PART 1 – p53 adapted preoperative radiotherapy for T2 and T3 rectal cancer. A study of the p53 research group

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.