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

TY - JOUR

T1 - 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

AU - Dietzsch, Stefan

AU - Placzek, Felix

AU - Pietschmann, Klaus

AU - von Bueren, André O

AU - Matuschek, Christiane

AU - Glück, Albrecht

AU - Guckenberger, Matthias

AU - Budach, Volker

AU - Welzel, Jutta

AU - Pöttgen, Christoph

AU - Schmidberger, Heinz

AU - Heinzelmann, Frank

AU - Paulsen, Frank

AU - Escudero, Montserrat Pazos

AU - Schwarz, Rudolf

AU - Hornung, Dagmar

AU - Martini, Carmen

AU - Grosu, Anca Ligia

AU - Stueben, Georg

AU - Jablonska, Karolina

AU - Dunst, Juergen

AU - Stranzl-Lawatsch, Heidi

AU - Dieckmann, Karin

AU - Timmermann, Beate

AU - Pietsch, Torsten

AU - Warmuth-Metz, Monika

AU - Bison, Brigitte

AU - Kwiecien, Robert

AU - Benesch, Martin

AU - Gerber, Nicolas U

AU - Grotzer, Michael A

AU - Pfister, Stefan M

AU - Clifford, Steven C

AU - von Hoff, Katja

AU - Klagges, Sabine

AU - Rutkowski, Stefan

AU - Kortmann, Rolf-Dieter

AU - Mynarek, Martin

N1 - © 2020 The Authors.

PY - 2020/12/12

Y1 - 2020/12/12

N2 - 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.

AB - 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.

U2 - 10.1016/j.adro.2020.09.018

DO - 10.1016/j.adro.2020.09.018

M3 - SCORING: Journal article

C2 - 33305077

VL - 5

SP - 1158

EP - 1169

JO - ADV RADIAT ONCOL

JF - ADV RADIAT ONCOL

SN - 2452-1094

IS - 6

ER -