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Molekularpathologisch determinierte multimodale Therapie gastrointestinaler Stromatumoren

Decision-making for multimodal treatment of gastrointestinal stromal tumors based on molecular profiling

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  • Published:
Wiener klinisches Magazin Aims and scope

Zusammenfassung

Hintergrund

Gastrointestinale Stromatumoren (GIST) lassen sich mithilfe moderner molekularpathologischer Methoden zunehmend besser molekular differenzieren. Die Bestimmung des Genotyps ist integraler Bestandteil bei der Entwicklung eines Behandlungskonzepts.

Ziel

Es erfolgt die Darstellung der aktuell verfügbaren Daten mit Relevanz für Therapieentscheidungen.

Resultate und Schlussfolgerungen

Patienten mit KIT-Mutationen in Exon 11 und einem hohen Rückfallrisiko profitieren von einer perioperativen Therapie mit Imatinib. Für Patienten mit Exon-9- oder den noch selteneren primären Exon-13- und –17-Mutationen ist die Studienlage weniger klar. Im Kontext lokal fortgeschrittener Tumoren, bei denen eine erhöhte Operations-bedingte Morbidität zu erwarten ist, haben sich neoadjuvante Therapien bei Imatinib-sensiblen Mutationen etabliert. Der Einsatz multimodaler Therapien in der metastasierten Situation sollte bei Imatinib-sensiblen Genotypen zum Zeitpunkt des maximalen Therapieansprechens erwogen werden – wenn eine makroskopisch komplette Resektion möglich erscheint. Inwieweit operative Therapien im Kontext neuer Inhibitoren wie Ripretinib bei stark vorbehandelten Patienten oder Avapritinib bei GIST mit PDGFRA-D842V-Mutationen („platelet-derived growth factor receptor A“) auch sinnvoll sind, wird sich erst in den kommenden Jahren zeigen.

Abstract

Background

Gastrointestinal stromal tumors (GIST) comprise a broad spectrum of different molecular subtypes. Due to improved accessibility to molecular pathology, genotyping has become an integral part of interdisciplinary case discussions.

Aim

To provide an overview on existing literature on the relevance of genotyping for treatment decisions in GIST.

Results and conclusions

Most patients with KIT exon 11 mutations and high risk of relapse benefit from adjuvant imatinib treatment. The evidence for this benefit is weak for less frequent KIT genotypes (e.g., exon 9, 13, and 17 mutations). Neoadjuvant treatment is particularly relevant in imatinib-sensitive subtypes when significant surgery-related morbidity is expected. For patients in the metastatic setting, multimodal treatment can be considered in responding patients when macroscopically complete resection seems feasible. Next generation inhibitors such as ripretinib in pretreated GIST and particularly avapritinib in GIST with PDGFRA (platelet-derived growth factor receptor A) mutations are associated with relevant tumor regression. The role for multimodal approaches in the respective treatment settings remains to be determined.

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Abbreviations

AFIP:

Armed Forces Institute of Pathology

BRAF:

„Homolog B, rapidly accelerated fibrosarcoma (serine/threonine-protein kinase)“

GIST:

Gastrointestinaler Stromatumor

KIT:

„Proto-oncogene tyrosine-protein kinase Kit (c-kit), CD117, mast/stem cell growth factor receptor precursor (SCFR)“

mg:

Milligramm

NIH:

National Institutes of Health

PDGFRA:

„Platelet-derived growth factor receptor A“

SDH:

Succinat-Dehydrogenase

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Authors and Affiliations

  1. Innere Klinik (Tumorforschung) und Sarkomzentrum am Westdeutschen Tumorzentrum, Universitätsklinik Essen, Universität Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Deutschland

    Lennart Schardt,  Moritz Kaths &  Sebastian Bauer

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  1. Lennart Schardt
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Correspondence to Sebastian Bauer.

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Interessenkonflikt

S. Bauer: Beratende Funktion: Blueprint Medicines, Novartis, Daiichi, Lilly, Plexxikon, Deciphera; CME-Honorare: Novartis, Pfizer, Bayer, PharmaMar; Forschungsunterstützung: Blueprint Medicines, Incyte, Novartis. L. Schardt und M. Kaths geben an, dass kein Interessenkonflikt besteht.

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

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Schardt, L., Kaths, M. & Bauer, S. Molekularpathologisch determinierte multimodale Therapie gastrointestinaler Stromatumoren. Wien klin Mag 26, 68–73 (2023). https://doi.org/10.1007/s00740-023-00488-x

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