Abstract
Purpose
An overview of the field of predictive assays is presented. It has been written with the many clinicians and scientists in mind who would like to become better acquainted with the general scope, principles and themes in the field.
Results
Predictive assays have yielded much valuable information about the radiobiology of tumors, e.g. the overall treatment time for rapidly proliferating tumors should be kept to a minimum. However, alteration of current treatment protocols basedon results from predictive assays is still a matter of debate. What justification do we have to change established treatment protocols? A necessary and sufficient justification would be when the test value indicated an alternative treatment producing a better outcome, i.e. higher survival, improved local control, etc. Necessary but not always sufficient justification is correlation between the parameter measured and clinical outcome, if insufficient clinical benefit can be derived even when this is know. It is not sufficient that a test be demonstrated to be discriminatory. It must discriminate a sufficient number of patients, and its use must provide the patient with useful therapeutic alternatives. These parameters measured by predictive assays may well interact radiobiologically, and restricting observations to just one assay is probably insufficient for reliable indications. In the future, it is more likely that a panel of tests will be performed, and clinical decisions based on multi-parametric analysis of biopsy material.
Conclusion
In the following overview general predictive assay theory is presented followed by a brief introduction to some of the more established assays and finally some guidelines are suggested for the development of new assays.
Zusammenfassung
Ziel
Die folgende Übersicht zum Thema “prädiktive Tests” in der Radiotherapie richtet sich an Kliniker und Naturwissenschafter, die sich mit den allgemeinen Zielsetzungen, den Verfahren und den besonderen Fragen auf diesem Gebiet vertraut machen wollen.
Ergebnisse
Prädiktive Tests haben wertvolle Erkenntnisse über die Strahlenbiologie von Tumoren ermöglicht, so zum Beispiel, daß die gesamte Behandlungszeit für schnell proliferierende Tumoren möglichst kurz gehalten werden sollte. Allerdings stößt die Abänderung gegenwärtig üblicher Behandlungsprotokolle, die sich auf Ergebnisse prädiktiver Analysen stützt, immer noch auf unterschiedliche Reaktionen. Was rechtfertig denn eine Änderung bestehender Behandlungsprotokolle? Eine notwendige und ausreichende Rechtfertigung würde dann vorliegen, wenn die Testwerte auf eine alternative Behandlung mit verbessertem Verlauf hinweisen würden, das heißt eine höhere Überlebensrate oder eine verbesserte lokale Kontrolle zu erwarten wäre. Die Änderung der bestehenden Protokolle ist nicht gerechtfertigt, wenn zwischen den gemessenen Testparametern und dem klinischen Verlauf zwar eine Korrelation besteht, aber keine klinischen Vorteile resultieren. Es genügt auch nicht, lediglich den selektiven Charakter eines Tests nachzuweisen. Er muß eine genügende Anzahl von Patienten selektionieren und eine für die Patienten nützliche therapeutische Alternative aufzeigen. Die durch prädiktive Tests ermittelten Parameter könnten sich gegenseitig beeinflussen, weshalb es für zuverlässige Indikationen wahrscheinlich nicht genügt, nur einen Test durchzuführen. Es erscheint wahrscheinlich, daß in Zukunft eine Palette von Prüfverfahren zur Verfügung stehen muß, damit die klinischen Entscheide auf Ergebnissen multi parametrischer Analysen von Biopsiematerial abgestützt werden können.
Schlußfolgerungen
Im folgenden überblick werden grundlegende Theorien, die prädiktiven Tests zugrunde liegen, vorgestellt und durch kurze Zusammenfassungen über bereits eingeführte Verfahren ergänzt. Abschließend folgen einige Vorschläge zur Entwicklung neuer Tests.
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Crompton, N.E.A., Ozsahin, M., Schweizer, P. et al. Theory and practice of predictive assays in radiation therapy. Strahlenther. Onkol. 173, 58–67 (1997). https://doi.org/10.1007/BF03038924
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DOI: https://doi.org/10.1007/BF03038924