Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07)

Beier D, Proescholdt M, Reinert C, Pietsch T, Jones DTW, Pfister SM, Hattingen E, Seidel C, Dirven L, Luerding R, Reijneveld J, Warmuth-Metz M, Bonsanto M, Bremer M, Combs SE, Rieken S, Herrlinger U, Kuntze H, Mayer-Steinacker R, Moskopp D, Schneider T, Beringer A, Schlegel U, Stummer W, Welker H, Weyerbrock A, Paulsen F, Rutkowski S, Weller M, Wick W, Kortmann RD, Bogdahn U, Hau P (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 20

Pages Range: 400-410

Journal Issue: 3

DOI: 10.1093/neuonc/nox155

Abstract

Background. Medulloblastoma in adult patients is rare, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. No prospective data on the feasibility of radiochemotherapy exist. The German Neuro-Oncology Working Group (NOA) performed a prospective descriptive multicenter single-arm phase II trial to evaluate feasibility and toxicity of radio-polychemotherapy Methods. The NOA-07 trial combined craniospinal irradiation with vincristine, followed by 8 cycles of cisplatin, lomustine, and vincristine. Adverse events, imaging and progression patterns, histological and genetic markers, health-related quality of life (HRQoL), and cognition were evaluated. Primary endpoint was the rate of toxicity-related treatment terminations after 4 chemotherapy cycles, and the toxicity profile. The feasibility goal was reached if at least 45% of patients received at least 4 cycles of maintenance chemotherapy. Results. Thirty patients were evaluable. Each 50% showed classic and desmoplastic/nodular histology. Sixty-seven percent were classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13% in wingless (WNT), and 17% in non-WNT/non-SHH. Four cycles of chemotherapy were feasible in the majority (n = 21; 70.0%). Hematological side effects and polyneuropathy were prevalent toxicities. During the active treatment period, HRQoL and verbal fluency improved significantly. The 3-year event-free survival rate was 66.6% at the time of databank lock. Conclusions. Radio-polychemotherapy did lead to considerable toxicity and a high amount of dose reductions throughout the first 4 chemotherapy cycles that may affect efficacy. Thus, we propose frequent patient surveillance using this regimen. Modifications of the regimen may increase feasibility of radio-polychemotherapy of adult patients with medulloblastoma.

Involved external institutions

University of Southern Denmark / Syddansk Universitet Denmark (DK) Universitätsklinikum Regensburg Germany (DE) Universität Regensburg Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Universitätsklinikum Bonn Germany (DE) Universitätsklinikum Leipzig Germany (DE) Leiden University Netherlands (NL) Vrije Universiteit Amsterdam (VU) / University Amsterdam Netherlands (NL) Universitätsklinikum Würzburg Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Universitätsklinikum Ulm Germany (DE) Vivantes - Netzwerk für Gesundheit GmbH Germany (DE) Universitätsklinikum Magdeburg A.ö.R. Germany (DE) Ruhr-Universität Bochum (RUB) Germany (DE) Klinikum Stuttgart Germany (DE) Universitätsklinikum Freiburg Germany (DE) Universitätsklinikum Tübingen Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsspital Zürich (USZ) Switzerland (CH) Universitätsklinikum Münster Germany (DE)

How to cite

APA:

Beier, D., Proescholdt, M., Reinert, C., Pietsch, T., Jones, D.T.W., Pfister, S.M.,... Hau, P. (2018). Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07). Neuro-Oncology, 20(3), 400-410. https://doi.org/10.1093/neuonc/nox155

MLA:

Beier, Dagmar, et al. "Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07)." Neuro-Oncology 20.3 (2018): 400-410.

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