1. Evaluation of Prognostic Factors and Role of Participation in a Randomized Trial or a Prospective Registry in Pediatric and Adolescent Nonmetastatic Medulloblastoma – A Report From the HIT 2000 Trial
- Author
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Stefan Dietzsch, André O. von Bueren, Anca-Ligia Grosu, Frank Paulsen, Heinz Schmidberger, Michael A. Grotzer, Beate Timmermann, Robert Kwiecien, Christiane Matuschek, Martin Mynarek, Stefan M. Pfister, Frank Heinzelmann, Georg Stueben, Carmen Martini, Martin Benesch, Heidi Stranzl-Lawatsch, Klaus Pietschmann, Christoph Pöttgen, Steven C. Clifford, Stefan Rutkowski, Felix Placzek, Sabine Klagges, Karin Dieckmann, Nicolas U. Gerber, Albrecht Glück, Monika Warmuth-Metz, Jutta Welzel, Volker Budach, Katja von Hoff, Rudolf Schwarz, Juergen Dunst, Torsten Pietsch, Montserrat Pazos Escudero, Karolina Jablonska, Rolf-Dieter Kortmann, Brigitte Bison, Matthias Guckenberger, and Dagmar Hornung
- Subjects
Oncology ,medicine.medical_specialty ,Multivariate analysis ,medicine.medical_treatment ,Medizin ,Treatment results ,030218 nuclear medicine & medical imaging ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Medicine ,Radiology, Nuclear Medicine and imaging ,Scientific Article ,ddc:610 ,Medulloblastoma ,Univariate analysis ,ddc:618 ,business.industry ,Hazard ratio ,Retrospective cohort study ,medicine.disease ,Radiation therapy ,030220 oncology & carcinogenesis ,business - Abstract
Purpose: We aimed to compare treatment results in and outside of a randomized trial and to confirm factors influencing outcome in a large retrospective cohort of nonmetastatic medulloblastoma treated in Austria, Switzerland and Germany. Methods and Materials: Patients with nonmetastatic medulloblastoma (n = 382) aged 4 to 21 years and primary neurosurgical resection between 2001 and 2011 were assessed. Between 2001 and 2006, 176 of these patients (46.1%) were included in the randomized HIT SIOP PNET 4 trial. From 2001 to 2011 an additional 206 patients were registered to the HIT 2000 study center and underwent the identical central review program. Three different radiation therapy protocols were applied. Genetically defined tumor entity (former molecular subgroup) was available for 157 patients. Results: Median follow-up time was 7.3 (range, 0.09-13.86) years. There was no difference between HIT SIOP PNET 4 trial patients and observational patients outside the randomized trial, with 7 years progression-free survival rates (PFS) of 79.5% ± 3.1% versus 78.7% ± 3.1% (P= .62). On univariate analysis, the time interval between surgery and irradiation (≤ 48 days vs ≥ 49 days) showed a strong trend to affect PFS (80.4% ± 2.2% vs 64.6% ± 9.1%;P= .052). Furthermore, histologically and genetically defined tumor entities and the extent of postoperative residual tumor influenced PFS. On multivariate analyses, a genetically defined tumor entity wingless-related integration site-activated vs non-wingless-related integration site/non-SHH, group 3 hazard ratio, 5.49;P= .014) and time interval between surgery and irradiation (hazard ratio, 2.2;P= .018) were confirmed as independent risk factors. Conclusions: Using a centralized review program and risk-stratified therapy for all patients registered to the study center, outcome was identical for patients with nonmetastatic medulloblastoma treated on and off the randomized HIT SIOP PNET 4 trial. The prognostic values of prolonged time to RT and genetically defined tumor entity were confirmed.
- Published
- 2020