Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers.

Young Adult Humans Neoplasms / diagnosis Germ-Line Mutation Genetic Predisposition to Disease Prospective Studies Syndrome Precision Medicine / methods
biomarker hereditary cancer precision medicine prevention rare cancer targeted therapy

Journal

Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735

Informations de publication

Date de publication:
11 2022
Historique:
received: 06 03 2022
revised: 04 07 2022
accepted: 18 07 2022
pubmed: 22 8 2022
medline: 2 11 2022
entrez: 21 8 2022
Statut: ppublish

Résumé

Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers. Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies. Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation. Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.

Sections du résumé

BACKGROUND
Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers.
PATIENTS AND METHODS
Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies.
RESULTS
Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation.
CONCLUSIONS
Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.

Identifiants

DOI: 10.1016/j.annonc.2022.07.008 PMID: 35988656
pubmed: 35988656
pii: S0923-7534(22)01859-2
doi: 10.1016/j.annonc.2022.07.008
pii:
doi:

Types de publication

Multicenter Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1186-1199

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure AJ: Honoraria: AstraZeneca. CH: Honoraria: Roche, Novartis; research funding: Boehringer Ingelheim; consulting or advisory board: Boehringer Ingelheim. CVG: Employed by Illumina since August 2021. LM reports non-financial support from Celgene outside the submitted work (travel expenses). MAu: Consulting or advisory board membership: Bristol-Myers Squibb, Ipsen, Merck KGaA, MSD Sharp & Dohme, Novartis, Pfizer, Roche, PharmaMar; research funding: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Exelixis, Ipsen, Merck KGaA, Novartis, Pfizer, PharmaMar, Roche; honoraria: Blueprint Medicines, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, Merck KGaA, Pfizer, PharmaMar. PHoh: Advisory board membership: Roche, Deciphera, PharmaMar, Pfizer, BluMedicine, GSK; honoraria: Bristol-Meyers-Squibb, Astrazeneca; research funding: Novartis, Siemens. MK: Honoraria: Bayer, MSD, Eisai, Ipsen, Eli Lilly; research funding: Eli Lilly, Ipsen, Loxo Oncology. RFS: Consulting or advisory board membership: Astellas, Bristol-Myers Squibb, Celgene, Pfizer; research funding: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Pfizer, PharmaMar, Roche; honoraria: Daiichi Sankyo, Pfizer. GF: Honoraria: Amgen, Armo Biosciences, Bayer, Bristol-Myers Squibb, Eli Lilly, HRA Pharma, Merck KGaA, MSD Sharp & Dohme, Pierre Fabre, Roche, Sanofi, Servier, Shire; research funding: Merck KGaA. SB: Consulting or advisory board membership: ADC Therapeutics, Blueprint Medicines, Daichii-Sankyo, Deciphera, Eli Lilly, Exelixis, Janssen-Cilag, Mundipharma, Novartis, Plexxikon; honoraria: Bayer, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, PharmaMar; research funding: Blueprint Medicines, Incyte, Novartis. JTS: Consulting or advisory board membership: AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Immunocore, Novartis, Roche, Shire; honoraria: AstraZeneca, Aurikamed, Baxalta, Bristol Myers Squibb, Celgene, Falk Foundation, iomedico, Immunocore, Novartis, Roche, Shire; research funding: Bristol-Myers Squibb, Celgene, Roche; minor equity in iTheranostics and Pharma15; member of the Board of Directors for Pharma15, all outside the submitted work. ALI: Honoraria: Bristol-Myers Squibb, Janssen-Cilag, Takeda, Roche. NvB: Consulting or advisory board membership: Novartis; honoraria: Novartis, Takeda. PJJ: Consulting or advisory board membership, honoraria, research funding, travel or accommodation expenses: Abbvie, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Novartis, Pfizer, Roche, Servier. KHM: Consulting: Celgene/BMS, Novartis, Jazz Pharmaceuticals, Pfizer; honoraria: Celgene/BMS, Daiichi Sankyo, Astellas, AbbVie, Novartis; research funding: Celgene. AS: Consulting or advisory board membership, honoraria: AGCT, AstraZeneca, Bayer, Bristol-Myers Squibb, Chugai, Eli Lilly, Illumina, Janssen, MSD Sharp & Dohme, Novartis, Pfizer, Roche, Seattle Genetics, Takeda, Thermo Fisher; research funding: Bayer, Bristol-Myers Squibb, Chugai. WW: Consulting or advisory board membership, honoraria: Agilent, Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Illumina, Merck, MSD Sharp & Dohme, Pfizer, NewOncology, Novartis, Roche, Takeda; research funding: AstraZeneca, Bristol-Myers Squibb, MSD Sharp & Dohme, Roche. SF: Consulting or advisory board membership: Bayer, Illumina, Roche; honoraria: Amgen, Eli Lilly, PharmaMar, Roche; research funding: AstraZeneca, Pfizer, PharmaMar, Roche; travel or accommodation expenses: Amgen, Eli Lilly, Illumina, PharmaMar, Roche. ES: Honoraria: AstraZeneca, Illumina. All other authors have declared no conflicts of interest. Data sharing All evaluated germline variants can be found in Supplementary Table S5, available at https://doi.org/10.1016/j.annonc.2022.07.008. Sequencing data have been deposited in the European Genome-phenome Archive (https://www.ebi.ac.uk/ega/datasets) under accession EGAS00001005537.

Auteurs

A Jahn (A)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; German Cancer Consortium (DKTK) Dresden, Germany; National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

A Rump (A)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; German Cancer Consortium (DKTK) Dresden, Germany; National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

T J Widmann (TJ)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; German Cancer Consortium (DKTK) Dresden, Germany; National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

C Heining (C)

German Cancer Consortium (DKTK) Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Department of Translational Medical Oncology, NCT Dresden and DKFZ, Dresden, Germany.

P Horak (P)

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.

B Hutter (B)

Computational Oncology Group, Molecular Precision Oncology Program, NCT Heidelberg and DKFZ, Heidelberg, Germany; Division of Applied Bioinformatics, DKFZ, Heidelberg, Germany.

N Paramasivam (N)

Computational Oncology Group, Molecular Precision Oncology Program, NCT Heidelberg and DKFZ, Heidelberg, Germany.

S Uhrig (S)

Computational Oncology Group, Molecular Precision Oncology Program, NCT Heidelberg and DKFZ, Heidelberg, Germany; Division of Applied Bioinformatics, DKFZ, Heidelberg, Germany.

L Gieldon (L)

Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany.

S Drukewitz (S)

German Cancer Consortium (DKTK) Dresden, Germany; Core Unit for Molecular Tumor Diagnostics, NCT Dresden and DKFZ, Dresden, Germany.

A Kübler (A)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

M Bermudez (M)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

K Hackmann (K)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

J Porrmann (J)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

J Wagner (J)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

M Arlt (M)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

M Franke (M)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

J Fischer (J)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Z Kowalzyk (Z)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

D William (D)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; German Cancer Consortium (DKTK) Dresden, Germany; National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Core Unit for Molecular Tumor Diagnostics, NCT Dresden and DKFZ, Dresden, Germany.

V Weth (V)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany.

S Oster (S)

German Cancer Consortium (DKTK) Dresden, Germany; Core Unit for Molecular Tumor Diagnostics, NCT Dresden and DKFZ, Dresden, Germany.

M Fröhlich (M)

Computational Oncology Group, Molecular Precision Oncology Program, NCT Heidelberg and DKFZ, Heidelberg, Germany; Division of Applied Bioinformatics, DKFZ, Heidelberg, Germany.

J Hüllein (J)

Computational Oncology Group, Molecular Precision Oncology Program, NCT Heidelberg and DKFZ, Heidelberg, Germany; Division of Applied Bioinformatics, DKFZ, Heidelberg, Germany.

C Valle González (C)

Division of Applied Bioinformatics, DKFZ, Heidelberg, Germany; University of Seville, Seville, Spain.

S Kreutzfeldt (S)

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.

A Mock (A)

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Medical Oncology, NCT Heidelberg and Heidelberg University Hospital, Heidelberg, Germany.

C E Heilig (CE)

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.

D B Lipka (DB)

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.

L Möhrmann (L)

German Cancer Consortium (DKTK) Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Department of Translational Medical Oncology, NCT Dresden and DKFZ, Dresden, Germany.

D Hanf (D)

German Cancer Consortium (DKTK) Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Department of Translational Medical Oncology, NCT Dresden and DKFZ, Dresden, Germany.

M Oleś (M)

Computational Oncology Group, Molecular Precision Oncology Program, NCT Heidelberg and DKFZ, Heidelberg, Germany.

V Teleanu (V)

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.

M Allgäuer (M)

Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

L Ruhnke (L)

Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Department of Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

O Kutz (O)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany.

A Knurr (A)

Department of Medical Informatics for Translational Oncology, DKFZ, Heidelberg, Germany.

A Laßmann (A)

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.

V Endris (V)

Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

O Neumann (O)

Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

R Penzel (R)

Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

K Beck (K)

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.

D Richter (D)

German Cancer Consortium (DKTK) Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Department of Translational Medical Oncology, NCT Dresden and DKFZ, Dresden, Germany.

U Winter (U)

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.

S Wolf (S)

German Cancer Consortium (DKTK), Heidelberg, Germany; High-Throughput Sequencing Unit, Genomics and Proteomics Core Facility, DKFZ, Heidelberg, Germany.

K Pfütze (K)

German Cancer Consortium (DKTK), Heidelberg, Germany; Sample Processing Laboratory, Molecular Diagnostics Program, NCT Heidelberg and DKFZ, Heidelberg, Germany.

C Geörg (C)

German Cancer Consortium (DKTK), Heidelberg, Germany; Sample Processing Laboratory, Molecular Diagnostics Program, NCT Heidelberg and DKFZ, Heidelberg, Germany.

B Meißburger (B)

German Cancer Consortium (DKTK), Heidelberg, Germany; Sample Processing Laboratory, Molecular Diagnostics Program, NCT Heidelberg and DKFZ, Heidelberg, Germany.

I Buchhalter (I)

Omics IT and Data Management Core Facility, DKFZ, Heidelberg, Germany.

M Augustin (M)

Department of Hematology and Oncology, Klinikum Nuremberg, Paracelsus Medical University, Nuremberg, Germany.

W E Aulitzky (WE)

Department of Hematology, Oncology and Palliative Medicine, Robert Bosch Hospital, Stuttgart, Germany.

P Hohenberger (P)

Sarcoma Unit, Interdisciplinary Tumor Center Mannheim, Mannheim University Medical Center, Heidelberg University, Mannheim, Germany; Division of Surgical Oncology and Thoracic Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

M Kroiss (M)

Department of Medicine I, Würzburg University Hospital, Würzburg, Germany; Comprehensive Cancer Mainfranken, University of Würzburg, Würzburg, Germany; Department of Medicine IV, University Hospital, Ludwig Maximilians University Munich, Munich, Germany.

P Schirmacher (P)

German Cancer Consortium (DKTK), Heidelberg, Germany; Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

R F Schlenk (RF)

German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Medical Oncology, NCT Heidelberg and Heidelberg University Hospital, Heidelberg, Germany; Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany; NCT Trial Center, NCT Heidelberg and DKFZ, Heidelberg, Germany.

U Keilholz (U)

Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany; DKTK, Berlin, Germany.

F Klauschen (F)

DKTK, Berlin, Germany; Institute of Pathology, Charité - Universitätsmedizin Berlin, and Berlin Institute of Health, Berlin, Germany; Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany.

G Folprecht (G)

German Cancer Consortium (DKTK) Dresden, Germany; Department of Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

S Bauer (S)

Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; DKTK, Essen, Germany.

J T Siveke (JT)

Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; DKTK, Essen, Germany; Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Solid Tumor Translational Oncology, DKTK, Essen, and DKFZ, Heidelberg, Germany.

C H Brandts (CH)

University Cancer Center (UCT) Frankfurt, University Hospital Frankfurt, Goethe University, Frankfurt, Germany; Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany; Frankfurt Cancer Institute, Frankfurt, Germany; DKTK, Frankfurt, Germany.

T Kindler (T)

UCT Mainz, Johannes Gutenberg University Mainz, Mainz, Germany; Department of Hematology, Medical Oncology and Pneumology, University Medical Center, Mainz, Germany; DKTK, Mainz, Germany.

M Boerries (M)

Comprehensive Cancer Center Freiburg, University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Institute of Medical Bioinformatics and Systems Medicine, University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; DKTK, Freiburg, Germany.

A L Illert (AL)

Comprehensive Cancer Center Freiburg, University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; DKTK, Freiburg, Germany; Department of Internal Medicine I, University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

N von Bubnoff (N)

DKTK, Freiburg, Germany; Department of Hematology and Oncology, University Hospital of Schleswig-Holstein, Lübeck, Germany.

P J Jost (PJ)

Department of Hematology and Oncology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany; Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Graz, Austria; DKTK, Munich, Germany.

K H Metzeler (KH)

Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.

M Bitzer (M)

Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany; DKTK, Tübingen, Germany.

K Schulze-Osthoff (K)

DKTK, Tübingen, Germany; Department of Molecular Medicine, Interfaculty Institute for Biochemistry, University of Tübingen, Tübingen, Germany.

C von Kalle (C)

Clinical Study Center, Charité - Universitätsmedizin Berlin, and Berlin Institute of Health, Berlin, Germany.

B Brors (B)

German Cancer Consortium (DKTK), Heidelberg, Germany; Division of Applied Bioinformatics, DKFZ, Heidelberg, Germany.

A Stenzinger (A)

German Cancer Consortium (DKTK), Heidelberg, Germany; Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

W Weichert (W)

DKTK, Munich, Germany; Institute of Pathology, Technical University Munich, Munich, Germany.

D Hübschmann (D)

German Cancer Consortium (DKTK), Heidelberg, Germany; Computational Oncology Group, Molecular Precision Oncology Program, NCT Heidelberg and DKFZ, Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Heidelberg, Germany.

S Fröhling (S)

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.

H Glimm (H)

German Cancer Consortium (DKTK) Dresden, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Department of Translational Medical Oncology, NCT Dresden and DKFZ, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.

E Schröck (E)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; German Cancer Consortium (DKTK) Dresden, Germany; National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Core Unit for Molecular Tumor Diagnostics, NCT Dresden and DKFZ, Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. Electronic address: Evelin.Schroeck@uniklinikum-dresden.de.

B Klink (B)

Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany, ERN-GENTURIS, Hereditary Cancer Syndrome Center, Dresden, Germany; German Cancer Consortium (DKTK) Dresden, Germany; National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Core Unit for Molecular Tumor Diagnostics, NCT Dresden and DKFZ, Dresden, Germany; National Center of Genetics (NCG), Laboratoire National de Santé (LNS), Dudelange, Luxembourg; Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), Luxembourg, Luxembourg.

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Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

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