Molecular Subgroup Is the Strongest Predictor of Medulloblastoma Outcome in a Resource-Limited Country

Abstract

Purpose: Medulloblastoma is composed of four clinically and prognostically distinct molecular subgroups (WNT, SHH, group 3, and group 4). However, the clinical implications of these subgroups in the context of the unique challenges of low- to middle-income countries are rarely reported.

Methods: We assembled an institutional cohort of children (3-18 years) diagnosed with medulloblastoma and treated in Jordan between 2003 and 2016. Tumors were subgrouped by NanoString and correlated with clinical and radiologic characteristics.

Results: Eighty-eight patients were identified (63% male); median age was 6.9 years (interquartile range 4.8-9.2) and median symptom duration was 6 weeks (interquartile range 4-11). Radiotherapy was implemented as standard-risk in 41 patients (47%) and high-risk in 47 patients (53%). Subgrouping revealed 17 WNT (19%), 22 SHH (25%), 21 group 3 (24%), and 28 group 4 tumors (32%). Median time between craniotomy and radiotherapy was 45 days (17-155); 44% of them > 49 days. Median duration of radiotherapy was 44 days (36-74). Seventy-two patients (82%) received chemotherapy afterward. With a median follow-up of 4.6 years (0.2-14.9), 5-year progression-free survival (PFS) and overall survival were 73.5% and 69.4%, respectively, with no statistically significant survival difference between standard-risk and high-risk patients. Metastasis was significant for overall survival (P = .011). Patients with SHH and group 4 tumors had very good PFS (83.4% and 87.0%, respectively) and those with group 3 tumors had dismal outcomes (PFS 44.9%), whereas WNT tumors had less-than expected PFS (70.5%). PFS was statistically significant in patients with nonmetastatic tumors receiving radiotherapy ≤ 49 days (P = .011), particularly group 3 tumors.

Conclusion: Patients with SHH and group 4 medulloblastoma had excellent survival comparable with high-income countries. Compliance with treatment protocols and avoiding radiotherapy delays are important in achieving adequate survival in low- to middle-income country settings. Subgroup-driven treatment protocols should be considered in countries with limited resources.

FIG 1

Graphs demonstrating 5-year PFS and OS: (A) PFS and OS of all patients (product-limit survival estimate), (B) PFS and OS according to risk stratification (Kaplan-Meier plot), (C) PFS and OS according to presence or absence of metastasis (Kaplan-Meier plot), and (D) PFS and OS according to medulloblastoma subgroup. G, group; mets, metastasis; OS, overall survival; PFS, progression-free survival.

FIG 2

Selected MRI images (at the level of the brain stem) from the patient with WNT tumor who developed radiation-induced diffuse intrinsic pontine glioma. (A) Axial T1 WI showing an infiltrative hypointense lesion involving and expanding the pons (more on the left side) and the Lt middle cerebellar peduncle. (B and C) Axial T2 and FLAIR WI, respectively, showing hyperintense signal of the lesion with minimal involvement of the Lt cerebellar white matter. There is also an area of gliosis at the medial aspect of the right cerebellum that appeared stable compared with previous MRI studies (not shown). This is related to the previous surgery. (D and E) Enhanced coronal and sagittal T1 WI, respectively, showing enhancement of the infiltrative brain stem lesion with infiltration of the medulla oblongata. FLAIR, fluid-attenuated inversion recovery; Lt, left; MRI, magnetic resonance imaging; WI, weighted image.