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 Moskopp; Thomas 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

doi:https://doi.org/10.1093/neuonc/nox155

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 journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	400-410
Number of pages	11
Journal	Neuro-oncology
Volume	20
Issue number	3
Early online date	2017
DOIs	https://doi.org/10.1093/neuonc/nox155
Publication status	Published - 19 Feb 2018

Keywords

Journal Article

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https://doi.org/10.1093/neuonc/nox155

Cite this

Beier, D., Proescholdt, M., Reinert, C., Pietsch, T., Jones, D. T. W., Pfister, S. M., Hattingen, E., Seidel, C., Dirven, L., Luerding, R., Reijneveld, J., Warmuth-Metz, M., Bonsanto, M., Bremer, M., Combs, S. E., Rieken, S., Herrlinger, U., Kuntze, H., Mayer-Steinacker, R., ... 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

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

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.",

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

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volume = "20",

pages = "400--410",

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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, R-D, Bogdahn, U & Hau, P 2018, 'Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07)', Neuro-oncology, vol. 20, no. 3, pp. 400-410. https://doi.org/10.1093/neuonc/nox155

TY - JOUR

T1 - Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07)

AU - Beier, Dagmar

AU - Proescholdt, Martin

AU - Reinert, Christiane

AU - Pietsch, Torsten

AU - Jones, David T W

AU - Pfister, Stefan M

AU - Hattingen, Elke

AU - Seidel, Clemens

AU - Dirven, Linda

AU - Luerding, Ralf

AU - Reijneveld, Jaap

AU - Warmuth-Metz, Monika

AU - Bonsanto, Matteo

AU - Bremer, Michael

AU - Combs, Stephanie E

AU - Rieken, Stefan

AU - Herrlinger, Ulrich

AU - Kuntze, Holger

AU - Mayer-Steinacker, Regine

AU - Moskopp, Dag

AU - Schneider, Thomas

AU - Beringer, Andreas

AU - Schlegel, Uwe

AU - Stummer, Walter

AU - Welker, Helmut

AU - Weyerbrock, Astrid

AU - Paulsen, Frank

AU - Rutkowski, Stefan

AU - Weller, Michael

AU - Wick, Wolfgang

AU - Kortmann, Rolf-Dieter

AU - Bogdahn, Ulrich

AU - Hau, Peter

PY - 2018/2/19

Y1 - 2018/2/19

N2 - 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.

AB - 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.

KW - Journal Article

U2 - https://doi.org/10.1093/neuonc/nox155

DO - https://doi.org/10.1093/neuonc/nox155

M3 - Article

C2 - 29016837

SN - 1522-8517

VL - 20

SP - 400

EP - 410

JO - Neuro-oncology

JF - Neuro-oncology

IS - 3

ER -