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Augmenting Large Language Models With Automated, Bibliometrics-Powered Literature Search for Knowledge Distillation: A Pilot Study for Common Spinal Pathologies
Kurland, David B; Alber, Daniel A; Palla, Adhith; de Souza, Daniel N; Lau, Darryl; Laufer, Ilya; Frempong-Boadu, Anthony K; Kondziolka, Douglas; Oermann, Eric K
BACKGROUND AND OBJECTIVES/OBJECTIVE:Scholarly output is accelerating in medical domains, making it challenging to keep up with the latest neurosurgical literature. The emergence of large language models (LLMs) has facilitated rapid, high-quality text summarization. However, LLMs cannot autonomously conduct literature reviews and are prone to hallucinating source material. We devised a novel strategy that combines Reference Publication Year Spectroscopy-a bibliometric technique for identifying foundational articles within a corpus-with LLMs to automatically summarize and cite salient details from articles. We demonstrate our approach for four common spinal conditions in a proof of concept. METHODS:Reference Publication Year Spectroscopy identified seminal articles from the corpora of literature for cervical myelopathy, lumbar radiculopathy, lumbar stenosis, and adjacent segment disease. The article text was split into 1024-token chunks. Queries from three knowledge domains (surgical management, pathophysiology, and natural history) were constructed. The most relevant article chunks for each query were retrieved from a vector database using chain-of-thought prompting. LLMs automatically summarized the literature into a comprehensive narrative with fully referenced facts and statistics. Information was verified through manual review, and spine surgery faculty were surveyed for qualitative feedback. RESULTS:Our tandem approach cost less than $1 for each condition and ran within 5 minutes. Generative Pre-trained Transformer-4 was the best-performing model, with a near-perfect 97.5% citation accuracy. Surveys of spine faculty helped refine the prompting scheme to improve the cohesion and accessibility summaries. The final artificial intelligence-generated text provided high-fidelity summaries of each pathology's most clinically relevant information. CONCLUSION/CONCLUSIONS:We demonstrate the rapid, automated summarization of seminal articles for four common spinal pathologies, with a generalizable workflow implemented using consumer-grade hardware. Our tandem strategy fuses bibliometrics and artificial intelligence to bridge the gap toward fully automated knowledge distillation, obviating the need for manual literature review and article selection.
PMID: 40662770
ISSN: 1524-4040
CID: 5897082
Extended nnU-Net for Brain Metastasis Detection and Segmentation in Contrast-Enhanced Magnetic Resonance Imaging With a Large Multi-Institutional Data Set
Yoo, Youngjin; Gibson, Eli; Zhao, Gengyan; Re, Thomas J; Parmar, Hemant; Das, Jyotipriya; Wang, Hesheng; Kim, Michelle M; Shen, Colette; Lee, Yueh; Kondziolka, Douglas; Ibrahim, Mohannad; Lian, Jun; Jain, Rajan; Zhu, Tong; Comaniciu, Dorin; Balter, James M; Cao, Yue
PURPOSE/OBJECTIVE:The purpose of this study was to investigate an extended self-adapting nnU-Net framework for detecting and segmenting brain metastases (BM) on magnetic resonance imaging (MRI). METHODS AND MATERIALS/METHODS:Six different nnU-Net systems with adaptive data sampling, adaptive Dice loss, or different patch/batch sizes were trained and tested for detecting and segmenting intraparenchymal BM with a size ≥2 mm on 3 Dimensional (3D) post-Gd T1-weighted MRI volumes using 2092 patients from 7 institutions (1712, 195, and 185 patients for training, validation, and testing, respectively). Gross tumor volumes of BM delineated by physicians for stereotactic radiosurgery were collected retrospectively and curated at each institute. Additional centralized data curation was carried out to create gross tumor volumes of uncontoured BM by 2 radiologists to improve the accuracy of ground truth. The training data set was augmented with synthetic BMs of 1025 MRI volumes using a 3D generative pipeline. BM detection was evaluated by lesion-level sensitivity and false-positive (FP) rate. BM segmentation was assessed by lesion-level Dice similarity coefficient, 95-percentile Hausdorff distance, and average Hausdorff distance (HD). The performances were assessed across different BM sizes. Additional testing was performed using a second data set of 206 patients. RESULTS:. Mean values of Dice similarity coefficient, 95-percentile Hausdorff distance, and average HD of all detected BMs were 0.758, 1.45, and 0.23 mm, respectively. Performances on the second testing data set achieved a sensitivity of 0.907 at an FP rate of 0.57 ± 0.85 for all BM sizes, and an average HD of 0.33 mm for all detected BM. CONCLUSIONS:Our proposed extension of the self-configuring nnU-Net framework substantially improved small BM detection sensitivity while maintaining a controlled FP rate. Clinical utility of the extended nnU-Net model for assisting early BM detection and stereotactic radiosurgery planning will be investigated.
PMID: 39059508
ISSN: 1879-355x
CID: 5696192
Vestibular Schwannoma Koos Grade I International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS-K1 Study
Bin-Alamer, Othman; 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; Dayawansa, Samantha; Mashiach, Elad; Vasconcellos, Fernando De Nigris; Bernstein, Kenneth; Schnurman, Zane; Alzate, Juan; Kondziolka, Douglas; Sheehan, Jason P
BACKGROUND AND OBJECTIVE/OBJECTIVE:This investigation evaluates the safety and efficacy of stereotactic radiosurgery (SRS) vs observation for Koos grade I vestibular schwannomas (VS). METHODS:In a multicenter study, we retrospectively analyzed data of patients with Koos grade I VS who underwent SRS (SRS group) or were observed (observation group). Propensity score matching was used to equilibrate demographics, tumor size, and audiometric data across groups. The outcome analyzed included tumor control, preservation of serviceable hearing, and neurological function. RESULTS:The study matched 142 patients, providing a median follow-up period of 36 months. SRS significantly enhanced tumor control compared with observation, with a 100% control rate at both 5- and 8-year marks in the SRS group vs 48.6% and 29.5% in the observation group at the same time intervals, respectively ( P < .001). Preservation of serviceable hearing outcomes between groups showed no significant difference at 5 and 8 years, ensuring a comparable quality of auditory function (SRS 70.1% vs observation 53.4% at 5 years; P = .33). Furthermore, SRS was associated with a reduced likelihood of tinnitus (odds ratio [OR] = 0.46, P = .04), vestibular dysfunction (OR = 0.17, P = .002), and overall cranial nerve dysfunction (OR = 0.49, P = .03) at last follow-up. CONCLUSION/CONCLUSIONS:SRS management of patients with Koos grade I VS was associated with superior tumor control and reduced odds for cranial nerve dysfunction, while not compromising hearing preservation compared with observation. These findings support the safety and efficacy of SRS as a primary care approach for this patient population.
PMID: 39503441
ISSN: 1524-4040
CID: 5763952
Vestibular Schwannoma Koos Grade II International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS-K2 Study
Bin-Alamer, Othman; 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; Dayawansa, Samantha; Mashiach, Elad; Vasconcellos, Fernando De Nigris; Bernstein, Kenneth; Schnurman, Zane; Alzate, Juan; Kondziolka, Douglas; Sheehan, Jason P
BACKGROUND AND OBJECTIVES/OBJECTIVE:This study assessed the efficacy and safety of stereotactic radiosurgery (SRS) in comparison with watchful waiting for managing Koos grade II vestibular schwannomas (VS). METHODS:A retrospective, multicentric analysis was conducted, focusing on patients with Koos grade II VS who either received SRS (SRS group) or were observed (observation group). To ensure comparability between groups, propensity score matching was used, including factors such as demographic characteristics, tumor dimensions, and hearing assessments. The primary end points examined were tumor control, maintenance of serviceable hearing, and neurological outcomes. RESULTS:A total of 92 patients were equally matched across both cohorts, with a median follow-up of 37 months for the SRS group and 27.5 months for those observed. The SRS cohort exhibited superior tumor control over observation across 3, 5, and 8 years, achieving a 100% control rate vs 47.9%, 40.1%, and 34.3% for the observation group at these time intervals, respectively ( P < .001). Serviceable hearing preservation rates were comparable between the 2 groups throughout 3, 5, and 7 years (72.9% for SRS vs 65.4% for observation at 3 years; P = .86). Moreover, SRS management correlated with a lower incidence of vestibular symptoms (odds ratio = 0.11, P = .002), with no significant disparity in the deterioration of cranial nerve (CN) V or CN VII functions. Notably, the likelihood of experiencing any CN impairment was significantly diminished in the SRS cohort (odds ratio = 0.47, P = .04). CONCLUSION/CONCLUSIONS:For patients with Koos grade II VS, SRS offers superior tumor control rate and a lower risk of CN dysfunction without sacrificing hearing preservation.
PMID: 39503444
ISSN: 1524-4040
CID: 5763962
Case Report: Unlocking opportunities in HER2-targeted antibody-drug conjugates for bulky leptomeningeal metastatic breast cancer [Case Report]
Leal, Alessandro; Kondziolka, Douglas; Pacione, Donato; Antwi, Stacy; Kurz, Sylvia; Lin, Nancy; Adams, Sylvia
Leptomeningeal carcinomatosis (LC) is a severe complication of metastatic breast cancer (mBC), with rising incidence. The prognosis for patients with LC has been poor, with a median overall survival of approximately four months. However, recent therapeutic advances, in particular the introduction of trastuzumab deruxtecan have dramatically changed the landscape of CNS metastases and improved outcomes. Here, we present the case of a 42-year-old woman with recurrent HER2+ breast cancer who developed extensive LC after multiple lines of treatment. Despite progressive disease, the patient exhibited a sustained response to trastuzumab deruxtecan, a novel antibody-drug conjugate (ADC), for 15 months, which was further extended by adding tucatinib. This case underscores the potential of ADCs, like trastuzumab deruxtecan, in controlling both brain metastases and leptomeningeal disease, offering hope for prolonged survival in patients with aggressive HER2+ mBC. Additionally, we highlight the evolving role of clinical trials, molecular profiling, and interdisciplinary care in managing this challenging condition. Ongoing trials continue to investigate new therapeutic options for HER2+ mBC with CNS involvement, promising to further improve outcomes and quality of life for patients facing this devastating disease.
PMCID:12380859
PMID: 40881856
ISSN: 2234-943x
CID: 5910772
Risk of new tumor, carotid stenosis, and stroke after Stereotactic Radiosurgery for Pituitary Tumor: A multicenter study of 2254 patients with imaging follow-up
Dumot, Chloe; Mantziaris, Georgios; Dayawansa, Sam; Brantley, Carson; Lee, Cheng-Chia; Yang, Huai-Che; Peker, Selcuk; Samanci, Yavuz; Mathieu, David; Tourigny, Jean-Nicolas; Moreno, Nuria Martinez; Alvarez, Roberto Martinez; Chytka, Thomas; Liscak, Roman; Speckter, Herwin; Lazo, Erwin; Brito, Anderson; Picozzi, Piero; Franzini, Andrea; Alzate, Juan; Mashiach, Elad; Bernstein, Kenneth; Kondziolka, Douglas; Tripathi, Manjul; Bowden, Greg N; Warnick, Ronald E; Sheehan, Darrah; Sheehan, Kimball; Fuentes, Angelica; Jane, John A; Lee Vance, Mary; Sheehan, Jason P
BACKGROUND:Higher risk of secondary brain tumor, carotid stenosis and stroke has been reported after conventional sella irradiation for pituitary neuroendocrine tumors (PitNET). Stereotactic radiosurgery (SRS), which is a more focused approach, is now increasingly used instead. The aim was to assess the risk of secondary brain tumor, carotid stenosis/occlusion and stroke after SRS. METHODS:In this multicentric retrospective study, 2,254 patients with PitNET were studied, 1,377 in the exposed group and 877 in the control group. RESULTS:There were 9,840.1 patient-years at risk for the SRS and 5,266.5 for the control group. The 15-year cumulative probability of secondary intracranial tumor was 2.3% (95%CI:0.5%, 4.1%) for SRS and 3.7% (95%CI:0%, 8.7%) for the control group (p=0.6), with an incidence rate of 1.32 per 1,000 and 0.95 per 1,000, respectively. SRS was not associated with increased risk of tumorigenesis when stratified by age (HR: 1.59 [95%CI: 0.57, 4.47], p=0.38). The 15-year probability of new carotid stenosis/occlusion was 0.9% (95%CI: 0.2, 1.6) in the SRS and 2% (95%CI: 0, 4.4) in the control group (p=0.8). The 15-year probability of stroke was 2.6% (95%CI: 0.6%, 4.6%) in the SRS and 11.1% (95%CI: 6%, 15.9%) in the control group (p<0.001). In cox multivariate analysis stratified by age, SRS (HR 1.85[95%CI:0.64, 5.35], p=0.26) was not associated with risk of new stroke. CONCLUSION/CONCLUSIONS:No increased risk of long-term secondary brain tumor, new stenosis or occlusion and stroke was demonstrated in SRS group compared to control in this study with imaging surveillance.
PMID: 39028740
ISSN: 1523-5866
CID: 5732072
Understanding Permeability Changes in Vestibular Schwannomas as Part of the Dynamic Response to Radiosurgery Using Golden-Angle Radial Sparse Parallel Imaging: A Retrospective Study
Meng, Ying; Lee, Matthew D; Berger, Assaf; Wiggins, Roy; O'Callaghan, James; Bernstein, Kenneth; Santhumayor, Brandon; Block, Kai Tobias; Fatterpekar, Girish; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:Vestibular schwannomas demonstrate different responses after stereotactic radiosurgery (SRS), commonly including a transient loss of internal enhancement on postcontrast T1-weighted MRI thought to be due to an early reduction in tumor vascularity. We used dynamic contrast-enhanced based golden-angle radial sparse parallel (GRASP) MRI to characterize the vascular permeability changes underlying this phenomenon, with correlations to long-term tumor regression. METHODS:Consecutive patients with vestibular schwannoma who underwent SRS between 2017 and 2019, had a transient loss of enhancement after SRS, and had long-term longitudinal GRASP studies (6, 18, and 30 months) were included in this retrospective cohort analysis (n = 19). Using GRAVIS ( https://gravis-imaging.org/gravis/ ), an analysis pipeline for GRASP studies, we extracted the key parameters normalized to the venous sinus from a region of interest within the tumor. RESULTS:The peak, area under the curve (AUC), and wash-in phase slope were significantly reduced at 6, 18, and 30 months after SRS (corrected P < .05), even while the internal enhancement returned in the tumors. Larger pre-SRS tumors were more likely to have a greater reduction in peak ( P = .013) and AUC ( P = .029) at 6 months. In a subset of patients (N = 13) with long-term follow-up, the median percentage reduction in tumor volume was 58% at a median of 62 months. These patients showed a strong correlation between peak, AUC, and wash-in phase slope changes at 6 months and tumor volume at the last follow-up. CONCLUSION/CONCLUSIONS:After SRS and loss of internal contrast uptake within vestibular schwannomas, a slow vascular permeability dynamic persisted, suggesting the presence of postradiation processes such as fibrosis. We show for the first time, using GRASP, a quantitative assessment of the vascular radiobiological effect.
PMID: 39625281
ISSN: 1524-4040
CID: 5804392
A General Framework for Characterizing Inaccuracy in Stereotactic Systems
Jensen, Michael A; Neimat, Joseph S; Kerezoudis, Panagiotis; Ali, Rushna; Richardson, R Mark; Halpern, Casey H; Ojemann, Steven; Ponce, Francisco A; Lee, Kendall H; Haugen, Laura M; Klassen, Bryan T; Kondziolka, Douglas; Miller, Kai J
BACKGROUND AND OBJECTIVES/OBJECTIVE:Identifying and characterizing sources of targeting error in stereotactic procedures is essential to maximizing accuracy, potentially improving surgical outcomes. We aim to describe a generic framework which characterizes sources of stereotactic inaccuracy. METHODS:We assembled a list of stereotactic systems: ROSA, Neuromate, Mazor Renaissance, ExcelsiusGPS, Cirq, STarFix (FHC), Nexframe, ClearPoint, CRW, and Leksell. We searched the literature for qualitative and quantitative work identifying and quantifying potential sources of inaccuracy and describing each system's implementation using Standards for Reporting Qualitative Research guidelines. Our literature search spanned 1969 to 2024, and various studies were included, with formats ranging from phantom studies to systematic reviews. Keyword searches were conducted, and the details about each system were used to create a framework for identifying and describing the unique targeting error profile of each system. RESULTS:We describe and illustrate the details of various sources of stereotactic inaccuracies and generate a framework to unify these sources into a single framework. This framework entails 5 domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. This framework was applied to 10 stereotactic systems. CONCLUSION/CONCLUSIONS:This framework provides a rubric to analyze the sources of error for any stereotactic system. Illustrations allow the reader to understand sources of error conceptually so that they may apply them to their practice.
PMID: 39627169
ISSN: 2332-4260
CID: 5780152
Outcomes of Radiosurgery for WHO Grade 2 Meningiomas: The Role of Ki-67 Index in Guiding the Tumor Margin Dose
Meng, Ying; Bernstein, Kenneth; Mashiach, Elad; Santhumayor, Brandon; Kannapadi, Nivedha; Gurewitz, Jason; Snuderl, Matija; Pacione, Donato; Sen, Chandra; Donahue, Bernadine; Silverman, Joshua S; Sulman, Erik; Golfinos, John; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:The management of World Health Organization (WHO) grade 2 meningiomas is complicated by their diverse clinical behaviors. Stereotactic radiosurgery (SRS) can be an effective management option. Literature on SRS dose selection is limited but suggests that a higher dose is better for tumor control. We characterize the predictors of post-SRS outcomes that can help guide planning and management. METHODS:We reviewed a cohort of consecutive patients with pathologically-proven WHO grade 2 meningiomas who underwent SRS at a single institution between 2011 and 2023. RESULTS:Ninety-nine patients (median age 62 years) underwent SRS, 11 of whom received hypofractionated SRS in 5 fractions. Twenty-two patients had received previous irradiation. The median follow-up was 49 months. The median overall survival was 119 months (95% CI 92-NA) with estimated 5- and 10-year survival of 83% and 27%, respectively. The median progression-free survival (PFS) was 40 months (95% CI 32-62), with 3- and 5-year rates at 54% and 35%, respectively. The median locomarginal PFS was 63 months (95% CI 51.8-NA) with 3- and 5-year rates at 65% and 52%. Nine (9%) patients experienced adverse events, 2 Common Terminology Criteria for Adverse Events grade 3 and 7 grade 2, consisting of worsening neurologic deficit from edema. In the single-session cohort, Ki-67 significantly predicted both overall survival and intracranial PFS. Tumors with Ki-67 >10% had 2.17 times the risk of locomarginal progression compared with Ki-67 ≤10% (P = .018) adjusting for covariates. Sex, prescription dose, tumor volume, and location also predicted tumor control. In tumors with Ki-67 >10%, margin dose ≥14 Gy was associated with significantly better tumor control but not for tumors with Ki-67 ≤10%. CONCLUSION/CONCLUSIONS:The management of WHO grade 2 meningiomas requires a multimodality approach. This study demonstrates the value of a targeted SRS approach in patients with limited disease and further establishes predictive biomarkers that can guide planning through a personalized approach.
PMID: 39526756
ISSN: 1524-4040
CID: 5752612
Outcomes Associated With Stereotactic Radiosurgery After Multiple Resections of Nonfunctioning Pituitary Macroadenomas: An International, Multicenter Case Series
Grogan, Dayton; Dumot, Chloe; Mantziaris, Georgios; Tos, Salem M; Tewari, Anant; Dayawansa, Sam; Sheehan, Kimball; Sheehan, Darrah; Peker, Selcuk; Samanci, Yavuz; Nabeel, Ahmed M; Reda, Wael A; Tawadros, Sameh R; AbdelKarim, Khaled; El-Shehaby, Amr M N; Emad, Reem M; Abdelsalam, Ahmed Ragab; Liscak, Roman; May, Jaromir; Mashiach, Elad; Vasconcellos, Fernando De Nigris; Bernstein, Kenneth; Kondziolka, Douglas; Speckter, Herwin; Mota, Ruben; Brito, Anderson; Bindal, Shray Kumar; Niranjan, Ajay; Lunsford, L Dade; Benjamin, Carolina Gesteira; Almeida, Timoteo Abrantes de Lacerda; Mathieu, David; Tourigny, Jean-Nicolas; Tripathi, Manjul; Palmer, Joshua David; Mao, Jennifer; Matsui, Jennifer; Crooks, Joseph; Wegner, Rodney E; Shepard, Matthew J; Sheehan, Jason
BACKGROUND AND OBJECTIVES/OBJECTIVE:Stereotactic radiosurgery (SRS) represents an effective treatment for nonfunctioning pituitary adenomas (NFPAs). However, no data have yet been published regarding results of SRS on NFPAs after multiple previous resections. METHODS:Retrospective multicentric data of patients diagnosed with NFPA and who underwent multiple resections (≥2) before SRS were reviewed and analyzed. The treatment interval spanned the period of 1992 to 2022. Cox regression and Kaplan-Meier curves were used to assess predictive factors and the probability of tumor control and hypopituitarism. RESULTS:Among the 311 patients (median age: 50.2 [IQR: 18.0] years), 226 (72.7%) had undergone ≥2 previous resections. The median margin dose was 14 Gy (IQR: 4.0 Gy), and the median tumor volume 3.6 cm3 (IQR: 4.8). Overall, the probability of tumor control after SRS was 93.3% (CI 95%: 89.9-96.9) and 86.7% (CI 95%: 81.1-92.6) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with a decreased risk of tumor progression (hazard ratio = 0.33, CI 95% = 0.15-0.75, P = .008). At a last clinical follow-up of 4.1 (IQR 6.1) years, 10.1% (30/296) developed at least 1 new hormone deficiency after SRS. The cumulative probability of new hormone deficiency was 6.1% (95% CI: 3.0-9.1), 10.3% (95% CI: 5.8-14.6), and 18.9% (95% CI: 11.5-25.8) at 3, 5, and 10 years after SRS, respectively. The average latency between SRS and development of new hormone deficiencies was 3.3 years (IQR 4.1). A maximum point dose to the pituitary stalk >10 Gy was associated with a new deficiency (hazard ratio = 4.06, CI 95% = 1.57-10.5, P-value = .004). CONCLUSION/CONCLUSIONS:For patients with NFPA with multiple previous resections, SRS offers effective local tumor control and a low risk of delayed hypopituitarism for managing these challenging adenomas. SRS should be strongly considered in patients with NFPA with 2 previous resections compared with considering a third resection.
PMID: 39508579
ISSN: 1524-4040
CID: 5752032