Abstract
BackgroundClinically, metastatic rectal cancer has been considered a subset of left-sided colon cancer. However, heterogeneity has been proposed to exist between high and middle/low rectal cancers. We aimed to examine the efficacy of anti-epidermal growth factor receptor (EGFR) treatment for middle/low rectal and left-sided colon cancers.MethodsThis study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy. They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum. The efficacy of first-line and non-first-line anti-EGFR treatment was analysed. Genomic differences in colorectal cancer data from The Cancer Genome Atlas (TCGA) were investigated and visualised with OncoPrint and a clustered heatmap.ResultsOn first-line anti-EGFR treatment, patients with middle/low rectal tumours had significantly lower progression-free survival, overall survival, and overall response rates (6.8 months, 27.8 months and 43%, respectively) than those with left-sided colon cancer (10.1 months, 38.3 months and 66%, respectively). Similar outcomes were also identified on non-first-line anti-EGFR treatment. In TCGA analysis, rectal tumours displayed genetic heterogeneity and shared features with both left- and right-sided colon cancer.ConclusionsAnti-EGFR treatment has lower efficacy in metastatic middle/low rectal cancer than in left-sided colon cancer.
Highlights
Colorectal cancer (CRC) originating from the right and left side of the colon differs in embryologic, epidemiologic, genetic and molecular aspects [1,2,3,4]
In the era of targeted therapy, primary tumour location has been found to play an important role in predicting the treatment response and prognosis of metastatic CRC
Patients were classified based on their primary tumour locations, including the right-sided colon, the left-sided colon, and the middle/low rectum (≤10 cm from the anal verge)
Summary
Colorectal cancer (CRC) originating from the right and left side of the colon differs in embryologic, epidemiologic, genetic and molecular aspects [1,2,3,4]. The sidedness of primary tumours determines the efficacy of targeted therapy in treating mCRC, as is the case for anti-epidermal growth factor receptor (EGFR) agents [8,9,10,11]. These results were obtained by retrospective analyses of CALGB/SWOG 80405, CRYSTAL and FIRE-3 [12, 13]. METHODS: This study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum.
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