Impact of KRAS mutation status on outcomes in peritoneal metastatic mucinous adenocarcinoma of the colon and appendix following CRS-HIPEC: A retrospective analysis.

Abstract

e15578 Background: KRAS mutations (MT) are seen in 40-45% of colon and 55% of appendiceal carcinoma. They are associated with poor prognosis in colon cancer but favorable prognosis in appendiceal cancer. We conducted a retrospective analysis to evaluate survival differences among patients (pts) with KRAS MT vs wild-type (WT) in cases of mucinous adenocarcinoma of the colon (MAC) and appendix (MAAP) with peritoneal metastases following CRS-HIPEC. Methods: We retrospectively analyzed KRAS status in pts with MAC and MAAP with peritoneal metastases. We excluded pts with Low-Grade Appendiceal Mucinous Neoplasm (LAMN). Survival analysis was performed using Kaplan-Meier curves and Cox regression model. Results: Our cohort had 49 pts, 34 with MAC and 15 with MAAP. In the colon cohort, 21 pts were KRAS MT including 5 pts with G12D mutation. Men who had MAC were more likely to be KRAS MT (11/21, 52.4%) than WT (1/13, 7.7%), p=0.023. In the colon cohort, median survival was 65 months in the KRAS MT group compared to 71 months in the WT group (p=0.9). At 1 year, disease free survival (DFS) was noted in 46% of pts in the WT group compared to 30% in the KRAS MT group (p=0.2). Overall survival (OS) at 1 year was 85% for KRAS WT compared to 76% for KRAS MT (p=0.9). In the appendiceal cohort, 9 pts were KRAS MT including 5 pts with G12D. At 1 year, 89% of KRAS MT patients exhibited DFS, compared to 50% in the KRAS WT (p=0.2). All pts with MAAP were alive at 1 year, regardless of KRAS status. Conclusions: KRAS MT are prevalent in both MAC and MAAP cohorts, with a notable proportion of pts harboring the G12D. In MAC cohort, at 1 year, the DFS and OS were lower in the KRAS MT group compared to the WT. In contrast to MAC, MAAP showed numerically favorable DFS at 1 year in pts with KRAS MT. OS was numerically favorable as well, but the impact of subsequent therapies may have influenced it. Though limited by sample size, these findings warrant validation in a larger study in pts with mucinous carcinoma to better assess the prognostic role of KRAS mutations. MAC (n=34) MAAP(n=15) KRAS-MT KRAS-WT KRAS-MT KRAS-WT No. of pts 21 13 9 6 Mean Age (yrs) 56.38 53.54 56.78 59.83 Race(A/AA/L/W) 1/1/1/31 0/0/0/15 Neoadjuvant response %(CR/PR/SD/PD) 1(5.3)/7(36.8)/7(36.8)/4(21.1) 0(0)/8(88.9)/1(11.1)/0(0) 0(0)/2(33.3)/4(66.7)/0(0) 0(0)/0(0)/4(80)/1(20) DFS %,(95%CI)12-month24-month36-month 30 (15-59)20 (8-48)0 (-, -) 46 (24-88)46 (24-88)46 (24-88) 89 (71-100)67(42-100)44(18,100) 50(22-100)25(5-100)25(5-100) OS %,(95%CI)12-month36-month60-month 76 (60-97)65 (44-96)65 (44-96) 85 (67-100)68 (47-100)55 (31-98) 100 (100-100)100(100-100)67(30-100) 100 (100-100)60(29-100)60(29-100) G12D/non-G12D/Unknown 5/13/3 5/4/0