AIMS: Embryonal tumours with PLAGL1 or PLAGL2 amplification (ET, PLAGL) show substantial heterogeneity regarding their clinical characteristics and have been treated inconsistently, resulting in diverse outcomes. In this study, we aimed to evaluate the clinical behaviour of ET, PLAGL and elucidate their response pattern across the different applied treatment regimens. METHODS: We conducted an in-depth retrospective analysis of clinical and serial imaging data of 18 patients with ET, PLAGL (nine each of PLAGL1 and PLAGL2 amplified). RESULTS: Patients with PLAGL1-amplified tumours (ET, PLAGL1) had fewer relapses (3/9), while PLAGL2-amplified tumours (ET, PLAGL2) were prone to early relapse or progression (8/9) and to distant, leptomeningeal and intraventricular relapses. Progression-free survival differed significantly between the subtypes (log-rank test, p = 0.0055). Postoperative treatment included chemotherapy (n = 17, various protocols), alone (n = 8) or combined with radiotherapy (n = 9). Responses to chemotherapy were observed in both subtypes, and incomplete resection was not associated with inferior survival. All three survivors with ET, PLAGL2 were treated with induction and high-dose chemotherapy with (n = 1-low-dose CSI and boost) or without (n = 2) radiotherapy, whereas five patients with less intensive chemotherapy relapsed. All six survivors with ET, PLAGL1 were treated with conventional chemotherapy regimens, with (n = 4-local radiotherapy n = 3; CSI and boost n = 1) or without (n = 2) radiotherapy. Two patients with ET, PLAGL1 relapsed after 8 years. CONCLUSIONS: Adjuvant therapy should be considered for all ET, PLAGL patients: Patients with ET, PLAGL2 might benefit from intensified chemotherapy regimens. In contrast, patients with ET, PLAGL1 showed superior outcomes without high-dose chemotherapy or craniospinal irradiation.

• Klíčová slova
• PLAGL1, PLAGL2, ET, PLAGL, embryonal CNS tumour, treatment,
• MeSH
• amplifikace genu MeSH
• dítě MeSH
• DNA vazebné proteiny * genetika   MeSH
• dospělí MeSH
• germinální a embryonální nádory * genetika   terapie   patologie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory centrálního nervového systému * genetika   terapie   patologie   diagnostické zobrazování   MeSH
• nádory mozku * genetika   terapie   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• DNA vazebné proteiny * MeSH

Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.

• Klíčová slova
• Brain tumor, EWSR1, Gene fusion, MN1, Neuroepithelial, Neurooncology, PATZ1, Pediatric,
• MeSH
• dítě MeSH
• fúzní onkogenní proteiny genetika   MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory mozku genetika   patologie   MeSH
• neuroepitelové nádory genetika   patologie   MeSH
• onkogenní fúze MeSH
• předškolní dítě MeSH
• represorové proteiny genetika   MeSH
• transkripční faktory Krüppel-like genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fúzní onkogenní proteiny MeSH
• nádorové biomarkery MeSH
• PATZ1 protein, human MeSH Prohlížeč
• represorové proteiny MeSH
• transkripční faktory Krüppel-like MeSH

Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n = 23) and ALL (n = 9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrent PDGFRA amplification and loss of CDKN2A/B and an absence of somatic hotspot mutations in genes encoding histone 3 variants or IDH1/2, uncovering diagnostic markers and potentially actionable targets.

• MeSH
• amplifikace genu * MeSH
• chromozomální delece MeSH
• dítě MeSH
• dospělí MeSH
• genetická transkripce MeSH
• genom lidský MeSH
• genová přestavba genetika   MeSH
• gliom genetika   patologie   MeSH
• inhibitor p15 cyklin-dependentní kinasy metabolismus   MeSH
• inhibitor p16 cyklin-dependentní kinasy metabolismus   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   MeSH
• metylace DNA genetika   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• regulace genové exprese u nádorů MeSH
• růstový faktor odvozený z trombocytů - receptor alfa genetika   metabolismus   MeSH
• shluková analýza MeSH
• záření MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CDKN2A protein, human MeSH Prohlížeč
• CDKN2B protein, human MeSH Prohlížeč
• inhibitor p15 cyklin-dependentní kinasy MeSH
• inhibitor p16 cyklin-dependentní kinasy MeSH
• růstový faktor odvozený z trombocytů - receptor alfa MeSH

BACKGROUND: Only few data are available on treatment-associated behavior of distinct rare CNS embryonal tumor entities previously treated as "CNS-primitive neuroectodermal tumors" (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumors with multilayered rosettes (ETMR) are needed for development of differentiated treatment strategies. METHODS: Within this retrospective, international study, tumor samples of clinically well-annotated patients with the original diagnosis of CNS-PNET were analyzed using DNA methylation arrays (n = 307). Additional cases (n = 66) with DNA methylation pattern of CNS NB-FOXR2 were included irrespective of initial histological diagnosis. Pooled clinical data (n = 292) were descriptively analyzed. RESULTS: DNA methylation profiling of "CNS-PNET" classified 58 (19%) cases as ETMR, 57 (19%) as high-grade glioma (HGG), 36 (12%) as CNS NB-FOXR2, and 89(29%) cases were classified into 18 other entities. Sixty-seven (22%) cases did not show DNA methylation patterns similar to established CNS tumor reference classes. Best treatment results were achieved for CNS NB-FOXR2 patients (5-year PFS: 63% ± 7%, OS: 85% ± 5%, n = 63), with 35/42 progression-free survivors after upfront craniospinal irradiation (CSI) and chemotherapy. The worst outcome was seen for ETMR and HGG patients with 5-year PFS of 18% ± 6% and 22% ± 7%, and 5-year OS of 24% ± 6% and 25% ± 7%, respectively. CONCLUSION: The historically reported poor outcome of CNS-PNET patients becomes highly variable when tumors are molecularly classified based on DNA methylation profiling. Patients with CNS NB-FOXR2 responded well to current treatments and a standard-risk CSI-based regimen may be prospectively evaluated. The poor outcome of ETMR across applied treatment strategies substantiates the necessity for evaluation of novel treatments.

• Klíčová slova
• CNS NB-FOXR2, CNS embryonal tumor, CNS-PNET, DNA methylation profiling, ETMR,
• MeSH
• forkhead transkripční faktory MeSH
• germinální a embryonální nádory * diagnóza   genetika   terapie   MeSH
• lidé MeSH
• molekulární patologie MeSH
• nádory centrálního nervového systému * diagnóza   genetika   terapie   MeSH
• nádory mozku * diagnóza   genetika   terapie   MeSH
• primitivní neuroektodermové nádory * diagnóza   genetika   terapie   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• forkhead transkripční faktory MeSH
• FOXR2 protein, human MeSH Prohlížeč

In the clinical management of paediatric solid tumours, histological examination of tumour tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumour is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumour samples. This methylation pattern can be detected in the cell-free DNA. Here, we provide proof-of-concept of histopathologic classification of paediatric tumours using cell-free reduced representation bisulphite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. We determined the correct tumour type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free DNA. We demonstrate that the majority of misclassifications were associated with sample quality and not with the extent of disease. Our approach has the potential to help tackle some of the remaining diagnostic challenges in paediatric oncology in a cost-effective and minimally invasive manner.

• Klíčová slova
• DNA methylation, biomarker, cell-free DNA, diagnosis, infinium, liquid biopsy, pediatric oncology, reduced representation bisulfite sequencing,
• MeSH
• dítě MeSH
• lidé MeSH
• metylace DNA MeSH
• nádory * MeSH
• retrospektivní studie MeSH
• sekvenční analýza DNA MeSH
• siřičitany MeSH
• volné cirkulující nukleové kyseliny * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hydrogen sulfite MeSH Prohlížeč
• siřičitany MeSH
• volné cirkulující nukleové kyseliny * MeSH

The knowledge of clinical features and, particularly, histopathological spectrum of EWSR1-PATZ1-rearranged spindle and round cell sarcomas (EPS) remains limited. For this reason, we report the largest clinicopathological study of EPS to date. Nine cases were collected, consisting of four males and five females ranging in age from 10 to 81 years (average: 49 years). Five tumors occurred in abdominal wall soft tissues, three in the thorax, and one in the back of the neck. Tumor sizes ranged from 2.5 to 18 cm (average 6.6 cm). Five patients had follow-up with an average of 38 months (range: 18-60 months). Two patients had no recurrence or metastasis 19 months after diagnosis. Four patients developed multifocal pleural or pulmonary metastasis and were treated variably by surgery, radiotherapy, and chemotherapy. The latter seemed to have little to no clinical benefit. One of the four patients was free of disease 60 months after diagnosis, two patients were alive with disease at 18 and 60 months, respectively. Morphologically, low, intermediate, and high-grade sarcomas composed of a variable mixture of spindled, ovoid, epithelioid, and round cells were seen. The architectural and stromal features also varied, resulting in a broad morphologic spectrum. Immunohistochemically, the following markers were most consistently expressed: S100-protein (7/9 cases), GFAP (7/8), MyoD1 (8/9), Pax-7 (4/5), desmin (7/9), and AE1/3 (4/9). By next-generation sequencing, all cases revealed EWSR1-PATZ1 gene fusion. In addition, 3/6 cases tested harbored CDKN2A deletion, while CDKN2B deletion and TP53 mutation were detected in one case each. Our findings confirm that EPS is a clinicopathologic entity, albeit with a broad morphologic spectrum. The uneventful outcome in some of our cases indicates that a subset of EPS might follow a more indolent clinical course than previously appreciated. Additional studies are needed to validate whether any morphological and/or molecular attributes have a prognostic impact.

• MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• fúze genů MeSH
• genetická predispozice k nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   genetika   MeSH
• nádory měkkých tkání chemie   genetika   patologie   chirurgie   MeSH
• protein EWS vázající RNA genetika   MeSH
• represorové proteiny genetika   MeSH
• sarkom chemie   genetika   patologie   chirurgie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkripční faktory Krüppel-like genetika   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH
• Názvy látek
• EWSR1 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• PATZ1 protein, human MeSH Prohlížeč
• protein EWS vázající RNA MeSH
• represorové proteiny MeSH
• transkripční faktory Krüppel-like MeSH

Histone H3.3 glycine 34 to arginine/valine (G34R/V) mutations drive deadly gliomas and show exquisite regional and temporal specificity, suggesting a developmental context permissive to their effects. Here we show that 50% of G34R/V tumors (n = 95) bear activating PDGFRA mutations that display strong selection pressure at recurrence. Although considered gliomas, G34R/V tumors actually arise in GSX2/DLX-expressing interneuron progenitors, where G34R/V mutations impair neuronal differentiation. The lineage of origin may facilitate PDGFRA co-option through a chromatin loop connecting PDGFRA to GSX2 regulatory elements, promoting PDGFRA overexpression and mutation. At the single-cell level, G34R/V tumors harbor dual neuronal/astroglial identity and lack oligodendroglial programs, actively repressed by GSX2/DLX-mediated cell fate specification. G34R/V may become dispensable for tumor maintenance, whereas mutant-PDGFRA is potently oncogenic. Collectively, our results open novel research avenues in deadly tumors. G34R/V gliomas are neuronal malignancies where interneuron progenitors are stalled in differentiation by G34R/V mutations and malignant gliogenesis is promoted by co-option of a potentially targetable pathway, PDGFRA signaling.

• Klíčová slova
• GSX2, H3.3 G34R/V, PDGFRA, cell-of-origin, chromatin conformation, gliomas, interneuron progenitors, oncohistones, pediatric cancer, single-cell transcriptome,
• MeSH
• astrocyty metabolismus   patologie   MeSH
• biologické modely MeSH
• buněčný rodokmen MeSH
• chromatin metabolismus   MeSH
• embryo savčí metabolismus   MeSH
• epigeneze genetická MeSH
• genetická transkripce MeSH
• gliom genetika   patologie   MeSH
• histony genetika   metabolismus   MeSH
• interneurony metabolismus   MeSH
• karcinogeneze genetika   patologie   MeSH
• lysin metabolismus   MeSH
• mutace genetika   MeSH
• myši inbrední C57BL MeSH
• nádory mozku genetika   patologie   MeSH
• nervové kmenové buňky metabolismus   MeSH
• oligodendroglie metabolismus   MeSH
• přední mozek embryologie   MeSH
• přeprogramování buněk genetika   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• regulace genové exprese u nádorů MeSH
• růstový faktor odvozený z trombocytů - receptor alfa genetika   metabolismus   MeSH
• stupeň nádoru MeSH
• transkriptom genetika   MeSH
• umlčování genů MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• chromatin MeSH
• histony MeSH
• lysin MeSH
• růstový faktor odvozený z trombocytů - receptor alfa MeSH

Embryonal tumours with multilayered rosettes (ETMRs) are aggressive paediatric embryonal brain tumours with a universally poor prognosis1. Here we collected 193 primary ETMRs and 23 matched relapse samples to investigate the genomic landscape of this distinct tumour type. We found that patients with tumours in which the proposed driver C19MC2-4 was not amplified frequently had germline mutations in DICER1 or other microRNA-related aberrations such as somatic amplification of miR-17-92 (also known as MIR17HG). Whole-genome sequencing revealed that tumours had an overall low recurrence of single-nucleotide variants (SNVs), but showed prevalent genomic instability caused by widespread occurrence of R-loop structures. We show that R-loop-associated chromosomal instability can be induced by the loss of DICER1 function. Comparison of primary tumours and matched relapse samples showed a strong conservation of structural variants, but low conservation of SNVs. Moreover, many newly acquired SNVs are associated with a mutational signature related to cisplatin treatment. Finally, we show that targeting R-loops with topoisomerase and PARP inhibitors might be an effective treatment strategy for this deadly disease.

• MeSH
• DEAD-box RNA-helikasy genetika   MeSH
• DNA-topoisomerasy I genetika   MeSH
• germinální a embryonální nádory diagnóza   genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• mutace MeSH
• PARP inhibitory MeSH
• poly(ADP-ribosa)polymerasy genetika   MeSH
• recidiva MeSH
• ribonukleasa III genetika   MeSH
• RNA dlouhá nekódující MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• DEAD-box RNA-helikasy MeSH
• DICER1 protein, human MeSH Prohlížeč
• DNA-topoisomerasy I MeSH
• mikro RNA MeSH
• MIR17HG, human MeSH Prohlížeč
• PARP inhibitory MeSH
• poly(ADP-ribosa)polymerasy MeSH
• ribonukleasa III MeSH
• RNA dlouhá nekódující MeSH
• TOP1 protein, human MeSH Prohlížeč

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome. The low methylation group is enriched for somatic NRAS and CBL mutations, as well as for Noonan patients, and has a good prognosis. The intermediate methylation group (IM) shows enrichment for monosomy 7 and somatic KRAS mutations. Hypermethylation is associated with repressed chromatin, genes regulated by RAS signaling, frequent co-occurrence of RAS pathway mutations and upregulation of DNMT1 and DNMT3B, suggesting a link between activation of the DNA methylation machinery and mutational patterns in JMML.

• MeSH
• biopsie MeSH
• chromatin genetika   metabolismus   MeSH
• dítě MeSH
• DNA-(cytosin-5-)methyltransferasa metabolismus   MeSH
• DNA-(cytosin-5)-methyltransferasa 1 metabolismus   MeSH
• DNA-methyltransferasa 3B MeSH
• epigenomika MeSH
• juvenilní myelomonocytární leukemie genetika   mortalita   patologie   terapie   MeSH
• kojenec MeSH
• lidé MeSH
• metylace DNA * MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• Noonanové syndrom genetika   patologie   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• prospektivní studie MeSH
• protinádorové látky terapeutické užití   MeSH
• protoonkogenní proteiny c-cbl MeSH
• protoonkogenní proteiny p21(ras) genetika   metabolismus   MeSH
• regulace genové exprese u leukemie MeSH
• signální transdukce genetika   MeSH
• transplantace hematopoetických kmenových buněk MeSH
• tyrosinfosfatasa nereceptorového typu 11 genetika   metabolismus   MeSH
• upregulace MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chromatin MeSH
• DNA-(cytosin-5-)methyltransferasa MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• DNMT1 protein, human MeSH Prohlížeč
• KRAS protein, human MeSH Prohlížeč
• protinádorové látky MeSH
• protoonkogenní proteiny c-cbl MeSH
• protoonkogenní proteiny p21(ras) MeSH
• PTPN11 protein, human MeSH Prohlížeč
• tyrosinfosfatasa nereceptorového typu 11 MeSH

BACKGROUND: Pineoblastoma is a rare pineal region brain tumor. Treatment strategies have reflected those for other malignant embryonal brain tumors. PATIENTS AND METHODS: Original prospective treatment and outcome data from international trial groups were pooled. Cox regression models were developed considering treatment elements as time-dependent covariates. RESULTS: Data on 135 patients with pineoblastoma aged 0.01-20.7 (median 4.9) years were analyzed. Median observation time was 7.3 years. Favorable prognostic factors were age ≥4 years (hazard ratio [HR] for progression-free survival [PFS] 0.270, P < .001) and administration of radiotherapy (HR for PFS 0.282, P < .001). Metastatic disease (HR for PFS 2.015, P = .006), but not postoperative residual tumor, was associated with unfavorable prognosis. In 57 patients <4 years old, 5-year PFS/overall survival (OS) were 11 ± 4%/12 ± 4%. Two patients survived after chemotherapy only, while 3 of 16 treated with craniospinal irradiation (CSI) with boost, and 3 of 5 treated with high-dose chemotherapy (HDCT) and local radiotherapy survived. In 78 patients aged ≥4 years, PFS/OS were 72 ± 7%/73 ± 7% for patients without metastases, and 50 ± 10%/55 ± 10% with metastases. Seventy-three patients received radiotherapy (48 conventionally fractionated CSI, median dose 35.0 [18.0-45.0] Gy, 19 hyperfractionated CSI, 6 local radiotherapy), with (n = 68) or without (n = 6) chemotherapy. The treatment sequence had no impact; application of HDCT had weak impact on survival in older patients. CONCLUSION: Survival is poor in young children treated without radiotherapy. In these patients, combination of HDCT and local radiotherapy may warrant further evaluation in the absence of more specific or targeted treatments. CSI combined with chemotherapy is effective for older non-metastatic patients.

• Klíčová slova
• high-dose chemotherapy, pediatric, pineoblastoma, radiotherapy, treatment,
• MeSH
• databáze faktografické MeSH
• dítě MeSH
• dospělí MeSH
• epifýza mozková účinky léků   patologie   účinky záření   MeSH
• kojenec MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory mozku farmakoterapie   mortalita   radioterapie   terapie   MeSH
• pinealom farmakoterapie   mortalita   radioterapie   terapie   MeSH
• předškolní dítě MeSH
• přežití bez známek nemoci MeSH
• prospektivní studie MeSH
• protinádorové látky terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH
• Názvy látek
• protinádorové látky MeSH