Embryonic Origin of Primary Colon Cancer Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colon Cancer Liver Metastases

Abstract

Background To determine the prognostic value of embryonic origin in patients undergoing resection after chemotherapy for colon cancer liver metastases (CCLM). Methods We identified 725 patients with primary colon cancer and known RAS mutation status who underwent hepatic resection after preoperative chemotherapy for CCLM (1990-2015). Survival after resection of CCLM from midgut origin (n=238) and hindgut origin (n=487) was analyzed. Predictors of pathologic response and survival were determined. Prognostic value of embryonic origin was validated with a separate cohort of 252 patients with primary colon cancer who underwent resection of CCLM without preoperative chemotherapy. Results Recurrence-free survival (RFS) and overall survival (OS) after hepatic resection were worse in patients with midgut origin tumors (RFS rate at 3 years: 15% vs. 27%, P<0.001; OS rate at 3 years: 46% vs. 68%, P<0.001). Independent factors associated with minor pathologic response were midgut embryonic origin (odds ratio [OR] 1.55, P=0.010), absence of bevacizumab (OR 1.42, P=0.034), and mutant RAS (OR 1.41, P=0.043). Independent factors associated with worse OS were midgut embryonic origin (hazard ratio [HR] 2.04, P<0.001), carcinoembryonic antigen value ≥5 ng/mL at hepatic resection (HR 1.46, P=0.0021), synchronous CCLM (HR 1.45, P=0.012), and mutant RAS (HR 1.43, P=0.0040). In the validation cohort, patients with CCLM of midgut origin had a worse 3-year OS rate (55% vs. 78%, P=0.003). Conclusion Compared to CCLM from hindgut origin, CCLM from midgut origin are associated with worse pathologic response to chemotherapy and worse survival after resection. This effect appears to be independent of RAS mutation status.

Prognostic Factors for Survival after Resection of Liver Metastases from Colorectal Cancer: A Single Institution Analysis of 655 Cases

“…Similar with earlier analyses, demographic variables such age and gender were not associated with OS in the present study. Unlike recent reports which revealed that right sided colon tumors were associated with poorer OS after resection of CLMs (26,27), in the present analysis, the location of the primary did not significantly influence survival. Metastatic right sided tumors portend a more aggressive biology (than left-sided tumors), reflected mainly in more frequent hepatic and extrahepatic metastases and unresectable CLMs, but the influence of the primary tumor sidedness in patients with resectable CLMs was not proved in our series.…”

Meta-analysis of the association between primary tumour location and prognosis after surgical resection of colorectal liver metastases

“… Flow diagram showing study selection process *Two cohorts were enrolled in the study from Yamashita et al …”

“…Adam et al 30 Umeda et al 31 Huang et al 32 Mavros et al 33 Viganò et al 34 Connor et al 35 Eefsen et al 36 Schirripa et al 37 Norén et al 38 Sasaki et al 20 Shindoh et al 39 Amikura et al 40 Creasy et al 22 Dupré et al 41 Liang et al 43 Rhu et al 44 Sultana et al 45 Wang et al 46 Yamashita et al 21 Yamashita et al 21 Goto et al 47 Berardi et al 48 Cremolini et al 49 Engstrand et al 50 Goffredo et al 51 lmai et al 52 Koch et al 53 Laengle et al 54 Ledys et al 55 Liao et al 56 Lionti et al 57 Loosen et al 58 Makowiec et al 59 Margonis et al 60 Marques et al 24 Oshi et al 61 Palkovics et al 62 Shigematsu et al 63 Vallance et al 64 Wang et al 23 Wang et al 65 Zheng et al 66 Prediction interval 0·1 0 ·5 1 2 10…”

“…Several single centres have recently investigated the prognostic role of primary tumour location (PTL) in patients with CRLM receiving surgical resection. Some studies showed that right‐sided PTL was an independent predictor of poorer overall survival (OS) and disease‐free survival (DFS) after hepatectomy compared with left‐sided PTL, but others found no prognostic difference. Whether PTL could act as an effective prognostic parameter in patients with surgically treated CRLM is still controversial and needs further investigation.…”

Search for Theragnostic Biomarkers in Colorectal Liver Metastases: Focus on the Host Immune Cells

“…Apart from T-status, N-status, and poor differentiation, which are two well-known prognostic factors (14,(17)(18)(19)(20), it is interesting to note that recently there was a countertendency about the location of the primary tumor. Historically, tumors in the rectum were thought to be the most aggressive (7,8,14), but recently some studies underlined how tumors in the right colon may be the most aggressive (21). Indeed, it has been shown that the embryonic origin of the colon cancer (midgut versus hindgut) may be associated with different pattern of response to preoperative therapies and consequentially to different rates of survival.…”