TumorDiagnostik & Therapie 2018; 39(02): 124-132
DOI: 10.1055/s-0044-100825
Thieme Onkologie aktuell
© Georg Thieme Verlag KG Stuttgart · New York

Präzisionsonkologie und molekulare Tumorboards – Konzepte, Chancen und Herausforderungen

Precision Oncology and „Molecular Tumor Boards“ – Concepts, Chances and Challenges
Julian Walter Holch
Medizinische Klinik und Poliklinik III, Klinikum der Universität München
,
Christoph Benedikt Westphalen
Medizinische Klinik und Poliklinik III, Klinikum der Universität München
,
Wolfgang Hiddemann
Medizinische Klinik und Poliklinik III, Klinikum der Universität München
,
Volker Heinemann
Medizinische Klinik und Poliklinik III, Klinikum der Universität München
,
Andreas Jung
Medizinische Klinik und Poliklinik III, Klinikum der Universität München
,
Klaus Hans Metzeler
Medizinische Klinik und Poliklinik III, Klinikum der Universität München
› Author Affiliations
Further Information

Publication History

Publication Date:
02 March 2018 (online)

Zusammenfassung

Die immer umfassendere molekulare Charakterisierung von Tumoren ermöglicht eine „Präzisionsonkologie“ mit besonders effektiven und nebenwirkungsarmen Therapien. „Targeted Therapies“ erzielen bei bestimmten Tumorentitäten große Erfolge. Jedoch bestehen Schwierigkeiten in der praktischen Umsetzung und Nutzenbewertung zunehmend individualisierter Behandlungsansätze.

Abstract

Recent developments in genomics allow a more and more comprehensive genetic analysis of human malignancies, and have sparked hopes that this will contribute to the development of novel targeted, effective and well-tolerated therapies.

While targeted therapies have improved the prognosis of many cancer patients with certain tumor types, “precision oncology” also brings along new challenges. Highly personalized treatment strategies require new strategies for clinical trials and translation into routine clinical practice. We review the current technical approaches for “universal genetic testing” in cancer, and potential pitfalls in the interpretation of such data. We then provide an overview of the available evidence supporting treatment strategies based on extended genetic analysis. Based on the available data, we conclude that “precision oncology” approaches that go beyond the current standard of care should be pursued within the framework of an interdisciplinary “molecular tumor board”, and preferably within clinical trials.

 
  • Literatur

  • 1 Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med 2015; 372: 793-795
  • 2 Subbiah V, Kurzrock R. Universal Genomic Testing Needed to Win the War Against Cancer: Genomics IS the Diagnosis. JAMA Oncol 2016; 2: 719-720
  • 3 West HJ. No Solid Evidence, Only Hollow Argument for Universal Tumor Sequencing: Show Me the Data. JAMA Oncol 2016; 2: 717-718
  • 4 Horak P, Fröhling S, Glimm H. Integrating next-generation sequencing into clinical oncology: strategies, promises and pitfalls. ESMO Open 2016; 1: e000094
  • 5 Chalmers ZR, Connelly CF, Fabrizio D. et al. Analysis of 100000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Medicine 2017; 9: 1-14
  • 6 Campbell PJ, Yachida S, Mudie LJ. et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 2010; 467: 1109-1113
  • 7 Butler TM, Spellman PT, Gray J. Circulating-tumor DNA as an early detection and diagnostic tool. Curr. Opin. Genet. Dev 2017; 42: 14-21
  • 8 Frampton GM, Fichtenholtz A, Otto GA. et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol 2013; 31: 1023-1031
  • 9 Kuderer NM, Burton KA, Blau S. et al. Comparison of 2 Commercially Available Next-Generation Sequencing Platforms in Oncology. JAMA Oncol 2017; 3: 996-998
  • 10 Li MM, Datto M, Duncavage EJ. et al. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn 2017; 19: 4-23
  • 11 Jennings LJ, Arcila ME, Corless C. et al. Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels. The Journal of Molecular Diagnostics 2017; 19: 341-365
  • 12 Vogelstein B, Papadopoulos N, Velculescu VE. et al. Cancer genome landscapes. Science 2013; 339: 1546-1558
  • 13 Hoskinson DC, Dubuc AM, Mason-Suares H. The current state of clinical interpretation of sequence variants. Curr Opin Genet Dev 2017; 42: 33-39
  • 14 Van Allen EM, Miao D, Schilling B. et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 2015; 350: 207-211
  • 15 Rizvi NA, Hellmann MD, Snyder A. et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015; 348: 124-128
  • 16 Hyman DM, Puzanov I, Subbiah V. et al. Vemurafenib in Multiple Nonmelanoma Cancers with BRAFV600 Mutations. N Engl J Med 2015; 373: 726-736
  • 17 Janku F, Wheler JJ, Westin SN. et al. PI3K/AKT/mTOR Inhibitors in Patients With Breast and Gynecologic Malignancies Harboring PIK3CAMutations. J Clin Oncol 2012; 30: 777-782
  • 18 Sun C, Hobor S, Bertotti A. et al. Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3. Cell Reports 2014; 7: 86-93
  • 19 Soria J-C, Massard C, Izzedine H. From Theoretical Synergy to Clinical Supra-Additive Toxicity. J Clin Oncol 2009; 27: 1359-1361
  • 20 Engelhardt M, Selder R, Pandurevic M. et al. Multidisciplinary Tumor Boards: Facts and Satisfaction Analysis of an Indispensable Comprehensive Cancer Center Instrument. Dtsch Med Wochenschr 2017; 142: e51-e60
  • 21 Schwaederle M, Zhao M, Lee JJ. et al. Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials. J Clin Oncol 2015; 33: 3817-3825
  • 22 Schwaederle M, Zhao M, Lee JJ. et al. Association of Biomarker-Based Treatment Strategies With Response Rates and Progression-Free Survival in Refractory Malignant Neoplasms: A Meta-analysis. JAMA Oncol 2016; 2: 1452-1459
  • 23 Joffe E, Iasonos A, Younes A. Clinical Trials in the Genomic Era. J Clin Oncol 2017; 35: 1011-1017
  • 24 Harris MH, DuBois SG, Glade BenderJL. et al. Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors. JAMA Oncol 2016; 2: 608-608
  • 25 Meric-Bernstam F, Brusco L, Shaw K. et al. Feasibility of Large-Scale Genomic Testing to Facilitate Enrollment Onto Genomically Matched Clinical Trials. J Clin Oncol 2015; 33: 2753-2762
  • 26 Hirshfield KM, Tolkunov D, Zhong H. et al. Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers. The Oncologist 2016; 21: 1315-1325
  • 27 Le TourneauC, Delord J-P, Gonçalves A. et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol 2015; 16: 1324-1334
  • 28 Tsimberidou A-M, Kurzrock R. Precision medicine: lessons learned from the SHIVA trial. Lancet Oncol 2015; 16: e579-e580
  • 29 Massard C, Michiels S, Ferté C. et al. High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial. Cancer Discovery 2017; 7: 586-595
  • 30 Heining C, Horak P, Gröschel S. et al. Personalisierte Medizin: Strukturen, Tumorboards, Visionen. Medizinische Genetik 2017; 28: 452-459
  • 31 Horak P, Klink B, Heining C. et al. Precision oncology based on omics data: The NCT Heidelberg experience. Int J Cancer 2017; 141: 877-886
  • 32 Long GV, Stroyakovskiy D, Gogas H. et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 2014; 371: 1877-1888