TY - JOUR A1 - Gaab, Christine A1 - Adolph, Jonas E. A1 - Tippelt, Stephan A1 - Mikasch, Ruth A1 - Obrecht, Denise A1 - Mynarek, Martin A1 - Rutkowski, Stefan A1 - Pfister, Stefan M. A1 - Milde, Till A1 - Witt, Olaf A1 - Bison, Brigitte A1 - Warmuth-Metz, Monika A1 - Kortmann, Rolf-Dieter A1 - Dietzsch, Stefan A1 - Pietsch, Torsten A1 - Timmermann, Beate A1 - Sträter, Ronald A1 - Bode, Udo A1 - Faldum, Andreas A1 - Kwiecien, Robert A1 - Fleischhack, Gudrun T1 - Local and systemic therapy of recurrent medulloblastomas in children and adolescents: results of the P-HIT-REZ 2005 Study JF - Cancers N2 - 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. KW - medulloblastoma KW - refractory KW - recurrent KW - children KW - chemotherapy KW - surgery KW - radiotherapy KW - re-irradiation KW - intraventricular therapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254809 SN - 2072-6694 VL - 14 IS - 3 ER - 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 - Adolph, Jonas E. A1 - Fleischhack, Gudrun A1 - Gaab, Christine A1 - Mikasch, Ruth A1 - Mynarek, Martin A1 - Rutkowski, Stefan A1 - Schüller, Ulrich A1 - Pfister, Stefan M. A1 - Pajtler, Kristian W. A1 - Milde, Till A1 - Witt, Olaf A1 - Bison, Brigitte A1 - Warmuth-Metz, Monika A1 - Kortmann, Rolf-Dieter A1 - Dietzsch, Stefan A1 - Pietsch, Torsten A1 - Timmermann, Beate A1 - Tippelt, Stephan T1 - Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies JF - Journal of Neuro-Oncology N2 - Purpose Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN. Methods Systemic chemotherapeutic treatment of 138 patients enrolled in the German HIT-REZ-studies was analyzed. Survival depending on the use of chemotherapy, disease-stabilization rates (RR), duration of response (DOR) and time to progression (TTP) were estimated. Results Median age at first recurrence was 7.6 years (IQR: 4.0–13.6). At first recurrence, median PFS and OS were 15.3 (CI 13.3–20.0) and 36.9 months (CI 29.7–53.4), respectively. The Hazard Ratio for the use of chemotherapy in local recurrences in a time-dependent Cox-regression analysis was 0.99 (CI 0.74–1.33). Evaluable responses for 140 applied chemotherapies were analyzed, of which sirolimus showed the best RR (50%) and longest median TTP [11.51 (CI 3.98; 14.0) months] in nine patients, with the strongest impact found when sirolimus was used as a monotherapy. Seven patients with progression-free survival > 12 months after subtotal/no-resection facilitated by chemotherapy were found. No definitive survival advantage for any drug in a specific molecularly defined EPN type was found. Conclusion No survival advantage for the general use of chemotherapy in recurrent EPN was found. In cases with incomplete resection, chemotherapy was able to extend survival in individual cases. Sirolimus showed the best RR, DOR and TTP out of all drugs analyzed and may warrant further investigation. KW - ependymoma KW - chemotherapy KW - recurrence KW - children KW - sirolimus Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308302 SN - 0167-594X SN - 1573-7373 VL - 155 IS - 2 ER -