Verlaufsbeobachtung des fernmetastasierten Melanoms mit der Laktatdehydrogenase und dem C-reaktiven Protein

Zusammenfassung

Zur Evaluierung von serologischen Verlaufsparametern der fernmetastasierten Melanom-Erkrankung wurden drei prospektive Studien durchgeführt. Die Ergebnisse der Staging-Untersuchungen wurden als unabhängiger Referenz-Standard zur Diagnose einer Erkrankungs-Progredienz verwandt, und Interleukin-6 (Il-6), sein Surrogat C-reaktives Protein (CRP) und der konventionelle Parameter Laktatdehydrogenase (LDH) wurden zum Zeitpunkt der Staging-Untersuchungen im Serum bestimmt. Zum Vergleich wurden die Melanom-Marker S100β und „melanoma inhibitory activity” (MIA) in den Seren gemessen. Die Patienten mit Progredienz der Metastasierung wiesen statistisch signifikant höhere Konzentrationen der Serumparameter als die Patienten mit Therapieansprechen auf, wenn beide Gruppen durch Medianwerte verglichen wurden. Mit der Fläche unter den „Receiver Operating Characteristic” (ROC)-Kurven zeigten sich sowohl Il-6, sein Surrogat CRP und die LDH als auch S100β und MIA geeignet, eine Progression der Metastasierung tendenziell zu erkennen. In der multiplen logistischen Regressions-Analyse resultierte die LDH als relevanter Faktor. Aufgrund ihrer hohen Korrelationen mit der LDH konnten S100β und MIA die Information der LDH nur geringfügig verbessern. Unter Anwendung von „classification and regression trees” (CART) erwies sich das CRP mit einem Grenzwert von 0,5 mg/dl als der am meisten relevante Parameter.

Abstract

Monitoring melanoma patients suffering from distant metastases (American Joint Committee on Cancer stage IV), we evaluated serum markers for the ability to discriminate progressive from non-progressive disease. In three prospective studies, results of staging examinations were used as independent reference standard for diagnosing progressive disease, and interleukin-6 (Il-6), its surrogate C-reactive protein (CRP) and the conventional parameter lactate dehydrogenase (LDH) were determined in serum just before. For comparison, the melanoma markers S100β and melanoma inhibitory activity (MIA) were measured in the sera. We found all tested serum parameters to be significantly elevated in progressive disease by median values. Calculating the areas under the Receiver Operating Characteristic (ROC) curves, Il-6, its surrogate CRP and LDH as well as S100β and MIA were useful in diagnosing progressive disease. By multiple logistic regression analysis, LDH resulted as relevant factor. S100β and MIA did not provide additional significant information as they highly correlated with LDH with respect to clinical outcome. Applying classification and regression trees (CART), we found CRP with a cut off value of 0.5 mg/dl to be the most relevant serum marker.

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