KRAS mutations vary depending on the location of the primary tumor in pancreatic ductal carcinoma (PDAC) and may influence local recurrence, according to a study presented at the 2018 AACR Pancreatic Cancer: Advances in Science and Clinical Care conference in Boston, Massachusetts.1
“KRAS mutations are a hallmark event in PDAC, with substantial genomic heterogeneity within KRAS-mutant tumors,” the authors wrote.
The most common KRASmutation found in PDAC is G12D, which is associated with poorer survival after tumor resection. The aim of this study was to determine the effect of other KRAS mutations on patterns of disease recurrence among patients with resected PDAC.
The multicenter study included 356 patients who underwent PDAC resection. Next-generation sequencing was used to evaluate tumor tissue for different KRASmutations. These mutations were then compared with baseline clinicopathologic characteristics.
KRAS mutations were present in 92% of patients, with the most common being G12D in 40%, followed by G12V in 33%, G12R in 15%, and other rarer, codon 61 mutations in 7% of patients.
Tumors located in the pancreatic head/uncinate harbored KRAS G12D and G12V mutations in 81% and 80% of patients, respectively. G12R and codon 61 mutations were present less frequently in the pancreatic head/uncinate, at 57% and 54%, respectively. Lymphovascular invasion was more likely to occur with G12D mutations — 63% of patients compared with 46% of patients with G12V, 34% with G12R, and 35% with codon 61 mutations.
The study also evaluated a validation cohort of patients with PDAC harboring KRAS mutations whose tumors were analyzed by a validated institutional next-generation sequencing panel —which found a similar proportion of KRAS mutations in tumors located within the pancreatic head/uncinate (G12D, 58%; G12V, 56%; G12R, 60%). Codon 61 mutations, however, were primarily located within he pancreatic tail (65%) in this cohort.
In the resection cohort, local-only recurrence occurred as the first site of failure more frequently with G12R mutations (odds ratio [OR], 9.81; 95% CI, 2.8-34.4; P= .031) or codon 61 mutations (OR, 7.65; 95% CI, 1.75-33.4; P= .16) compared with other mutations.
The authors concluded that these data suggest that different KRASmutations may be associated with differing primary tumor locations. They noted that “KRAS 612R and codon 61 mutations were associated with local recurrence after surgical resection, suggesting a potential role for more aggressive local therapy in patients whose tumors harbor these mutations.”
- Morales-Oyarvide V, Rubinson DA, Dunne RF, et al. Not all KRASmutations in pancreatic ductal adenocarcinoma are created equal: associations with clinicopathologic characteristics and patterns of disease recurrence. Presententation at: AACR Pancreatic Cancer: Advances in Science and Clinical Care; Boston, Massachusetts: September 21-24, 2018. Abstract A029.