scholarly journals Genomic Profiling for KRAS, NRAS, BRAF, Microsatellite Instability, and Mismatch Repair Deficiency Among Patients With Metastatic Colon Cancer

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Martin E. Gutierrez ◽  
Kristin S. Price ◽  
Richard B. Lanman ◽  
Rebecca J. Nagy ◽  
Irfan Shah ◽  
...  

PURPOSE Genomic testing is recognized in national guidelines as essential to guide appropriate therapy selection in metastatic colorectal cancer. Previous studies report adherence to testing guidelines is suboptimal, but current testing rates have not been assessed. This study reports testing rates in metastatic colon cancer (mCC) for guideline-recommended biomarkers in a US-based population. MATERIALS AND METHODS A retrospective review of data extracted from electronic medical records was performed to identify patients with pathologically confirmed mCC and describe patterns of guideline-aligned biomarker testing. Data were extracted from the electronic health records of 1,497 patients treated at 23 practices across the United States. Both community and academic centers were represented. RESULTS A total of 1,497 patients with mCC diagnosed between January 1, 2013 and December 31, 2017 were identified. Guideline-aligned biomarker testing rates for RAS, BRAF, and microsatellite instability/mismatch repair deficiency over this study period were 41%, 43%, and 51%, respectively. Patients were more likely to have guideline-aligned testing for RAS and BRAF if they were treated at an academic center, were diagnosed with de novo metastatic disease, and were female. In addition, patients < 65 years of age were more likely to have guideline-aligned RAS testing. Of the 177 patients (12% of cohort) who received anti–epidermal growth factor receptor therapy, only 50 (28%) had complete guideline-aligned biomarker testing. CONCLUSION Despite guideline recommendations and significant therapeutic implications, overall biomarker testing rates in mCC remain suboptimal. Adherence to guideline-recommended biomarker testing would potentially reduce exposure to expensive and ineffective therapies, resulting in improved patient outcomes.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15123-e15123
Author(s):  
Martin Gutierrez ◽  
Kristin Sedgwick Price ◽  
Richard B. Lanman ◽  
Rebecca Nagy ◽  
Irfan Shah ◽  
...  

e15123 Background: Molecular genotyping is essential to optimal treatment selection in metastatic colon cancer (mCC) as mutations in exons 2,3,4 of KRAS and NRAS (expanded RAS) and BRAF V600E predict lack of response to anti-HER2 therapy, and microsatellite instability high (MSI-H) predicts positive response to immune checkpoint inhibitor (ICPI)s. The National Comprehensive Cancer Network (NCCN) first recommended molecular genotyping for mCC in 2009 and by 2016 recommended all pts with mCC have expanded RAS, BRAF, and mismatch repair deficiency (MMRd) testing. This study updates genotyping rates in metastatic colon cancer (mCC) in a real-world practice setting. Methods: We performed a retrospective review of genomic testing patterns from pts with mCC diagnosed between January 2013 and December 2017 from 22 academic and community health centers in the United States who contributed to COTA’s de-identified Real World Evidence database. Results: 563 pts with mCC were identified in the Cota database over the 5-year period. 341 (61%) pts with mCC had testing for KRAS, 130 (23%) for NRAS, 177 (31%) for BRAF, and 297 (53%) for MMRd. Testing rates for NRAS, BRAF and MMRd all increased from 2013 to 2017 but remained suboptimal with undergenotyping rates of 48%, 45% and 12% respectively by 2017. 33 (6%) pts received cetuximab and/or panitumumab without prior testing for both KRAS and NRAS, despite established lack of benefit. Between 2016 and 2017, when NCCN recommended testing for KRAS, NRAS, BRAF and MMRd, only 24% of mCC pts were tested for all biomarkers. Conclusions: Although molecular genotyping rates increased over the described 5-year period, since 2016, less than one quarter of all mCC pts in this cohort received guideline recommended genotyping. Approaches that may improve complete genotyping rates in mCC, such as plasma-based comprehensive genomic profiling, may improve optimal treatment selection and should be tested in prospective trials.


Author(s):  
Sebastian Dwertmann Rico ◽  
Doris Höflmayer ◽  
Franziska Büscheck ◽  
David Dum ◽  
Andreas M. Luebke ◽  
...  

AbstractMucin 5AC (MUC5AC) is a secreted gel-forming mucin expressed by several epithelia. In the colon, MUC5AC is expressed in scattered normal epithelial cells but can be abundant in colorectal cancers. To clarify the relationship of MUC5AC expression with parameters of tumor aggressiveness and mismatch repair deficiency (dMMR) in colorectal cancer, a tissue microarray containing 1812 colorectal cancers was analyzed by immunohistochemistry. MUC5AC expression was found in 261 (15.7%) of 1,667 analyzable colorectal cancers. MUC5AC expression strongly depended on the tumor location and gradually decreased from proximal (27.4% of cecum cancers) to distal (10.6% of rectal cancers; p < 0.0001). MUC5AC expression was also strongly linked to dMMR. dMMR was found in 21.3% of 169 cancers with MUC5AC positivity but in only 4.6% of 1051 cancers without detectable MUC5AC expression (p < 0.0001). A multivariate analysis showed that dMMR status and tumor localization predicted MUC5AC expression independently (p < 0.0001 each). MUC5AC expression was unrelated to pT and pN status. This also applied to the subgroups of 1136 proficient MMR (pMMR) and of 84 dMMR cancers. The results of our study show a strong association of MUC5AC expression with proximal and dMMR colorectal cancers. However, MUC5AC expression is unrelated to colon cancer aggressiveness.


2018 ◽  
Vol 51 ◽  
pp. 71-75 ◽  
Author(s):  
Matthew Grant ◽  
Andrew Haydon ◽  
Lewis Au ◽  
Simon Wilkins ◽  
Karen Oliva ◽  
...  

Oncogene ◽  
2002 ◽  
Vol 21 (37) ◽  
pp. 5758-5764 ◽  
Author(s):  
Liya Gu ◽  
Brandee Cline-Brown ◽  
Fujian Zhang ◽  
Lu Qiu ◽  
Guo-Min Li

Sign in / Sign up

Export Citation Format

Share Document