N. Nweze1, F. Zih1, B. Luo1, E. Sigurdson1, S. Reddy1, E. Lamb1, J. M. Farma1 1Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA
Introduction:
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third leading cause of cancer death in the United States in both men and women. CRC has been shown to be a heterogeneous disease with genetic variations. Next-generation sequencing (NGS) is commonly being used to further elucidate treatment options in CRC patients. Our goal was to review our experience using NGS in CRC patients at a tertiary cancer center.
Methods:
We performed an IRB-approved, retrospective study of 100 patients with the diagnosis of CRC who underwent molecular profiling within our institution between January 2006 and January 2016. Our in house NGS platform evaluates for 50 commonly mutated cancer genes. We tested patients with recurrent CRC or metastatic disease. We then identified the most commonly mutated genes, as well as patterns of clinical outcomes including recurrence rates and survival outcomes.
Results:
We evaluated 100 patients with CRC, 65% were male and 79% were White. The mean age at diagnosis in years was 59.2 ± 12.9 (SD). 100% had adenocarcinoma. 11% had mucinous subtype, 6% had signet ring cell subtype and 2% had mixed subtype with neuroendocrine features. The mean BMI was 27.7 ± 6.3 (SD) and 59.7% had a smoking history. 68% had colon CA and 32% had rectal CA. 10% had no mutations, 27% had 1 mutation, 32% had 2 mutations, 19% had 3 mutations, 7% had 4 mutations and 5% had 5 mutations. The most common mutations were p53 (n=64), APC (n=37), and KRAS (n=35). Other mutations detected were: PIK3CA (n=13), SMAD4 (n=12), BRAF (n=6), PTEN (n=4), CTNNB1 (n=3), NRAS (n=3), GNAS (n=2), FBXW7 (n=2), FGFR3 (n=2), STK11 (n=2), ABL1, AKT1, CDKN2A, IDH1, KDR, PDGFRA, PTPN11, (n=1). 59% had stage 4 disease; 88.1% of these patients had at least 1 mutation, 59.3% had 2 or more mutations and 11.8% had no mutations. 79.6% had unresectable stage 4 disease (n=47); 87.2% of these patients had at least one mutation, 57.4% had 2 or more mutations and 12.7% did not have any mutations. 20.3% had stage 4 disease that was amendable to R0 resection (n=12); 100% of these patients had at least 1 mutation and 66.6% had 2 or more mutations. 53% presented with resectable disease and 96.2% of these patients had a recurrence within 2 years (n=51). 94.1% had at least 1 mutation, 66.6% had 2 or more mutations and 5.8% had no mutations. Median length of follow up was 2.2 years. 14% had no evidence of disease at the time of follow up, 61% were alive with disease and 25% had died of the disease.
Conclusion:
The majority of CRC patients with metastatic disease or recurrent disease who underwent NSG at our institution were found to have at least one mutation. P53, APC and KRAS were the most commonly mutated genes. NGS was used as an adjunct to guide treatment therapy, however it remains to be seen whether the information provided by molecular profiling changes recurrence or survival outcomes.