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.

Gene expression profiling of Group 3 medulloblastomas defines a clinically tractable stratification based on KIRREL2 expression

“…Risk stratification and accurate outcome prediction of future Grp 3 MB cohorts in the absence of high-throughput profiling techniques may be enhanced by assessing KIRREL2 expression in routine neuropathology. For example, single gene RQ-PCR quantification, Taqman low-density arrays, or Nanostring-based analyses evaluating expression of this gene might be easily developed in neuropathological practice after elaboration of optimal cut-off levels for each method applied [ 1 , 5 , 6 , 10 , 14 , 31 ]. In addition, KIRREL2 protein expression was defined here as a prognostic indicator.…”

Factors influencing outcomes of older children with medulloblastoma over 15 years in Peru, a resource‐limited setting

“…We are beginning to see improvement in access in some LMIC centers either performed locally or in collaboration with centers in HIC. 44,45 Consortiums between LMIC and HIC could potentially aid in improving outcomes for medulloblastomas. The Latin American Brain Tumor Board (LATB), a weekly multidisciplinary pediatric neuro-oncology-specific teleconference, connects institutions from Latin America with those in Canada, Spain, and the United States.…”

Risk Factors for Survival in Patients With Medulloblastoma: A Systematic Review and Meta-Analysis

“…Hydrocephalus management (25), fourth ventricular floor involvement (37), ≥20% aggresomes (43), male sex (39), and brainstem involvement (37) might influence EFS. Molecular typing also appears promising for evaluating the prognosis of MB (46,(54)(55)(56)(57)(58)(59), but additional studies and meta-analyses will be necessary to determine their prognostic value. Future studies and meta-analyses should examine these factors on the prognosis of MB.…”