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Diagnostik und Therapie von Krebserkrankungen mit unbekanntem Primärtumor (CUP-Syndrom)

Diagnostic and treatment of cancer of unknown primary site (CUP syndrome)

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best practice onkologie Aims and scope

Zusammenfassung

Bei Krebserkrankungen mit unbekanntem Primärtumor (CUP, „carcinoma of unknown primary site“) handelt es sich um ein heterogenes onkologisches Krankheitsbild, bei dem nach Abschluss einer umfangreichen Primärdiagnostik kein Ursprungstumor identifiziert werden kann, jedoch histologisch und/oder zytologisch gesicherte Metastasen vorliegen. Diagnostische Bemühungen richten sich v. a. auf die Identifikation prognostisch günstiger Subgruppen sowie die Bestimmung des Disseminationsgrads. Sie umfassen neben klinischen und radiologischen Untersuchungen insbesondere eine ausführliche Histologie und Immunhistochemie. Molekulargenetische Methoden können helfen, einen wahrscheinlichen Primärtumor sowie Mutationen für den Einsatz zielgerichteter Therapien zu identifizieren. Sie finden derzeit v. a. in klinischen Studien Anwendung, sind aber bisher nicht als Routinediagnostik implementiert. Während prognostisch günstige Subgruppen eine spezifische Therapie in Anlehnung an den klinisch-pathologisch wahrscheinlichen Primärtumor erhalten, ist eine empirische, platinbasierte Kombinationschemotherapie derzeit therapeutischer Standard zur Behandlung des prognostisch ungünstigen CUP-Syndroms. Die Prognose ist dabei mit einem medianen Überleben von etwa einem Jahr schlecht. Der Einsatz von zielgerichteten, mutationsspezifischen Therapien und Immuncheckpointinhibitoren wird in aktuellen Studien untersucht.

Abstract

Carcinoma of unknown primary site (CUP) is a heterogenous oncologic disease for which extensive primary diagnostic workup fails to identify a primary tumor although histologically and/or cytologically proven metastases are present. Diagnostic efforts focus primarily on identification of prognostically favorable subsets and dissemination stage of the disease. They include thorough clinical examination, radiology, and especially comprehensive histology and immunohistochemistry. Molecular methods may help to find the putative primary or identify mutations amenable to targeted therapy. For the most part these methods are currently used in the context of clinical trials and not (yet) part of routine diagnostics. While favorable subsets are treated with regimens established for the respective putative primary cancers, the current standard for unfavorable-subset patients is empiric platinum-based combination chemotherapy. The prognosis of unfavorable CUP patients is dismal, with a median survival of less than 1 year. The use of targeted mutation-specific therapy and immune checkpoint inhibitors is being investigated in ongoing clinical trials.

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Abbreviations

AFP:

Alpha-Fetoprotein

AUC:

„Area under the curve“

β‑hCG:

Humanes Choriongonadotropin

CDKN2A:

cyclin-dependent kinase Inhibitor 2A

CDX‑2:

„Homeoboxprotein“, Transkriptionsfaktor

CEA:

Karzinoembryonales Antigen

CK:

Zytokeratin

CT:

Computertomographie

CUP:

„Carcinoma of unknown primary (site)“

EGFR:

Epidermaler Wachstumsfaktorrezeptor

ECOG:

Eastern Cooperative Oncology Group

ER:

Östrogenrezeptor

ESMO:

European Society for Medical Oncology

GCDFP-15:

„Gross cystic disease fluid protein-15“

GEP:

Genexpressionsprofil

HMB45:

„Human melanoma black“, Antikörper

K-RAS:

Kirsten rat sarcoma viral oncogene homolog, eine GTPase

LDH:

Laktatdehydrogenase

miRNA:

„micro RNA“, kurze, hoch konservierte, nichtcodierende RNA

mRNA:

„Messenger RNA“, einzelsträngiges RNA-Transkript eines zu einem Gen gehörigen Teilabschnitts der DNA

MRT:

Magnetresonanztomographie

MUO:

„Malignancy of unknown primary origin“

NGS:

„Next generation sequencing“

PET:

Positronenemissionstomographie

PLAP:

Plazentare alkalische Phosphatase

PR:

Progesteronrezeptor

PS:

„Performance status“, z. B. ECOG

PSA:

Prostataspezifisches Antigen

TMB:

„Tumor mutational burden“, Tumormutationslast

TP 53:

Tumorsuppressor-Gen

TTF‑1:

Thyroidaler Transkriptionsfaktor 1

VEGF:

Vaskulärer endothelialer Wachstumsfaktor

WT‑1 :

„Wilms tumor gene 1“

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Authors and Affiliations

  1. Medizinische Klinik V, Universität Heidelberg, Im Neuenheimer Feld 280, 69120, Heidelberg, Deutschland

    G. R. Boeckel, M. Pouyiourou, L. Claßen,  T. Bochtler &  A. Krämer

  2. Klinische Kooperationseinheit Molekulare Hämatologie/Onkologie, Deutsches Krebsforschungszentrum (DKFZ) und Medizinische Klinik V, Universität Heidelberg, Heidelberg, Deutschland

    T. Bochtler &  A. Krämer

  3. Onkologie der Thoraxtumoren, Thoraxklinik, Universität Heidelberg, Heidelberg, Deutschland

    T. Bochtler

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  1. G. R. Boeckel
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  2. M. Pouyiourou
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  3. L. Claßen
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  4. T. Bochtler
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  5. A. Krämer
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Correspondence to A. Krämer.

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G.R. Boeckel, M. Pouyiourou, L. Claßen, T. Bochtler und A. Krämer geben 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.

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Boeckel, G.R., Pouyiourou, M., Claßen, L. et al. Diagnostik und Therapie von Krebserkrankungen mit unbekanntem Primärtumor (CUP-Syndrom). best practice onkologie 15, 76–84 (2020). https://doi.org/10.1007/s11654-020-00207-6

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