Suchergebnisse

The legal basis for the use of laboratory diagnostics has been fundamentally changed by the European In-vitro Diagnostics Regulation (EU) 2017/746 ("IVDR"). Until this set of regulations comes into full force in May 2022, the entire laboratory diagnostics industry in Germany will only have a short transitional phase to adapt its processes. This affects laboratories that partly or predominantly use in-house tests; here, substantial new requirements must be met. Since the implementation of IVDR is committed to improving patient safety, a prolongation of the transition period by politicians - despite the COVID-19 crisis - is not likely. On the one hand, laboratories need to prepare for increased regulatory supervision of in-house tests. On the other hand, with respect to infringements of competition law, there is a risk that individual diagnostic manufacturers will take action against laboratories using in-house tests, even though a comparable commercial test is available. One of the problematic consequences for patient care can also be that tests covering rare diseases, so called "niche tests", that were previously commercially available but have low sales, could be withdrawn from the market by manufacturers due to the considerably increasing documentation requirements. Even though the adaptation of national regulations and implementation rules is not yet finished, every medical laboratory is strongly advised to already start dealing with the innovations brought by the IVDR. ; Die rechtlichen Grundlagen für die Verwendung von Labordiagnostika haben sich durch die Europäische Verordnung über In-vitro -Diagnostika (EU) 2017/746 ("IVDR") fundamental geändert. Bis zum vollen Inkrafttreten dieses Regelwerkes im Mai 2022 bleibt der gesamten Labordiagnostik in Deutschland nur noch eine kurze Übergangsphase für die Anpassung ihrer Prozesse. Betroffen sind hiervon insbesondere Labore, die zum Teil oder überwiegend Tests aus Eigenherstellung anwenden; hier müssen wesentliche neue Anforderungen eingehalten werden. Da die ...

NTRK-Genfusionen sind seltene genetische Alterationen, die tumorentitätenübergreifend vorkommen können. Während sie in den meisten soliden Tumoren nur sehr niederfrequent vorkommen, lassen sie sich in bestimmten Tumoren wie dem infantilen Fibrosarkom, dem kongenitalen mesoblastischen Nephrom und dem sekretorischen Mamma- oder Speicheldrüsenkarzinom jedoch häufig nachweisen. NTRK-Genfusionen bzw. TRK-Fusionsproteine gelten als starke onkogene Treiber. Bei Nachweis von NTRK-Genfusionen können TRK-Inhibitoren unabhängig von der Tumorentität eingesetzt werden. Vertreter sind Entrectinib und Larotrectinib. Bislang ist nur Larotrectinib in der Europäischen Union zugelassen. Für beide wurden Wirksamkeit und Verträglichkeit in Phase-I- und Phase-II-Studien gezeigt. Die Seltenheit der TRK-Fusionstumoren stellt diagnostische und klinische Prozesse vor große Herausforderungen: Einerseits sollen alle Patienten mit TRK-Fusionstumoren identifiziert werden, andererseits sind epidemiologische und histologische Aspekte sowie Ressourcen zu berücksichtigen. Basierend auf diesen Punkten möchten wir einen Diagnosealgorithmus für TRK-Fusionstumoren vorschlagen, außerdem stellen wir aktuelle Daten zu den TRK-Inhibitoren vor. ; NTRK gene fusions are sporadic genetic alterations that can occur across tumor entities. Whereas they are quite rare in most solid tumors they are present at much higher frequencies in certain rare tumors such as infantile fibrosarcoma, congenital mesoblastic nephroma, secretory breast, or salivary gland carcinoma. NTRK gene fusions or TRK fusion proteins are considered strong oncogenic drivers. If NTRK gene fusions are detected, TRK inhibitors such as entrectinib and larotrectinib can be used regardless of the tumor entity. So far only larotrectinib is approved in the European Union. Both drugs have been shown to be effective and well tolerated in phase I and phase II studies. The low prevalence of TRK fusion-positive cancers poses challenges for diagnostic and clinical work-flows. On one hand, patients with NTRK gene fusions should be identified; on the other hand, epidemiological, histological, and resource-related aspects have to be taken into account. Based on these premises, we suggest a diagnostic algorithm for TRK fusion cancers and present current data on TRK inhibitors.

NTRK gene fusions are sporadic genetic alterations that can occur across tumor entities. Whereas they are quite rare in most solid tumors they are present at much higher frequencies in certain rare tumors such as infantile fibrosarcoma, congenital mesoblastic nephroma, secretory breast, or salivary gland carcinoma. NTRK gene fusions or TRK fusion proteins are considered strong oncogenic drivers. If NTRK gene fusions are detected, TRK inhibitors such as entrectinib and larotrectinib can be used regardless of the tumor entity. So far only larotrectinib is approved in the European Union. Both drugs have been shown to be effective and well tolerated in phase I and phase II studies. The low prevalence of TRK fusion-positive cancers poses challenges for diagnostic and clinical work-flows. On one hand, patients with NTRK gene fusions should be identified; on the other hand, epidemiological, histological, and resource-related aspects have to be taken into account. Based on these premises, we suggest a diagnostic algorithm for TRK fusion cancers and present current data on TRK inhibitors.