TY - JOUR A1 - Sabel, Magnus A1 - Fleischhack, Gudrun A1 - Tippelt, Stephan A1 - Gustafsson, Göran A1 - Doz, François A1 - Kortmann, Rolf A1 - Massimino, Maura A1 - Navajas, Aurora A1 - von Hoff, Katja A1 - Rutkowski, Stefan A1 - Warmuth-Metz, Monika A1 - Clifford, Steven C. A1 - Pietsch, Torsten A1 - Pizer, Barry A1 - Linnering, Birgitta T1 - Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study JF - Journal of Neurooncology N2 - 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. KW - High-dose chemotherapy KW - Childhood medulloblastoma KW - Adolescents KW - Primitive neuroectodermal KW - Tumors KW - Recurrent medulloblastoma KW - Childrens-cancer KW - Phase-II KW - Trial KW - Therapy KW - Reirradiation KW - Medulloblastoma KW - Relapse KW - Survival KW - Treatment KW - Clinical trial KW - Chemotherapy KW - Radiotherapy KW - Paediatric KW - Secondary tumours Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187498 VL - 129 IS - 3 ER - TY - JOUR A1 - Kandels, Daniela A1 - Pietsch, Torsten A1 - Bison, Brigitte A1 - Warmuth‐Metz, Monika A1 - Thomale, Ulrich‐Wilhelm A1 - Kortmann, Rolf‐Dieter A1 - Timmermann, Beate A1 - Hernáiz Driever, Pablo A1 - Witt, Olaf A1 - Schmidt, René A1 - Gnekow, Astrid K. T1 - Loss of efficacy of subsequent nonsurgical therapy after primary treatment failure in pediatric low‐grade glioma patients—Report from the German SIOP‐LGG 2004 cohort JF - International Journal of Cancer N2 - First‐line treatment of pediatric low‐grade glioma using surgery, radio‐ or chemotherapy fails in a relevant proportion of patients. We analyzed efficacy of subsequent surgical and nonsurgical therapies of the German cohort of the SIOP‐LGG 2004 study (2004‐2012, 1558 registered patients; median age at diagnosis 7.6 years, median observation time 9.2 years, overall survival 98%/96% at 5/10 years, 15% neurofibromatosis type 1 [NF1]). During follow‐up, 1078/1558 patients remained observed without (n = 217), with 1 (n = 707), 2 (n = 124) or 3 to 6 (n = 30) tumor volume reductions; 480/1558 had 1 (n = 332), 2 (n = 80), 3 or more (n = 68) nonsurgical treatment‐lines, accompanied by up to 4 tumor‐reductive surgeries in 215/480; 265/480 patients never underwent any neurosurgical tumor volume reduction (163/265 optic pathway glioma). Patients with progressing tumors after first‐line adjuvant treatment were at increased risk of suffering further progressions. Risk factors were young age (<1 year) at start of treatment, tumor dissemination or progression within 18 months after start of chemotherapy. Progression‐free survival rates declined with subsequent treatment‐lines, yet remaining higher for patients with NF1. In non‐NF1‐associated tumors, vinblastine monotherapy vs platinum‐based chemotherapy was noticeably less effective when used as second‐line treatment. Yet, for the entire cohort, results did not favor a certain sequence of specific treatment options. Rather, all can be aligned as a portfolio of choices which need careful balancing of risks and benefits. Future molecular data may predict long‐term tumor biology. KW - chemotherapy KW - pediatric low‐grade glioma KW - progression KW - radiotherapy KW - surgery Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216130 VL - 147 IS - 12 SP - 3471 EP - 3489 ER - 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 -