RESUMO
BACKGROUND: Although it is accepted that metastatic colorectal cancers (mCRCs) that carry activating mutations in KRAS are unresponsive to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, a significant fraction of KRAS wild-type (wt) mCRCs are also unresponsive to anti-EGFR therapy. Genes encoding EGFR ligands amphiregulin (AREG) and epiregulin (EREG) are promising gene expression-based markers but have not been incorporated into a test to dichotomise KRAS wt mCRC patients with respect to sensitivity to anti-EGFR treatment. METHODS: We used RT-PCR to test 110 candidate gene expression markers in primary tumours from 144 KRAS wt mCRC patients who received monotherapy with the anti-EGFR antibody cetuximab. Results were correlated with multiple clinical endpoints: disease control, objective response, and progression-free survival (PFS). RESULTS: Expression of many of the tested candidate genes, including EREG and AREG, strongly associate with all clinical endpoints. Using multivariate analysis with two-layer five-fold cross-validation, we constructed a four-gene predictive classifier. Strikingly, patients below the classifier cutpoint had PFS and disease control rates similar to those of patients with KRAS mutant mCRC. CONCLUSION: Gene expression appears to identify KRAS wt mCRC patients who receive little benefit from cetuximab. It will be important to test this model in an independent validation study.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Cetuximab , Neoplasias Colorretais/secundário , Resistencia a Medicamentos Antineoplásicos/genética , Expressão Gênica , Humanos , Proteínas Proto-Oncogênicas p21(ras)RESUMO
To improve efficiency, the special procedures division of a radiology department at a Florida hospital chose to implement an acuity system designed specifically to ease patient scheduling problems. The matrix-based acuity system minimized overtime hours for radiologic technologists, nurses and physicians while maximizing patient throughput and staff utilization. The acuity system was tested using General Purpose Simulation System (GPSS). Test results were positive, and the hospital plans to implement the system for patient scheduling.
