Comprehensive genetic profiling and molecularly guided treatment for patients with primary CNS tumors

Julia C. Kuehn; Patrick Metzger; Nicolas Neidert; Uta Matysiak; Linda Gräßel; Ulrike Philipp; Sabine Bleul; Thomas Pauli; Julia Falkenstein; Henriette Bertemes; Stepan Cysar; Maria Elena Hess; Anna Verena Frey; Jesús Duque-Afonso; Elisabeth Schorb; Marcia Machein; Jürgen Beck; Oliver Schnell; Nikolas von Bubnoff; Anna L. Illert; Christoph Peters; Tilman Brummer; Marco Prinz; Cornelius Miething; Heiko Becker; Silke Lassmann; Martin Werner; Melanie Börries; Justus Duyster; Dieter H. Heiland; Roman Sankowski; Florian Scherer

doi:10.1038/s41698-024-00674-y

Comprehensive genetic profiling and molecularly guided treatment for patients with primary CNS tumors

Julia C. Kuehn, Patrick Metzger, Nicolas Neidert, Uta Matysiak, Linda Gräßel, Ulrike Philipp, Sabine Bleul, Thomas Pauli, Julia Falkenstein, Henriette Bertemes, Stepan Cysar, Maria Elena Hess, Anna Verena Frey, Jesús Duque-Afonso, Elisabeth Schorb, Marcia Machein, Jürgen Beck, Oliver Schnell, Nikolas von Bubnoff, Anna L. IllertChristoph Peters, Tilman Brummer, Marco Prinz, Cornelius Miething, Heiko Becker, Silke Lassmann, Martin Werner, Melanie Börries, Justus Duyster, Dieter H. Heiland, Roman Sankowski, Florian Scherer^*

^*Corresponding author for this work

11 Citations (Scopus)

Abstract

Despite major advances in molecular profiling and classification of primary brain tumors, personalized treatment remains limited for most patients. Here, we explored the feasibility of individual molecular profiling and the efficacy of biomarker-guided therapy for adult patients with primary brain cancers in the real-world setting within the molecular tumor board Freiburg, Germany. We analyzed genetic profiles, personalized treatment recommendations, and clinical outcomes of 102 patients with 21 brain tumor types. Alterations in the cell cycle, BRAF, and mTOR pathways most frequently led to personalized treatment recommendations. Molecularly informed therapies were recommended in 71% and implemented in 32% of patients with completed molecular diagnostics. The disease control rate following targeted treatment was 50% and the overall response rate was 30%, with a progression-free survival 2/1 ratio of at least 1.3 in 31% of patients. This study highlights the efficacy of molecularly guided treatment and the need for biomarker-stratified trials in brain cancers.

Original language	English
Article number	180
Journal	NPJ precision oncology
Volume	8
Issue number	1
ISSN	2397-768X
DOIs	https://doi.org/10.1038/s41698-024-00674-y
Publication status	Published - 12.2024

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Research Area: Luebeck Integrated Oncology Network (LION)

DFG Research Classification Scheme

2.22-14 Hematology, Oncology

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10.1038/s41698-024-00674-y

Cite this

Kuehn, J. C., Metzger, P., Neidert, N., Matysiak, U., Gräßel, L., Philipp, U., Bleul, S., Pauli, T., Falkenstein, J., Bertemes, H., Cysar, S., Hess, M. E., Frey, A. V., Duque-Afonso, J., Schorb, E., Machein, M., Beck, J., Schnell, O., von Bubnoff, N., ... Scherer, F. (2024). Comprehensive genetic profiling and molecularly guided treatment for patients with primary CNS tumors. NPJ precision oncology, 8(1), Article 180. https://doi.org/10.1038/s41698-024-00674-y

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title = "Comprehensive genetic profiling and molecularly guided treatment for patients with primary CNS tumors",

abstract = "Despite major advances in molecular profiling and classification of primary brain tumors, personalized treatment remains limited for most patients. Here, we explored the feasibility of individual molecular profiling and the efficacy of biomarker-guided therapy for adult patients with primary brain cancers in the real-world setting within the molecular tumor board Freiburg, Germany. We analyzed genetic profiles, personalized treatment recommendations, and clinical outcomes of 102 patients with 21 brain tumor types. Alterations in the cell cycle, BRAF, and mTOR pathways most frequently led to personalized treatment recommendations. Molecularly informed therapies were recommended in 71\% and implemented in 32\% of patients with completed molecular diagnostics. The disease control rate following targeted treatment was 50\% and the overall response rate was 30\%, with a progression-free survival 2/1 ratio of at least 1.3 in 31\% of patients. This study highlights the efficacy of molecularly guided treatment and the need for biomarker-stratified trials in brain cancers.",

author = "Kuehn, \{Julia C.\} and Patrick Metzger and Nicolas Neidert and Uta Matysiak and Linda Gr{\"a}{\ss}el and Ulrike Philipp and Sabine Bleul and Thomas Pauli and Julia Falkenstein and Henriette Bertemes and Stepan Cysar and Hess, \{Maria Elena\} and Frey, \{Anna Verena\} and Jes{\'u}s Duque-Afonso and Elisabeth Schorb and Marcia Machein and J{\"u}rgen Beck and Oliver Schnell and \{von Bubnoff\}, Nikolas and Illert, \{Anna L.\} and Christoph Peters and Tilman Brummer and Marco Prinz and Cornelius Miething and Heiko Becker and Silke Lassmann and Martin Werner and Melanie B{\"o}rries and Justus Duyster and Heiland, \{Dieter H.\} and Roman Sankowski and Florian Scherer",

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year = "2024",

month = dec,

doi = "10.1038/s41698-024-00674-y",

language = "English",

volume = "8",

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Kuehn, JC, Metzger, P, Neidert, N, Matysiak, U, Gräßel, L, Philipp, U, Bleul, S, Pauli, T, Falkenstein, J, Bertemes, H, Cysar, S, Hess, ME, Frey, AV, Duque-Afonso, J, Schorb, E, Machein, M, Beck, J, Schnell, O, von Bubnoff, N, Illert, AL, Peters, C, Brummer, T, Prinz, M, Miething, C, Becker, H, Lassmann, S, Werner, M, Börries, M, Duyster, J, Heiland, DH, Sankowski, R & Scherer, F 2024, 'Comprehensive genetic profiling and molecularly guided treatment for patients with primary CNS tumors', NPJ precision oncology, vol. 8, no. 1, 180. https://doi.org/10.1038/s41698-024-00674-y

TY - JOUR

T1 - Comprehensive genetic profiling and molecularly guided treatment for patients with primary CNS tumors

AU - Kuehn, Julia C.

AU - Metzger, Patrick

AU - Neidert, Nicolas

AU - Matysiak, Uta

AU - Gräßel, Linda

AU - Philipp, Ulrike

AU - Bleul, Sabine

AU - Pauli, Thomas

AU - Falkenstein, Julia

AU - Bertemes, Henriette

AU - Cysar, Stepan

AU - Hess, Maria Elena

AU - Frey, Anna Verena

AU - Duque-Afonso, Jesús

AU - Schorb, Elisabeth

AU - Machein, Marcia

AU - Beck, Jürgen

AU - Schnell, Oliver

AU - von Bubnoff, Nikolas

AU - Illert, Anna L.

AU - Peters, Christoph

AU - Brummer, Tilman

AU - Prinz, Marco

AU - Miething, Cornelius

AU - Becker, Heiko

AU - Lassmann, Silke

AU - Werner, Martin

AU - Börries, Melanie

AU - Duyster, Justus

AU - Heiland, Dieter H.

AU - Sankowski, Roman

AU - Scherer, Florian

PY - 2024/12

Y1 - 2024/12

N2 - Despite major advances in molecular profiling and classification of primary brain tumors, personalized treatment remains limited for most patients. Here, we explored the feasibility of individual molecular profiling and the efficacy of biomarker-guided therapy for adult patients with primary brain cancers in the real-world setting within the molecular tumor board Freiburg, Germany. We analyzed genetic profiles, personalized treatment recommendations, and clinical outcomes of 102 patients with 21 brain tumor types. Alterations in the cell cycle, BRAF, and mTOR pathways most frequently led to personalized treatment recommendations. Molecularly informed therapies were recommended in 71% and implemented in 32% of patients with completed molecular diagnostics. The disease control rate following targeted treatment was 50% and the overall response rate was 30%, with a progression-free survival 2/1 ratio of at least 1.3 in 31% of patients. This study highlights the efficacy of molecularly guided treatment and the need for biomarker-stratified trials in brain cancers.

AB - Despite major advances in molecular profiling and classification of primary brain tumors, personalized treatment remains limited for most patients. Here, we explored the feasibility of individual molecular profiling and the efficacy of biomarker-guided therapy for adult patients with primary brain cancers in the real-world setting within the molecular tumor board Freiburg, Germany. We analyzed genetic profiles, personalized treatment recommendations, and clinical outcomes of 102 patients with 21 brain tumor types. Alterations in the cell cycle, BRAF, and mTOR pathways most frequently led to personalized treatment recommendations. Molecularly informed therapies were recommended in 71% and implemented in 32% of patients with completed molecular diagnostics. The disease control rate following targeted treatment was 50% and the overall response rate was 30%, with a progression-free survival 2/1 ratio of at least 1.3 in 31% of patients. This study highlights the efficacy of molecularly guided treatment and the need for biomarker-stratified trials in brain cancers.

UR - https://www.scopus.com/pages/publications/85201367124

U2 - 10.1038/s41698-024-00674-y

DO - 10.1038/s41698-024-00674-y

M3 - Journal articles

AN - SCOPUS:85201367124

SN - 2397-768X

VL - 8

JO - NPJ precision oncology

JF - NPJ precision oncology

IS - 1

M1 - 180

ER -

Comprehensive genetic profiling and molecularly guided treatment for patients with primary CNS tumors

Abstract

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

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