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

Abstract

<jats:sec> <jats:title>OBJECT</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>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).</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>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.</jats:p></jats:sec>

Reirradiation of Recurrent Tumors in Central Nervous System in Children and Adolescents

“…Seventeen patients were included in this series: 11 male and 6 female, with a median age at the time of the reirradiation of 14.0-years CI 95%. [12][13][14][15][16][17] Among those reirradiated the median of time of disease relapse was 8 to 9-years from the first to the second irradiation. Four patients received CS plus tumor volume reirradiation, while the rest only to the primary site of recurrence.…”

“…11,17,19 During their evolution, there are relapses, that could occur a few months to years after the first irradiation. 9,[13][14][15] Rao et al 8 reported reirradiation in 67 children with recurrent CNS malignancies and found that the median overall survival after the completion of repeated radiation therapy (RT) was 12.8-months for the entire cohort and concluded that CNS reirradiation could be a reasonable treatment option. In our study, a similar range of median overall survival was obtained (12.2-months).…”

Malignant brainstem tumors in children, excluding diffuse intrinsic pontine gliomas

“…There are but a few case reports or small case series in the literature of embryonal tumors, with the most commonly described example of this group being a primitive neuroectodermal tumor (PNET). 1,4,[12][13][14]38,40,44 We present our experience with these unusual and challenging neoplasms.…”

Screening Key Pathogenic Genes and Small Molecule Compounds for PNET

“… 2 To date, few effective approaches are available to improve the prognosis of patients. 3 Therefore, a comprehensive analysis is needed to discover biomarkers of the disease and small molecule drugs that can improve the patients’ treatment strategy.…”

“…Accompanied by the low incidence rate, it features high-lever of malignancy, rapid progress, high recurrence and metastasis rate, and poor prognosis 2. To date, few effective approaches are available to improve the prognosis of patients 3. Therefore, a comprehensive analysis is needed to discover biomarkers of the disease and small molecule drugs that can improve the patients’ treatment strategy.…”