Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions in patients with rare cancers

Peter Horak; Christoph Heining; Simon Kreutzfeldt; Barbara Hutter; Andreas Mock; Jennifer Hüllein; Martina Fröhlich; Sebastian Uhrig; Arne Jahn; Andreas Rump; Laura Gieldon; Lino Möhrmann; Dorothea Hanf; Veronica Teleanu; Christoph E. Heilig; Daniel B. Lipka; Michael Allgäuer; Leo Ruhnke; Andreas Laßmann; Volker Endris; Olaf Neumann; Roland Penzel; Katja Beck; Daniela Richter; Ulrike Winter; Stephan Wolf; Katrin Pfütze; Christina Geörg; Bettina Meißburger; Ivo Buchhalter; Marinela Augustin; Walter E. Aulitzky; Peter Hohenberger; Matthias Kroiss; Peter Schirmacher; Richard F. Schlenk; Ulrich Keilholz; Frederick Klauschen; Gunnar Folprecht; Sebastian Bauer; Jens Thomas Siveke; Christian H. Brandts; Thomas Kindler; Melanie Boerries; Anna L. Illert; Nikolas Von Bubnoff; Philipp J. Jost; Karsten Spiekermann; Michael Bitzer; Klaus Schulze-Osthoff; Christof Von Kalle; Barbara Klink; Benedikt Brors; Albrecht Stenzinger; Evelin Schröck; Daniel Hübschmann; Wilko Weichert; Hanno Glimm; Stefan Fröhling

doi:10.1158/2159-8290.CD-21-0126

Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions in patients with rare cancers

Peter Horak, Christoph Heining, Simon Kreutzfeldt, Barbara Hutter, Andreas Mock, Jennifer Hüllein, Martina Fröhlich, Sebastian Uhrig, Arne Jahn, Andreas Rump, Laura Gieldon, Lino Möhrmann, Dorothea Hanf, Veronica Teleanu, Christoph E. Heilig, Daniel B. Lipka, Michael Allgäuer, Leo Ruhnke, Andreas Laßmann, Volker EndrisOlaf Neumann, Roland Penzel, Katja Beck, Daniela Richter, Ulrike Winter, Stephan Wolf, Katrin Pfütze, Christina Geörg, Bettina Meißburger, Ivo Buchhalter, Marinela Augustin, Walter E. Aulitzky, Peter Hohenberger, Matthias Kroiss, Peter Schirmacher, Richard F. Schlenk, Ulrich Keilholz, Frederick Klauschen, Gunnar Folprecht, Sebastian Bauer, Jens Thomas Siveke, Christian H. Brandts, Thomas Kindler, Melanie Boerries, Anna L. Illert, Nikolas Von Bubnoff, Philipp J. Jost, Karsten Spiekermann, Michael Bitzer, Klaus Schulze-Osthoff, Christof Von Kalle, Barbara Klink, Benedikt Brors, Albrecht Stenzinger, Evelin Schröck, Daniel Hübschmann, Wilko Weichert, Hanno Glimm^*, Stefan Fröhling^*

^*Corresponding author for this work

Clinic of Hematology and Oncology

70 Citations (Scopus)

Abstract

The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population.

Original language	English
Journal	Cancer Discovery
Volume	11
Issue number	11
Pages (from-to)	2780-2795
Number of pages	16
ISSN	2159-8274
DOIs	https://doi.org/10.1158/2159-8290.CD-21-0126
Publication status	Published - 11.2021

Research Areas and Centers

Centers: University Cancer Center Schleswig-Holstein (UCCSH)

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

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10.1158/2159-8290.CD-21-0126

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Horak, P., Heining, C., Kreutzfeldt, S., Hutter, B., Mock, A., Hüllein, J., Fröhlich, M., Uhrig, S., Jahn, A., Rump, A., Gieldon, L., Möhrmann, L., Hanf, D., Teleanu, V., Heilig, C. E., Lipka, D. B., Allgäuer, M., Ruhnke, L., Laßmann, A., ... Fröhling, S. (2021). Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions in patients with rare cancers. Cancer Discovery, 11(11), 2780-2795. https://doi.org/10.1158/2159-8290.CD-21-0126

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abstract = "The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population.",

author = "Peter Horak and Christoph Heining and Simon Kreutzfeldt and Barbara Hutter and Andreas Mock and Jennifer H{\"u}llein and Martina Fr{\"o}hlich and Sebastian Uhrig and Arne Jahn and Andreas Rump and Laura Gieldon and Lino M{\"o}hrmann and Dorothea Hanf and Veronica Teleanu and Heilig, {Christoph E.} and Lipka, {Daniel B.} and Michael Allg{\"a}uer and Leo Ruhnke and Andreas La{\ss}mann and Volker Endris and Olaf Neumann and Roland Penzel and Katja Beck and Daniela Richter and Ulrike Winter and Stephan Wolf and Katrin Pf{\"u}tze and Christina Ge{\"o}rg and Bettina Mei{\ss}burger and Ivo Buchhalter and Marinela Augustin and Aulitzky, {Walter E.} and Peter Hohenberger and Matthias Kroiss and Peter Schirmacher and Schlenk, {Richard F.} and Ulrich Keilholz and Frederick Klauschen and Gunnar Folprecht and Sebastian Bauer and Siveke, {Jens Thomas} and Brandts, {Christian H.} and Thomas Kindler and Melanie Boerries and Illert, {Anna L.} and {Von Bubnoff}, Nikolas and Jost, {Philipp J.} and Karsten Spiekermann and Michael Bitzer and Klaus Schulze-Osthoff and {Von Kalle}, Christof and Barbara Klink and Benedikt Brors and Albrecht Stenzinger and Evelin Schr{\"o}ck and Daniel H{\"u}bschmann and Wilko Weichert and Hanno Glimm and Stefan Fr{\"o}hling",

note = "Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research.",

year = "2021",

month = nov,

doi = "10.1158/2159-8290.CD-21-0126",

language = "English",

volume = "11",

pages = "2780--2795",

journal = "Cancer Discovery",

issn = "2159-8274",

number = "11",

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Horak, P, Heining, C, Kreutzfeldt, S, Hutter, B, Mock, A, Hüllein, J, Fröhlich, M, Uhrig, S, Jahn, A, Rump, A, Gieldon, L, Möhrmann, L, Hanf, D, Teleanu, V, Heilig, CE, Lipka, DB, Allgäuer, M, Ruhnke, L, Laßmann, A, Endris, V, Neumann, O, Penzel, R, Beck, K, Richter, D, Winter, U, Wolf, S, Pfütze, K, Geörg, C, Meißburger, B, Buchhalter, I, Augustin, M, Aulitzky, WE, Hohenberger, P, Kroiss, M, Schirmacher, P, Schlenk, RF, Keilholz, U, Klauschen, F, Folprecht, G, Bauer, S, Siveke, JT, Brandts, CH, Kindler, T, Boerries, M, Illert, AL, Von Bubnoff, N, Jost, PJ, Spiekermann, K, Bitzer, M, Schulze-Osthoff, K, Von Kalle, C, Klink, B, Brors, B, Stenzinger, A, Schröck, E, Hübschmann, D, Weichert, W, Glimm, H & Fröhling, S 2021, 'Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions in patients with rare cancers', Cancer Discovery, vol. 11, no. 11, pp. 2780-2795. https://doi.org/10.1158/2159-8290.CD-21-0126

TY - JOUR

T1 - Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions in patients with rare cancers

AU - Horak, Peter

AU - Heining, Christoph

AU - Kreutzfeldt, Simon

AU - Hutter, Barbara

AU - Mock, Andreas

AU - Hüllein, Jennifer

AU - Fröhlich, Martina

AU - Uhrig, Sebastian

AU - Jahn, Arne

AU - Rump, Andreas

AU - Gieldon, Laura

AU - Möhrmann, Lino

AU - Hanf, Dorothea

AU - Teleanu, Veronica

AU - Heilig, Christoph E.

AU - Lipka, Daniel B.

AU - Allgäuer, Michael

AU - Ruhnke, Leo

AU - Laßmann, Andreas

AU - Endris, Volker

AU - Neumann, Olaf

AU - Penzel, Roland

AU - Beck, Katja

AU - Richter, Daniela

AU - Winter, Ulrike

AU - Wolf, Stephan

AU - Pfütze, Katrin

AU - Geörg, Christina

AU - Meißburger, Bettina

AU - Buchhalter, Ivo

AU - Augustin, Marinela

AU - Aulitzky, Walter E.

AU - Hohenberger, Peter

AU - Kroiss, Matthias

AU - Schirmacher, Peter

AU - Schlenk, Richard F.

AU - Keilholz, Ulrich

AU - Klauschen, Frederick

AU - Folprecht, Gunnar

AU - Bauer, Sebastian

AU - Siveke, Jens Thomas

AU - Brandts, Christian H.

AU - Kindler, Thomas

AU - Boerries, Melanie

AU - Illert, Anna L.

AU - Von Bubnoff, Nikolas

AU - Jost, Philipp J.

AU - Spiekermann, Karsten

AU - Bitzer, Michael

AU - Schulze-Osthoff, Klaus

AU - Von Kalle, Christof

AU - Klink, Barbara

AU - Brors, Benedikt

AU - Stenzinger, Albrecht

AU - Schröck, Evelin

AU - Hübschmann, Daniel

AU - Weichert, Wilko

AU - Glimm, Hanno

AU - Fröhling, Stefan

PY - 2021/11

Y1 - 2021/11

N2 - The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population.

AB - The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population.

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U2 - 10.1158/2159-8290.CD-21-0126

DO - 10.1158/2159-8290.CD-21-0126

M3 - Journal articles

C2 - 34112699

AN - SCOPUS:85112734046

SN - 2159-8274

VL - 11

SP - 2780

EP - 2795

JO - Cancer Discovery

JF - Cancer Discovery

IS - 11

ER -

Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions in patients with rare cancers

Abstract

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