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Client Context
Client Context
A multi-institutional cancer research consortium aimed to improve clinical decision-making in medulloblastoma, a common pediatric brain tumor. The consortium sought to integrate genomic data from multiple studies to refine risk classification and inform therapy choices.
Business Challenge
Business Challenge
Traditional clinical risk categories do not fully account for underlying genomic heterogeneity in medulloblastoma. In particular, there was ambiguity around whether patients with iso17 alterations should be classified as high risk, and how this classification compares with patients whose tumors harbor MYC amplification. Without precise stratification, patients may receive suboptimal intensity of therapy—either overtreatment or undertreatment.
Analytical Approach
Analytical Approach
Researchers developed and deployed a Medulloblastoma Meta-Analysis Portal, aggregating genomic, clinical, and survival data from large-scale studies.
The analysis included:
Genomic profiling to identify iso17 structural variants and MYC amplification events
Survival analysis (e.g., Kaplan–Meier curves) comparing outcomes across genomic subgroups
Comparative risk modeling to quantify the prognostic impact of iso17 versus MYC alterations
Integration of results into an interactive portal to facilitate exploration and hypothesis testing
Key Insights
Key Insights
Patients with MYC amplification consistently exhibited poorer overall and progression-free survival, confirming its status as a high-risk genomic marker.
Tumors containing the iso17 alteration showed intermediate outcomes, suggesting that classifying all iso17 cases as high risk may overestimate true clinical risk.
The meta-analysis highlighted that genomic context matters: iso17 in combination with other high-risk features (e.g., TP53 mutation or chromosome imbalance) showed worse outcomes than iso17 alone.
Risk stratification models that included both structural variants and co-occurring genomic events outperformed models based on single markers.
Business Impact
Business Impact
Provided a data-driven framework for clinical risk stratification beyond traditional clinical features.
Informed clinicians and trial designers that MYC amplification should be prioritized as a high-risk identifier, whereas iso17 requires contextual interpretation.
Guided refinement of clinical trial eligibility criteria and therapeutic intensity decisions, improving alignment between treatment aggressiveness and true biological risk.
Outcome
Outcome
The genomic risk stratification model informed by the Medulloblastoma Meta-Analysis Portal:
Enhanced prognostic accuracy for patients
Reduced potential for overtreatment among iso17 cases without high-risk co-features
Supported personalized treatment planning and future biomarker-driven clinical trials
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