Intraoperatively Observed Site of Origin and Growth Pattern of Medulloblastoma

• Conditions: Medulloblastoma

• Registration Number: NCT06814353
• Lead Sponsor: Christian Dorfer

Brief Summary

The goal of this observational study is to provide accurate and systematic data on the site of origin and growth pattern of medulloblastoma from a neurosurgical perspective. By integrating intraoperative, radiological and genetic classification data, this study will contribute to our current understanding of the development, site of origin and growth pattern of medulloblastoma and advance the predictive accuracy of radiogenomics models. Patients with histologically confirmed medulloblastoma who undergo surgical resection at a high-volume center with expertise in pediatric neurosurgery will be included.

The main questions it aims to answer are:

* Is there a significant difference between the intraoperatively observed site of origin and the preoperatively or postoperatively radiologically assessed site of origin of medulloblastoma?

* How does the intraoperatively observed site of origin align with the site of origin associated with the molecular group based on the developmental cell lineage concept of medulloblastoma?

* Does incorporating the intraoperatively observed site of origin as a feature improve the predictive accuracy of radiomic models for molecular group classification?

Participants will:

* Undergo intraoperative assessment of site of origin and growth pattern by an experienced pediatric neurosurgeon.

* Have their site of origin and growth pattern evaluated on pre- and postoperative magnetic resonance imaging by an neuroradiologist with expertise in pediatric brain tumors.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-01
• Study First Submitted: 2024-12-26
• Status Verified: 2025-02
• Study First Submitted QC: 2025-02-02
• Last Update Submitted: 2025-02-02
• Study First Posted: 2025-02-07
• Last Update Posted: 2025-02-07
• Primary Completion: 2026-03
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Patients who are referred for surgical resection of a medulloblastoma at a hospital with expertise in pediatric neurooncology
• Both pediatric patients (aged < 18 years at the time of diagnosis) and adult patients (aged > 18 years at the time of diagnosis)

Exclusion Criteria

• Patients who are preoperatively admitted with severe tumor hemorrhage accompanied by clinical deterioration are excluded because these patients frequently do not receive magnetic resonance imaging as would be necessary for the present study, and the intraoperative assessment of the STO is limited in accuracy due to decreased visibility caused by the intra- and extratumoral hemorrhage.
• If an intraoperative complication occurs (e.g. bleeding) which impairs visibility of the neuroanatomic structures and does not allow an accurate assessment of the STO, the patient is excluded.
• If the histopathological and molecular analysis does not confirm the diagnosis of a MB, the patient has to be excluded as well.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Rate of agreement between the intraoperatively observed site of origin and preoperatively radiologically assessed site of origin of medulloblastoma	From enrollment to the end of treatment at 6 weeks	The intraoperatively observed site of origin is categorized into brainstem, cerebellar hemispheres and cerebellar vermis.The intraoperatively observed site of origin is assessed by an experienced pediatric neurosurgeon blinded to subgroup allocation and systemically documented in surgical forms.; The location and site of origin is assessed by one expert neuroradiologist with expertise in pediatric brain tumor imaging who is blinded to the group allocation.; Preoperative magnetic resonance imaging (MRI) includes at least T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR) and contrast-enhanced, T1-weighted sequences. The presumed site of origin is analyzed following a simplification of the concept of Patay et al., 2015 with the following levels: posterior/posterolateral brainstem, midline vermis or cerebellar hemispheres based on the preoperative imaging aspect.; The rate of agreement between both measures is reported.

Secondary Outcome Measures

Name	Time	Method
The rate of agreement between the intraoperatively observed site of origin and the site of origin presumably associated with a molecular group (standard of reference) based on the developmental cell lineage concept of medulloblastoma	From enrollment to the end of treatment at 6 weeks	The intraoperatively observed site of origin is categorized into brainstem, cerebellar hemispheres and cerebellar vermis. The intraoperatively observed site of origin is assessed by an experienced pediatric neurosurgeon blinded to subgroup allocation and systemically documented in surgical forms.; Histopathological and genetic data are used to identify the molecular subgroup of the MB.; According to the current literature (Northcott et al., 2019), the site of origin presumably associated with the molecular group is categorized as brainstem for WNT-MB, the cerebellar hemisphere for SHH-MB and the cerebellar vermis for non-WNT/non-SHH-MB.; The rate of agreement between the intraoperatively observed site of origin (brainstem, cerebellar hemisphere, cerebellar vermis) and the site of origin presumably associated with a molecular group (brainstem, cerebellar hemisphere, cerebellar vermis) is reported for each molecular group separately.
The neurological outcome measured as KPS scores stratified by the intraoperatively observed site of origin	From enrollment to the end of treatment at 6-weeks	The intraoperatively observed site of origin is categorized into brainstem, cerebellar hemispheres and cerebellar vermis. The intraoperatively observed site of origin is assessed by an experienced pediatric neurosurgeon blinded to subgroup allocation and systemically documented in surgical forms.; The neurological outcome at 6 weeks- follow-up is assessed using the Karnofsy Performance Scale.; Patients are stratified by the intraoperatively observed site of origin into three groups (brainstem, cerebellar hemispheres, cerebellar vermis).; The KPS scores are reported as boxplots with median and interquartile range for the three groups separately.
Predictive accuracy of radiogenomic models	From enrollment to the end of treatment at 6 weeks	For construction of nomograms, the entire study sample will be split into a training cohort (TC) and a validation cohort (VC) in the ratio 7:3. Independent binary nomograms will be developed for each of the 4 subgroups. Receiver operating characteristics (ROC) curves will be generated following application of individual subgroup-specific nomograms to assign scores for patients in the TC. The methodology will be repeated in the VC. Optimal cutoff of total scores for individual subgroup-specific nomograms will be generated from the ROC curves from the TC for acceptable range of specificity and sensitivity, and their applicability was subsequently tested in the VC. Area under the curve (AUC) with 95% CI will be used for interpretation and reporting. MRI-based nomograms will be constructed two times, with the intraopely observed site of origin being the only additional feature. AUCs with 95% CI will be compared among the nomograms.

Trial Locations

Locations (4)

Department of Neurosurgery, Medical University of Vienna; 🇦🇹 Vienna, Austria

Department of Neurosurgery, Charité Berlin; 🇩🇪 Berlin, Germany

Section of Pediatric Neurosurgery, University Hospital of Tuebingen; 🇩🇪 Tuebingen, Germany

Department of Neurosurgery, Princess Maxima Centre for Pediatric Oncology; 🇳🇱 Utrecht, Netherlands