Neoadjuvante Immuntherapie bei Kopf-Hals- Plattenepithelkarzinomen

Zusammenfassung

Das Konzept der neoadjuvanten Immuntherapie stellt einen bedeutenden Paradigmenwechsel bei der Behandlung von potenziell heilbaren Kopf-Hals-Plattenepithelkarzinomen (HNSCC, head and neck squamous cell carcinoma) dar. Die derzeitigen Therapien sind zwar hochgradig individualisiert und innovativ, erreichen aber oft keine zufriedenstellenden Langzeitüberlebensraten und sind häufig mit einer erheblichen Morbidität verbunden.

Der Hauptvorteil dieses Ansatzes liegt in dem Potenzial, die Therapie mit einer spezifischen Behandlungsmodalität zu intensivieren und zu verbessern, die den bestehenden Dreiklang aus Chirurgie, Strahlentherapie und Chemotherapie ergänzt. Checkpoint-Inhibitoren spielen bei dieser Entwicklung eine Vorreiterrolle. Sie zeigen einen moderaten, aber signifikanten Überlebensvorteil bei rezidivierten oder metastasierten Krebserkrankungen mit einem relativ besseren Sicherheitsprofil im Vergleich zu konventionellen Behandlungen. Somit sind sie vielversprechend, wenn sie für frühere Stadien des HNSCC in Betracht gezogen werden.

Ein wesentlicher Vorteil der Einführung einer neoadjuvanten Immuntherapie ist die Möglichkeit einer Deeskalation der Behandlung. Durch die Verringerung der Tumorlast vor der Operation könnte diese Strategie zu weniger invasiven chirurgischen Eingriffen führen. Die Aussicht auf organschonende Protokolle ist in diesem Zusammenhang ein erstrebenswertes Ziel. Darüber hinaus könnte die frühzeitige Anwendung von Immuntherapien eine wirksamere und dauerhaftere Immunreaktion auslösen. Die Induktion eines Immungedächtnisses kann möglicherweise zu einer effektiveren Überwachung der Krankheit durch das Immunsystem führen, die Raten lokaler, regionaler und Fernmetastasen senken und so das Gesamtüberleben und das rezidivfreie Überleben verbessern.

Die neoadjuvante Immuntherapie ist jedoch nicht risikofrei. Eines der Hauptprobleme ist das Sicherheits- und Nebenwirkungsprofil. Zwar deuten die Daten darauf hin, dass unerwünschte Ereignisse relativ selten und überschaubar sind, doch ist das langfristige Sicherheitsprofil bei der neoadjuvanten Behandlung, insbesondere im Kontext der langfristigen, kurativen Absicht, weiterhin Gegenstand laufender Forschungsarbeiten. Ein weiteres ungelöstes Problem liegt in der genauen Bewertung des Ansprechens auf die Behandlung. Es lässt sich eine Diskrepanz zwischen der radiologischen Bewertung anhand der RECIST-Kriterien und den histologischen Befunden feststellen, was auf eine mangelnde Fähigkeit der derzeitigen bildgebenden Verfahren hinweist, das tatsächliche Ansprechen auf Immuntherapie genau wiederzugeben. Diese Diskrepanz unterstreicht die Notwendigkeit verbesserter bildgebender Verfahren und der Entwicklung neuer radiologischer und pathologischer Kriterien, die auf die genaue Bewertung des Ansprechens auf eine Immuntherapie zugeschnitten sind.

Kombinationsbehandlungen und das Timing der Therapie stellen eine weitere komplexe Herausforderung dar. Es gibt eine Vielzahl von Möglichkeiten, Immuntherapeutika mit konventioneller Chemotherapie, zielgerichtete Krebstherapie (eng. targeted therapy), Bestrahlung und experimentellen Ansätzen zu kombinieren. Die Bestimmung des optimalen Behandlungsschemas für den einzelnen Patienten wird zu einer komplizierten Aufgabe, insbesondere wenn kleine, einarmige, nicht randomisierte Studien mit unterschiedlichen Schemata und Ergebnismessungen verglichen werden.

Außerdem muss die Bedeutung der prä- und intraoperativen Entscheidungsfindung im Zusammenhang mit der neoadjuvanten Immuntherapie berücksichtigt werden. Mit zunehmender Erfahrung mit diesem Behandlungsparadigmen besteht das Potenzial für maßgeschneiderte chirurgische Ansätze auf der Grundlage der verbleibenden Tumorlast des Patienten nach der neoadjuvanten Behandlung. Diese Überlegung ist besonders bei umfangreichen Operationen von Bedeutung, bei denen organschonende Protokolle evaluiert werden könnten.

Im klinischen Alltag führt der multimodale Charakter dieser Behandlungsstrategie zu praktischen Herausforderungen, insbesondere außerhalb klinischer Studien. Die Patienten müssen sich einer der Behandlungslandschaft zurechtzufinden, die eine Koordination verschiedener medizinischer Disziplinen erfordert. Dies unterstreicht die Notwendigkeit eingespielter Behandlungspfade in spezialisierten Zentren, um ein effektives Behandlungsmanagement zu ermöglichen, sollte der neoadjuvante Ansatz in der Praxis eingeführt werden.

Diese potenziellen Herausforderungen und offenen Fragen unterstreichen die dringende Notwendigkeit sorgfältig konzipierter klinischer Studien und translationaler Untersuchungen, um Sicherheit und Wirksamkeit für die Patienten zu gewährleisten. Nur so kann sichergestellt werden, dass dieser neue Behandlungsansatz auf ethische Weise eingeführt wird und sein Potential erfüllt.

Schlüsselwörter

neoadjuvante Therapie - Immuntherapie - des Kopf-Hals- Plattenepithelkarzinome - Checkpoint-Inhibitoren - Tumormikroumgebung

Keywords

neoadjuvant therapy - immunotherapy - head and neck squamous cell carcinoma - checkpoint inhibitor - tumor microenvironment

Publication History

Article published online:
02 May 2024

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