Zusammenfassung
GRUNDLAGEN: Die Wirkung der Strahlentherapie beruht auf DNA-Schädigung, wobei das p53 Gen eine wichtige Rolle bei der Induktion des Zelltodes spielt. p53 ist in Tumoren häufig inaktiviert, was eine DNA-Schaden-Induzierte Apoptose verhindert. METHODIK: In der vorliegenden Arbeit werden Aspekte zur Durchführung einer prädiktiven Markerstudie erörtert. Diese Studie ist zur klinischen Umsetzung einer auf p53 als prädiktivem Marker basierenden, individualisierten Krebstherapie erforderlich. ERGEBNISSE: PART 1 ist eine akademische, prospektiv randomisierte klinische Studie, welche sich erstmals mit markeradaptierter Strahlentherapie befasst. Patienten mit Rektumkarzinom Stadium T2/T3, welche für eine präoperative Strahlentherapie geeignet sind, werden in die Studie eingebracht. Das Studiendesign erlaubt die Untersuchung, ob der p53-Genotyp ein valider Marker zur Therapiewahl ist. Eine verlängerte Wartezeit zwischen Bestrahlung und Operation soll die Strahlenwirkung auf den Tumor sichtbar machen. SCHLUSSFOLGERUNGEN: Die Markerstudie ist ausgelegt um auf hohem Evidenzniveau (Level 1) zu zeigen, dass der p53 Genotyp und der Zeitpunkt der Operation prognostische Faktoren sind. Weiters soll der prädiktive Wert des p53 Genotyps als Selektionsmarker für Patienten zur Strahlentherapie evaluiert werden.
Summary
BACKGROUND: Cell killing by ionizing radiation is triggered by DNA-damage involving the p53 gene as major player in cell death induction. p53 is frequently inactivated in cancer which prevents apoptosis after extensive DNA-damage. METHOD: We summarize considerations to conduct a predictive marker trial mandatory before clinical application of p53 for individualized therapy. RESULTS: PART 1 is an academic driven prospective randomized trial addressing individualized, marker adapted radiation therapy for the first time. Patients suffering from T2/T3 rectal cancer appropriate for preoperative radiation will be included. The design qualifies the trial to determine the relevance of p53 gene mutation as a marker guiding the choice of therapy. A delay of surgery after radiation is implemented to improve detection of the radiation effect on the tumor. CONCLUSIONS: This predictive marker trial intends to provide the level of evidence I that the p53 genotype and time of surgery are prognostic markers. Furthermore should the predictive value of p53 genotype be evaluated as marker to select patients for preoperative radiation therapy.
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Wolf, B., Kührer, I., Akan, B. et al. PART 1 – p53 adapted preoperative radiotherapy for T2 and T3 rectal cancer. A study of the p53 research group. Eur Surg 42, 18–23 (2010). https://doi.org/10.1007/s10353-010-0514-5
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DOI: https://doi.org/10.1007/s10353-010-0514-5