title: Medulloblastoma in China: clinicopathologic analyses of SHH, WNT, and non-SHH/WNT molecular subgroups reveal different therapeutic responses to adjuvant chemotherapy.
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.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pathology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Kay Ka-Wai
authors.initials: KK
authors.lastname: Li
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhong
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Liang-Fu
authors.initials: LF
authors.lastname: Zhou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002528:Cerebellar Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D002681:China; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003399:Craniotomy; D018572:Disease-Free Survival; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000145:classification / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D051153:Wnt Proteins / Q000235:genetics*; D060449:Wnt Signaling Pathway; D055815:Young Adult; D051176:beta Catenin / Q000032:analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C495270:CTNNB1 protein, human; C098587:GAB1 protein, human; D053823:Hedgehog Proteins; D009363:Neoplasm Proteins; C509239:SHH protein, human; D051153:Wnt Proteins; D051176:beta Catenin