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Ann Surg. 2019 Aug 5. doi: 10.1097/SLA.0000000000003504. [Epub ahead of print]

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.

Author information

1
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
2
Department of Population Medicine, Harvard Pilgrim Health Care Institute and the Department of Dermatology, Massachusetts General Hospital, Boston: Massachusetts.
3
Department of General Surgery, Medical University of Graz, Graz, Austria.
4
Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio.
5
Department of General Surgery, Medical University of Vienna, Vienna, Austria.
6
Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany.
7
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
8
Department of Clinical Science, University of Bergen, and Department of Oncology, Haukeland University, Hospital, Bergen, Norway.
9
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
10
Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio.
11
Department of Surgery, Stanford University School of Medicine, Stanford, California.

Abstract

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.

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