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

Beier, Dagmar and Proescholdt, Martin and Reinert, Christiane and Pietsch, Torsten and Jones, David T. W. and Pfister, Stefan M. and Hattingen, Elke and Seidel, Clemens and Dirven, Linda and Luerding, Ralf and Reijneveld, Jaap and Warmuth-Metz, Monika and Bonsanto, Matteo and Bremer, Michael and Combs, Stephanie E. and Rieken, Stefan and Herrlinger, Ulrich and Kuntze, Holger and Mayer-Steinacker, Regine and Moskopp, Dag and Schneider, Thomas and Beringer, Andreas and Schlegel, Uwe and Stummer, Walter and Welker, Helmut and Weyerbrock, Astrid and Paulsen, Frank and Rutkowski, Stefan and Weller, Michael and Wick, Wolfgang and Kortmann, Rolf-Dieter and Bogdahn, Ulrich and Hau, Peter (2018) Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07). NEURO-ONCOLOGY, 20 (3). pp. 400-410. ISSN 1522-8517, 1523-5866

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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.

Item Type: Article
Uncontrolled Keywords: CENTRAL-NERVOUS-SYSTEM; QUALITY-OF-LIFE; CRANIOSPINAL RADIATION-THERAPY; AVERAGE-RISK MEDULLOBLASTOMA; ADJUVANT CHEMOTHERAPY; ONCOLOGY-GROUP; BRAIN-TUMOR; PHASE-III; CHILDHOOD; CHILDREN; cognition; imaging; health-related quality of life; medulloblastoma; radiochemotherapy
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Neurologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 12 Mar 2020 12:20
Last Modified: 12 Mar 2020 12:20
URI: https://pred.uni-regensburg.de/id/eprint/14931

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