KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases

Margonis, Georgios Antonios; Sasaki, Kazunari; Andreatos, Nikolaos; Kim, Yuhree; Merath, Katiuscha; Wagner, Doris; Wilson, Ana; Buettner, Stefan; Amini, Neda; Antoniou, Efstathios; Pawlik, Timothy M.

doi:10.1245/s10434-016-5609-1

Cited by 75 publications

(65 citation statements)

References 34 publications

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“…As such, it is possible that patients with 4 or more lesions have such aggressive underlying disease biology that technical considerations (use of combined resection and RFA vs. resection alone) have a comparably minor impact on outcomes. Similarly, previous studies from our group and others have shown that the technical adequacy of a resection as measured by the achievement of negative surgical margins has no measurable impact on outcomes among high-risk patients with aggressive disease biology (24,25). However, surgeons should still strive for an R0 resection when technically feasible, as the present study lacks the statistical power to conclusively prove the equivalence of combined resection and RFA vs. hepatic resection alone (26).…”

Section: Discussionmentioning

confidence: 50%

Combined Hepatic Resection and Radio-frequency Ablation for Patients with Colorectal Cancer Liver Metastasis: A Viable Option for Patients with a Large Number of Tumors

et al. 2018

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Background/Aim: Radiofrequency ablation (RFA) is thought to result in inferior prognosis than hepatic resection among patients with colorectal liver metastasis (CRLM). However, resection plus RFA may be an option for patients with a large number of tumors (≥4 liver lesions) and borderline resectability. Materials and Methods: A total of 717 patients with CRLM who underwent hepatic resection +/-RFA at two tertiary institutions between 09/01/2000-12/01/2015 were eligible for inclusion in this study. Results: Among patients with <4 lesions (n=568), OS in the resection + RFA group (n=48) was significantly worse than in the resection alone group (n=520) (5-year OS: 34.4 % versus 58.9%, p=0.007). Conversely, in patients with ≥4 lesions, OS in the resection + RFA (n=68) and resection alone(n=81) groups were not significantly different (5-year OS: 31.9% versus 34.1%, p=0.48). In patients with <4 lesions, carcinoembryonic antigen (CEA) ≥30 ng/ml, extrahepatic metastasis, preoperative chemotherapy and resection + RFA were independently associated with poor prognosis. Interestingly, in patients with ≥4 lesions, positive primary lymph nodes, KRAS mutation, CEA ≥30 ng/ml and extrahepatic metastasis were independent predictors of poor prognosis; however, the combination of hepatic resection with RFA was not associated with worse survival (p=0.93). Conclusion: Although surgeons should always strive for R0 resection when feasible, combined resection and RFA may be a viable alternative for CRLM patients with a large number of tumors. Currently, the principal treatment strategy for patients with colorectal cancer liver metastasis (CRLM) is systemic chemotherapy, while hepatic resection can further improve survival in carefully selected patients (1-5). On the contrary, many reports concur that radio-frequency ablation (RFA) results in inferior outcomes than hepatic resection in patients with CRLM and should only be employed when surgical resection cannot be performed (6-9). Nonetheless, the presence of extensive metastatic tumor number in the liver, (especially four or more lesions) often precludes a curative hepatic resection due to either technical challenges or inadequate remnant liver function and is a wellknown poor prognostic factor (4, 5, 10-12). In fact, historically, specifically ≥4 CRLM, was considered to be a contraindication for liver resection (13, 14). Similarly, a study on a contemporary cohort (treated after 2005) demonstrated that the prognosis of patients with ≥4 CRLM who undergo surgery has not improved despite the development of modern chemotherapies (14). Interestingly, our group and others have demonstrated that hepatectomy + RFA may achieve long-term outcomes that are comparable to hepatectomy alone (15, 16). Nonetheless, the impact of combined resection and RFA on survival among patients with different levels of tumor number 6353 This article is freely accessible online.

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Section: Discussionmentioning

confidence: 50%

Combined Hepatic Resection and Radio-frequency Ablation for Patients with Colorectal Cancer Liver Metastasis: A Viable Option for Patients with a Large Number of Tumors

et al. 2018

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“…The current evidence showed that a margin clearance of 1-4 mm is associated with improved survival compared to R1 only for wild-type KRAS tumors (14). In cases of mutated KRAS tumors were observed no differences between R1 resections or a clearance margin of 1-4, 5-9, or ≥ 10 mm (14). As a strategy for resection, the parenchymal-sparing hepatectomy can be performed safely without compromising oncological outcomes, even for deep-placed or advanced (≥ four lesions with a diameter ≤50 mm) CRLMs (15,16).…”

Section: Discussion Discussionmentioning

confidence: 65%

“…Historically, a 1-cm resection margin was considered associated with better outcomes following CRLMs resection (13). The current evidence showed that a margin clearance of 1-4 mm is associated with improved survival compared to R1 only for wild-type KRAS tumors (14). In cases of mutated KRAS tumors were observed no differences between R1 resections or a clearance margin of 1-4, 5-9, or ≥ 10 mm (14).…”

Section: Discussion Discussionmentioning

confidence: 80%

Right Hemihepatectomy for Colon Cancer Metachronous Liver Metastasis in a Patient with Crohn\'s Disease: Case Report and Review of the Literature

Negoi¹,

Runcanu²,

Păun³

et al. 2016

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A 53-year old female patient was admitted to our hospital for a colon cancer metachronous liver metastasis. The patient was diagnosed for more than ten years with colonic Crohn's disease and ankylosing spondylitis. She had a Hartmann's type resection for sigmoid colon adenocarcinoma four years ago, and a secondary resection of the transverse colon with a right transverse colostomy for colonic stenosis one month before current admission. Abdominal Computed Tomography revealed a liver metastasis of 10/11 cm located in segments 6, 7, 8, in close contact with the right and middle hepatic veins and right Glissonian pedicle. A right hemihepatectomy was performed, using Pringle maneuver for 30 minutes. The patient was discharged after 12 days, without additional morbidities. Patients with liver metastases of colorectal origin in the presence of Crohn's disease come with significant clinical challenges. Inside the multimodality approach, liver resection represents the therapeutic approach associated with the best long-term oncological results.

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“…While a 1-4 mm margin clearance in patients with wtKRAS tumors was associated with improved survival, wider resection width did not confer an additional survival benefit. In contrast, margin status, including a 1 cm margin, did not improve survival among patients with mutKRAS tumours (29).…”

Section: R0: Which Resection Margin Width?mentioning

confidence: 71%

The Impact of Resection Margins on the Overall and Disease-free Survival of Hepatic Colorectal Metastases

Zanghì

Cavallaro

Mongiovì

et al. 2018

SGO

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Background: Liver resection for colorectal liver metastasis (CRLM) represents a valid therapeutic option. It can offer a chance of good long-term survival, with a 5 year survival of 25-40%. Recent studies have shown that achieving a minimum of 1 cm surgical margin is not essential for long-term survival, and a microscopic free liver resection margin can be sufficient. The aim of this study is to evaluate the impact of the resection margin on recurrence, disease free survival and the overall survival. Materials and Method: All the primary liver resections with curative intention for CRLM at our surgical division between 2000 and 2010 were retrospectively reviewed. The liver resection margins were stratified according to their width. The positive and negative prognostic factors were analyzed in a univariate analysis. Results: A total of 130 patients met the study inclusion criteria. Twenty-four patients underwent major hepatectomies, while 106 patients underwent minor hepatectomies. On statistical analysis, surgical margin width (p=0.045), advanced age (p<0.001), metachronous metastasis (p=0.018) and multiple tumours (p=0.019) were associated with lower long-term survival rates. In addition, advanced age (p=0.0004), rectal tumour (p=0.004), metachronous metastases (p=0.026), multiple tumours (p=0.017), lower width in surgical margin (p=0.002) were linked to a reduced disease-free survival. Conclusion: Our study confirms that the extent of the resection margin is a powerful factor influencing prognosis after hepatectomy for CRLM. According to our experience, resection margin width is significantly associated with a higher risk of intra and extra-hepatic recurrence and less disease-free survival. However, the impossibility of achieving a resection margin greater than or equal to 10 mm should not be considered as a contraindication to surgery.

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KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases

Abstract: While a 1-4 mm margin clearance in patients with wtKRAS tumors was associated with improved survival, wider resection width did not confer an additional survival benefit. In contrast, margin status-including a 1 cm margin-did not improve survival among patients with mutKRAS tumors.

Cited by 75 publications

References 34 publications

Combined Hepatic Resection and Radio-frequency Ablation for Patients with Colorectal Cancer Liver Metastasis: A Viable Option for Patients with a Large Number of Tumors

Combined Hepatic Resection and Radio-frequency Ablation for Patients with Colorectal Cancer Liver Metastasis: A Viable Option for Patients with a Large Number of Tumors

Right Hemihepatectomy for Colon Cancer Metachronous Liver Metastasis in a Patient with Crohn\'s Disease: Case Report and Review of the Literature

The Impact of Resection Margins on the Overall and Disease-free Survival of Hepatic Colorectal Metastases

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