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Primary Versus Adjuvant Stereotactic Radiosurgery for Cavernous Sinus Meningiomas: A Propensity Score-Matched Comparative Analysis

Yurtluk, Mehmet Denizhan; Wei, Chris Z; Reyes, Jheremy S; Puccio, David; Kondziolka, Douglas; Flickinger, John C; Hadjipanayis, Constantinos G; Niranjan, Ajay; Lunsford, L Dade
BACKGROUND AND OBJECTIVES/OBJECTIVE:The initial management of symptomatic cavernous sinus meningioma (CSM) remains a matter of debate. This study compares long-term tumor control and neurological outcomes in patients who underwent either primary stereotactic radiosurgery (SRS) or initial surgery followed by adjuvant SRS for both residual and progressive disease. METHODS:We identified 292 patients with CSM who underwent Gamma Knife radiosurgery between 1987 and 2024 (median follow-up, 77 months). The initial management included 167 patients who underwent primary SRS and 125 patients who had adjuvant SRS after surgical resection. Propensity score matching (1:1) was performed to control for potential selection bias differences, resulting in 150 matched patients. The primary outcomes included tumor control, neurological improvement, and neurological worsening. Kaplan-Meier analysis and logistic regression were performed. RESULTS:Compared with adjuvant SRS, primary SRS was associated with enhanced tumor control (log-rank P = .049) at 5 years (96.5% vs 90.5%) and 10 years (89.5% vs 77.8%). Neurological improvement rates were greater in the primary SRS group (10-year: 39.3% vs 25.2%, log-rank P = .008; odds ratio = 2.84, 95% CI: 1.33-6.07, P = .01), often related to improved abducens nerve function (log-rank P = .025) in primary SRS patients. The risk of neurological worsening was no different between primary and adjuvant SRS patients (P = .995). CONCLUSION/CONCLUSIONS:This study provides further evidence that primary SRS is a better option than initial surgery followed by adjuvant SRS for the initial management of patients with symptomatic CSM.
PMID: 42059602
ISSN: 1524-4040
CID: 6029562

A Multi-AI Agent Framework for Interactive Neurosurgical Education and Evaluation: From Vignettes to Virtual Conversations

Sangwon, Karl L; Zhang, Jeff; Steele, Robert; Stryker, Jaden; Choi, Joanne J; Lee, Jin Vivian; Alber, Daniel Alexander; Valliani, Aly; Kannapadi, Nivedha; Ryoo, James; Feng, Austin; Khan, Hammad A; Neifert, Sean; Orillac, Cordelia; Weiss, Hannah K; Kim, Nora C; Kurland, David; Riina, Howard A; Kondziolka, Douglas; Mankowski, Michal; Oermann, Eric Karl
BACKGROUND AND OBJECTIVES/OBJECTIVE:Traditional medical board examinations present clinical information in static vignettes with multiple-choices (MC), fundamentally different from how physicians gather and integrate data in practice. Recent advances in large language models (LLMs) offer promising approaches to creating more realistic clinical interactive conversations. However, these approaches are limited in neurosurgery, where patient communication capacity varies significantly and diagnosis heavily relies on objective data such as imaging and neurological examinations. We aimed to develop and evaluate a multi-artificial intelligence (AI) agent conversation framework for neurosurgical case assessment that enables realistic clinical interactions through simulated patients and structured access to objective clinical data. METHODS:We developed a framework to convert 608 Self-Assessment in Neurological Surgery first-order diagnosis questions into conversation sessions using 3 specialized AI agents: patient AI for subjective information, system AI for objective data, and clinical AI for diagnostic reasoning. We evaluated generative pretrained transformer 4o's (GPT-4o's) diagnostic accuracy across traditional vignettes, patient-only conversations, and patient + system AI interactions, with human benchmark testing from 10 neurosurgery residents. RESULTS:= .0030) using fewer interactions and reported high educational value of the interactive format. CONCLUSION/CONCLUSIONS:This multi-AI agent framework provides both a more challenging evaluation method for LLMs and an engaging educational tool for neurosurgical training. The significant performance drops in conversational formats suggest that traditional MC testing may overestimate LLMs' clinical reasoning capabilities, while the framework's interactive nature offers promising applications for enhancing medical education.
PMCID:13075903
PMID: 41982325
ISSN: 2834-4383
CID: 6027772

Evaluation of disparities in timely stereotactic radiosurgery for brain metastases in a safety net hospital system through a centralized workflow

Santhumayor, Brandon A; Domogauer, Jason D; Bernstein, Kenneth; Donahue, Bernadine; Meng, Ying; Kurland, David; Gurewitz, Jason; Cooper, Benjamin; Kondziolka, Douglas
PMID: 41974956
ISSN: 1573-7373
CID: 6027542

Single-Fraction Stereotactic Radiosurgery for Residual, Recurrent, or Metastatic Intracranial Solitary Fibrous Tumors: An IRRF Study Toward Management Guidance

Tos, Salem M; Shaaban, Ahmed; Hamdan, Dawood; Mantziaris, Georgios; Hajikarimloo, Bardia; Ishaque, Mariam; Shinya, Yuki; Lohia, Vanshika; Wei, Zhishuo; Askeroglu, Orbay; Amezquita-Contreras, Christian; Becerril-Gaitan, Andrea; Verma, Onam; Douri, Keiss; Lora, Nathalia; de Moura, Anais C M A; Yap, Eugene; Bailey, David; Speckter, Herwin; Cohen, Salomon Cohen; Benjamin, Carolina; Blanco, Angel I; Esquenazi, Yoshua; Tripathi, Manjul; Zacharia, Brad E; Warnick, Ronald E; Liscak, Roman; Guseynova, Khumar; Lee, Cheng-Chia; Yang, Huai-Che; Franzini, Andrea; Picozzi, Piero; Duzkalir, A Haluk; Peker, Selcuk; Palmer, Joshua D; Mathieu, David; Bowden, Greg N; Niranjan, Ajay; Lunsford, L Dade; Kondziolka, Douglas; Sheehan, Jason P
BACKGROUND:Intracranial solitary fibrous tumors (SFTs) are rare, aggressive neoplasms with high local recurrence. This study evaluates the efficacy and prognostic factors of single-fraction stereotactic radiosurgery (SRS). METHODS:This multicenter retrospective study included 107 patients (253 SFTs) treated with single-fraction SRS at 18 centers (1989-2024). We analyzed local control (LC), intracranial tumor control (ITC), overall tumor control (OTC), progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). Cox regression identified prognostic factors. RESULTS:Median follow-up was 33 months. LC was 68.4% (5-yr: 56.8% and 10-yr: 38.8%). ITC 54.2% (5-yr: 48.5%) and OTC 50.5% (5-yr: 44.0%). PFS was 56.3% and 30.2% at 5 and 10 years, respectively. DSS remained high at 89.7% (5-yr) and 79.7% (10-yr), while OS was 79.3% (5-yr) and 55.2% (10-yr). Independent predictors of LC included recurrent vs. metastatic SFTs (HR: 1.96, p = 0.028), margin dose ≤16 Gy (HR: 2.35, p = 0.006), larger tumor volume (HR: 1.05, p < 0.001), and longer diagnosis-to-SRS duration (HR : 1.02, p < 0.001). Older age (HR: 1.03, p = 0.014) and longer resection-to-SRS duration (HR: 1.02, p = 0.018) predicted worse ITC. Age significantly affected OS (HR: 1.06, p < 0.001) and PFS (HR: 1.03, p = 0.037). Longer diagnosis-to-SRS (HR: 1.03, p = 0.002) and resection-to-SRS durations (HR : 1.02, p = 0.030) predicted worse PFS. KPS score >70 predicted better outcomes across ITC, OTC, DSS and OS. Radiation-related adverse effects occured in 2.8%. CONCLUSION/CONCLUSIONS:SRS offers reasonable tumor control and favorable long-term survival in the adjuvant and salvage setting for patients with residual, recurrent, or metastatic intracranial SFTs. Key prognostic factors included tumor volume, recurrence status, and timing of SRS.
PMID: 41592232
ISSN: 1523-5866
CID: 6003202

Stereotactic Radiosurgery for Primary Central Nervous System Lymphoma: Results From the International Radiosurgery Research Foundation

Kite, Trent; Wegner, Rodney E; Karlovits, Steven; Herbst, John; Lister, John; Knox, Henry; Palmer, Joshua D; Yap, Eugene R; Bailey, David; Dejuk, Mariana; Mahase, Sean; Zacharia, Brad E; Amezquita-Contreras, Christian; Blanco, Angel I; Esquenazi, Yoshua; Warnick, Ronald E; Douri, Keiss; Mathieu, David; Tripathi, Manjul; Kumar, Narendra; Lee, Cheng-Chia; Yang, Huai-Che; de Moura, Anais C M A; Reyes, Jheremy S; Hajkarimloo, Bardia; Kondziolka, Douglas; Niranjan, Ajay; Lunsford, L Dade; Sheehan, Jason P; Shepard, Matthew J
BACKGROUND AND OBJECTIVES/OBJECTIVE:Stereotactic radiosurgery (SRS) has been increasingly employed in the multimodal management of primary central nervous system lymphoma. Here, we evaluate the outcomes of SRS for the treatment of primary central nervous system lymphoma through a multicenter, international cohort study. METHODS:A multicenter, retrospective cohort study was conducted through the International Radiosurgery Research Foundation. Subgroups were defined according to treatment setting: up-front (primary treatment), boost (SRS after consolidative chemotherapy with or without whole-brain radiotherapy), and relapsed/refractory (recurrent/progressive disease after first-line therapy). The primary end point was local tumor control. Time-to-event analysis was conducted using the Kaplan-Meier method. Variables associated with local control were assessed using the Cox proportional hazard modeling. RESULTS:Fifty-four patients with 127 tumor sites were included in this analysis. Actuarial 12-month local and distant control rates for the entire cohort were 75.7% and 63.7%, respectively, with a median overall survival (OS) of 18 months (range: 1-176). Actuarial 12-month local control rates were significantly different at 95.6%, 78.3%, and 42.1% (P < .0001) for the up-front, relapsed/refractory groups, and boost cohorts, respectively. OS across all cohorts were similar with 12-month OS rates of 55.2%, 51.3%, and 53.5% for the up-front, relapsed/refractory, and boost cohorts, respectively. Rates of radiation necrosis were 18.5%, 20.8%, 15.4%, and 11.8% for the entire cohort, relapsed/refractory, boost, and up-front cohorts, respectively. Diminished OS was significantly associated with treatment volumes >27 cm3 (hazard ratio: 2.5, P = .04). CONCLUSION/CONCLUSIONS:SRS shows promising local tumor control rates for up-front and relapsed cohorts. Despite this, distant tumor progression limits total tumor control and may adversely affect OS.
PMID: 41532758
ISSN: 1524-4040
CID: 5986302

Radiosurgery for Sporadic Facial Nerve Schwannoma: An International Multi-institutional Study of 60 Cases

Marinelli, John P; Cottrell, Justin; Borsetto, Daniele; Mantziaris, Georgios; Lloyd, Simon K W; Steiner, Nejc; Babajanian, Eric E; Meng, Ying; Lohse, Christine M; Axon, Patrick; Sheehan, Jason P; Kondziolka, Douglas; Roland, J Thomas; Kutz, J Walter; Duke, Simon L; Link, Michael J; Carlson, Matthew L
OBJECTIVE:To characterize patient outcomes after primary stereotactic radiosurgery (SRS) for the management of sporadic facial nerve schwannoma. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Six tertiary referral centers across the United States and United Kingdom. PATIENTS/METHODS:Adults undergoing SRS from 2000 through 2023 for sporadic facial nerve schwannoma along any segment of the facial nerve were included. Patients with NF2-related schwannomatosis were excluded. INTERVENTION/METHODS:Stereotactic radiosurgery. MAIN OUTCOME MEASURE/METHODS:Long-term tumor control. RESULTS:Among 60 patients meeting inclusion, the median age at SRS was 52 years (IQR: 41 to 64) with a median tumor size of 19.5 mm (IQR: 14.7 to 22.8). Tumors commonly involved the internal auditory canal (73%), cisternal (49%), geniculate/labyrinthine (47%), and tympanic segments (22%). Two patients experienced SRS failure and underwent salvage treatment; salvage-free survival rates (95% CI; number still at risk) at 1, 3, 5, and 10 years after SRS were 100% (100 to 100; 55), 100% (100 to 100; 36), 100% (100 to 100; 18), and 87% (72 to 100; 9), respectively. Among 31 (52%) patients with House-Brackmann (HB) grade I facial function at presentation, only 6 demonstrated worse facial function at a median of 3.2 years (IQR: 1.7 to 6.6) after SRS. Of 18 patients with serviceable hearing (AAO-HNS class A/B) at SRS, 13 maintained serviceable hearing at a median of 1.0 years (IQR: 0.5 to 4.9) of post-SRS audiometric follow-up. CONCLUSIONS:Durable tumor control after primary SRS for sporadic facial nerve schwannoma is achieved in most patients. Among those with HB grade I facial function at presentation, treatment with SRS harbors limited additional risk of facial paresis beyond observation alone.
PMID: 41225703
ISSN: 1537-4505
CID: 5966882

Hypofractionation of Gamma Knife Radiosurgery for Intracranial Meningiomas: A Retrospective Multicenter Study and Systematic Review of Literature

Meng, Ying; Tsang, Derek S; Bernstein, Kenneth; Santhumayor, Brandon; Mashiach, Elad; Wang, Justin Z; Suppiah, Suganth; Sen, Chandra; Pacione, Donato; Donahue, Bernadine; Sulman, Erik; Silverman, Joshua; Golfinos, John; Zadeh, Gelareh; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:Hypofractionated Gamma Knife radiosurgery (hfGKRS) is increasingly considered for treating large or near-critical structure meningiomas because of potential safety advantages. However, data on optimal fractionation and long-term outcomes remain limited. This study evaluated the longer-term tumor control and toxicity after hfGKRS for intracranial meningiomas at 2 large centers, supplemented by a systematic review and meta-analysis of existing literature. METHODS:The analysis included 34 patients (site 1 = 25, site 2 = 9, median age 62.6 years) with 40 tumors (median volume 11.2 cm3). 62% was low-grade (World Health Organization grade 0-1) and 38% was high-grade (World Health Organization grade 2-3). The most common fractionation schemes were 20 Gy in 5 fractions for low-grade and 21 Gy in 3 fractions for high-grade tumors. The mean follow-up was 28.8 months. RESULTS:Only 6 of 34 patients did not have any previous treatment including surgery and/or radiotherapy. 82% of patient patients had neurological deficits before stereotactic radiosurgery. The estimated rate of 5-year tumor progression for low-grade and high-grade tumors was 7.7% (95% CI 0.41%-30%) and 36% (95% CI 12%-62%). Symptoms improved in 12 patients (35%) and worsened in 6 patients (16%), with 1 case attributed to tumor progression and no significant visual deterioration in 16 tumors within 3 mm of the optic apparatus. There was no statistically significant association between fractionation (3 vs 5) scheme and tumor control (P = .07) or survival (P = .12). Karnofsky Performance Status performance was a significant predictor of death (HR 0.89, P = .012) and tumor progression (HR 0.93, P = .048). The combined meta-analysis revealed a 5-year tumor control rate of 91.6% for low-grade and 37.9% for high-grade meningiomas. CONCLUSION/CONCLUSIONS:hfGKRS demonstrates durable control and acceptable safety for low-grade intracranial meningiomas. High-grade tumors showed less favorable outcomes comparable with single-session Gamma Knife radiosurgery historical data. Further prospective data are needed to confirm these findings and optimize fractionation strategies.
PMID: 41143532
ISSN: 1524-4040
CID: 5960972

Stereotactic Radiosurgery Versus Observation in Small- and Medium-Sized Vestibular Schwannoma Patients With Normal Hearing: A Retrospective International Multicenter Study

Hajikarimloo, Bardia; Bin-Alamer, Othman; Tos, Salem M; Mantziaris, Georgios; Ishaque, Mariam; Abou-Al-Shaar, Hussam; Peker, Selcuk; Samanci, Yavuz; Pelcher, Isabelle; Begley, Sabrina; Goenka, Anuj; Schulder, Michael; Tourigny, Jean-Nicolas; Mathieu, David; Hamel, Andréanne; Briggs, Robert G; Yu, Cheng; Zada, Gabriel; Giannotta, Steven L; Speckter, Herwin; Palque, Sarai; Tripathi, Manjul; Kumar, Saurabh; Kaur, Rupinder; Kumar, Narendra; Rogowski, Brandon; Shepard, Matthew J; Johnson, Bryan A; Trifiletti, Daniel M; Warnick, Ronald E; Mashiach, Elad; De Nigris Vasconcellos, Fernando; Bernstein, Kenneth; Schnurman, Zane; Alzate, Juan; Kondziolka, Douglas; Sheehan, Jason P
BACKGROUND AND OBJECTIVES/OBJECTIVE:The therapeutic approach for small- and medium-sized vestibular schwannoma (VS) with normal hearing function remains controversial, with limited comparative data regarding hearing outcomes after stereotactic radiosurgery (SRS) or observation (OBS). We evaluated the serviceable hearing preservation, loss of American Academy of Otolaryngology-Head and Neck Surgery class A hearing, and tumor control (TC) across individuals with Koos grade I and II VSs and normal hearing at presentation who underwent SRS or OBS. METHODS:In this multicenter international study, we retrospectively analyzed the hearing, radiological, and neurological outcomes of patients who underwent SRS (SRS group) or OBS (OBS group). The cohorts were matched using propensity scores based on age, sex, tumor volume, pure-tone average, and speech discrimination score at a 1:1 ratio without replacement. RESULTS:After matching, each group comprised 57 patients. The median follow-up was 49 and 37 months for the SRS and the OBS groups, respectively (P = .3). The 5- and 9-year serviceable hearing preservation rates in the SRS group were 76.2% and 42.4% vs 56.1% and 16.8% in the OBS group (P = .17). Class A preservation occurred in 57.9% (33/57) of the SRS and 52.6% (30/57) of the OBS cohorts (P = .70). Regarding the TC rates, SRS was associated with significantly higher TC rates (P < .0001). CONCLUSION/CONCLUSIONS:We found that SRS is significantly superior regarding TC and provided noninferior hearing outcomes compared with OBS in VS patients with American Academy of Otolaryngology-Head and Neck Surgery class A hearing at presentation. Therefore, we suggest performing SRS in individuals with VS and normal hearing function.
PMID: 40956102
ISSN: 1524-4040
CID: 5935102

Automating the Referral of Bone Metastases Patients With and Without the Use of Large Language Models

Sangwon, Karl L; Han, Xu; Becker, Anton; Zhang, Yuchong; Ni, Richard; Zhang, Jeff; Alber, Daniel Alexander; Alyakin, Anton; Nakatsuka, Michelle; Fabbri, Nicola; Aphinyanaphongs, Yindalon; Yang, Jonathan T; Chachoua, Abraham; Kondziolka, Douglas; Laufer, Ilya; Oermann, Eric Karl
BACKGROUND AND OBJECTIVES/OBJECTIVE:Bone metastases, affecting more than 4.8% of patients with cancer annually, and particularly spinal metastases require urgent intervention to prevent neurological complications. However, the current process of manually reviewing radiological reports leads to potential delays in specialist referrals. We hypothesized that natural language processing (NLP) review of routine radiology reports could automate the referral process for timely multidisciplinary care of spinal metastases. METHODS:We assessed 3 NLP models-a rule-based regular expression (RegEx) model, GPT-4, and a specialized Bidirectional Encoder Representations from Transformers (BERT) model (NYUTron)-for automated detection and referral of bone metastases. Study inclusion criteria targeted patients with active cancer diagnoses who underwent advanced imaging (computed tomography, MRI, or positron emission tomography) without previous specialist referral. We defined 2 separate tasks: task of identifying clinically significant bone metastatic terms (lexical detection), and identifying cases needing a specialist follow-up (clinical referral). Models were developed using 3754 hand-labeled advanced imaging studies in 2 phases: phase 1 focused on spine metastases, and phase 2 generalized to bone metastases. Standard McRae's line performance metrics were evaluated and compared across all stages and tasks. RESULTS:In the lexical detection, a simple RegEx achieved the highest performance (sensitivity 98.4%, specificity 97.6%, F1 = 0.965), followed by NYUTron (sensitivity 96.8%, specificity 89.9%, and F1 = 0.787). For the clinical referral task, RegEx also demonstrated superior performance (sensitivity 92.3%, specificity 87.5%, and F1 = 0.936), followed by a fine-tuned NYUTron model (sensitivity 90.0%, specificity 66.7%, and F1 = 0.750). CONCLUSION/CONCLUSIONS:An NLP-based automated referral system can accurately identify patients with bone metastases requiring specialist evaluation. A simple RegEx model excels in syntax-based identification and expert-informed rule generation for efficient referral patient recommendation in comparison with advanced NLP models. This system could significantly reduce missed follow-ups and enhance timely intervention for patients with bone metastases.
PMID: 40823772
ISSN: 1524-4040
CID: 5908782

The 35-Year Evolution of Stereotactic Radiosurgery for Meningiomas

Wei, Chris Z; Niranjan, Ajay; Deng, Hansen; Puccio, David; Shanahan, Regan; McKendrick, Lindsay; Flickinger, John C; Kondziolka, Douglas; Hadjipanayis, Constantinos G; Lunsford, L Dade; ,
BACKGROUND AND OBJECTIVES/OBJECTIVE:Since the introduction of the Leksell Gamma Knife to North America in 1987, stereotactic radiosurgery (SRS) has increasingly been used for patients with intracranial meningiomas. We evaluated the evolving application and outcomes of meningioma patients managed with both primary and adjuvant SRS during a 35-year interval. METHODS:The authors reviewed the outcomes of meningioma patients (1229 female, 69.8%; 2220 tumors) who underwent single-fraction SRS from August 1987 to March 2022 and who had a minimum of 6-month follow-up. The rates of treated tumor control and overall survival up to 20 years after SRS were measured. Risk factors analyzed included age, sex, tumor volume, margin dose, Ki-67, anatomical location, and pre-SRS surgical resection. RESULTS:Primary SRS showed superior tumor control compared with adjuvant SRS after previous resection. Overall, 191 of 2220 patients (8.6%) had local progression at last follow-up with the 5-year, 10-year, 15-year, and 20-year tumor control rates were 92.1%, 88.3%, 84.1%, and 81.1%, respectively. The median overall survival after SRS was 17.4 years, and 2.6% of patients died related to meningioma progression. Patients treated so that ≥60% of the tumor received at least 16 Gy demonstrated significantly superior tumor control. Fifty-eight patients (3.3%) experienced symptomatic adverse radiation effects after SRS. CONCLUSION/CONCLUSIONS:SRS provided excellent local tumor control rates that extended beyond 20 years. Primary SRS was an effective strategy for patients with unresected or known WHO grade I meningiomas. Adjuvant SRS was an important option to enhance tumor control and survival in patients with residual or progressive tumors after resection.
PMID: 40844288
ISSN: 1524-4040
CID: 5909372