Paul Martin Harary

All Publications

• Management of neurovascular compromise of the vestibulocochlear nerve: A systematic review and illustrative case series WORLD NEUROSURGERY-X Ong, V., Harary, P. M., Persad, A. R., Hori, Y. S., Emrich, S. C., Ustrzynski, L., Tayag, A., Park, D. J., Chang, S. D. 2026; 29

  View details for DOI 10.1016/j.wnsx.2025.100557

  View details for Web of Science ID 001633495400002

• Thyroid carcinoma brain metastases: radiosurgery outcomes and genomic characterization across histologic subtypes. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Izhar, M., Kattaa, A. H., Harary, P. M., Hori, Y. S., Lam, F. C., Kalra, N., Zagzoog, N., Tayag, A., Ustrzynski, L., Emrich, S. C., Gephart, M. H., Park, D. J., Chang, S. D. 2026; 152: 112184

  Abstract

  Thyroid carcinoma brain metastases (TCBM) are rare and bear a poor prognosis. While stereotactic radiosurgery (SRS) has been used as a minimally invasive treatment option for TCBM, data on clinical outcomes remain limited. Here, we assess local control, overall survival, and adverse effects of SRS for TCBM patients. In addition, we perform an exploratory analysis of genetic variants across histologic subtypes of thyroid cancer with brain involvement.We retrospectively analyzed 17 patients with thyroid carcinoma who underwent SRS for a total of 65 brain metastases. Demographic, clinical, tumor, and treatment characteristics were collected. Next-generation sequencing (NGS) was performed using a targeted sequencing panel. Survival outcomes were assessed using Kaplan-Meier (KM) analysis. Univariate and multivariate Cox proportional hazards models were performed to identify predictors of local tumor progression.The cohort consisted of 10 males (58.8%) and 7 females (41.2%), with a mean age of 62 ± 14.2 years. Papillary thyroid carcinoma was the most common histology (70.6%). Median Karnofsky Performance Status was 80 (IQR, 70-90). All lesions were treated with SRS, with a median target volume of 0.11 cc and a median prescribed dose of 24 Gy. Cumulative local control rates were 87.5% at 6 months and 81.6% at 9, 12, and 24 months. DIF occurred in 4 of 17 patients (24%). KM-estimated DIC was 94% at 6 and 9 months, 86% at 12 months, and 54% at 24 months. Overall survival rates were 88.2% at 6 months, 82.4% at 9 months, 76.5% at 12 months, and 55.6% at 24 months. Median overall survival was 33 months (95% CI, 12.6-53.4). Genetic testing suggested variations in molecular profiles across the primary histologic subtypes. Radiation necrosis occurred in 5 of 65 lesions (7.7%), and seizures were reported in 2 patients (11.8%).SRS provides durable local control with acceptable toxicity in patients with TCBM. Despite the small cohort size, these findings support SRS as an effective and safe treatment modality. Larger, prospective studies are warranted to better define prognostic factors and optimize patient selection.

  View details for DOI 10.1016/j.jocn.2026.112184

  View details for PubMedID 42424981

• Laser interstitial thermal therapy (LITT) for brain metastases: a systematic review and pooled analysis of Efficacy/Safety and the role of combination treatments. Journal of neuro-oncology Mizutani, Y., Hori, Y. S., Kattaa, A. H., Harary, P. M., Lam, F. C., Kalra, N., Zagzoog, N., Tayag, A., Ustrzynski, L., Emrich, S. C., Park, D. J., Chang, S. D. 2026; 178 (2)

  Abstract

  Laser interstitial thermal therapy (LITT) has been used for brain metastases (BM), particularly for recurrent lesions and radiation necrosis after stereotactic radiosurgery (SRS). As SRS is increasingly used, differentiating tumor recurrence from radiation necrosis has become a frequent clinical problem. Recently, LITT has also been combined with other treatments to improve outcomes. However, prior reviews have primarily focused on LITT monotherapy and have provided limited evaluation of emerging multimodal strategies. We aim to summarize the current literature on LITT for BM, with particular attention to local control, safety, factors associated with outcomes, and the potential role of combination treatment strategies.PubMed, Scopus, and Web of Science were searched following PRISMA guidelines. We included studies reporting local control outcomes following LITT for BM or radiation necrosis secondary to previously treated BM. We used a combination of the following terms: ("laser interstitial thermal therapy" OR "LITT" OR "laser ablation") AND ("brain" OR "cerebral" OR "intracranial") AND ("metastases" OR "metastasis"). Graphical data were extracted using WebPlotDigitizer. A proportional meta-analysis was conducted to estimate pooled LTC rates at 6 and 12 months following treatment.A total of 254 studies were identified after duplicate removal, of which 30 met the inclusion criteria. These included 26 studies on LITT monotherapy and 4 on combination therapies, comprising 972 patients. Median age ranged from 51 to 69 years and median tumor volume from 2.2 to 8.5 cm. SRS was the most common prior treatment. Among patients treated with LITT monotherapy, pooled 6- and 12-month LTC rates were 74.4% and 67.9%, respectively. In subgroup analyses, corresponding rates were 74.0% and 67.9% for brain tumor metastases, and 76.6% and 65.7% for radiation necrosis. Studies of combination therapy reported local control rates of 76% for LITT+SRT (stereotactic radiotherapy), 94.7% for LITT+ICB (immune checkpoint blockade), and 100% at 12 months in both studies for LITT+cSRS (consolidation SRS). Transient neurological deficits were the most common adverse events, whereas permanent deficits were less frequent and procedure-related complications were reported in 20 patients. Significant predictive factors for better local control included greater extent of ablation, smaller pre-treatment tumor volume, pathology consistent with radiation necrosis and post-LITT chemotherapy.Current evidence suggests that LITT may provide favorable local control with an acceptable safety profile in selected patients, and combination approaches may further improve outcomes. However, the available evidence remains largely retrospective and heterogeneous, and further prospective studies are needed to better define the role of LITT and combination treatment strategies.

  View details for DOI 10.1007/s11060-026-05645-w

  View details for PubMedID 42265512

• Outcome of CyberKnife stereotactic radiosurgery for the brain metastases in patients with Li Fraumeni syndrome. Journal of neuro-oncology Izhar, M., Hori, Y. S., Kattaa, A. H., Harary, P. M., Lam, F. C., Kalra, N., Zagzoog, N., Tayag, A., Ustrzynski, L., Emrich, S. C., Park, D. J., Chang, S. D. 2026; 178 (1)

  Abstract

  Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 mutations and an increased risk of radiation-induced malignancies, posing significant challenges in the management of brain metastases (BM). Data regarding the safety and efficacy of stereotactic radiosurgery (SRS) for BM in this population remain limited.We performed a retrospective analysis of patients with LFS who underwent SRS for BM at our institution. Patient-level, lesion-level, and treatment-related data were collected. Outcomes assessed included local tumor control (LTC), overall survival (OS), distant progression-free survival (DPFS), radiographic response, and treatment-related adverse events.A total of 5 patients with 16 BM lesions were treated with SRS. The median age at treatment was 49 years (range, 37-65). Lesions were typically small (median diameter 6.1 mm) and predominantly supratentorial (87.5%). Most lesions (93.7%) were treated with single-fraction SRS with a median prescribed dose of 24 Gy. LTC was 100% at 3 months, 6 months, and the last follow-up. Median OS and DPFS were 11.03 months (95% CI, 9.53-12.54) and 7.5 months (95% CI, 7.3-7.7), with all deaths attributable to systemic disease rather than neurological causes. Importantly, no cases of radiation necrosis or radiation-induced secondary malignancies were observed during a median follow-up of 45 weeks.SRS demonstrated a short-term favorable local control and safety profile for the treatment of BM in patients with LFS. Given the tendency for lesions to be small and multifocal, along with the need to minimize radiation exposure, SRS represents a rational, focal treatment approach in this high-risk population. However, longer follow-up and prospective studies are needed to better define long-term safety, particularly regarding the risk of radiation-induced malignancies.Not applicable.

  View details for DOI 10.1007/s11060-026-05610-7

  View details for PubMedID 42149268

  View details for PubMedCentralID 1858532

• Genetic and Immunohistochemical Profiling of Malignant Mesothelioma With Brain Metastasis: A Report of Two Cases. Cancer reports (Hoboken, N.J.) Harary, P. M., Hori, Y. S., Jain, R., Kattaa, A. H., Gephart, M. H., Gensheimer, M. F., Soltys, S. G., Park, D. J., Chang, S. D. 2026; 9 (5): e70571

  Abstract

  Brain metastasis (BM) occurs in < 3% of malignant mesothelioma (MM) cases and is associated with an aggressive disease course. While genomic profiling has provided insight into molecular alterations in MM, the characteristics of MM with brain involvement remain unexplored. Data are particularly limited for MM of pericardial origin, an exceedingly rare tumor which comprises < 1% of mesotheliomas.We describe the clinical course and genetic profiles of two patients with BM from MM, both of whom exhibited atypical presentations, including neurological symptoms, diagnosis at extremes of age for this condition, and absence of prior asbestos exposure. In Case 1, a 20-25-year-old male with pericardial MM presented for left arm shaking, with brain MRI at this time revealing 14 total lesions, 85.7% of which had vasogenic edema. He underwent whole-brain radiotherapy (WBRT), passing away 21.25 months following initial diagnosis. In Case 2, an 85-90-year-old male reported expressive aphasia and was found to have a large hemorrhagic frontotemporal lesion. He was subsequently diagnosed with pleural MM and received stereotactic radiosurgery (SRS) for management of BM, with a favorable treatment response on follow-up imaging. He succumbed to systemic progression 6 months after diagnosis of BM. Next-generation sequencing identified a missense mutation in RAD51C in Case 1, and NF2 splice-site and TP53 frameshift mutations in Case 2.To our knowledge, this represents the first reported genetic profiling of MM with BM. The TP53 frameshift mutation is unusual for MM, and its potential association with rapid disease progression warrants further investigation. Given the aggressive nature of MM, SRS may be preferable to WBRT due to its shorter treatment time and ease of combination with systemic regimens.

  View details for DOI 10.1002/cnr2.70571

  View details for PubMedID 42101078

• The impact of CHEK2 status on radiosurgical outcomes in breast cancer brain metastases. Neurosurgical review Harary, P. M., Hori, Y. S., Kattaa, A. H., Tan, S. K., Lam, F. C., Kalra, N., Zagzoog, N., Tayag, A., Ustrzynski, L., Emrich, S. C., Gibbs, I. C., Li, G., Kuno, A., Park, D. J., Chang, S. D. 2026; 49 (1)

  View details for DOI 10.1007/s10143-026-04272-3

  View details for PubMedID 41963546

  View details for PubMedCentralID 3698070

• Surgical resection versus stereotactic radiosurgery for succinate dehydrogenase-related hereditary head and neck paragangliomas. Journal of neuro-oncology Harary, P. M., Hori, Y. S., Lam, F. C., Abu-Reesh, D., Emrich, S. C., Tayag, A., Ustrzynski, L., Alyono, J., Holsinger, F. C., Dodd, R. L., Gibbs, I. C., Li, G., Park, D. J., Chang, S. D. 2026; 176 (2): 168

  View details for DOI 10.1007/s11060-025-05405-2

  View details for PubMedID 41533247

  View details for PubMedCentralID 1735225

• Radiosurgical management of pathology-proven low-grade glioma: a systematic review across the pre- and post-molecular classification era. Journal of neurosurgical sciences Mizutani, Y., Hori, Y. S., Harary, P. M., Annagiri, S., Jain, R., Liu, J., Izhar, M., Reesh, D. A., Lam, F. C., Emrich, S. C., Ustrzynski, L., Tayag, A., Park, D. J., Chang, S. D. 2025

  Abstract

  Low-grade gliomas (LGGs) are slow-growing heterogeneous tumors that remain challenging when complete resection is not feasible. While maximal safe resection remains standard, the evolving World Health Organization (WHO) classification emphasizing molecular characteristics has shifted perspectives on adjuvant therapies. In this context, the role of stereotactic radiosurgery (SRS) continues to be explored. This systematic review synthesizes literature on radiosurgical management of pathology-proven LGGs across pre- and post-molecular classification eras.A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Scopus, and Web of Science were searched in August 2024 for studies on pathology-proven LGGs treated with SRS. An additional search was performed to incorporate studies reporting molecular characteristics.Of the initially included eight studies, none reported molecular characteristics required by the 2021 World Health Organization classification, and an additional search identified one study reporting molecular characteristics, which was added to the review. Nine studies with 308 patients were included. Local control rates ranged from 66% to 94%. Several studies reported superior outcomes with surgery for recurrence, adjuvant rather than salvage SRS, and no prior radiotherapy. Adverse events were predominantly mild to moderate, including headache, dizziness, nausea, and transient neurological symptoms.SRS offers a non-invasive management option for selected LGGs with durable control and acceptable safety. Prognosis appears to be influenced by treatment history, including prior radiotherapy and surgical management. Lack of molecular stratification highlights the need for studies focused on IDH (isocitrate dehydrogenase)-mutant LGGs to clarify the role of SRS in the molecular era.

  View details for DOI 10.23736/S0390-5616.25.06656-1

  View details for PubMedID 41364089

• Enhancing radiation sensitivity in malignant brain tumors with chloroquine: a systematic review. Journal of neuro-oncology Harary, P. M., Hori, Y. S., Annagiri, S., Abe, K., Tatekoshi, Y., Hosoda, R., Saga, Y., Park, D. J., Kuno, A., Chang, S. D. 2025; 176 (1): 106

  Abstract

  Chloroquine (CQ) has been studied for over 50 years as a potential adjuvant to cancer therapy. However, clinical studies investigating CQ combined with radiotherapy for brain tumors have yielded conflicting results. We aimed to synthesize existing evidence on the safety and efficacy of adjuvant CQ with radiotherapy for treatment of high-grade gliomas (HGG) and brain metastases.We conducted a systematic review using the PubMed, Embase, Scopus, and Web of Science databases with no date restrictions. We included English-language clinical studies (n ≥ 5 patients) that evaluated the combination of CQ or its analogues with radiotherapy for HGG or brain metastases and reported overall survival (OS) outcomes. Pre-clinical studies and reviews were excluded.We identified 13 eligible studies with 789 patients. Across both HGG and brain metastases, the median CQ dose was 250 mg daily, with whole-brain radiotherapy as the most common radiotherapy modality. For HGG, 3 out of 8 controlled trials reported significant benefit from treatment, with median survival ranging from 7.9 to 36.6 months. By comparison, only a single study of brain metastases found significantly improved progression-free survival relative to control. The safety profile of adjuvant CQ was generally favorable, with mild adverse effects reported in both patient populations.For HGG, CQ combined with radiotherapy shows promise but modest, inconsistent survival benefits. For brain metastases, evidence is limited and less favorable, with no consistent benefit across tumor types or study designs. Adverse events are generally mild, though most studies used low CQ doses and long‑term safety remains uncertain.

  View details for DOI 10.1007/s11060-025-05362-w

  View details for PubMedID 41348255

  View details for PubMedCentralID 3403847

• Peripheral neural crest tumor brain metastases management: a single-institution retrospective study. Journal of neuro-oncology Kattaa, A. H., Persad, A. R., Hori, Y. S., Harary, P. M., Izhar, M., Ustrzynski, L., Emrich, S. C., Tayag, A., Hiniker, S. M., Park, D. J., Chang, S. D. 2025; 176 (1): 65

  View details for DOI 10.1007/s11060-025-05247-y

  View details for PubMedID 41182459

  View details for PubMedCentralID 3633592

• INTERIM ANALYSIS OF A PHASE IIA TRIAL OF LAT1-TARGETED QBS72S IN BREAST CANCER LEPTOMENINGEAL DISEASE Carlson-Clarke, B., Rout, S., Roy-O'reilly, M., Taiwo, R., Harary, P. M., Granucci, M., Chernikova, S. B., Trinh, T. T. H., Bertrand, S., Therkelsen, K., Han, S., Gu, B., Ringold, G., Holland, J., Weitzman, R., Nagpal, S., Gephart, M. OXFORD UNIV PRESS INC. 2025: v143

  View details for DOI 10.1093/neuonc/noaf201.0566

  View details for Web of Science ID 001612039100014

• LAT1 EXPRESSION SCALE AND ADAPTIVE DESIGN FOR A PHASE IIA TRIAL OF QBS72S IN BREAST CANCER BRAIN METASTASES Taiwo, R., Harary, P. M., Trinh, T. T. H., Granucci, M., Bertrand, S., Carlson-Clarke, B., Chernikova, S. B., Therkelsen, K., Arora, M., Melisko, M. E., Iv, M., Vogel, H., Han, S., Xie, C., Brain, S., Lee, V., Bharani, K. L., Nagpal, S., Gephart, M. OXFORD UNIV PRESS INC. 2025: v143-v144

  View details for DOI 10.1093/neuonc/noaf201.0568

  View details for Web of Science ID 001613298600005

• 'Time is brain': Enhancing stroke knowledge and emergency response readiness in seniors HEALTH EDUCATION JOURNAL Sadeghzadeh, S., Adu-Brimpong, J., Abikenari, M. A., Bhatia, A., Harary, P. M., Bhanot, P., Muller, R. K., Escalante, R., Schonfeld, E., Jain, B., Nageeb, G., Wu, A., Hsin, G. S., Vora, N., Dodd, R. L. 2025

  View details for DOI 10.1177/00178969251371488

  View details for Web of Science ID 001586652700001

• Optimizing patient positioning for exoscopic cranial surgery. Neurosurgical focus: Video Harary, P. M., Park, D. J., Chang, S. D., Schulder, M. 2025; 13 (2): V20

  View details for DOI 10.3171/2025.3.FOCVID2524

  View details for PubMedID 41113728

  View details for PubMedCentralID PMC12533504

• Stereotactic radiosurgery for brain metastases from non-uterine Leiomyosarcoma: A retrospective case series WORLD NEUROSURGERY-X Cardona, J. J., Hori, Y. S., Kattaa, A. H., Harary, P. M., Lam, F. C., Abu-Reesh, D., Ustrzynski, L., Emrich, S. C., Tayag, A., Hayden-Gephart, M., Park, D. J., Chang, S. D. 2025; 28

  View details for DOI 10.1016/j.wnsx.2025.100517

  View details for Web of Science ID 001572405400001

• Stereotactic radiosurgery for brain metastases from extra-renal clear cell carcinoma: A series of four patients and review of the literature. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Harary, P. M., Hori, Y. S., Kattaa, A. H., Lam, F. C., Abu-Reesh, D., Emrich, S. C., Tayag, A., Ustrzynski, L., Pollom, E. L., Park, D. J., Gephart, M. H., Chang, S. D. 2025; 141: 111602

  Abstract

  Clear cell carcinoma occurring outside of the kidney represents an aggressive histological subtype which is frequently resistant to standard chemotherapy. Brain metastases (BM) from extra-renal clear cell carcinoma (erCCC) are exceedingly rare, and the optimal treatment approach for this histology remains uncertain. To our knowledge, stereotactic radiosurgery (SRS) has not been specifically investigated for this patient population.We performed a retrospective review of patients with erCCC treated with SRS at our institution from 2003 to 2024, identifying 4 cases with a total of 13 BM. Additionally, we conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to summarize prior reports of erCCC BM. The Embase, PubMed/MEDLINE, Scopus, and Web of Science databases were queried for initial identification of records. Gray literature was additionally searched. Baseline patient characteristics, treatment modality, and treatment outcomes were extracted from reports which met inclusion criteria.The median age at initial erCCC diagnosis was 54 years, with an interval to BM ranging from 0 to 3 years. The median lesion diameter was 5.1 mm, with a median size reduction of 52.9 % at the 3-month follow-up. The local control rates were 100 %, 100 %, and 100 % at 6, 12, and 18 months, respectively. Radiation necrosis was detected in a single lesion on 18-month MRI. The mean overall survival (OS) was 23.8 months (SD: 14.5). Twenty items met the inclusion criteria for our review, 19 of which reported a single case of erCCC BM. The majority of erCCC cases were associated with the ovary, followed by those of unknown origin. Among articles reporting the stage of the primary erCCC, 64.3 % were early stage while the remaining 35.7 % were advanced stage. Surgical resection and whole-brain radiotherapy were the most common treatments, with a median OS of 7 months. Genetic characteristics were available for only 2 cases, which identified pathogenic mutations in PIK3CA (p.E545K) or BRCA2 (p.K3326*).Our case series indicates that SRS may be an effective management option for erCCC BM, demonstrating high local control rates and a favorable safety profile. Our systematic review underscores significant variability in treatment outcomes and geographical incidence of this condition, along with existing gaps in genetic characterization and neurosurgical outcomes. Given known differences in clinical behavior between erCCC and other subtypes from the same site of origin, histology-directed treatment strategies may support improved outcomes.

  View details for DOI 10.1016/j.jocn.2025.111602

  View details for PubMedID 40897159

• Adenoid cystic carcinoma brain metastases treated with stereotactic radiosurgery: A single institution retrospective cohort study and comprehensive literature review. Neurosurgical review Kattaa, A. H., Hori, Y. S., Harary, P. M., Akhavan-Sigari, A., Zamarud, A., Persad, A. R., Tayag, A., Ustrzynski, L., Emrich, S. C., Park, D. J., Chang, S. D. 2025; 48 (1): 618

  Abstract

  Adenoid cystic carcinoma (ACC) is a malignant neoplasm arising from the minor and major salivary glands that tend to spread by perivascular and perineural routes. Brain metastases (BM) secondary to ACC are extremely rare, and the standard management strategy has not been well reported due to the rarity. Notably, no previous study has specifically examined the efficacy of stereotactic radiosurgery (SRS) for BM from ACC. We retrospectively reviewed cases of BM from ACC treated with CyberKnife (CK) SRS at our institution between 1998 and 2024. A total of 40 lesions from 5 patients were included. Tumor control was defined based on radiological response to CK SRS as a complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) per response evaluation criteria in solid tumors (RECIST) guidelines. The median Follow-up duration was 11 months (Range: 3-51 months). The median age at treatment was 52 years with a male-to-female ration of 3:2. The median maximum diameter of the lesions was 7.mm. The median prescription dose delivered was 24 Gy. The treatment responses at the first follow-up were CR/PR/SD/PD: 9/19/12/0. At the last follow-up, 5 lesions had local progression, with one lesion at 39 months, and 4 lesions at 11 months after CK SRS, while 16 lesions remained CR. The cumulative 3-months, 6-months, and 12-months local control rates were 100%, 100%, and 89%, respectively. To date, this is the largest study examining the efficacy of SRS for ACC BM. Our results showed sufficient local control following the treatment.

  View details for DOI 10.1007/s10143-025-03761-1

  View details for PubMedID 40848204

  View details for PubMedCentralID 6037598

• Stereotactic Radiosurgery for Recurrent Meningioma: A Systematic Review of Risk Factors and Management Approaches. Cancers Mizutani, Y., Hori, Y. S., Harary, P. M., Lam, F. C., Reesh, D. A., Emrich, S. C., Ustrzynski, L., Tayag, A., Park, D. J., Chang, S. D. 2025; 17 (17)

  Abstract

  Background/Objectives: Recurrent meningiomas remain difficult to manage due to the absence of effective systemic therapies and comparatively high treatment failure rates, particularly in high-grade tumors. Stereotactic radiosurgery (SRS) offers a minimally-invasive and precise option, particularly for tumors in surgically complex locations. However, the risks associated with re-irradiation, and recent changes in the WHO classification of CNS tumors highlight the need for more personalized and strategic treatment approaches. This systematic review evaluates the safety, efficacy, and clinical considerations for use of SRS for recurrent meningiomas. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted using the PubMed, Scopus, and Web of Science databases for studies reporting outcomes of SRS in recurrent, pathologically confirmed intracranial meningiomas. Studies were excluded if they were commentaries, reviews, case reports with fewer than three cases, or had inaccessible full text. The quality and risk of bias of the included studies were assessed using the modified Newcastle-Ottawa Scale. Data on patient and tumor characteristics, SRS treatment parameters, clinical outcomes, adverse effects, and statistical analysis results were extracted. Results: Sixteen studies were included. For WHO Grade I tumors, 3- to 5-year progression-free survival (PFS) ranged from 85% to 100%. Grade II meningiomas demonstrated more variable outcomes, with 3-year PFS ranging from 23% to 100%. Grade III tumors had consistently poorer outcomes, with reported 1-year and 2-year PFS rates as low as 0% and 46%, respectively. SRS performed after surgery alone was associated with superior outcomes, with local control rates of 79% to 100% and 5-year PFS ranging from 40.4% to 91%. In contrast, tumors previously treated with radiotherapy, with or without surgery, showed substantially poorer outcomes, with 3- to 5-year PFS ranging from 26% to 41% and local control rates as low as 31%. Among patients with prior radiotherapy, outcomes were particularly poor in Grade II and III recurrent tumors. Toxicity rates ranged from 3.7% to 37%, and were generally higher for patients with prior radiation. Predictors of worse PFS included prior radiation, older age, and Grade III histology. Conclusions: SRS may represent a reasonable salvage option for carefully selected patients with recurrent meningioma, particularly following surgery alone. Outcomes were notably worse in high-grade recurrent meningiomas following prior radiotherapy, emphasizing the prognostic significance of both histological grade and treatment history. Notably, the lack of molecular and genetic data in most existing studies represents a key limitation in the current literature. Future prospective studies incorporating molecular profiling may improve risk stratification and support more personalized treatment strategies.

  View details for DOI 10.3390/cancers17172750

  View details for PubMedID 40940847

• Adaptive cohort design and LAT1 expression scale: study protocol for a Phase 2a trial of QBS72S in breast cancer brain metastases. BMC cancer Taiwo, R., Harary, P. M., Trinh, T. T., Granucci, M., Bertrand, S., Carlson-Clarke, B., Chernikova, S. B., Therkelsen, K., Arora, M., Melisko, M. E., Iv, M., Vogel, H., Han, S., Xie, C., Brain, S., Lee, V., Bharani, K. L., Nagpal, S., Hayden Gephart, M. 2025; 25 (1): 1316

  Abstract

  Breast cancer is the most common cause of cancer death among women and frequently metastasizes to the brain. Up to 30% of patients with breast-to-brain metastases will develop leptomeningeal disease (LMD), with poor survival, rapid neurologic decline, and no durable treatment options. The novel agent QBS72S, also known as QBS10072S, is designed to leverage the high expression of L-type amino acid transporter 1 (LAT1) on breast cancer cells and the blood-brain barrier. By conjugating an amino acid analogue with a DNA alkylating moiety, QBS72S can exploit LAT1 for specific delivery into the brain and metastatic tumor cells.We designed a single-arm, Phase 2a study to test the preliminary efficacy and safety of QBS72S for breast-to-brain metastasis in two distinct cohorts: intraparenchymal metastasis (Cohort 1; no LMD), and LMD (Cohort 2; with or without intraparenchymal metastasis). The primary endpoint is overall response rate across evaluable participants in Cohort 1. Secondary endpoints include progression-free survival, overall survival, duration of response, and treatment-related adverse events in Cohort 1. Exploratory endpoints include correlation of LAT1 expression in formalin-fixed paraffin-embedded samples with treatment response, CSF pharmacokinetics, perfusion MRI, and novel CSF-based biomarkers.Adaptive clinical trial design enables rapid enrollment and tailored endpoints for patient cohorts with baseline disparate outcomes. Our LAT1 staining protocol will allow ongoing trials in glioblastoma (NCT02977780) and future studies in brain metastases to correlate LAT1 expression to drug efficacy. Our exploratory endpoints may facilitate identification of more rapid and reliable biomarkers of LMD treatment response and resistance.ClinicalTrials.gov NCT05305365.

  View details for DOI 10.1186/s12885-025-14282-x

  View details for PubMedID 40813655

  View details for PubMedCentralID 3656565

• Radiosensitizers in Cancer Therapy: A Global Bibliometric Analysis. bioRxiv : the preprint server for biology Annagiri, S., Harary, P. M., Hori, Y. S., Lam, F. C., AbuReesh, D., Tayag, A., Ustrzynski, L., Emrich, S. C., Chang, S. D., Park, D. J. 2025

  Abstract

  Background/Objectives: Radiosensitizers are compounds given concurrently with radiotherapy to enhance the killing of cancer cells while sparing healthy tissue. Radiosensitization research has involved a diverse range of therapeutic agents. In the present study, we aimed to investigate international trends in the development of radiosensitizers across the most common cancer types.Methods: A bibliometric analysis was performed of the field of radiosensitizer research from 1956 to 2024. Individual author impacts and trends, collaborations between and productivity of countries, and themes/keywords were analyzed.Results: Our search yielded 12,690 results. The most highly represented countries were the United States of America, China, and Germany. Radiosensitizer studies for breast cancers demonstrated the highest rate of annual growth in record count by comparison with other cancer types, while publications for gynecological cancers showed the slowest growth. The most common radiosensitizers investigated included ATM kinase inhibitors, chemotherapies, gold nanoparticles, mTOR inhibitors, natural compounds such as caffeine or curcumin, and poly (ADP-ribose) polymerase inhibitors.Conclusions: The United States, Germany, and China were the most productive countries during the study period, with China demonstrating the greatest increase in annual publication rate. Additionally, pre-clinical studies primarily investigated gold particles and targeted therapies. By comparison, clinical studies focused on radiosensitizing chemotherapies.

  View details for DOI 10.1101/2025.06.26.661878

  View details for PubMedID 40667051

• Radiosurgical management of SDHx-related paraganglioma. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Harary, P. M., Hori, Y. S., Zamarud, A., Lam, F. C., Abu-Reesh, D., Emrich, S. C., Tayag, A., Ustrzynski, L., Pollom, E. L., Soltys, S. G., Li, G., Park, D. J., Chang, S. D. 2025; 138: 111387

  Abstract

  BACKGROUND AND OBJECTIVES: Paragangliomas (PGLs) are rare neuroendocrine tumors which frequently occur in the head and neck. Mutations in subunits of the succinate dehydrogenase complex (SDHx) account for approximately 50% of hereditary PGLs and are associated with increased rates of malignancy, recurrence, and multifocality. While the use of stereotactic radiosurgery (SRS) for PGLs has expanded, there is a lack of data correlating genetic background with outcomes in this distinct patient population. We aimed to evaluate the safety and efficacy of SRS, specifically long-term local control and treatment-related complications, for management of the 3 major subtypes of SDHx-related PGL.METHODS: Patients with confirmed SDHx-related PGL who underwent SRS at a single institution were retrospectively reviewed. Lesions were stratified based on location and affected SDHx gene. Primary endpoints were local control, overall survival, and symptom improvement. The secondary endpoint was treatment-related adverse events. To contextualize our results, a review of prior studies assessing SRS for head and neck PGL was performed.RESULTS: Five female and 2 male patients with SDHx mutations received SRS for 10 total PGLs during the study period. Median age at PGL diagnosis was 32years (range: 16-56), with a median age at SRS treatment of 45.5years (range: 18-59). The cohort included 2 SDHB, 1 SDHC, and 4 SDHD patients. Subtotal resection was performed for 3 of 10 lesions prior to SRS. The glomus jugulare was the most common anatomic site, followed by the carotid body and glomus vagale. Treatment volume and maximum diameter ranged from 0.3 to 30.8cm3 and 11 to 50mm, respectively. Median marginal dose was 21Gy (range: 16-25). Median follow-up was 164, 160, and 21.8months for SDHB, SDHC, and SDHD patients, respectively, with an aggregate local control rate of 100%. Symptom improvement occurred in 80% of cases with preoperative symptoms. A single patient experienced a post-SRS adverse event, late dysphagia, requiring additional treatment. Our systematic review included 9 large SRS studies reporting a total of 593 patients. Median follow-up ranged from 35 to 102months, while the median local control rate was 94.8%.CONCLUSION: To our knowledge, this represents the first analysis correlating genetic subtype of SDHx-related PGL with SRS treatment outcomes. SRS appears to provide durable local control with minimal side effects across the 3 major subtypes of SDHx-related PGL, comparable to prior reports without genetically-defined cohorts. This reaffirms its applicability as a treatment strategy for this hereditary condition.

  View details for DOI 10.1016/j.jocn.2025.111387

  View details for PubMedID 40513256

• Male Breast Cancer Brain Metastases: Genetic Profiles and Radiosurgery Outcomes NEUROSURGERY PRACTICE Hori, Y. S., Harary, P. M., Zamarud, A., Kattaa, A. H., Persad, A. R. L., Tayag, A., Ustrzynski, L., Emrich, S. C., Park, D. J., Li, G., Chang, S. D. 2025; 6 (2)

  View details for DOI 10.1227/neuprac.0000000000000141

  View details for Web of Science ID 001487521400001

• Male Breast Cancer Brain Metastases: Genetic Profiles and Radiosurgery Outcomes. Neurosurgery practice Hori, Y. S., Harary, P. M., Zamarud, A., Kattaa, A. H., Persad, A. R., Tayag, A., Ustrzynski, L., Emrich, S. C., Park, D. J., Li, G., Chang, S. D. 2025; 6 (2): e00141

  Abstract

  Male breast cancer (MBC) is very rare, and previous reports of brain metastases (BM) from MBC are limited. To date, the genetic characteristics of MBC with BM have not been explored. In addition, there is only a single case report documenting the use of stereotactic radiosurgery (SRS) for MBC BM. The aim of this study was to summarize genetic alterations associated with BM in patients with MBC and evaluate the safety and efficacy of SRS in this population.Four male patients with a total of 20 MBC BMs treated with SRS were retrospectively reviewed. We defined treatment response as complete response, partial response, stable disease, and local progression (LP), per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate cumulative incidence rate of LP.The median overall survival was 16.3 months (95% confidence interval: 1.4-31.3 months). The mean age at treatment was 59 years (IQR: 56-60.5 years). Three patients had estrogen receptor-positive lesions, whereas one patient had triple-negative disease. Three patients had notable pathogenic alterations (including in AURKA, BRCA1, BRCA2, CCND1, CHEK2, ERBB2, FLT3, RAF1, and SPINK1). The median lesion size was 5.7 mm (IQR: 3.9-8.6 mm). The median delivered dose was 23 Gy (IQR: 22-24 Gy). Follow-up imaging at 3 months showed a reduction in median lesion size (3.3 mm). The percentage of lesions which were classified as complete response:partial response:stable disease:LP was 0%:45%:55%:0%, respectively. Cumulative 6-month and 12-month local control rates were 100% and 100%, respectively. Only one lesion demonstrated LP at the last follow-up (15 months).This is the first report of genetic profiling of MBC with BM and excellent SRS outcomes. The receptor status and genetic alterations across our patients with MBC BM suggest heterogeneity in disease. Larger studies are needed to further explore MBC BM characteristics and treatment outcomes.

  View details for DOI 10.1227/neuprac.0000000000000141

  View details for PubMedID 41163992

  View details for PubMedCentralID PMC12560722

• Paired molecular profiling of malignant transformation of an epidermoid cyst for potential genetic drivers: illustrative case. Journal of neurosurgery. Case lessons Harary, P. M., Hori, Y. S., Kassu, R., Persad, A. R., Tayag, A., Ustrzynski, L., Emrich, S. C., Gibbs, I. C., Park, D. J., Chang, S. D., Fernandez-Miranda, J. C. 2025; 9 (18)

  Abstract

  Malignant transformation of an intracranial epidermoid cyst (EC) into squamous cell carcinoma (SCC) is an exceedingly rare occurrence that is typically diagnosed on postoperative histology. The mechanisms underlying transformation remain poorly understood, with limited characterization of genetic changes associated with progression.A 55-year-old female presented with a large cerebellopontine angle EC with an enhancing nodule in the left tectum, for which she underwent resection. Three months following surgery, rapid enlargement of the residual tectal component required reoperation, with pathology showing SCC. Paired next-generation sequencing of the EC and SCC revealed multiple shared variants, including a pathogenic TP53 mutation. Additionally, the SCC contained a pathogenic PTEN variant absent in the EC, suggesting a second driver mutation contributing to malignant transformation of an EC (MTEC). Her SCC was resistant to volumetric modulated arc therapy, requiring subsequent chemotherapy and pembrolizumab combined with stereotactic radiosurgery. Despite a favorable initial response, she died 26 months following MTEC diagnosis.To the authors' knowledge, this represents the first use of paired molecular profiling to link intracranial SCC to an EC precursor, enhancing precision of this rare diagnosis. Additionally, this case identifies specific genetic alterations associated with transformation, providing insight into the largely unknown mechanisms underlying MTEC. https://thejns.org/doi/10.3171/CASE24849.

  View details for DOI 10.3171/CASE24849

  View details for PubMedID 40324326

• Stereotactic radiosurgery for treatment resistant depression: Systematic review WORLD NEUROSURGERY-X Vanleuven, J., Hori, Y. S., Osama, T., Harary, P. M., Lui, A., Persad, A. R., Tayag, A., Emrich, S. C., Ustrzynski, L., Purger, D., Park, D. J., Chang, S. D. 2025; 26

  View details for DOI 10.1016/j.wnsx.2025.100451

  View details for Web of Science ID 001461516800001

• Stereotactic radiosurgery for brain metastases secondary to adrenal ganglioneuroblastoma: illustrative case. Journal of neurosurgery. Case lessons Cardona, J. J., Hori, Y. S., Harary, P. M., Persad, A. R., Ustrzynski, L., Emrich, S. C., Tayag, A., Park, D. J., Chang, S. D. 2025; 9 (12)

  Abstract

  Neuroblastic tumors, including malignant neuroblastoma, ganglioneuroblastoma (GNB), and benign ganglioneuroma, are embryonal tumors derived from neural crest cells. GNB often metastasizes to the bone marrow and bone, with lung and brain metastases (BMs) remaining extremely rare. To date, only 2 prior reports of GNB BM exist, with both cases documenting resection alone. Therefore, the management of GNB BM has yet to be fully investigated.The present study describes an 11-year-old male with BM secondary to primary adrenal GNB and the use of stereotactic radiosurgery (SRS) to treat these lesions. These are both without precedent in the current literature. The patient initially underwent 2 surgical interventions, with the second surgery performed due to local recurrence. He subsequently received 3 rounds of SRS treatment with favorable short-term outcomes, including complete resolution of the relatively large left temporal lesion.A primary surgical approach enabled pathological analysis and contributed to initial prolonged survival. However, a second surgery was required due to local progression. Subsequent SRS showed favorable outcomes after the 3 interventions without impairing the clinical course with systemic therapy. Comparative studies are needed to optimize the treatment strategy between surgical management and SRS as stand-alone or adjuvant therapy. https://thejns.org/doi/10.3171/CASE24820.

  View details for DOI 10.3171/CASE24820

  View details for PubMedID 40127476

• The spectrum of radiation therapy options for craniopharyngioma: a systematic review. Journal of neuro-oncology Harary, P. M., Rajaram, S., Hori, Y. S., Park, D. J., Chang, S. D. 2025

  Abstract

  Craniopharyngiomas (CPs) are rare, slow-growing brain tumors which originate in the sellar region. CPs may present with symptoms secondary to compression of surrounding structures, particularly the pituitary gland, and surgical removal has traditionally been the mainstay of treatment. However, due to high recurrence rates for CPs, especially when gross total resection is not feasible, radiotherapy has played an increasingly significant role in their management. Here, we review radiation modalities, treatment settings, and future directions in the management of CP. In addition, we outline emerging therapeutic combinations involving targeted therapies.A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search of the MEDLINE/PubMed, Embase, and Web of Science databases was used for initial identification of articles. Included studies were then grouped into the following treatment modalities: conventional radiotherapy (CRT), intensity-modulated radiotherapy (IMRT), proton therapy, fractionated stereotactic radiotherapy (FSRT) /stereotactic radiosurgery (SRS), and brachytherapy.A total of 60 studies met inclusion criteria, comprising 3041 patients, with a median sample size of 33 (range: 10-242) and age ranging from 6 to 55. This review included 8, 15, 3, 12, and 29 reports corresponding to brachytherapy, CRT, IMRT, proton therapy, and FSRT/SRS, respectively. Proton therapy and FSRT had the highest median 5-year progression-free survival (PFS), with rates of 92% and 89%, respectively. IMRT and proton therapy were primarily investigated in pediatric patients (median ages of 8.2 and 10.3 years, respectively). By comparison, FSRT and SRS research has mainly been in adult cohorts.Precision radiotherapy appears to be associated with high rates of tumor control in CP, suggesting these approaches bear further investigation. Selection of the appropriate radiation modality from those reviewed likely depends on several patient-specific factors. Important considerations include tumor location and volume, patient age, prior treatments for CP, and patient preference.

  View details for DOI 10.1007/s11060-025-05001-4

  View details for PubMedID 40063185

  View details for PubMedCentralID 9379650

• Coexisting sellar Rathke cleft cyst and planum sphenoidale meningioma: illustrative case. Journal of neurosurgery. Case lessons Akhavan-Sigari, A., Park, D. J., Harary, P. M., Chivakula, M., Theodros, D., Bharani, K. L., Hori, Y. S., Persad, A. R., Lam, F. C., Emrich, S. C., Ustrzynski, L., Tayag, A., Chang, S. D. 2025; 9 (3)

  Abstract

  The co-occurrence of Rathke cleft cysts (RCCs) and meningiomas in the sellar and parasellar regions represents an exceedingly rare clinical entity. Achieving maximal resection through a single operative approach while minimizing adverse events is challenging, often necessitating multiple surgical approaches, as suggested by previous reports.The authors report the case of a 49-year-old female with a history of kidney transplant who presented with headaches and was diagnosed with coexisting RCC and meningioma in the sellar and planum sphenoidale regions, respectively. Given the prolonged, refractory nature of her symptoms and based on her treatment preferences, a two-stage surgical approach was planned. This involved an endoscopic transnasal transsphenoidal approach followed by a right craniotomy to achieve maximal tumor resection while minimizing potential complications. No residual disease or tumor remnants were present at the 6-month follow-up. The pituitary gland was preserved, and the patient's preoperative symptoms had fully resolved.The preoperative diagnosis of concurrent skull base tumors is essential for effective management planning and determining the optimal surgical approach. The proximity of these tumors to critical neurovascular structures necessitates meticulous surgical planning to minimize adverse effects while ensuring maximal tumor resection. https://thejns.org/doi/10.3171/CASE24551.

  View details for DOI 10.3171/CASE24551

  View details for PubMedID 39832313

• Genomic predictors of radiation response: recent progress towards personalized radiotherapy for brain metastases. Cell death discovery Harary, P. M., Rajaram, S., Chen, M. S., Hori, Y. S., Park, D. J., Chang, S. D. 2024; 10 (1): 501

  Abstract

  Radiotherapy remains a key treatment modality for both primary and metastatic brain tumors. Significant technological advances in precision radiotherapy, such as stereotactic radiosurgery and intensity-modulated radiotherapy, have contributed to improved clinical outcomes. Notably, however, molecular genetics is not yet widely used to inform brain radiotherapy treatment. By comparison, genetic testing now plays a significant role in guiding targeted therapies and immunotherapies, particularly for brain metastases (BM) of lung cancer, breast cancer, and melanoma. Given increasing evidence of the importance of tumor genetics to radiation response, this may represent a currently under-utilized means of enhancing treatment outcomes. In addition, recent studies have shown potentially actionable mutations in BM which are not present in the primary tumor. Overall, this suggests that further investigation into the pathways mediating radiation response variability is warranted. Here, we provide an overview of key mechanisms implicated in BM radiation resistance, including intrinsic and acquired resistance and intratumoral heterogeneity. We then discuss advances in tumor sampling methods, such as a collection of cell-free DNA and RNA, as well as progress in genomic analysis. We further consider how these tools may be applied to provide personalized radiotherapy for BM, including patient stratification, detection of radiotoxicity, and use of radiosensitization agents. In addition, we describe recent developments in preclinical models of BM and consider their relevance to investigating radiation response. Given the increase in clinical trials evaluating the combination of radiotherapy and targeted therapies, as well as the rising incidence of BM, it is essential to develop genomically informed approaches to enhance radiation response.

  View details for DOI 10.1038/s41420-024-02270-2

  View details for PubMedID 39695143

  View details for PubMedCentralID PMC11655559

• Stereotactic radiosurgery for pancreatic neuroendocrine tumor brain Metastases: Systematic review and Illustrative case presentation. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Harary, P. M., Hori, Y. S., Annagiri, S., Akhavan-Sigari, A., Persad, A. R., Ustrzynski, L., Emrich, S. C., Tayag, A., Park, D. J., Chang, S. D. 2024; 130: 110927

  Abstract

  Neuroendocrine tumor (NET) brain metastases (BM) are rare malignancies which frequently bear a poor prognosis and have the potential to secrete hormones. The optimal treatment approach for these metastases remains unclear, with significant heterogeneity occurring both across and within primary tumor types, and outcome data are limited. Pancreatic neuroendocrine tumor (pNET) BM may be particularly aggressive. While stereotactic radiosurgery (SRS) for other NET BM has previously been described, no report has specifically investigated SRS for management of pNET BM.A comprehensive literature search was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search terms included ("neuroendocrine tumor" OR "neuroendocrine neoplasm" OR "neuroendocrine carcinoma" OR "NET") AND ("brain metastasis" OR "brain metastases" OR "intracranial metastases") AND ("stereotactic radiosurgery" OR "stereotactic body" OR "CyberKnife" OR "GammaKnife").Our search strategy yielded 230 articles. After screening, a total of 16 articles with 256 patients were identified. Number of patients per study cohort ranged from 1 to 101 (mean = 16). Ten articles were single case reports. The most commonly investigated primary site was lung (5 studies), followed by skin (2 case reports), and uterine cervix (2 case reports). Median survival post-SRS ranged from 5 to 42 months. Median tumor volume ranged from 0.08 cm3 to 33.62 cm3. Local control rate was provided in 3 of 6 of the reviewed retrospective analyses. A pulmonary cohort of 101 patients reported a recurrence rate of 13.8 % at 12 months. A pulmonary case series similarly reported local progression in only 1 of 8 patients. The mixed primary cohort (33 patients) had a long-term local failure rate of 16.7 %. In addition, we describe a first reported individual case of pNET BM treated with SRS. Nearly 6-years after initial pNET diagnosis, multiple intracranial enhancing lesions were found, which were subsequently treated with SRS. Follow-up imaging demonstrated a statistically significant decrease in lesion diameter (p < 0.001), with none of the 18 BM progressing.Given the recently increase in age-adjusted incidence of NET BM, determining an optimal treatment approach for these malignancies is of growing importance. Prognosis generally remains poor, with BM being a significant predictor of overall survival. Our review indicated large variability in outcomes both between and within primary tumor types, suggesting a need for further investigation of predictive molecular biomarkers. In addition, to the authors' knowledge, this represents the first reported case of pNET BM successfully treated with SRS.

  View details for DOI 10.1016/j.jocn.2024.110927

  View details for PubMedID 39571478

• Stereotactic Radiosurgery for Choriocarcinoma Brain Metastases: Illustrative Case Presentation and Systematic Review. World neurosurgery Akhavan-Sigari, A., Hori, Y. S., Harary, P. M., Persad, A. R., Kassu, R., Tayag, A., Ustrzynski, L., Emrich, S. C., Park, D. J., Chang, S. D. 2024

  Abstract

  Choriocarcinoma (CC) is a rare and aggressive form of germ cell tumor. There is limited evidence reporting outcomes in patients with primary CC and brain metastases (BM). To date, only a few single case reports have documented the use of SRS for CC BM.We retrospectively assessed patients who were treated with SRS for pure CC BM from 1998-2024. Lesion follow-up sizes and local tumor control status were evaluated after SRS treatment using RECIST criteria. A comprehensive literature search was performed for CC BM in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.In our series, 3 patients with 7 CC BM underwent SRS. Two were male with testicular CC and one was female with gestational CC. The median diameter of the lesions was 8 mm with a median volume of 0.14 cm3 at treatment. The MRIs at 3 and 6 months demonstrated reductions in median diameters to 6 mm and 4 mm, respectively. At the last follow-up visits, one lesion had local progression at 15 months after SRS and one lesion had sustained complete response. Our systematic review yielded 249 articles. After screening, a total of 18 reports were identified for CC BM. Among these, only three single cases documented the use of SRS for CC BM.SRS is a feasible and viable approach for CC BM, particularly in cases where immediate surgical management is not necessary. This is yet the largest report evaluating the outcome of CC BM treated with SRS.

  View details for DOI 10.1016/j.wneu.2024.10.116

  View details for PubMedID 39491621

• KEAP1-mutant atypical meningioma: illustrative case. Journal of neurosurgery. Case lessons Harary, P. M., Hori, Y. S., Persad, A. R., Tayag, A., Ustrzynski, L., Emrich, S. C., Rahimy, E., Park, D. J., Li, G., Chang, S. D. 2024; 8 (11)

  Abstract

  While genetic testing of tumors is commonly used to inform the selection of systemic therapies, there is limited evidence for the application of radiotherapy for brain cancer. Recent studies have shown that Kelch-like ECH-associated protein 1 (KEAP1), a key regulator of cellular responses to oxidative and electrophilic stress, is associated with radioresistance in multiple cancer types. Several studies have reported the clinical significance of KEAP1 mutation in brain metastasis; however, the effect of KEAP1 mutations on radioresponse in meningioma has never been reported.The authors present the case of a 40-year-old female with a KEAP1 mutation-positive atypical meningioma that was initially treated with resection followed by intensity-modulated radiation therapy (IMRT). Recurrence was observed at 15 months, requiring reoperation and adjuvant stereotactic radiosurgery (SRS). An excellent treatment response was observed at 7 months post-SRS with an improvement in reported symptoms, although bevacizumab was required for the resolution of radiation necrosis observed 2 months post-SRS.To the authors' knowledge, this is the first report of KEAP1-mutant meningioma, including its clinical course after comprehensive management. Notably, treatment included multimodal radiotherapy with IMRT followed by SRS. SRS led to an excellent treatment response at the 7-month follow-up. However, radiation necrosis developed after both radiotherapy treatments, suggesting that radiological modification can be beneficial in patients with KEAP1 mutations. https://thejns.org/doi/10.3171/CASE24387.

  View details for DOI 10.3171/CASE24387

  View details for PubMedID 39250830

• Cell Replacement Therapy for Brain Repair: Recent Progress and Remaining Challenges for Treating Parkinson's Disease and Cortical Injury. Brain sciences Harary, P. M., Jgamadze, D., Kim, J., Wolf, J. A., Song, H., Ming, G. L., Cullen, D. K., Chen, H. I. 2023; 13 (12)

  Abstract

  Neural transplantation represents a promising approach to repairing damaged brain circuitry. Cellular grafts have been shown to promote functional recovery through "bystander effects" and other indirect mechanisms. However, extensive brain lesions may require direct neuronal replacement to achieve meaningful restoration of function. While fetal cortical grafts have been shown to integrate with the host brain and appear to develop appropriate functional attributes, the significant ethical concerns and limited availability of this tissue severely hamper clinical translation. Induced pluripotent stem cell-derived cells and tissues represent a more readily scalable alternative. Significant progress has recently been made in developing protocols for generating a wide range of neural cell types in vitro. Here, we discuss recent progress in neural transplantation approaches for two conditions with distinct design needs: Parkinson's disease and cortical injury. We discuss the current status and future application of injections of dopaminergic cells for the treatment of Parkinson's disease as well as the use of structured grafts such as brain organoids for cortical repair.

  View details for DOI 10.3390/brainsci13121654

  View details for PubMedID 38137103

  View details for PubMedCentralID PMC10741697

• Protocol for human brain organoid transplantation into a rat visual cortex to model neural repair. STAR protocols Jgamadze, D., Harary, P. M., Castellanos, M., Blue, R., Song, H., Ming, G. L., Chen, H. I. 2023; 4 (3): 102470

  Abstract

  Human stem-cell-derived organoids represent a promising substrate for transplantation-based neural repair. Here, we describe a protocol for transplanting forebrain organoids into an injured adult rat visual cortex. This protocol includes surgical details for craniectomy, aspiration injury, organoid transplantation, and cranioplasty. This platform represents a valuable tool for investigating the efficacy of organoids as structured grafts for neural repair. For complete details on the use and execution of this protocol, please refer to Jgamadze et al.1.

  View details for DOI 10.1016/j.xpro.2023.102470

  View details for PubMedID 37585295

  View details for PubMedCentralID PMC10436235

• Effects of Human Brain Organoid Age on Post-Transplant Growth in the Rat Motor Cortex Blue, R., Fu, M., Harary, P., Jgamadze, D., Rahaman, I., Singh, S., Ming, G., Song, H., Chen, H. LIPPINCOTT WILLIAMS & WILKINS. 2023: 117

  View details for Web of Science ID 001043164400271

• Structural and functional integration of human forebrain organoids with the injured adult rat visual system. Cell stem cell Jgamadze, D., Lim, J. T., Zhang, Z., Harary, P. M., Germi, J., Mensah-Brown, K., Adam, C. D., Mirzakhalili, E., Singh, S., Gu, J. B., Blue, R., Dedhia, M., Fu, M., Jacob, F., Qian, X., Gagnon, K., Sergison, M., Fruchet, O., Rahaman, I., Wang, H., Xu, F., Xiao, R., Contreras, D., Wolf, J. A., Song, H., Ming, G. L., Chen, H. I. 2023; 30 (2): 137-152.e7

  Abstract

  Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the visual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Visual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.

  View details for DOI 10.1016/j.stem.2023.01.004

  View details for PubMedID 36736289

  View details for PubMedCentralID PMC9926224

• Characterization of functional activity of forebrain organoids using longitudinal multiphoton calcium imaging Harary, P., Kurzion, R., Mensah-Brown, K., Jgamadze, D., Song, H., Ming, G., Chen, H. AMER SOC CELL BIOLOGY. 2023: 1218

  View details for Web of Science ID 001051001304392

• Human brain organoid transplantation: ethical implications of enhancing specific cerebral functions in small-animal models Molecular Psychology: Brain, Behavior, and Society Harary, P. M., Blue, R., Castellanos, M., Dedhia, M., Hamimi, S., Jgamadze, D., Rees, B., Seshadri, N., Singh, S., Moreno, J., Wolf, J., Song, H., Ming, G., Chen, H. 2023; 2

  View details for DOI 10.12688/molpsychol.17544.1