The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status: A Study By the International Genetic Consortium for Colorectal Liver Metastasis.

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OBJECTIVE

To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status.

BACKGROUND

Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors.

METHODS

Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status.

RESULTS

277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38).

CONCLUSIONS

This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors.

Investigators
Abbreviation
Ann. Surg.
Publication Date
2019-08-05
Pubmed ID
31389831
Medium
Print-Electronic
Full Title
The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status: A Study By the International Genetic Consortium for Colorectal Liver Metastasis.
Authors
Margonis GA, Amini N, Buettner S, Kim Y, Wang J, Andreatos N, Wagner D, Sasaki K, Beer A, Kamphues C, Morioka D, Løes IM, Imai K, He J, Pawlik TM, Kaczirek K, Poultsides G, Lønning PE, Burkhart R, Endo I, Baba H, Mischinger HJ, Aucejo FN, Kreis ME, Wolfgang CL, Weiss MJ