scholarly journals ATRT-05. RESULTS OF MULTICENTER TRIAL CONCERNING THE TREATMENT OF CHILDREN WITH ATYPICAL TERATOID/RHABDOID TUMORS (ATRT) OF THE CENTRAL NERVOUS SYSTEM

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii276-iii276
Author(s):  
Olga Zheludkova ◽  
Lyudmila Olkhova ◽  
Yuri Kushel’ ◽  
Armen Melikyan ◽  
Marina Ryzhova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
Intrathecal Methotrexate ◽  
Subtotal Resection ◽  
Tumor Biopsy ◽  
Atypical Teratoid ◽  
The Central Nervous System ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

Abstract We analyzed 105 patients under 18 years. The median age was 21 months. There were 54 boys and 51 girls. The supratentorial tumors were in 53 patients, infratentorial in 48, and in spinal cord in 4. 60 had stage M0,29-М+and 16-Mx. All the patients got surgical treatment:total tumor removal in 34,subtotal in 37,partial in 30,and biopsy in 4;75 patients got chemoradiotherapy to ATRT-2006;6-CWS;13-EU-RHAB;5-HIT-SKK;individual schemes in 6. RESULTS: 47 are alive,1 was LFU, and 57 died. PFS was 32%±0.05; the five-year OS 40%±0.05. The median survival-30 months, the median progression-free survival-12 months, and the median of follow-up-23 months. PFS was significantly better in patients more than 12 months compared to patients younger than 12 months:40 and 12%;p=0.00161.After total resection PFS was higher compared to subtotal resection, partial resection, and tumor biopsy:48,38,0,and 0%(p=0.025). After chemoradiotherapy, PFS was higher compared to patients without radiotherapy: 49and 0%(р=0.0000000).PFS for stage M0 was higher compared to stage M+and stage Mx:41,15,and 27%,respectively(р=0.00032).PFS was better for the tumors in the spinal cord and infratentorial location compared to the supratentorial location:67,37,and 25%(p=0.0876).The survival rate was higher among the patients who got treatment according to the ATRT-2006 protocol compared to EU-RHAB, individual regimens, CWS, and HIT-SKK:39,19,17,17,and 0% respectively;p=0.00159.The survival was higher among the patients who got intraventricular/intrathecal Methotrexate,Cytarabine, Prednisolone than among the patients who got only Methotrexate or none at all:40,0,and 5%, respectively; p=0.00015. CONCLUSIONS: Survival was significantly better in patients more than 12month, without metastases, with total removal tumor, chemotheradiotherapy by ATRT-2006 protocol with i/t, i/v Methotrexate/Cytarabine/Prednisolone.

scholarly journals Atypical teratoid/rhabdoid tumors of the central nervous system in children: the state of the problem today. Literature review

2019 ◽  
Vol 5 (4) ◽  
pp. 60-73 ◽  
Author(s):  
Yu. V. Dinikina ◽  
M. B. Belogurova
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Conflict Of Interest ◽  
Malignant Tumors ◽  
Young Patients ◽  
Genetic Profile ◽  
Atypical Teratoid ◽  
The Central Nervous System ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

Atypical teratoid/rhabdoid tumors (AT/RT) are a group of rare highly aggressive malignant tumors in young patients. Among all the malignant tumors of the central nervous system (CNS) in children, they are 1–2 %, which, due to the small number of groups, makes it difficult to develop uniform recommendations for antitumor therapy. The molecular genetic profile of AT/RT, which largely determines the characteristics of the disease, has been studied sufficiently. Despite the large number of ongoing clinical studies, the results of treatment of AT/RT CNS in the world today remain unsatisfactory. The early age of patients limits the use of radiation therapy, which leads to the need to intensify chemotherapy regimens and to choose the optimal strategy in the toxicity – benefit ratio. The article describes modern approaches to the treatment of central nervous system disorders in children, presents the results of studies with the largest number of included patients, using the multimodal treatment strategy, identifies current trends in targeted therapy.Conflict of interest. The authors declare no conflict of interest.Funding. The study was performed without external funding.

Spinal cord atypical teratoid/rhabdoid tumors in children: Clinical, genetic, and outcome characteristics in a representative European cohort

2019 ◽  
Vol 67 (1) ◽  
Author(s):  
Martin Benesch ◽  
Karolina Nemes ◽  
Petra Neumayer ◽  
Martin Hasselblatt ◽  
Beate Timmermann ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Clinical Genetic ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

CT and MR imaging in atypical teratoid/rhabdoid tumors of the central nervous system

2008 ◽  
Vol 50 (5) ◽  
pp. 447-452 ◽  
Author(s):  
Monika Warmuth-Metz ◽  
Brigitte Bison ◽  
Elke Dannemann-Stern ◽  
Rolf Kortmann ◽  
Stefan Rutkowski ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mr Imaging ◽  
Atypical Teratoid ◽  
The Central Nervous System ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

Loss of BRG1 (SMARCA4) Immunoexpression in a Pediatric Non-Central Nervous System Tumor Cohort

2019 ◽  
Vol 23 (2) ◽  
pp. 132-138
Author(s):  
Jessica Saunders ◽  
Katrina Ingley ◽  
Xiu Qing Wang ◽  
Melissa Harvey ◽  
Linlea Armstrong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Soft Tissue Sarcomas ◽  
Central Nervous System Tumor ◽  
Complex Protein ◽  
Atypical Teratoid ◽  
The Central Nervous System ◽  
System Tumor ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

Malignant rhabdoid tumors and atypical teratoid/rhabdoid tumors of the central nervous system are primitive malignancies associated with a poor prognosis. These tumors have previously been characterized by inactivation of the switch/sucrose nonfermenting (SWI/SNF) chromatin remodeling complex protein integrase interactor 1 (INI1), encoded by the SMARCB1 gene. In the last decade, sporadic publications have shown that a different SWI/SNF protein, brahma-related gene 1 (BRG1), encoded by the SMARCA4 gene, is associated with a similar rhabdoid phenotype and possible germline mutation termed rhabdoid tumor predisposition syndrome type 2. We sought to determine the presence of BRG1 expression in pediatric embryonal tumors. Using a local tissue microarray consisting of 28 tumors diagnosed as having an undifferentiated, polyphenotypic, or rhabdoid morphology, expression of BRG1 by immunohistochemistry was performed. Four cases showed loss of INI1, while 3 of the remaining 24 cases demonstrated loss of BRG1. Two cases were diagnosed as soft tissue sarcomas, and 1 case was diagnosed as a small cell carcinoma of the ovary, hypercalcemic type. Survival ranged from less than 6 months after diagnosis to more than 5 years at the time of last follow-up. In conclusion, we demonstrate that BRG1 immunohistochemistry is a useful second-line immunostain for the workup of undifferentiated, polyphenotypic or rhabdoid pediatric tumors that demonstrate retained expression of INI1.

scholarly journals Clinicopathologic comparison of familial versus sporadic atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system

2010 ◽  
Vol 56 (7) ◽  
pp. 1026-1031 ◽  
Author(s):  
Carol S. Bruggers ◽  
Steven B. Bleyl ◽  
Theodore Pysher ◽  
Philip Barnette ◽  
Zeinab Afify ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Atypical Teratoid ◽  
The Central Nervous System ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

scholarly journals Atypical teratoid/rhabdoid tumors (ATRTs) with SMARCA4 mutation are molecularly distinct from SMARCB1-deficient cases

2020 ◽  
Author(s):  
Dörthe Holdhof ◽  
Pascal D. Johann ◽  
Michael Spohn ◽  
Michael Bockmayr ◽  
Sepehr Safaei ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Location ◽  
Molecular Subgroup ◽  
Signature Genes ◽  
Childhood Malignancies ◽  
Atypical Teratoid ◽  
The Central Nervous System ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors ◽  
Location Type

AbstractAtypical teratoid/rhabdoid tumors (ATRTs) are very aggressive childhood malignancies of the central nervous system. The underlying genetic cause are inactivating bi-allelic mutations in SMARCB1 or (rarely) in SMARCA4. ATRT-SMARCA4 have been associated with a higher frequency of germline mutations, younger age, and an inferior prognosis in comparison to SMARCB1 mutated cases. Based on their DNA methylation profiles and transcriptomics, SMARCB1 mutated ATRTs have been divided into three distinct molecular subgroups: ATRT-TYR, ATRT-SHH, and ATRT-MYC. These subgroups differ in terms of age at diagnosis, tumor location, type of SMARCB1 alterations, and overall survival. ATRT-SMARCA4 are, however, less well understood, and it remains unknown, whether they belong to one of the described ATRT subgroups. Here, we examined 14 ATRT-SMARCA4 by global DNA methylation analyses. We show that they form a separate group segregating from SMARCB1 mutated ATRTs and from other SMARCA4-deficient tumors like small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) or SMARCA4 mutated extra-cranial malignant rhabdoid tumors. In contrast, medulloblastoma (MB) samples with heterozygous SMARCA4 mutations do not group separately, but with established MB subgroups. RNA sequencing of ATRT-SMARCA4 confirmed the clustering results based on DNA methylation profiling and displayed an absence of typical signature genes upregulated in SMARCB1 deleted ATRT. In summary, our results suggest that, in line with previous clinical observations, ATRT-SMARCA4 should be regarded as a distinct molecular subgroup.

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