Tumor Biology Rather Than Surgical Technique Dictates Prognosis in Colorectal Cancer Liver Metastases

Margonis, Georgios Antonios; Sasaki, Kazunari; Kim, Yuhree; Samaha, Mario; Buettner, Stefan; Amini, Neda; Antoniou, Efstathios; Pawlik, Timothy M.

doi:10.1007/s11605-016-3198-8

Cited by 64 publications

(58 citation statements)

References 44 publications

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“…will help to enhance the comparative studies of our data. KRAS mutations have been shown to be associated with a worse survival after resection of CRLM in a preliminary report, in particular, also in ALPPS [73, 74]. A finding like this will sharpen our selection criteria and help to avoid most probably futile and high-risk surgery.…”

mentioning

confidence: 89%

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy in the Treatment of Colorectal Liver Metastases: Current Scenario

Lang¹,

Baumgart²,

Mittler³

2018

Dig Surg

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Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has expanded the surgical armamentarium for patients with advanced and bilateral colorectal liver metastases. However, the enthusiasm that the medical fraternity had about ALPPS was hampered by a high mortality rate and early and frequent tumor recurrence. While surgical safety has improved, mainly due to technical refinements and a better patient selection, the oncological value in the face of early tumor recurrence remains unclear. The only randomized controlled trial on ALPPS versus two-stage hepatectomy (TSH) so far confirmed that ALPPS led to higher resectability with comparable perioperative complication rate, but oncological outcome was not measured. Robust data regarding long-term outcome are still missing. TSH and ALPPS might be complementary strategies for the resection of colorectal liver metatsases (CRLM) with ALPPS being reserved for patients with no other surgical option, that is, after failed portal vein embolization or those with an extremely small future liver remnant. In other words, ALPPS can be considered a supplementary tool and a last resort in the liver surgeon’s hand to offer resectability in otherwise nonresectable CRLM. In these individual cases, and always embedded into a multimodal treatment setting, ALPPS may offer a chance of complete tumor removal and prolonged survival and even a chance for cure.

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mentioning

confidence: 89%

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy in the Treatment of Colorectal Liver Metastases: Current Scenario

Lang¹,

Baumgart²,

Mittler³

2018

Dig Surg

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“…The KRAS activating mutations are present in 35-45% of patients with CRLM and have been associated with poor survival, poor radiologic/pathologic responses to chemotherapy, and high rates of margin-positive resections [11,19,20]. In our series, patients with MT-KRAS had a median OS of 15.3 months, compared to 38.3 months for those with WT-KRAS.…”

Section: Discussionmentioning

confidence: 60%

The ALPPS Approach for Colorectal Liver Metastases: Impact of KRAS Mutation Status in Survival

Serenari

Alvarez²,

Ardiles³

et al. 2017

Dig Surg

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Background/Aims: Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations influence survival after hepatectomy for colorectal liver metastases (CRLM). However, their prognostic significance has never been evaluated in patients who undergo Associating Liver Partition and Portal vein occlusion for Staged hepatectomy (ALPPS). Methods: Between June 2011 and March 2016, 26 patients underwent ALPPS for CRLM. Complications were classified according to the Clavien-Dindo classification. Bi- and multivariate cox analyses were performed to evaluate variables potentially associated with survival. Results: Overall, morbidity grade ≥3a and 90-day mortality were 38.5 and 0%, respectively. The median follow-up from the time of discharge was 21.5 months (interquartile range 9.6-35.6). One- and 3-year overall survival (OS) was 83.4 and 48.9%, respectively. Patients with mutated (MT) KRAS had a median OS of 15.3 vs. 38.3 months for those with wild-type (WT) KRAS (p < 0.0001). Median disease-free survival was 7.9, 5.6 vs. 12.3 months for MT and WT KRAS, respectively (p = 0.023). KRAS mutation was found to be an independent risk factor for OS (hazard ratio 7.15, 95% CI 1.50-34.11; p = 0.014). Conclusion: KRAS mutation is an independent predictor of poor survival after ALPPS. This finding will help to optimize patient selection, both avoiding futile surgical indication and maximizing the benefit for patients with extensive disease who are otherwise subjected to high-risk aggressive surgery.

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“…Factors that are associated with aggressive or advanced tumor biology ( e.g ., bilobar disease, multiple metastasis, large metastasis, and metastasis in difficult locations) are also associated with technically complex cases and are as such being at higher risk for a potential R1 resection. These data therefor suggests that it is the cancer biology, and not the R1 resection, that is related to worse survival[17]. Similar results were showed in a study were recurrence-free and OS were examined after treatment for CRLM with liver resection followed by adjuvant hepatic arterial infusion and chemotherapy.…”

Section: Role Of Kras In Resected Crlmmentioning

confidence: 55%

“…It seems that there is a higher rate of KRAS mutation in patients with extrahepatic metastasis and non-resectable CRLM[12,14], that there is a higher risk of subsequent recurrence in all sites (brain, bone, liver and lungs) for patients with KRAS mutations[15,16] and, that KRAS mutation in patients with resectable CRLM suggests a more aggressive disease with shorter progression free and OS[12]. Indeed, as shown[17], the difference in survival after liver resection was attributed to having either wild type KRAS or mutant KRAS , rather than achieving an R0 or R1 situation. This emphasizes the role of inherent cancer biology rather than resection margins.…”

Section: Role Of Kras In Resected Crlmmentioning

confidence: 99%

Can molecular biomarkers replace a clinical risk score for resectable colorectal liver metastasis?

Veen

Søreide

2017

WJGO

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In resectable colorectal liver metastasis (CRLM) the role and use of molecular biomarkers is still controversial. Several biomarkers have been linked to clinical outcomes in CRLM, but none have so far become routine for clinical decision making. For several reasons, the clinical risk score appears to no longer hold the same predictive value. Some of the reasons include the ever expanding indications for liver resection, which now increasingly tend to involve extrahepatic disease, such as lung metastases (both resectable and non-resectable) and the shift in indication from “what is taken out” (e.g., how much liver has to be resected) to “what is left behind” (that is, how much functional liver tissue the patient has after resection). The latter is amenable to modifications by using adjunct techniques of portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy techniques to expand indications for liver resection. Added to this complexity is the increasing number of molecular markers, which appear to hold important prognostic and predictive information, for which some will be discussed here. Beyond characteristics of tissue-based genomic profiles will be liquid biopsies derived from circulating tumor cells and cell-free circulating tumor DNA in the blood. These markers are present in the peripheral circulation in the majority of patients with metastatic cancer disease. Circulating biomarkers may represent more readily available methods to monitor, characterize and predict cancer biology with future implications for cancer care.

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Tumor Biology Rather Than Surgical Technique Dictates Prognosis in Colorectal Cancer Liver Metastases

Abstract: The impact of margin status differed by KRAS mutation status. An R0 margin only provided a survival benefit to patients with wtKRAS tumors. Tumor biology and not surgical technique determined prognosis.

Cited by 64 publications

References 44 publications

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy in the Treatment of Colorectal Liver Metastases: Current Scenario

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy in the Treatment of Colorectal Liver Metastases: Current Scenario

The ALPPS Approach for Colorectal Liver Metastases: Impact of KRAS Mutation Status in Survival

Can molecular biomarkers replace a clinical risk score for resectable colorectal liver metastasis?

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