Primitive neuroectodermal tumors of the brainstem in children treated according to the HIT Trials: clinical findings of a rare disease

TY - JOUR

T1 - Primitive neuroectodermal tumors of the brainstem in children treated according to the HIT Trials: clinical findings of a rare disease

AU - Friedrich, Carsten

AU - Warmuth-Metz, Monika

AU - von Bueren, André O

AU - Nowak, Johannes

AU - Bison, Brigitte

AU - von Hoff, Katja

AU - Pietsch, Torsten

AU - Kortmann, Rolf D

AU - Rutkowski, Stefan

PY - 2015/3

Y1 - 2015/3

N2 - OBJECT: Primitive neuroectodermal tumors of the central nervous system (CNS-PNET) arising in the brainstem are extremely rare, and knowledge about them is limited. The few existing case series report fatal outcomes. The purpose of this study was to analyze clinical characteristics of and outcome for brainstem CNS-PNET patients treated according to the consecutive, population-based HIT studies covering a 19-year time period.METHODS: Between September 1992 and November 2011, 6 eligible children with histologically proven brainstem CNS-PNET not otherwise specified and 2 children with brainstem ependymoblastomas (3, partial resection; 3, subtotal resection; 2, biopsy), median age 3.3 years (range 1.2-10.6 years), were treated according to consecutive multimodal HIT protocols for CNS-PNET/medulloblastoma. Postoperative treatment was according to maintenance chemotherapy protocols (3, craniospinal irradiation [CSI] followed by maintenance chemotherapy), sandwich chemotherapy protocols (2, neoadjuvant chemotherapy, CSI, maintenance chemotherapy), or a therapy protocol for children younger than 4 years (3, postoperative chemotherapy followed by CSI).RESULTS: The median duration of prediagnostic symptoms, predominantly cranial nerve deficits (n = 7), pyramidal tract signs (n = 5), or ataxia (n = 5), was 5 weeks (range 1-13 weeks). The tumors were all located in the pons. Most involved more than half of the pontine axial diameter and were sharply marginated. All patients had postoperative residual disease, including metastasis in 1 case. With 1 exception all tumors progressed early during treatment within 3.9 months (range 2.5-10.4 months), leading to a 1-year event-free survival rate (± standard error) of 13% ± 12%. After progression, patients succumbed early to their disease resulting in a 1-year overall survival rate of 25% ± 15%. The only surviving patient had a partially resected CNS-PNET, received a sandwich chemotherapy protocol, and is without disease progression 14 months after diagnosis.CONCLUSIONS: CNS-PNET is a rare but important differential diagnosis in childhood brainstem tumors. So far, efficient therapies are lacking. The sampling of tumor material for improved biological understanding and identification of new therapeutic targets is important.

AB - OBJECT: Primitive neuroectodermal tumors of the central nervous system (CNS-PNET) arising in the brainstem are extremely rare, and knowledge about them is limited. The few existing case series report fatal outcomes. The purpose of this study was to analyze clinical characteristics of and outcome for brainstem CNS-PNET patients treated according to the consecutive, population-based HIT studies covering a 19-year time period.METHODS: Between September 1992 and November 2011, 6 eligible children with histologically proven brainstem CNS-PNET not otherwise specified and 2 children with brainstem ependymoblastomas (3, partial resection; 3, subtotal resection; 2, biopsy), median age 3.3 years (range 1.2-10.6 years), were treated according to consecutive multimodal HIT protocols for CNS-PNET/medulloblastoma. Postoperative treatment was according to maintenance chemotherapy protocols (3, craniospinal irradiation [CSI] followed by maintenance chemotherapy), sandwich chemotherapy protocols (2, neoadjuvant chemotherapy, CSI, maintenance chemotherapy), or a therapy protocol for children younger than 4 years (3, postoperative chemotherapy followed by CSI).RESULTS: The median duration of prediagnostic symptoms, predominantly cranial nerve deficits (n = 7), pyramidal tract signs (n = 5), or ataxia (n = 5), was 5 weeks (range 1-13 weeks). The tumors were all located in the pons. Most involved more than half of the pontine axial diameter and were sharply marginated. All patients had postoperative residual disease, including metastasis in 1 case. With 1 exception all tumors progressed early during treatment within 3.9 months (range 2.5-10.4 months), leading to a 1-year event-free survival rate (± standard error) of 13% ± 12%. After progression, patients succumbed early to their disease resulting in a 1-year overall survival rate of 25% ± 15%. The only surviving patient had a partially resected CNS-PNET, received a sandwich chemotherapy protocol, and is without disease progression 14 months after diagnosis.CONCLUSIONS: CNS-PNET is a rare but important differential diagnosis in childhood brainstem tumors. So far, efficient therapies are lacking. The sampling of tumor material for improved biological understanding and identification of new therapeutic targets is important.

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Brain Stem Neoplasms

KW - Chemotherapy, Adjuvant

KW - Child

KW - Child, Preschool

KW - Disease Progression

KW - Disease-Free Survival

KW - Drug Administration Schedule

KW - Female

KW - Humans

KW - Infant

KW - Maintenance Chemotherapy

KW - Male

KW - Neoadjuvant Therapy

KW - Neoplasm, Residual

KW - Neuroectodermal Tumors, Primitive

KW - Pons

KW - Rare Diseases

U2 - 10.3171/2014.9.PEDS14213

DO - 10.3171/2014.9.PEDS14213

M3 - SCORING: Journal article

C2 - 25555122

VL - 15

SP - 227

EP - 235

JO - J NEUROSURG-PEDIATR

JF - J NEUROSURG-PEDIATR

SN - 1933-0707

IS - 3

ER -