No abstract

Purpose: Previously we developed membrane-arrays as a promising tool to detect circulating tumor cells (CTC) with KRAS oncogene in patients with malignancies.This study was conducted to determinate the predictive values of CTCs with KARS mutation by membrane-arrays for metastatic colorectal cancer patients treated with cetuximab plus chemotherapy. Experimental Design: Seventy-six metastatic colorectal cancer patients receiving cetuximab plus FOLFIRI or FOLFOX-4 chemotherapy were enrolled. KRAS mutation status in the peripheral blood of these patients was analyzed using membrane-arrays, and KRAS mutation status in tumors was analyzed by DNA sequencing. Results: Among 76 metastatic colorectal cancer patients, KRAS mutations in tumors and in peripheral blood were identified in 33 (43.4%) and 30 (39.5%) patients, respectively.The detection sensitivity, specificity, and accuracy of membrane-arrays for CTCs with KRAS oncogene were 84.4%, 95.3%, and 90.8%, respectively, and indeed a highly significant correlation to KRAS mutations in tumors (P < 0.0001) was observed. Forty-five (59.2%) patients responded to cetuximab plus chemotherapy, and 41 and 40 were wild-type KRAS in tumors and peripheral blood, respectively (both P < 0.0001). Patients with tumors that harbor wild-type KRAS are more likely to have a better progression-free survival and overall survival when treated with cetuximab plus chemotherapy (P < 0.0001). Likewise, patients with CTCs of wild-type KRAS in peripheral blood express a better progression-free survival and overall survival when treated with cetuximab plus chemotherapy (P < 0.0001). Conclusions: These findings provide evidence that detection of KRAS mutational status in CTCs, by gene expression array, has potential for clinical application in selecting metastatic colorectal cancer patients most likely to benefit from cetuximab therapy.Colorectal cancer is the second leading cause of cancer-related death in western countries and is the third major cause of cancerrelated death in Taiwan, with >9,000 new cases and 4,000 deaths per year. 12 In the past decade, significant improvements have been made in response rates, progression-free survival (PFS), and overall survival (OS) of metastatic colorectal cancer patients (1 -4). This prominent improvement is mainly due to the recent introduction of new combinations of standard chemotherapy, including 5-fluorouracil/folinic acid, irinotecan, and oxaliplatin, and to the new therapeutic agents targeting molecular events involved in colorectal carcinogenesis such as monoclonal antibodies (mAb) against epidermal growth factor receptor (EGFR) or mAbs against vascular endothelial growth factor. Previous studies (5 -11) showed that the benefits of the anti-EGFR mAb cetuximab among patients with metastatic colorectal cancer are limited to those who have colorectal tumor tissues with wild-type KRAS genes, and KRAS genes with mutations are 12

BackgroundTo identify factors affecting the harvest of lymph nodes (LNs) and to investigate the association between examining a minimum of 12 LNs and clinical outcomes in stage I-III colorectal cancer (CRC) patients.MethodsThe clinicopathologic features and the number of examined LNs for 1167 stage I-III CRC patients were analyzed to identify factors affecting the number of LNs harvested and the correlations between clinical outcomes and high harvests (≧12 LNs) and low harvests (<12 LNs).ResultsA multivariate analysis showed that age (P = 0.007), tumor size (P = 0.030), and higher T stage (P = 0.001) were independent factors affecting the examinations of LNs in colon cancer and that tumor size (P = 0.015) was the only independent factor in rectal cancer. Patients with low harvests had poorer overall survival with stage II and stage III CRC (stage II: P < 0.0001; III: P = 0.001) and poorer disease-free survival for stages I-III (stage I: P = 0.023; II: P < 0.0001; III: P = 0.001).ConclusionsThe factors influencing nodal harvest are multifactorial, and an adequate number of examined LNs (≧12) is associated with a survival benefit. Removal of at least 12 LNs will determine the lymph node status reliably.