Intraoperatively Observed Site of Origin and Growth Pattern of Medulloblastoma

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.

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Key information

Conditions

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

Sex eligibility

All sexes

Study type

Observational

Primary location

Department of Neurosurgery, Medical University of Vienna, Vienna, State of Vienna, Austria

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Other names: 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

Primary outcomes

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

Time frame: 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 outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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.

Sponsors and collaborators

Lead sponsor

Christian Dorfer

Other

Collaborators

Charite University, Berlin, Germany
Medical University of Vienna
University Hospital Tuebingen
Utrecht University

Registry information

Official study title

An International Multicenter Prospective Cohort Study Investigating the Intraoperatively Observed Site of Origin and Growth Pattern of the Molecular Groups of Medulloblastoma

Acronym: ISOP

Important dates

Study start: 2024
Primary completion: 2026
Study completion: 2026
First posted: Feb 7, 2025
Registry last updated: Feb 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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