TY - JOUR A1 - Dietzsch, Stefan A1 - Braesigk, Annett A1 - Seidel, Clemens A1 - Remmele, Julia A1 - Kitzing, Ralf A1 - Schlender, Tina A1 - Mynarek, Martin A1 - Geismar, Dirk A1 - Jablonska, Karolina A1 - Schwarz, Rudolf A1 - Pazos, Montserrat A1 - Weber, Damien C. A1 - Frick, Silke A1 - Gurtner, Kristin A1 - Matuschek, Christiane A1 - Harrabi, Semi Ben A1 - Glück, Albrecht A1 - Lewitzki, Victor A1 - Dieckmann, Karin A1 - Benesch, Martin A1 - Gerber, Nicolas U. A1 - Obrecht, Denise A1 - Rutkowski, Stefan A1 - Timmermann, Beate A1 - Kortmann, Rolf-Dieter T1 - Types of deviation and review criteria in pretreatment central quality control of tumor bed boost in medulloblastoma—an analysis of the German Radiotherapy Quality Control Panel in the SIOP PNET5 MB trial JF - Strahlentherapie und Onkologie N2 - Purpose In Germany, Austria, and Switzerland, pretreatment radiotherapy quality control (RT-QC) for tumor bed boost (TB) in non-metastatic medulloblastoma (MB) was not mandatory but was recommended for patients enrolled in the SIOP PNET5 MB trial between 2014 and 2018. This individual case review (ICR) analysis aimed to evaluate types of deviations in the initial plan proposals and develop uniform review criteria for TB boost. Patients and methods A total of 78 patients were registered in this trial, of whom a subgroup of 65 patients were available for evaluation of the TB treatment plans. Dose uniformity was evaluated according to the definitions of the protocol. Additional RT-QC criteria for standardized review of target contours were elaborated and data evaluated accordingly. Results Of 65 initial TB plan proposals, 27 (41.5%) revealed deviations of target volume delineation. Deviations according to the dose uniformity criteria were present in 14 (21.5%) TB plans. In 25 (38.5%) cases a modification of the RT plan was recommended. Rejection of the TB plans was rather related to unacceptable target volume delineation than to insufficient dose uniformity. Conclusion In this analysis of pretreatment RT-QC, protocol deviations were present in a high proportion of initial TB plan proposals. These findings emphasize the importance of pretreatment RT-QC in clinical trials for MB. Based on these data, a proposal for RT-QC criteria for tumor bed boost in non-metastatic MB was developed. KW - brain tumor KW - pediatric KW - focal radiotherapy KW - quality assurance KW - individual case review Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307812 SN - 0179-7158 SN - 1439-099X VL - 198 IS - 3 ER - TY - JOUR A1 - von Bueren, André O. A1 - Oehler, Christoph A1 - Shalaby, Tarek A1 - von Hoff, Katja A1 - Pruschy, Martin A1 - Seifert, Burkhardt A1 - Gerber, Nicolas U. A1 - Warmuth-Metz, Monika A1 - Stearns, Duncan A1 - Eberhart, Charles G. A1 - Kortmann, Rolf D. A1 - Rutkowski, Stefan A1 - Grotzer, Michael A. T1 - c-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients JF - BMC Cancer N2 - Background: To study whether and how c-MYC expression determines response to radio-and chemotherapy in childhood medulloblastoma (MB). Methods: We used DAOY and UW228 human MB cells engineered to stably express different levels of c-MYC, and tested whether c-MYC expression has an effect on radio-and chemosensitivity using the colorimetric 3-(4,5-dimethylthiazol- 2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, clonogenic survival, apoptosis assays, cell cycle analysis, and western blot assessment. In an effort to validate our results, we analyzed c-MYC mRNA expression in formalin-fixed paraffin-embedded tumor samples from well-documented patients with postoperative residual tumor and compared c-MYC mRNA expression with response to radio-and chemotherapy as examined by neuroradiological imaging. Results: In DAOY -and to a lesser extent in UW228 -cells expressing high levels of c-MYC, the cytotoxicity of cisplatin, and etoposide was significantly higher when compared with DAOY/UW228 cells expressing low levels of c-MYC. Irradiation-and chemotherapy-induced apoptotic cell death was enhanced in DAOY cells expressing high levels of c-MYC. The response of 62 of 66 residual tumors was evaluable and response to postoperative radio-(14 responders (CR, PR) vs. 5 non-responders (SD, PD)) or chemotherapy (23 CR/PR vs. 20 SD/PD) was assessed. c-MYC mRNA expression was similar in primary MB samples of responders and non-responders (Mann-Whitney U test, p = 0.50, ratio 0.49, 95% CI 0.008-30.0 and p = 0.67, ratio 1.8, 95% CI 0.14-23.5, respectively). Conclusions: c-MYC sensitizes MB cells to some anti-cancer treatments in vitro. As we failed to show evidence for such an effect on postoperative residual tumors when analyzed by imaging, additional investigations in xenografts and larger MB cohorts may help to define the exact function of c-MYC in modulating response to treatment. KW - Induced apoptosis KW - Down-regulation KW - Childhood medulloblastoma KW - Melanoma-cells KW - Cisplatin KW - Lines KW - Gene KW - Radiotherapy KW - Fibroblasts KW - Activation Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134185 VL - 11 IS - 74 ER -