This study was conducted adhering to the REporting recommendations for tumor MARKer prognostic studies (REMARK). All patients signed an informed consent before entering the randomized trials that included information regarding the use of their blood or tumor tissue to explore relevant molecular parameters. SNPs with significance for an association with outcomes in the discovery set were examined in the validation set and control ( supplementary Figure S2, available at Annals of Oncology online). In the discovery set, associations of SNPs with clinical outcomes were analyzed not only in all population, but also in subpopulations stratified by KRAS status. Two hundred twenty-eight (89%) patients from arm A of TRIBE, 248 (84%) KRAS exon2 ( KRAS) wild-type patients from the bevacizumab arm, and 248 (84%) KRAS wild-type patients from the cetuximab arm of FIRE3 were enrolled in this study as a discovery set, validation set, and control, respectively. Also, patients with samples available for analyzing genomic DNA were eligible for this study. Eligibility criteria of our study included patients with histologically confirmed colorectal adenocarcinoma, measurable metastatic disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and no previous exposure to systemic chemotherapy except for adjuvant chemotherapy, and all patients received FOLFIRI-based regimen as a first-line treatment.
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