The Interplay of Primary Tumor Location and KRAS Mutation Status in Patients with Synchronous Colorectal Cancer Liver Me
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EDITORIAL – HEPATOBILIARY TUMORS
The Interplay of Primary Tumor Location and KRAS Mutation Status in Patients with Synchronous Colorectal Cancer Liver Metastases: Current Data and Unanswered Questions Georgios Antonios Margonis, MD, PhD1,3, Nikolaos Andreatos, MD2, Martin E. Kreis, MD3, and Michael D’Angelica, MD1 1
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; 2Department of Internal Medicine and Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH; 3Department of Surgery, Campus Benjamin Franklin, Charite´, University Medicine, Berlin, Germany
Primary tumor location (PTL) and KRAS mutation status are gradually gaining acceptance as useful surrogates of tumor biology and have an evolving role in the prognostication of patients who undergo hepatectomy for colorectal cancer liver metastases (CRLM). Although the association of each of these factors with prognosis has been repeatedly assessed, data on their interplay are far more limited, rendering the present work pertinent.1 The authors first analyzed survival outcomes according to PTL [rightsided (RS) vs. left-sided (LS)] and KRAS mutation status [mutant KRAS (mutKRAS) vs. wild-type KRAS (wtKRAS)] among 227 patients who underwent resection for synchronous CRLM between 2006 and 2015 at the Severance Hospital in Seoul; subsequently, the outcomes of patients belonging to the 4 subgroups defined by the combination of PTL and KRAS mutation status (namely RS/mutKRAS, RS/wtKRAS, LS/mutKRAS and LS/ wtKRAS) were independently considered.1 To our knowledge, this is the first study to examine the interplay of these factors in patients with synchronous CRLM who are traditionally thought to exhibit a more aggressive disease course compared to patients with metachronous tumors.2 However, given the lack of definitive proof that
Ó Society of Surgical Oncology 2020 First Received: 31 August 2020 Accepted: 3 September 2020 G. A. Margonis, MD, PhD e-mail: [email protected]
synchronous and metachronous disease are really distinct entities, it would perhaps have been more interesting to assess both of these subgroups simultaneously. The study confirmed that patients with RS primary tumors experience worse outcomes, a finding in line with prior reports and a recent comprehensive meta-analysis; nonetheless, these results may be partly dependent on length of follow-up as the prognostic effect of primary tumor location has been shown to diminish over time.3,4 On the other hand, while trends suggesting that the presence of KRAS mutations may be associated with inferior prognosis were noted, they failed to reach statistical significance. As the statistical power of the study was significantly limited and the effect of KRAS mutation status on outcomes is now thought to be rather modest, these results are not surprising.5 In fact, a number of reports similarly failed to confirm the prognostic impact of KRAS mutation status, igniting a controversy that was only resolved via larger, more adequately powered studies and pooled analyses.6–8 While KR
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