MRI surrogates for molecular subgroups of medulloblastoma

Abstract

Background and purpose: Recently identified molecular subgroups of medulloblastoma have shown potential for improved risk stratification. We hypothesized that distinct MR imaging features can predict these subgroups.

Materials and methods: All patients with a diagnosis of medulloblastoma at one institution, with both pretherapy MR imaging and surgical tissue, served as the discovery cohort (n = 47). MR imaging features were assessed by 3 blinded neuroradiologists. NanoString-based assay of tumor tissues was conducted to classify the tumors into the 4 established molecular subgroups (wingless, sonic hedgehog, group 3, and group 4). A second pediatric medulloblastoma cohort (n = 52) from an independent institution was used for validation of the MR imaging features predictive of the molecular subtypes.

Results: Logistic regression analysis within the discovery cohort revealed tumor location (P < .001) and enhancement pattern (P = .001) to be significant predictors of medulloblastoma subgroups. Stereospecific computational analyses confirmed that group 3 and 4 tumors predominated within the midline fourth ventricle (100%, P = .007), wingless tumors were localized to the cerebellar peduncle/cerebellopontine angle cistern with a positive predictive value of 100% (95% CI, 30%-100%), and sonic hedgehog tumors arose in the cerebellar hemispheres with a positive predictive value of 100% (95% CI, 59%-100%). Midline group 4 tumors presented with minimal/no enhancement with a positive predictive value of 91% (95% CI, 59%-98%). When we used the MR imaging feature-based regression model, 66% of medulloblastomas were correctly predicted in the discovery cohort, and 65%, in the validation cohort.

Conclusions: Tumor location and enhancement pattern were predictive of molecular subgroups of pediatric medulloblastoma and may potentially serve as a surrogate for genomic testing.

Fig 1.

Patient characteristics of the discovery cohort according to the molecular subgroups and MR imaging features. CH indicates cerebellar hemisphere; LCA, large-cell anaplastic; enhancement pattern (asterisk), minimal to none, <10% tumor volume; solid, >90% tumor volume. Beveled rectangles represent statistical significance (Fisher exact test [P < .005], except for Ill-defined margins [P = .03]).

Fig 2.

Characteristic MR imaging features according to medulloblastoma molecular subgroups. A, In the top row, characteristic location of WNT tumors in the CP/CPA region is shown. B, In the second row, SHH tumors are predominantly located in the cerebellar hemispheres. C, In the third row, group 3 tumors are located in the midline/fourth ventricle and show enhancement and ill-defined features against the adjacent brain parenchyma. D, In the fourth row, group 4 tumors are also located in the midline fourth ventricle but tend to show minimal or no enhancement.