Abstract
International guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-EGFR agents for metastatic colorectal cancer (CRC) patients. Daily, new data emerges on the theranostic and prognostic role of molecular biomarkers; this is a strong incentive for a validated, sensitive, and broadly available molecular screening test. Next-generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. We report here our 2 years of clinical practice using NGS results to guide therapeutic decisions.The Ion Torrent AmpliSeq colon/lung cancer panel, which allows mutation detection in 22 cancer-related genes, was prospectively used in clinical practice (BELAC ISO 15189 accredited method). The DNA of 741 formalin-fixed paraffin-embedded CRC tissues, including primary tumors and metastasis, was obtained from 14 different Belgian institutions and subjected to targeted NGS.Of the tumors tested, 98% (727) were successfully sequenced and 89% (650) harbored at least one mutation. KRAS, BRAF and NRAS mutations were found in 335 (46%), 78 (11%) and 32 (4%) samples, respectively. These mutation frequencies were consistent with those reported in public databases. Moreover, mutations and amplifications in potentially actionable genes were identified in 464 samples (64%), including mutations in PIK3CA (14%), ERBB2 (0.4%), AKT1 (0.6%), and MAP2K1 (0.1%), as well as amplifications of ERBB2 (0.3%) and EGFR (0.3%). The median turnaround time between reception of the sample in the laboratory and report release was 8 calendar days.Overall, the AmpliSeq colon/lung cancer panel was successfully applied in daily practice and provided reliable clinically relevant information for CRC patients.
Highlights
Colorectal Cancer (CRC) is the second most frequent cancer in Europe, irrespective of gender, and still yields a high mortality rate, accounting for 12% of cancer deaths [1]
BRAF mutation is a strong negative prognostic biomarker and evidence is accumulating that patients with a BRAF mutant tumor do not benefit from anti-epidermal growth factor receptor (EGFR) therapy [2, 5]
A total of 741 FFPE samples from patients with colorectal cancer were received from 14 different institutions for Next-generation sequencing (NGS) testing from November 2013 to December 2015, each contributing from 1 to 153 samples (Figure 1)
Summary
Colorectal Cancer (CRC) is the second most frequent cancer in Europe, irrespective of gender, and still yields a high mortality rate, accounting for 12% of cancer deaths [1]. Current therapeutical guidelines for stage IV patients include a combination of cytotoxic and biological targeted agents [2]. Indications for standard-of-care molecular testing in colorectal carcinomas included testing for KRAS mutational status as a predictor of response to anti–EGFR agents [3]. American and European guidelines clearly emphasize expanded RAS (KRAS and NRAS) status as a mandatory precondition for use of anti-EGFR therapy [2, 4]. Is the benefit of anti-EGFR therapy confined to RAS wild type (wt) tumors, but treatment with anti-EGFR antibodies may even harm patients with a RAS mutation. BRAF mutation is a strong negative prognostic biomarker and evidence is accumulating that patients with a BRAF mutant tumor do not benefit from anti-EGFR therapy [2, 5]
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