Zusammenfassung
Hintergrund
Beim lokal fortgeschrittenen nichtkleinzelligen Lungenkarzinom (NSCLC) führt die Ergänzung der Strahlentherapie durch eine Chemotherapie und die Konsolidierung mit Durvalumab zu einer signifikanten Steigerung des Überlebens und stellt die gravierendste Innovation der letzten Dekade dar.
Ziel der Arbeit
Ziel war die Analyse neuer Möglichkeiten für die State-of-the-Art-Umsetzung definitiver Radiochemotherapiekonzepte.
Material und Methoden
Dazu erfolgte die Auswertung prospektiver und randomisierter Studien hinsichtlich der Verbesserungen der Behandlungsergebnisse.
Ergebnisse
Der Überlebensvorteil der konsolidierenden Checkpointinhibitortherapie nach kombinierter Radiochemotherapie mit Durvalumab beträgt in einer aktualisierten Analyse der PACIFIC-Studie für das 5‑Jahres-Überleben 43 % (95%-Konfidenzintervall, 95%-KI: 38–47 %) gegenüber 33 % (27–40 %) in der Placebogruppe, die stratifizierte Hazard Ratio für Tod beträgt 0,72 (95%-KI: 0,59–0,89; p = 0,0025). In den Studien zur Dosiseskalation sind erhöhte Nebenwirkungen an Lunge und Ösophagus beobachtet worden, sodass aus der Steigerung der lokalen Effektivität kein unmittelbarer klinischer Nutzen abzuleiten war. Verbesserte Bildgebung vor und während der Therapie und optimierte Möglichkeiten der Dosisapplikation, v. a. mittels intensitätsmodulierter Radiotherapie (IMRT), erlauben die selektive Schonung gesunder Strukturen, was die Fähigkeit zur sicheren Therapieintensivierung auch im Zusammenhang mit neuen immunmodulatorischen Substanzkombinationen erhöht.
Schlussfolgerung
Die Einbindung der Immuntherapie, der stringente Einsatz der Fluordesoxyglukose-Positronenemissionstomographie (FDG-PET) in Staging und Bestrahlungsplanung, die flächendeckende Anwendung hochkonformaler Bestrahlungstechniken (IMRT; volumenmodulierte Arc-Therapie, VMAT) und die konsequente Anwendung der bildgeführten Strahlentherapie haben zu signifikanten Verbesserungen der Behandlungsergebnisse geführt.
Abstract
Background
In locally advanced non-small-cell lung cancer (NSCLC), the addition of chemotherapy to radiotherapy and consolidation with durvalumab leads to a significant increase in overall survival and represents the most profound innovation of the last decade.
Objectives
Analysis of new possibilities for the state-of-the-art implementation of definitive radiochemotherapy concepts.
Materials and methods
Evaluation of prospective and randomised studies regarding improvements in treatment outcomes.
Results
Overall survival benefit of consolidating checkpoint inhibitor therapy after combined radiochemotherapy with durvalumab is 43% (95% confidence interval 38–47%) versus 33% (27–40%) in the placebo group in an updated analysis of the PACIFIC trial for 5‑year survival; stratified hazard ratio for death is 0.72 (95% CI 0.59–0.89, p = 0.0025). In the dose escalation studies, increased pulmonary and oesophageal side effects were observed, so no immediate clinical benefit could be derived from the increase in local efficacy. Improved imaging before and during therapy and optimised possibilities of dose application, especially by using intensity-modulated radiotherapy (IMRT), allow selective sparing of healthy structures, which increases the ability to safely intensify radiotherapy also in connection with new immunomodulatory substance combinations.
Conclusion
The integration of immunotherapy, the stringent use of fluorodeoxyglucose positron emission tomography (FDG-PET) in staging and radiation planning, the widespread use of highly conformal radiation techniques (IMRT; volumetric modulated arc therapy, VMAT) and the consistent application of image-guided radiotherapy have led to significant improvements in treatment outcomes.
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J. Fleckenstein gibt an, dass kein Interessenkonflikt besteht. C. Pöttgen ist als Referent für die Firmen AstraZeneca und Roche Pharma tätig. N. Reinmuth ist als Referent/Berater für die Firmen Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Hoffmann-La Roche, Lilly, Merck, MSD, Pfizer, und Takeda tätig.
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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Fleckenstein, J., Pöttgen, C. & Reinmuth, N. Moderne definitive Radiochemotherapie – State of the Art-Umsetzung und neue Konsolidierungsstrategien. Z Pneumologie 20, 267–272 (2023). https://doi.org/10.1007/s10405-023-00522-z
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DOI: https://doi.org/10.1007/s10405-023-00522-z