Skip to main content
SpringerLink
Log in

Systemische Therapie von Sarkomen

Neue Biomarker und Therapiestrategien

Systemic therapy of sarcomas

New biomarkers and therapeutic strategies

  • Schwerpunkt: Sarkome
  • Published:
Der Pathologe Aims and scope Submit manuscript

Zusammenfassung

Diagnostik und Therapie mesenchymaler Tumoren (Weichteilsarkome, gastrointestinale Stromatumoren und Knochensarkome) haben sich in den letzten Jahren dramatisch gewandelt. Molekulare und immunhistochemische Biomarker tragen erheblich zu einer verbesserten Diagnostik bei. Auch für die Therapieplanung spielen Biomarker eine zunehmende Rolle.

Die adjuvante Chemotherapie lokalisierter Sarkome wird auf der Basis des Gradings und tumortypspezifischer Überlebensdaten geplant. Für die Systemtherapie mit zielgerichteten Therapeutika gewinnen zunehmend rekurrente Genfusionen als prädiktive Marker an Bedeutung. Auch immunonkologische Ansätze zeigen erste Erfolge bei der Behandlung von Sarkomen. Die Bedeutung prädiktiver Biomarker, wie z. B. PD-L1, ist in diesem Kontext aber noch unklar. Es ist zu erwarten, dass umfangreiche genetische Analysen metastasierter Sarkome weitere therapeutische Zielstrukturen und korrespondierende Biomarker identifizieren.

Abstract

Diagnostics and treatment of mesenchymal tumors (i.e. soft tissue sarcomas, gastrointestinal stromal tumors, and bone sarcomas) have changed dramatically in the past few years. Molecular and immunohistochemical biomarkers contribute significantly to improved diagnostics. They also play an increasing role in terms of clinical treatment decisions.

Grading and tumor type-specific outcome data provide the basis for adjuvant chemotherapy of localized sarcomas. Recurrent gene fusions become more important as predictive biomarkers for targeted therapies in the context of systemic treatments. Immuno-oncology-based approaches are currently being studied in clinical trials, and the first responses of selected patients have been demonstrated. However, the role of predictive biomarkers in this field, such as PD-L1, still needs to be elucidated. Comprehensive genetic analyses of metastatic sarcomas will continue to identify additional therapeutic targets and the corresponding biomarkers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Abendroth A, Bauer S (2013) Adjuvant chemotherapy for soft tissue sarcoma? a clear no – well – yes-ish. Dtsch Med Wochenschr 138(41):2107–2110

    Article  CAS  Google Scholar 

  2. Frustaci S et al (2001) Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial. J Clin Oncol 19(5):1238–1247

    Article  CAS  Google Scholar 

  3. Frustaci S et al (2006) Adjuvant treatment of high-risk adult soft tissue sarcomas: a survey by the Italian Sarcoma Group. Tumori 92(2):92–97

    PubMed  Google Scholar 

  4. Pervaiz N et al (2008) A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer 113(3):573–581

    Article  Google Scholar 

  5. Woll PJ et al (2012) Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol 13(10):1045–1054

    Article  CAS  Google Scholar 

  6. Italiano A et al (2010) Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: a multivariate analysis of the French Sarcoma Group Database. Ann Oncol 21(12):2436–2441

    Article  CAS  Google Scholar 

  7. Gronchi A et al (2017) Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol 18(6):812–822

    Article  CAS  Google Scholar 

  8. Pasquali S et al (2018) High-risk soft tissue sarcomas treated with perioperative chemotherapy: Improving prognostic classification in a randomised clinical trial. Eur J Cancer 93:28–36

    Article  Google Scholar 

  9. Pasquali S et al (2019) The impact of chemotherapy on survival of patients with extremity and trunk wall soft tissue sarcoma: revisiting the results of the EORTC-STBSG 62931 randomised trial. Eur J Cancer 109:51–60

    Article  CAS  Google Scholar 

  10. Coindre JM (2006) Grading of soft tissue sarcomas. Review and update. Arch Pathol Lab Med 130:1448–1453

    PubMed  Google Scholar 

  11. Peters TL et al (2015) BCOR-CCNB3 fusions are frequent in undifferentiated sarcomas of male children. Mod Pathol 28(4):575–586

    Article  CAS  Google Scholar 

  12. Italiano A et al (2012) High prevalence of CIC fusion with double-homeobox (DUX4) transcription factors in EWSR1-negative undifferentiated small blue round cell sarcomas. Genes Chromosomes Cancer 51(3):207–218

    Article  CAS  Google Scholar 

  13. McBride MJ et al (2018) The SS18-SSX fusion Oncoprotein hijacks BAF complex targeting and function to drive synovial sarcoma. Cancer Cell 33(6):1128–1141e7

    Article  CAS  Google Scholar 

  14. Shimizu A et al (1999) The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B‑chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res 59(15):3719–3723

    CAS  PubMed  Google Scholar 

  15. Ugurel S et al (2014) Neoadjuvant imatinib in advanced primary or locally recurrent dermatofibrosarcoma protuberans: a multicenter phase II DeCOG trial with long-term follow-up. Clin Cancer Res 20(2):499–510

    Article  CAS  Google Scholar 

  16. Maki RG et al (2002) Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans. Int J Cancer 100(6):623–626

    Article  CAS  Google Scholar 

  17. Saab J et al (2017) Dermatofibrosarcoma Protuberans-Like Tumor With COL1A1 Copy Number Gain in the Absence of t(17;22). Am J Dermatopathol 39(4):304–309

    Article  Google Scholar 

  18. Dickson BC et al (2018) Dermatofibrosarcoma protuberans with a novel COL6A3-PDGFD fusion gene and apparent predilection for breast. Genes Chromosomes Cancer 57(9):437–445

    Article  CAS  Google Scholar 

  19. Cocco E, Scaltriti M, Drilon A (2018) NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 15(12):731–747

    Article  CAS  Google Scholar 

  20. Shi E et al (2016) FGFR1 and NTRK3 actionable alterations in “Wild-Type” gastrointestinal stromal tumors. J Transl Med 14(1):339

    Article  Google Scholar 

  21. Drilon A et al (2018) Efficacy of larotrectinib in TRK fusion—positive cancers in adults and children. N Engl J Med 378(8):731–739

    Article  CAS  Google Scholar 

  22. Wells AE, Mallen AM, Bui MM, Reed DR, Apte SM (2019) NTRK-1 fusion in endocervical fibroblastic malignant peripheral nerve sheath tumor marking eligibility for larotrectinib therapy: a case report Gynecol. Gynecol Oncol Rep 28:141–144

    Article  CAS  Google Scholar 

  23. Paoluzzi L et al (2016) Response to anti-PD1 therapy with nivolumab in metastatic sarcomas. Clin Sarcoma Res 6:24

    Article  CAS  Google Scholar 

  24. Tawbi HA et al (2017) Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 18(11):1493–1501

    Article  CAS  Google Scholar 

  25. Ben-Ami E et al (2017) Immunotherapy with single agent nivolumab for advanced leiomyosarcoma of the uterus: results of a phase 2 study. Cancer 123(17):3285–3290

    Article  CAS  Google Scholar 

  26. George S et al (2017) Loss of PTEN is associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma. Immunity 46(2):197–204

    Article  CAS  Google Scholar 

  27. Hamacher R et al (2018) Dramatic response of a PD-L1-positive advanced angiosarcoma of the scalp to pembrolizumab. JCO Precis Oncol (2):1–7. https://doi.org/10.1200/PO.17.00107

    Article  Google Scholar 

  28. D’Angelo SP et al (2018) Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. Lancet Oncol 19(3):416–426

    Article  Google Scholar 

  29. Kasper B et al (2015) Management of sporadic desmoid-type fibromatosis: a European consensus approach based on patients’ and professionals’ expertise – a sarcoma patients EuroNet and European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group initiative. Eur J Cancer 51(2):127–136

    Article  CAS  Google Scholar 

  30. Kasper B et al (2017) An update on the management of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG). Ann Oncol 28(10):2399–2408

    Article  CAS  Google Scholar 

  31. Gounder MM et al (2018) Sorafenib for advanced and refractory desmoid tumors. N Engl J Med 379(25):2417–2428

    Article  CAS  Google Scholar 

  32. Toulmonde M et al (2018) DESMOPAZ pazopanib (PZ) versus IV methotrexate/vinblastine (MV) in adult patients with progressive desmoid tumors (DT) a randomized phase II study from the French Sarcoma Group. J Clin Oncol 36(15_suppl):11501–11501

    Article  Google Scholar 

  33. George S et al (2018) Initial results of phase 1 study of DCC-2618, a broad-spectrum KIT and Pdgfrαinhibitor, IN patients (PTS) with gastrointestinal stromal tumor (GIST) by number of prior regimens. Ann Oncol 29(suppl_8):viii576–viii595. https://doi.org/10.1093/annonc/mdy299

    Article  Google Scholar 

  34. Heinrich M et al (2018) Avapritinib is highly active and well-tolerated in patients (PTS) with advanced GIST driven by diverse variety of oncogenic mutations in KIT and PDGFRA. CTOS 2018 Annual Meeting. Abstract 3027631(Paper 012)

    Google Scholar 

  35. Worst BC et al (2016) Next-generation personalised medicine for high-risk paediatric cancer patients – The INFORM pilot study. Eur J Cancer 65:91–101

    Article  Google Scholar 

  36. Grobner SN et al (2018) The landscape of genomic alterations across childhood cancers. Nature 555(7696):321–327

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sarkomzentrum am Westdeutschen Tumorzentrum, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Deutschland

    S. Bauer, U. Dirksen &  H.-U. Schildhaus

  2. Innere Klinik/Tumorforschung, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Deutschland

    S. Bauer

  3. Klinik für Kinderheilkunde III, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Deutschland

    U. Dirksen

  4. Institut für Pathologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Deutschland

    H.-U. Schildhaus

Authors
  1. S. Bauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U. Dirksen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H.-U. Schildhaus
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to S. Bauer or H.-U. Schildhaus.

Ethics declarations

Interessenkonflikt

H.‑U. Schildhaus erhält Honorare und Reisekostenunterstützung von Abbvie, BMS, MSD, Roche, Pfizer, Novartis, Zytomed, ZytoVision und nimmt an deren Advisory Boards teil. Außerdem erhält er Forschungsunterstützung von Novartis und ist Mitarbeiter der Targos Molecular Pathology GmbH. S. Bauer hat eine beratende Tätigkeit bei Blueprint Medicines, ADC Therapeutics, Lilly, Novartis, Daichii, Plexxikon, Nanobiotix, Deciphera; Exelixis, Janssen-Cilag und erhält CME Honorare von Novartis, Pfizer, Bayer, Lilly, Pharmamar sowie Forschungsunterstützung von Blueprint, Medicines, Incyte, Novartis. U. Dirksen gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

Schwerpunktherausgeber

M. Evert, Regensburg

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bauer, S., Dirksen, U. & Schildhaus, HU. Systemische Therapie von Sarkomen. Pathologe 40, 436–442 (2019). https://doi.org/10.1007/s00292-019-0628-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00292-019-0628-x

Schlüsselwörter

Keywords

Search

Navigation