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

Dagmar Beier, Martin Proescholdt, Christiane Reinert, Torsten Pietsch, David T W Jones, Stefan M Pfister, Elke Hattingen, Clemens Seidel, Linda Dirven, Ralf Luerding, Jaap Reijneveld, Monika Warmuth-Metz, Matteo Bonsanto, Michael Bremer, Stephanie E Combs, Stefan Rieken, Ulrich Herrlinger, Holger Kuntze, Regine Mayer-Steinacker, Dag MoskoppThomas Schneider, Andreas Beringer, Uwe Schlegel, Walter Stummer, Helmut Welker, Astrid Weyerbrock, Frank Paulsen, Stefan Rutkowski, Michael Weller, Wolfgang Wick, Rolf-Dieter Kortmann, Ulrich Bogdahn, Peter Hau

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)400-410
Number of pages11
JournalNeuro-Oncology
Volume20
Issue number3
DOIs
Publication statusPublished - 19 Feb 2018

Cite this

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