The University of Texas MD Anderson Cancer Center, Houston, TX
Hesham M. Hassabo , Ibrahim Halil Sahin , Syed Mohammad Ali Kazmi , Salwan S. Al Mutar , Diogo Bugano Diniz Gomes , Tunghi May Pini , Eduardo Vilar Sanchez , Arvind Dasari , Scott Kopetz , Michael J. Overman , Cathy Eng , Bryan K Kee , Jean-Nicolas Vauthey , Manal Hassan , Chris R. Garrett
Background: Evolving information is emerging regarding patient tumor molecular data and associations with patient clinical characteristics and survival outcomes; we sought to evaluate pt clinical data with CRC tumor mut status. Methods: Since January 2008 tumor pts with stage IV CRC (principally primary tumors) were analyzed for KRAS (codon 12, 13, and 61) mut status as standard-of-care. A subset of pts tumors underwent BRAF and KRAS codon 164 mut testing. Results: 1,891 pts with CRC whose tumors underwent molecular mut analysis were identified from the clinical record. There was no statistically significant difference in pt overall survival from time of diagnosis for stages I/II (data not shown) and III; for stage IV pts there was an inferior OS associated with BRAF mut tumors (see Table). Tumor BRAF mut was significantly detected among ever smokers (10.2%) as compared to never smokers (5.4%), p < 0.001; meanwhile, tumor KRAS mut and wild type distribution were similar between ever smokers and never smokers. KRAS mut was significantly observed in CRC patients with distant lymph node, hepatic and lung metastasis, p < 0.001. Type 2 diabetes, intake of metformin or ACE inhibitors, were not significantly correlated with tumor KRAS or BRAF mut status. Conclusions: Pts with stage IV CRC BRAF mut tumors have a higher likelihood of prior or current smoking history in addition to having an adverse survival prognosis; pts with stage IV KRAS mut tumors have an increased association with distant lymph node, hepatic, and lung metastases as compared to KRAS wild type and BRAF mut tumors. Studies are ongoing to determine how tumor molecular characteristics may help to predict clinical outcomes and provide a useful to guide pt care.
Mutation | Number (%) |
Stage III median survival (months) (95% CI*) |
P value | Stage IV median survival (months) (95% CI*) |
P value |
---|---|---|---|---|---|
KRAS mutant | 777 (41%) |
74.0 (56.1-91.8) |
P = 0.70 | 34.9 (30.8-38.9) |
P < 0.001 |
KRAS Wild type§ |
978 (52%) |
59.3 (53.5-65.1) |
37.8 (34.1-41.6) |
||
BRAF mutant | 136 (7%) |
43.9 (14.7-73.0) |
21.2 (11.5-30.8) |
*Abbreviation: CI, confidence interval. § Not all patients who were tested for KRAS tumor muts underwent BRAF mut analysis.
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