@article{PetersFrischStocketal.2022, author = {Peters, Sarah and Frisch, Sabine and Stock, Annika and Merta, Julien and B{\"a}umer, Christian and Blase, Christoph and Schuermann, Eicke and Tippelt, Stephan and Bison, Brigitte and Fr{\"u}hwald, Michael and Rutkowski, Stefan and Fleischhack, Gudrun and Timmermann, Beate}, title = {Proton beam therapy for pediatric tumors of the central nervous system — experiences of clinical outcome and feasibility from the KiProReg study}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {23}, issn = {2072-6694}, doi = {10.3390/cancers14235863}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297489}, year = {2022}, abstract = {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.}, language = {en} } @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{SabelFleischhackTippeltetal.2016, author = {Sabel, Magnus and Fleischhack, Gudrun and Tippelt, Stephan and Gustafsson, G{\"o}ran and Doz, Fran{\c{c}}ois and Kortmann, Rolf and Massimino, Maura and Navajas, Aurora and von Hoff, Katja and Rutkowski, Stefan and Warmuth-Metz, Monika and Clifford, Steven C. and Pietsch, Torsten and Pizer, Barry and Linnering, Birgitta}, title = {Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study}, series = {Journal of Neurooncology}, volume = {129}, journal = {Journal of Neurooncology}, number = {3}, organization = {SIOP-E Brain Tumour Group}, doi = {10.1007/s11060-016-2202-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187498}, pages = {515-524}, year = {2016}, abstract = {The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001-2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 +/- 2 \% and 78 +/- 2 \% respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 \%) were isolated local relapses in the posterior fossa (PF) and 59 (82 \%) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. > 5 years from diagnosis, occurred in six patients (8 \%). Relapse treatment consisted of combinations of surgery (25 \%), focal radiotherapy (RT 22 \%), high dose chemotherapy with stem cell rescue (HDSCR 21 \%) and conventional chemotherapy (90 \%). OS at 5 years after relapse was 6.0 +/- 4 \%. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour.}, language = {en} }