J Korean Med Sci.  2022 Feb;37(7):e59. 10.3346/jkms.2022.37.e59.

Risk Stratification of Childhood Medulloblastoma Using Integrated Diagnosis: Discrepancies With Clinical Risk Stratification

Affiliations
  • 1Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 2Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 3Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 4Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Abstract

Background
Recent genomic studies identified four discrete molecular subgroups of medulloblastoma (MB), and the risk stratification of childhood MB in the context of subgroups was refined in 2015. In this study, we investigated the effect of molecular subgroups on the risk stratification of childhood MB.
Methods
The nCounter® system and a customized cancer panel were used for molecular subgrouping and risk stratification in archived tissues.
Results
A total of 44 patients were included in this study. In clinical risk stratification, based on the presence of residual tumor/metastasis and histological findings, 24 and 20 patients were classified into the average-risk and high-risk groups, respectively. Molecular subgroups were successfully defined in 37 patients using limited gene expression analysis, and DNA panel sequencing additionally classified the molecular subgroups in three patients. Collectively, 40 patients were classified into molecular subgroups as follows: WNT (n = 7), SHH (n = 4), Group 3 (n = 8), and Group 4 (n = 21). Excluding the four patients whose molecular subgroups could not be determined, among the 17 average-risk group patients in clinical risk stratification, one patient in the SHH group with the TP53 variant was reclassified as very-high-risk using the new risk classification system. In addition, 5 of 23 patients who were initially classified as high-risk group in clinical risk stratification were reclassified into the low- or standard-risk groups in the new risk classification system.
Conclusion
The new risk stratification incorporating integrated diagnosis showed some discrepancies with clinical risk stratification. Risk stratification based on precise molecular subgrouping is needed for the tailored treatment of MB patients.

Keyword

Medulloblastoma; Integrated Diagnosis; Molecular Subgroup; Risk Stratification

Figure

  • Fig. 1 Risk stratification of patients. Clinical risk stratification using residual tumor/metastasis and histology and new risk stratification incorporating molecular subgroups are illustrated.

  • Fig. 2 Survival outcomes. Event-free and overall survival rates according to molecular subgroup, clinical risk stratification and new risk stratification are illustrated.HR = high risk, LR = low risk, SR = standard risk, VHR = very high risk.


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