Intraoperatively Observed Site of Origin and Growth Pattern of Medulloblastoma

NCT06814353 | Enrolling By Invitation

• 1 other identifier: ISOP (EK 1967/2023)
• Study Type: observational
• Target: 100
• Locations: 3 countries
• Sites: 4

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.

Conditions

Medulloblastoma

Keywords

Medulloblastoma

Outcome Measures

Primary Outcomes (1)

• Rate of agreement between the intraoperatively observed site of origin and preoperatively radiologically assessed site of origin of medulloblastoma

  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.

  From enrollment to the end of treatment at 6 weeks

Secondary Outcomes (3)

• 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 neurological outcome measured as KPS scores stratified by the intraoperatively observed site of origin

  From enrollment to the end of treatment at 6-weeks

• Predictive accuracy of radiogenomic models

  From enrollment to the end of treatment at 6 weeks

Study Arms (3)

WNT-MB

Patients with a medulloblastoma of the subgroup MB, WNT(Wingless)-activated according to the WHO classification 2021.

Procedure: Intraoperative assessment of the site of origin and growth pattern

SHH-MB

Patients with a medulloblastoma of the subgroup MB, SHH (Sonic Hedgehog)-activated according to the World Health Organization (WHO) classification 2021. This subgroup can be further differentiated into SHH-activated (SHH-MB) TP53-wildtype and MB, SHH-activated TP53-mutant.

Procedure: Intraoperative assessment of the site of origin and growth pattern

Group 3 and Group 4

Patients with a medulloblastoma of the subgroup MB, non-WNT/non-SHH activated MB (Group 3 and 4) according to the WHO classification 2021.

Procedure: Intraoperative assessment of the site of origin and growth pattern

Interventions

Intraoperative assessment of the site of origin and growth pattern PROCEDURE

The assessment of the epicenter and extension and therefore the assumed origin of tumor growth is conducted by an experienced pediatric neurosurgeon blinded to group allocation based on the intraoperative impression. The anatomical features and site of origin are systematically documented on the surgical form in all cases of this study.

Also known as: Assessment of the site and origin and growth pattern on preoperative MRI, Evaluation of anatomic features, Imaging feature extraction and characterization, Histopathological and molecular analysis

Group 3 and Group 4; SHH-MB; WNT-MB

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Both adult and pediatric patients who undergo surgical resection of a histologically confirmed medulloblastoma at a center with expertise in pediatric neurosurgery

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Christian Dorfer: lead
• Medical University of Vienna: collaborator
• University Hospital Tuebingen: collaborator
• Utrecht University: collaborator
• Charite University, Berlin, Germany: collaborator

Study Sites (4)

Department of Neurosurgery, Medical University of Vienna

Vienna, Vienna, 1090, Austria

Location

Department of Neurosurgery, Charité Berlin

Berlin, Germany

Location

Section of Pediatric Neurosurgery, University Hospital of Tuebingen

Tübingen, Germany

Location

Department of Neurosurgery, Princess Maxima Centre for Pediatric Oncology

Utrecht, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

Tumor samples which are gained during surgery will be analyzed. Histopathologic and genetic classification data are obtained by immunohistochemistry for β-Catenin, Yap1, Gab1, p53 and complementary mutation analysis of the by DNA methylation profiling (Illumina, San Diego, California), which is the current gold standard for the allocation to the molecular group of medulloblastoma.

MeSH Terms

Conditions

Medulloblastoma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assoc. Prof. Priv.-Doz. Dr. Christian Dorfer, MBA

Study Record Dates

• First Submitted: December 26, 2024
• First Posted: February 7, 2025
• Study Start: March 1, 2024
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: February 7, 2025

Record last verified: 2025-02

Locations

AU (1); DE (2); NL (1)