Mariska Sie

DNA methylation-based classification is increasingly a cornerstone of CNS tumor diagnostics. Recently,nanopore sequencing enables very rapid methylation profiling to support surgical decision making. Time-constrained sequencing yields sparse methylation profiles, necessitating specialized classifiers for accurate predictions. All publicly available sparse-profile classifiers rely on a single reference set of only 2,801 samples published in 2018 and its accompanying classification system. Here we present Sturgeon V2, trained on nearly 10,000 methylation profiles assembled from a range of public repositories and collaborations. To harmonize differences in tumor class labels, we developed an iterative semi-supervised relabeling strategy with a two-tiered concordance filter. We demonstrate that this filtering is essential for optimal performance. Compared to Sturgeon V1, we further redesigned the classifier architecture to provide more stable, and consistent confidence estimates while accumulating sequencing data and we introduce an updated class system including new classes, such as meningioma subtypes, PATZ-fusion neuroepithelial tumors and PLAG1/2-amplified embryonal tumors. In a retrospective intraoperative cohort of 94 pediatric cases, Sturgeon V2 was confidently correct in 85 cases (Sturgeon V1: 78) with one confident misclassification, and in simulated sequencing runs (n=1880) reduced the error rate among confident calls from 7.1% to 2.8%, outperforming publicly available alternatives. Sturgeon V2 is the first openly available, locally executable classifier for sparse methylation profiles trained beyond the 2018 reference era.

Background: Central nervous system (CNS) tumors represent the leading cause of pediatric cancer-related deaths. Primary treatment often involves neurosurgical tumor resection. Accurate diagnosis is crucial to perform the best-suited extent of resection. Recently, we published Sturgeon, an AI-based validated intraoperative nanopore sequencing tool, delivering accurate methylation-based diagnoses during surgery. Although several other nanopore sequencing strategies have been described, clear evidence of clinical impact remains critically absent. Here, we report a care evaluation analyzing the impact of Sturgeon on real-time pediatric neurosurgical decision-making. Methods: Since May 2023, a dual diagnostic neuro-oncological workflow incorporating intraoperative frozen section analyses and ultra-fast nanopore sequencing using Sturgeon has been fully implemented as standard of care at the Princess Máxima Center for Pediatric Oncology in the Netherlands. This intraoperative diagnostic workflow has been applied to all pediatric patients (<19 years of age) with primary CNS tumors and the multidisciplinary indication for tumor resection surgery. Results: Sturgeon delivered correct diagnoses in 82 out of 94 consecutive patients (87.2%, <90 minutes), no diagnosis in 11.7% and one incorrect diagnosis (1.1%). The diagnosis obtained by Sturgeon supported the intended surgical strategy (85.7%) or changed the strategy (14.3%) toward a more aggressive or limited resection. This contributed to a low complication rate and less second-look surgeries. Earlier communication of the histomolecular diagnosis to patients and their families was observed. Conclusions: Intraoperative use of Sturgeon provides essential guidance toward the most optimal neurosurgical strategy for pediatric CNS tumors and thereby has great potential to contribute to better clinical outcome.

BACKGROUND AND OBJECTIVES: Intraoperative ultrasound (iUS) is increasingly used in pediatric brain tumor surgery. However, accurate tumor tissue identification and localization within the patient with iUS remains challenging. Automatic tumor segmentation may overcome these difficulties by providing quicker, more consistent, and reliable image analysis. This study evaluated the feasibility of automatic 3-dimensional segmentation of pediatric brain tumors using navigated iUS. METHODS: A retrospective analysis was conducted on 109 navigated iUS acquisitions from 60 pediatric patients who underwent neurosurgical tumor resection. 3-dimensional nnU-Net was trained on 79 preresectional iUS acquisitions with corresponding tumor segmentations. Evaluation was performed on 30 iUS acquisitions against segmentations validated by 2 neurosurgeons. Performance benchmarks were set at a minimum Dice Similarity Coefficient (DSC) of 0.85 and a maximum mean surface distance and 95th percentile Hausdorff distance of 5 mm. RESULTS: The trained algorithm predicted tumor segmentations for all acquisitions in the test set, which met the predefined benchmark values with a median DSC of 0.89 (IQR: 0.13), a median mean surface distance of 1.1 mm (IQR: 1.0 mm), and a median 95th percentile Hausdorff distance of 5.6 mm (IQR: 3.5 mm). The lowest quartile of DSC values consisted of 5 patients, including craniopharyngiomas (n = 3) and high-grade gliomas (n = 2). Oversegmentation of the lateral ventricle as tumor was observed in 2 patients. In 1 high-grade glioma case, edema was misclassified as tumor because of unclear tumor boundaries. CONCLUSION: This study demonstrates that automatic segmentation of pediatric brain tumors using navigated iUS is feasible and achieved high performance in most cases, with few outliers that showed moderate performance in tumor prediction. Future efforts will focus on real-time segmentation of residual tumor tissue during tumor resection. Ultimately, real-time visualization of automatically segmented tumors in 3 dimensions could improve intraoperative navigation and support neurosurgical decision making.

For pediatric patients with central nervous system (CNS) tumors, primary treatment often involves neurosurgical tumor resection. Accurate diagnosis is crucial to perform the best-suited extent of resection. Since two years, Sturgeon, an AI-based validated intraoperative nanopore sequencing tool, has been fully integrated with frozen section analyses as standard of care in our nationwide centralized pediatric oncology hospital. This care evaluation is the first to demonstrate the impact of Sturgeon on neurosurgical decision-making. Sturgeon delivered correct diagnoses in 82 out of 94 consecutive patients (87.2%, <90 minutes), no diagnosis in 11.7% and 1 incorrect diagnosis. The diagnosis obtained by Sturgeon supported the intended surgical strategy (85.7%) or changed the strategy (14.3%) toward a more aggressive or limited resection. This resulted in only 3.2% second-look surgeries. In conclusion, intraoperative use of Sturgeon provides essential guidance toward the most optimal neurosurgical strategy and thereby has great potential to contribute to better clinical outcome.

Objective: To illustrate the possibility of spontaneous involution of a pineal cyst, justifying an initial observation strategy in patients without evident mass effect. Background: Pineal cysts are frequent radiological findings, with a reported overall prevalence from 0.6% to 40%. Historically, surgery has been reserved for patients with symptoms attributable to a mass effect of the cyst. Despite the high prevalence of pineal cysts, the clinical approach to patients with non‐specific symptoms remains controversial. Methods: We report on the spontaneous involution of a large pineal cyst in a 26‐year‐old female who presented in our outpatient clinic with transient symptoms of headache and nausea. PubMed and Web of Science databases were scrutinized using a predefined search strategy in accordance with the Population, Intervention, Comparison and Outcome (PICO) set‐up using “pineal cyst” and “surgery” as search terms. Only peer‐reviewed publications were considered eligible. Titles and abstracts of 1513 manuscripts were screened for relevance. After excluding 1420 publications evaluating non‐relevant pathology, the eligibility of the remaining 93 full‐text records was further assessed and included if they reported patients with pineal cysts presenting with intractable symptoms without hydrocephalus or Parinaud syndrome, and if they documented on their symptomatology and clinical management. Conclusion: Recent case series and reviews report favorable results of surgery in patients with pineal cysts but also a potentially high complication rate. However, the evidence offered by these reports is limited and a placebo effect cannot be ruled out. Therefore, surgery cannot be unequivocally advocated in these patients. Instead, an initial surveillance strategy is advocated. We concur with a previously propounded surveillance strategy of a single follow‐up magnetic resonance imaging at 12 months. This case report demonstrates the importance of an initial observation strategy since pineal cysts may also show a spontaneous involution.