TY  - JOUR
A1  - Peters, Sarah
A1  - Frisch, Sabine
A1  - Stock, Annika
A1  - Merta, Julien
A1  - Bäumer, Christian
A1  - Blase, Christoph
A1  - Schuermann, Eicke
A1  - Tippelt, Stephan
A1  - Bison, Brigitte
A1  - Frühwald, Michael
A1  - Rutkowski, Stefan
A1  - Fleischhack, Gudrun
A1  - Timmermann, Beate
T1  - Proton beam therapy for pediatric tumors of the central nervous system — experiences of clinical outcome and feasibility from the KiProReg study
JF  - Cancers
N2  - As radiotherapy is an important part of the treatment in a variety of pediatric tumors of the central nervous system (CNS), proton beam therapy (PBT) plays an evolving role due to its potential benefits attributable to the unique dose distribution, with the possibility to deliver high doses to the target volume while sparing surrounding tissue. Children receiving PBT for an intracranial tumor between August 2013 and October 2017 were enrolled in the prospective registry study KiProReg. Patient’s clinical data including treatment, outcome, and follow-up were analyzed using descriptive statistics, Kaplan–Meier, and Cox regression analysis. Adverse events were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 before, during, and after PBT. Written reports of follow-up imaging were screened for newly emerged evidence of imaging changes, according to a list of predefined keywords for the first 14 months after PBT. Two hundred and ninety-four patients were enrolled in this study. The 3-year overall survival of the whole cohort was 82.7%, 3-year progression-free survival was 67.3%, and 3-year local control was 79.5%. Seventeen patients developed grade 3 adverse events of the CNS during long-term follow-up (new adverse event n = 7; deterioration n = 10). Two patients developed vision loss (CTCAE 4°). This analysis demonstrates good general outcomes after PBT.
KW  - proton beam therapy
KW  - childhood cancer
KW  - brain cancer
KW  - adverse events
KW  - imaging changes
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297489
SN  - 2072-6694
VL  - 14
IS  - 23
ER  - 
TY  - JOUR
A1  - Galetzka, Danuta
A1  - Hansmann, Tamara
A1  - El Hajj, Nady
A1  - Weis, Eva
A1  - Irmscher, Benjamin
A1  - Ludwig, Marco
A1  - Schneider-Rätzke, Brigitte
A1  - Kohlschmidt, Nicolai
A1  - Beyer, Vera
A1  - Bartsch, Oliver
A1  - Zechner, Ulrich
A1  - Spix, Claudia
A1  - Haaf, Thomas
T1  - Monozygotic twins discordant for constitutive BRCA1 promoter methylation, childhood cancer and secondary cancer
JF  - Epigenetics
N2  - We describe monozygotic twins discordant for childhood leukemia and secondary thyroid carcinoma. We used bisulfite pyrosequencing to compare the constitutive promoter methylation of BRCA1 and several other tumor suppressor genes in primary fibroblasts. The affected twin displayed an increased BRCA1 methylation (12%), compared with her sister (3%). Subsequent bisulfite plasmid sequencing demonstrated that 13% (6 of 47) BRCA1 alleles were fully methylated in the affected twin, whereas her sister displayed only single CpG errors without functional implications. This between-twin methylation difference was also found in irradiated fibroblasts and untreated saliva cells. The BRCA1 epimutation may have originated by an early somatic event in the affected twin: approximately 25% of her body cells derived from different embryonic cell lineages carry one epigenetically inactivated BRCA1 allele. This epimutation was associated with reduced basal protein levels and a higher induction of BRCA1 after DNA damage. In addition, we performed a genome-wide microarray analysis of both sisters and found several copy number variations, i.e., heterozygous deletion and reduced expression of the RSPO3 gene in the affected twin. This monozygotic twin pair represents an impressive example of epigenetic somatic mosaicism, suggesting a role for constitutive epimutations, maybe along with de novo genetic alterations in recurrent tumor development.
KW  - BRCA1
KW  - childhood cancer
KW  - DNA Methylation
KW  - epimutation
KW  - monozygotic twins
KW  - secondary cancer
KW  - somatic mosaicism
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125386
VL  - 7
IS  - 1
ER  -