Behandlungsstrategie beim radiojodrefraktären differenzierten Schilddrüsenkarzinom

Zusammenfassung

Traditionell besteht das multimodale Therapiekonzept bei den differenzierten Schilddrüsenkarzinomen in der Thyreoidektomie mit Neck-Dissection (bei cN+-Halsstatus) und adjuvanten Radiojodablation mit abschließender risikoadaptierter TSH-Suppression. Das Ausmaß der Radiojodaufnahme beim metastasierten Schilddrüsenkarzinom spielt eine signifikante Rolle bei der Einschätzung der Prognose. Das fehlende Jodspeicherungsvermögen einer Läsion in Zusammenschau mit dem fehlenden Abfall des Tumormarkers Thyreoglobulin sowie radiologische Zeichen einer Tumorprogression charakterisieren den Radiojod-refraktären Patienten. Aufgrund des meistens über einen langen Zeitraum indolenten Verlaufs erscheint in den meisten Fällen ein abwartendes Verhalten in Kombination mit lokaler Metastasenbehandlung sowie Symptomlinderung primär sinnvoll zu sein. Der Nachweis einer Veränderung der Tumordynamik ist der Zeitpunkt, um eine Systemtherapie zu evaluieren. Diese beruht auf Multi-Tyrosinkinase-Inhibitoren (Sorafenib, Lenvatinib). Diese Substanzen sind größtenteils mit einem ungünstigen Nebenwirkungsprofil assoziiert (Diarrhö, Hautauschläge, arterielle Hypertonie mit hypertensiver Entgleisung, lokale Wundheilungsstörungen), welches zu einer nicht vernachlässigbaren Rate einer therapieassoziierten Morbidität sowie einer hohen Anzahl an Therapieunterbrechungen führt. Daher sind im Jahr 2020 2 selektive RET-Inhibitoren (Selpercatinib, Pralsetinib) für die differenzierten Schilddrüsenkarzinome von der FDA zugelassen worden. Eine neue Perspektive für die Zukunft wären die unterschiedlichen Redifferenzierungsstrategien, welche auf die Steigerung der Sensitivität der Tumorzellen auf Radiojod abzielen.

Abstract

Traditionally, the multimodal therapy concept for differentiated thyroid carcinomas consists of thyroidectomy with neck dissection (for cN + neck) and adjuvant radioiodine ablation with subsequent risk-adapted TSH suppression. The extent of radioiodine uptake in metastatic thyroid carcinomas plays a significant role is significant in terms of prognosis. Radioiodine refractory lesions are characterized by the lack of radioiodine uptake in combination with the lack of decrease in the tumor marker thyroglobulin as well as signs of progression on imaging. Due to the mostly indolent course over a long period of time, a wait-and-see strategy in combination with local management of distant metastase symptom relief appears to be primarily sufficient. By evidence for change in tumor dynamics, the need for a multi-tyrosine kinase inhibitor (sorafenib, lenvatinib)-based systemic therapy should be thoroughly evaluated. These substances are mostly associated with an unfavorable side-effect profile (diarrhea, rash, arterial hypertension, local wound healing disorders), which leads to a non-negligible rate of treatment-associated morbidity and a high number of treatment interruptions. For this reason, two selective RET inhibitors (selpercatinib, pralsetinib) for differentiated thyroid carcinomas were approved by the FDA in 2020. A new perspective for the future would be the variable re-differentiation strategies, which aim to increase the sensitivity of tumor cells to radioiodine.

Schlüsselwörter

Metastasiertes Schilddrüsenkarzinom - Differenziertes Schilddrüsenkarzinom - Radiojodrefraktäres Schilddrüsenkarzinom - Tyrosinkinase-Inhibitor - RET-Inhibitor

Keywords

metastasized thyroid cancer - differentiated thyroid cancer - radioiodine refractory thyroid cancer - tyrosine kinase inhibitor - RET inhibitor

Publication History

Received: 15 January 2021

Accepted after revision: 03 August 2021

Article published online:
28 September 2021

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