2

  View details for Web of Science ID 000441544800007

  View details for PubMedID 29767307

  View details for PubMedCentralID PMC6454875

• Acute Paraplegia as a Result of Hemorrhagic Spinal Ependymoma Masked by Spinal Anesthesia: Case Report and Review of Literature. Brain tumor research and treatment Lee, S. H., Park, D. J., Jeun, S. S. 2016; 4 (1): 30-4

  Abstract

  Ependymomas are the most common intramedullary spinal cord tumors in adults. Although a hemorrhage within spinal ependymoma on imaging studies is not uncommon, it has rarely been reported to bea cause of acute neurological deficit. In the present report, we describe a case of a 24-year-old female patient who developed acute paraplegia as a result of hemorrhagic spinal ependymoma immediately after a cesarean delivery under spinal regional anesthesia. We review the literature of hemorrhagic spinal ependymomas presenting with acute neurological deficit and discuss the most appropriate treatment for a good neurological recovery.

  View details for DOI 10.14791/btrt.2016.4.1.30

  View details for PubMedID 27195260

  View details for PubMedCentralID PMC4868815

• Remote Postoperative Epidural Hematoma after Brain Tumor Surgery. Brain tumor research and treatment Chung, H. J., Park, J. S., Park, J. H., Jeun, S. S. 2015; 3 (2): 132-7

  Abstract

  A postoperative epidural hematoma (EDH) is a serious and embarrassing complication, which usually occurs at the site of operation after intracranial surgery. However, remote EDH is relatively rare. We report three cases of remote EDH after brain tumor surgery. All three cases seemed to have different causes of remote postoperative EDH; however, all patients were managed promptly and showed excellent outcomes. Although the exact mechanism of remote postoperative EDH is unknown, surgeons should be cautious of the speed of lowering intracranial pressure and implement basic procedures to prevent this hazardous complication of brain tumor surgery.

  View details for DOI 10.14791/btrt.2015.3.2.132

  View details for PubMedID 26605271

  View details for PubMedCentralID PMC4656891

• Efficacy of Procarbazine, Lomustine, and Vincristine Chemotherapy for Recurrent Primary Central Nervous System Lymphomas. Brain tumor research and treatment Kim, Y. J., Choe, J. H., Park, J. H., Hong, Y. K. 2015; 3 (2): 75-80

  Abstract

  Optimal treatment for recurrent primary central nervous system lymphomas (PCNSLs) has not been defined yet and there is no general consensus about the salvage chemotherapy after high-dose methotrexate (HD-MTX)-based chemotherapy. The purpose of the present study was to evaluate the efficacy and safety of procarbazine, lomustine, and vincristine (PCV) chemotherapy for recurrent PCNSLs.We reviewed eight immunocompetent patients (five males/three females, mean age: 56 years) who received salvage PCV chemotherapy (procarbazine 60 mg/m(2), days 8 through 21: CCNU 110 mg/m(2), day 1: vincristine 2 mg, days 8 and 28) for recurrent PCNSL and two patients switched to PCV chemotherapy due to severe adverse effects of HD-MTX chemotherapy. Radiologic responses, survival, and adverse effects were analyzed.Of the eight recurrent PCNSLs, three patients (37.5%) showed radiologic complete response, one patient (12.5%) showed partial response, and four patients (50%) showed progressive disease after PCV chemotherapy. Median progression free survival (PFS) from the first administration of PCV to relapse or last follow-up was 7 months (range 5-32 months) and median overall survival was 8 months (range 2-41 months). The two patients who switched to PCV chemotherapy showed PFS of 9 and 5 months from the beginning of PCV to relapse. The common side effects were thrombocytopenia, neutropenia, and peripheral neuropathy. There were 4 grade III or IV myelo-suppression, but no fatal complications, including severe hemorrhage or infection, were observed.Salvage PCV chemotherapy has a moderate anti-lymphoma activity for recurrent PCNSLs after the HD-MTX-based chemotherapy with tolerable toxicity.

  View details for DOI 10.14791/btrt.2015.3.2.75

  View details for PubMedID 26605261

  View details for PubMedCentralID PMC4656899

• Treatment Strategy of Intracranial Hemangiopericytoma. Brain tumor research and treatment Kim, Y. J., Park, J. H., Kim, Y. I., Jeun, S. S. 2015; 3 (2): 68-74

  Abstract

  Recent studies suggest aggressive management combining a grossly total resection (GTR) with adjuvant radiotherapy (RT) as a treatment of choice for intracranial hemangiopericytoma (HPC). However, in these papers, the definitions of complete or GTR are equivocal. In the present study, we reviewed the relevant cases from our experience focused on the clinical efficacy of surgical grading of resection, and analyzed the optimal treatment strategies as well.From January 1995 through December 2014, 17 patients treated for intracranial HPC were included in this study. We analyzed clinical presentation, radiologic appearance, pathologic diagnosis, extent of resection, and follow-up outcomes.A total of 26 operations were performed including 9 recurrent intracranial HPCs. Every tumor was single and had no evidence of metastasis. Most common area of tumor was parasagittal (8 patients, 47.1%), which is adjoined to superior sagittal sinus. For the initial operation, GTR was performed in 16 cases (61.5%), partial resection (PR) in 8 cases (30.8%), and an endoscopic biopsy in 2 patients (7.7%). In Simpson grading system, grade 1 was done in 2 patients (7.7%), grade 2 in 11 patients (42.3%) and grade 3 in 3 patients (11.5%). Postoperative RT was delivered in 16 patients (94.1%) regardless of the extent of resection. The median 57.57 Gy (range, 50-60 Gy) was delivered in median 33 fractions (range, 30-40). The extent of resection (conventional classification and Simpson grading system) and adjuvant RT were significantly associated with recurrence-free survival.Surgical resection of intracranial HPC, in an attempt to reach Simpson grade 1 removal, is necessary for better outcome. Adjuvant RT should be done as recommended before, to prevent recurrence, regardless of surgical resection and pathological diagnosis.

  View details for DOI 10.14791/btrt.2015.3.2.68

  View details for PubMedID 26605260

  View details for PubMedCentralID PMC4656898

• Modified Graded Repair of Cerebrospinal Fluid Leaks in Endoscopic Endonasal Transsphenoidal Surgery. Journal of Korean Neurosurgical Society Park, J. H., Choi, J. H., Kim, Y. I., Kim, S. W., Hong, Y. K. 2015; 58 (1): 36-42

  Abstract

  Complete sellar floor reconstruction is critical to avoid postoperative cerebrospinal fluid (CSF) leakage during transsphenoidal surgery. Recently, the pedicled nasoseptal flap has undergone many modifications and eventually proved to be valuable and efficient. However, using these nasoseptal flaps in all patients who undergo transsphenoidal surgery, including those who had none or only minor CSF leakage, appears to be overly invasive and time-consuming.Patients undergoing endoscopic endonasal transsphenoidal tumor surgery within a 5 year-period were reviewed. Since 2009, we classified the intraoperative CSF leakage into grades from 0 to 3. Sellar floor reconstruction was tailored to each leak grade. We did not use any tissue grafts such as abdominal fat and did not include any procedures of CSF diversions such as lumbar drainage.Among 200 cases in 188 patients (147 pituitary adenoma and 41 other pathologies), intraoperative CSF leakage was observed in 27.4% of 197 cases : 14.7% Grade 1, 4.6% Grade 2a, 3.0% Grade 2b, and 5.1% Grade 3. Postoperative CSF leakage was observed in none of the cases. Septal bone buttress was used for Grade 1 to 3 leakages instead of any other foreign materials. Pedicled nasoseptal flap was used for Grades 2b and 3 leakages. Unused septal bones and nasoseptal flaps were repositioned.Modified classification of intraoperative CSF leaks and tailored repair technique in a multilayered fashion using an en-bloc harvested septal bone and vascularized nasoseptal flaps is an effective and reliable method for the prevention of postoperative CSF leaks.

  View details for DOI 10.3340/jkns.2015.58.1.36

  View details for PubMedID 26279811

  View details for PubMedCentralID PMC4534737

• Combination Therapy for Gliomas Using Temozolomide and Interferon-Beta Secreting Human Bone Marrow Derived Mesenchymal Stem Cells. Journal of Korean Neurosurgical Society Park, J. H., Ryu, C. H., Kim, M. J., Jeun, S. S. 2015; 57 (5): 323-8

  Abstract

  Malignant gliomas are the most common primary tumors of the central nervous system and the prognosis of patients with gliomas is poor. The combination of interferon-bata (IFN-β) and temozolomide (TMZ) has shown significant additive antitumor effects in human glioma xenograft models. Considering that the poor survival of patients with human malignant gliomas relates partly to the inability to deliver therapeutic agents to the tumor, the tropism of human bone marrow-derived mesenchymal stem cells (MSC) for malignant gliomas can be exploited to therapeutic advantages. We investigated the combination effects of TMZ and MSCs that secrete IFN-β on gliomas.We engineered human MSCs to secret mouse IFN-β (MSC-IFN-β) via adenoviral transduction and confirmed their secretory capacity using enzyme-linked immunosorbent assays. In vitro and in vivo experiments were performed to determine the effects of the combined TMZ and MSC-IFN-β treatment.In vitro, the combination of MSC-IFN-β and TMZ showed significantly enhanced antitumor effects in GL26 mouse glioma cells. In vivo, the combined MSC-IFN-β and TMZ therapy significantly reduced the tumor size and improved the survival rates compared to each treatment alone.These results suggest that MSCs can be used as an effective delivery vehicle so that the combination of MSC-IFN-β and TMZ could be considered as a new option for the treatment of malignant gliomas.

  View details for DOI 10.3340/jkns.2015.57.5.323

  View details for PubMedID 26113958

  View details for PubMedCentralID PMC4479712

• Thrombosed large middle cerebral artery aneurysm mimicking an intra-axial brain tumor: case report and review of literature. Brain tumor research and treatment Kim, Y. J., Jeun, S. S., Park, J. H. 2015; 3 (1): 39-43

  Abstract

  This case report presents a fully thrombosed large aneurysm of middle cerebral artery mimicking an intra-axial brain tumor in a 54-year-old male patient. A small mass like lesion was found incidentally in right frontal area. Brain magnetic resonance image showed dark signal intensity on T2-weighted images and peripheral high signal intensity on T1-weighted images with peripheral rim enhancement. We considered intra-axial tumors such as glioma or metastatic tumor as a differential diagnosis. The lesion was approached transcortically, and intraoperatively, the lesion was found to be a large thrombosed aneurysm originating from the lateral lenticulostriate artery of right middle cerebral artery. One vascular clip was applied at the parent artery, and the thrombosed aneurysm was totally removed. There have been many reports of other intracranial lesions wrongly diagnosed as intracranial neoplasms. And thrombosed aneurysms mimicking intracranial neoplasm have been reported in 4 cases previously. According to those case reports, there were no efficient imaging tools to differentiate between these thrombosed aneurysms and intracranial neoplasms. We reviewed those reports and considered about the efficient method to diagnosed accurately before surgery. To sum up, when a patient presents with an intracranial lesion lying on the course of major or distal cerebral arteries, the surgeon should have thrombosed aneurysm in mind as one of the differential diagnosis and be prepared when surgically treating such lesions.

  View details for DOI 10.14791/btrt.2015.3.1.39

  View details for PubMedID 25977906

  View details for PubMedCentralID PMC4426276

• Primary malignant melanoma in the pineal region. Journal of Korean Neurosurgical Society Park, J. H., Hong, Y. K. 2014; 56 (6): 504-8

  Abstract

  A 59-year-old male patient had 5-month history of gait disturbance and memory impairment. His initial brain computed tomography scan showed 3.5×2.8 cm sized mass with high density in the pineal region. The tumor was hypointense on T2 weighted magnetic resonance images and hyperintense on T1 weighted magnetic resonance images with heterogenous enhancement of central portion. The tumor was totally removed via the occipital transtentorial approach. Black mass was observed in the operation field, and after surgery, histopathological examination confirmed the diagnosis of malignant melanoma. Whole spine magnetic resonance images and whole body 18-fluoro-deoxyglucose positron emission tomography could not demonstrate the primary site of this melanoma. Scrupulous physical examination of his skin and mucosa was done and dark pigmented lesion on his left leg was found, but additional studies including magnetic resonance images and skin biopsy showed negative finding. As a result, final diagnosis of primary pineal malignant melanoma was made. He underwent treatment with the whole brain radiotherapy and extended local boost irradiation without chemotherapy. His preoperative symptoms were disappeared, and no other specific neurological deficits were founded. His follow-up image studies showed no recurrence or distant metastasis until 26 weeks after surgery. Primary pineal malignant melanomas are extremely rare intracranial tumors, and only 17 cases have been reported since 1899. The most recent case report showed favorable outcome by subtotal tumor resection followed by whole brain and extended local irradiation without chemotherapy. Our case is another result to prove that total tumor resection with radiotherapy can be the current optimal treatment for primary malignant melanoma in the pineal region.

  View details for DOI 10.3340/jkns.2014.56.6.504

  View details for PubMedID 25628812

  View details for PubMedCentralID PMC4303728

• Disseminated Hemangioblastoma of the Central Nervous System without Von Hippel-Lindau Disease. Brain tumor research and treatment Chung, S. Y., Jeun, S. S., Park, J. H. 2014; 2 (2): 96-101

  Abstract

  Hemangioblastoma (HB) of the central nervous system may occur sporadically or in association with von Hippel-Lindau (VHL) disease. Disseminated HB means malignant spread of the original primary HB without local recurrence at surgically resected site. It has been rarely reported previously, and rarer especially without VHL gene mutation. We report a case of disseminated HB without VHL disease. A 59-year-old man underwent a surgery for total removal of a cerebellar HB. From five years after the surgery, multiple dissemination of HB was identified intracranially and he subsequently underwent cyberknife radiosurgery. The lesions got smaller temporarily, but they soon grew larger. Nine years after the initial surgery for cerebellar HB, he showed severe back pain. His magnetic resonance image of spine revealed intradural extramedullary mass at T6-7 level. Complete surgical removal of the mass was performed and the pathological diagnosis was identical to the previous one. He had no evidence of VHL disease. And there was no recurrence of the tumor at the site of the original operation. The exact mechanism of dissemination is unknown, but the surgeon should be cautious of tumor cell spillage during surgery and prudently consider the decision to perform ventriculo-peritoneal shunt. In addition, continuous follow-up for recurrence or dissemination is necessary for patients even who underwent complete removal of cerebellar HB.

  View details for DOI 10.14791/btrt.2014.2.2.96

  View details for PubMedID 25408933

  View details for PubMedCentralID PMC4231619

• An intracranial chondroma with intratumoral hemorrhage: a case report and review of the literature. Brain tumor research and treatment Park, J. H., Jeun, S. S. 2013; 1 (1): 42-4

  Abstract

  A 55-year-old female presented to the emergency room with a complaint of aphasia. Her initial brain computed tomography scan showed an intracranial hemorrhage in the left frontal area. After surgery, histopathological examination confirmed the diagnosis of a chondroma. Intradural chondroma is a rare, slow growing, benign intracranial neoplasm, but is even rarer in combination with an intratumoral hemorrhage. Chondromas are generally avascular cartilaginous lesions. Our case was thought to be caused by the rupture of abnormally weak vessels derived from the friable tumor. Intradural chondromas may be included in the differential diagnosis of intracranial tumors with acute hemorrhages.

  View details for DOI 10.14791/btrt.2013.1.1.42

  View details for PubMedID 24904889

  View details for PubMedCentralID PMC4027121

• Pain assessment in brain tumor patients after elective craniotomy. Brain tumor research and treatment Kim, Y. D., Park, J. H., Yang, S. H., Kim, I. S., Hong, J. T., Sung, J. H., Son, B. C., Lee, S. W. 2013; 1 (1): 24-7

  Abstract

  This study was performed to assess the postoperative pain of brain tumor patients who underwent elective craniotomy and to evaluate the factors associated with pain intensity.From January 2010 to December 2011, 47 patients with newly diagnosed brain tumors who underwent craniotomy were enrolled. The postoperative pain status was assessed daily until discharge using the visual analogue scale (VAS).The study participants comprised of 22 males and 25 females with ages ranging from 18-76 years (median age, 50 years). Patients were divided into two groups: the painful group included patients who had a VAS score of more than 3 during their hospital stay after the craniotomy, and the tolerable group included patients who had a VAS score of 1 to 3 during their hospital stay. There were no differences between the two groups in terms of age, sex, location of surgery, history of diabetes, hypertension and smoking, body mass index, and hospital stay. Univariate analysis revealed that operating time, length of wound, head fixation, and perioperative administration of opioid were not associated with the intensity of postoperative pain. Daily assessment of VAS revealed the two peaks of pain on the operation day and the 4th postoperative day. The intensity of pain during the ambulation period was higher than that during intensive care unit (ICU) stay.Pain following elective craniotomy for brain tumor removal is insufficiently managed, especially after discharge from the ICU. More attention needs to be paid to patients' pain throughout the hospital stay.

  View details for DOI 10.14791/btrt.2013.1.1.24

  View details for PubMedID 24904885

  View details for PubMedCentralID PMC4027119

• Critical use of balloon angioplasty after recanalization failure with retrievable stent in acute cerebral artery occlusion. Journal of Korean Neurosurgical Society Park, J. H., Park, S. K., Jang, K. S., Jang, D. K., Han, Y. M. 2013; 53 (2): 77-82

  Abstract

  Sudden major cerebral artery occlusion often resists recanalization with currently available techniques or can results in massive symptomatic intracranial hemorrhage (sICH) after thrombolytic therapy. The purpose of this study was to examine mechanical recanalization with a retrievable self-expanding stent and balloon in acute intracranial artery occlusions.Twenty-eight consecutive patients with acute intracranial artery occlusions were treated with a Solitaire retrievable stent. Balloon angioplasty was added if successful recanalization was not achieved after stent retrieval. The angiographic outcome was assessed by Thrombolysis in Cerebral Infarction (TICI) and the clinical outcomes were assessed by the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS).At baseline, mean age was 69.4 years and mean initial NIHSS score was 12.5. A recanalization to TICI 2 or 3 was achieved in 24 patients (85%) after stent retrieval. Successful recanalization was achieved after additional balloon angioplasty in 4 patients. At 90-day follow-up, 24 patients (85%) had a NIHSS improvement of ≥4 and 17 patients (60%) had a good outcome (mRS ≤2). Although there was sICH, there was one death associated with the procedure.Mechanical thromboembolectomy with a retrievable stent followed by additional balloon angioplasty is a safe and effective first-line therapy for acute intracranial artery occlusions especially in case of unsuccessful recanalization after stent thrombectomy.

  View details for DOI 10.3340/jkns.2013.53.2.77

  View details for PubMedID 23560170

  View details for PubMedCentralID PMC3611063