@article{GaabAdolphTippeltetal.2022, author = {Gaab, Christine and Adolph, Jonas E. and Tippelt, Stephan and Mikasch, Ruth and Obrecht, Denise and Mynarek, Martin and Rutkowski, Stefan and Pfister, Stefan M. and Milde, Till and Witt, Olaf and Bison, Brigitte and Warmuth-Metz, Monika and Kortmann, Rolf-Dieter and Dietzsch, Stefan and Pietsch, Torsten and Timmermann, Beate and Str{\"a}ter, Ronald and Bode, Udo and Faldum, Andreas and Kwiecien, Robert and Fleischhack, Gudrun}, title = {Local and systemic therapy of recurrent medulloblastomas in children and adolescents: results of the P-HIT-REZ 2005 Study}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {3}, issn = {2072-6694}, doi = {10.3390/cancers14030471}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254809}, year = {2022}, abstract = {Recurrent medulloblastomas are associated with survival rates <10\%. Adequate multimodal therapy is being discussed as having a major impact on survival. In this study, 93 patients with recurrent medulloblastoma treated in the German P-HIT-REZ 2005 Study were analyzed for survival (PFS, OS) dependent on patient, disease, and treatment characteristics. The median age at the first recurrence was 10.1 years (IQR: 6.9-16.1). Median PFS and OS, at first recurrence, were 7.9 months (CI: 5.7-10.0) and 18.5 months (CI: 13.6-23.5), respectively. Early relapses/progressions (<18 months, n = 30/93) found mainly in molecular subgroup 3 were associated with markedly worse median PFS (HR: 2.34) and OS (HR: 3.26) in regression analyses. A significant survival advantage was found for the use of volume-reducing surgery as well as radiotherapy. Intravenous chemotherapy with carboplatin and etoposide (ivCHT, n = 28/93) showed improved PFS and OS data and the best objective response rate (ORR) was 66.7\% compared to oral temozolomide (oCHT, n = 47/93) which was 34.8\%. Intraventricular (n = 43) as well as high-dose chemotherapy (n = 17) at first relapse was not related to a significant survival benefit. Although the results are limited due to a non-randomized study design, they may serve as a basis for future treatment decisions in order to improve the patients' survival.}, language = {en} } @article{DietzschBraesigkSeideletal.2022, author = {Dietzsch, Stefan and Braesigk, Annett and Seidel, Clemens and Remmele, Julia and Kitzing, Ralf and Schlender, Tina and Mynarek, Martin and Geismar, Dirk and Jablonska, Karolina and Schwarz, Rudolf and Pazos, Montserrat and Weber, Damien C. and Frick, Silke and Gurtner, Kristin and Matuschek, Christiane and Harrabi, Semi Ben and Gl{\"u}ck, Albrecht and Lewitzki, Victor and Dieckmann, Karin and Benesch, Martin and Gerber, Nicolas U. and Obrecht, Denise and Rutkowski, Stefan and Timmermann, Beate and Kortmann, Rolf-Dieter}, title = {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}, series = {Strahlentherapie und Onkologie}, volume = {198}, journal = {Strahlentherapie und Onkologie}, number = {3}, issn = {0179-7158}, doi = {10.1007/s00066-021-01822-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307812}, pages = {282-290}, year = {2022}, abstract = {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.}, language = {en} } @article{BartelheimNemesSeeringeretal.2016, author = {Bartelheim, Kerstin and Nemes, Karolina and Seeringer, Angela and Kerl, Kornelius and Buechner, Jochen and Boos, Joachim and Graf, Norbert and D{\"u}rken, Matthias and Gerss, Joachim and Hasselblatt, Martin and Kortmann, Rolf-Dieter and Teichert von Luettichau, Irene and Nagel, Inga and Nygaard, Randi and Oyen, Florian and Quiroga, Eduardo and Schlegel, Paul-Gerhardt and Schmid, Irene and Schneppenheim, Reinhard and Siebert, Reiner and Solano-Paez, Palma and Timmermann, Beate and Warmuth-Metz, Monika and Fr{\"u}hwald, Michael Christoph}, title = {Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007}, series = {Cancer Medicine}, volume = {5}, journal = {Cancer Medicine}, number = {8}, doi = {10.1002/cam4.741}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164799}, pages = {1765-1775}, year = {2016}, abstract = {Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64\% (genetic analyses, FISH, MLPA, sequencing) up to 97\% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46\% (±0.10) and 45\% (±0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials.}, language = {en} }