Medulloblastoma in China: clinicopathologic analyses of SHH, WNT, and non-SHH/WNT molecular subgroups reveal different therapeutic responses to adjuvant chemotherapy.

Zhen-Yu Zhang,Jian Xu,Kay Ka-Wai Li,Ho-Keung Ng,Ping Zhong,Yong Ren,Liang-Fu Zhou,Yu Yao,Ying Mao,Javier S. Castresana

doi:10.1371/journal.pone.0099490

Abstract

Medulloblastoma (MB) is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE) tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS) rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found significantly improving the survival of children (p<0.001) while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028) than others (SHH and Non-SHH/WNT subtypes) given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001). Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB) (OS p<0.001, EFS p<0.001), SHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p = 0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055). Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB.

Highlights

Medulloblastoma is one of the most common primary central nervous system tumors in children, with an estimated incidence of 0.5/100,000 children [1,2]
The utility of several prognostic factors, either clinical or pathological, for predicting the clinical outcomes of medulloblastoma patients have been controversially discussed for a long time
We analyzed clinical outcomes and prognostic factors in 173 medulloblastoma patients treated at two institutions in China from 2002 to 2011

Summary

Introduction

Medulloblastoma is one of the most common primary central nervous system tumors in children, with an estimated incidence of 0.5/100,000 children [1,2]. Recent progress on medulloblastoma gene expression profiling demonstrated the disease is heterogeneous and consists of different molecular subgroups: SHH, WNT and Non-SHH/WNT medulloblastoma [9,10,11,12]. These molecular subgroups have been demonstrated to differ in demographic, genetic and clinical aspects. How to reduce adjuvant therapies in WNT medulloblastoma remains unclear. Is it safe to remove CHT from current treatment modality for WNT medulloblastoma? Is it safe to remove CHT from current treatment modality for WNT medulloblastoma? Since our knowledge on the sensitivity of different molecular subgroups to adjuvant RT or CHT is still limited, it may be difficult to answer this question

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Conclusion