The <i>RAS</i> mutation status predicts survival in patients undergoing hepatic resection for colorectal liver metastases: The results from a genetic analysis of all‐<i>RAS</i>

Amikura, Katsumi; Akagi, Kiwamu; Ogura, Toshiro; Takahashi, Akiko; Sakamoto, Hirohiko

doi:10.1002/jso.24910

Cited by 27 publications

(17 citation statements)

References 47 publications

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“…RAS mutations have consistently been found to be associated with more aggressive tumour biology and are identified in up to 45% of patients with metastatic CRC. For example, the studies published by Amikura et al[ 32 ] and Shindoh et al[ 54 ] both demonstrate that RAS mutational status is associated with significantly worse survival in CRCLM (Amikura et al[ 32 ]: 5-year OS: 42.4% vs 65.3%, P = 0.0006; Shindoh et al[ 54 ]: 3-year DFS 59.9 vs 83.6% P = 0.016). Of note, it has also been reported that among patients put forward for curative intent resection of CRCLMs, the incidence of RAS mutation is only around 10%-15%, indicating that underlying tumour biology, seemingly inseparably linked to PTL, exerts additional prognostic relevance as it appears to indirectly influence surgical candidacy[ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of primary tumour location on colorectal liver metastases: A systematic review

Bingham¹,

Shetye²,

Suresh³

et al. 2020

WJCO

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BACKGROUND Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide. Despite significant advances in screening, surgical management and adjuvant therapies, average 5-year survival seldom exceeds 60% in most developed nations. Metastatic disease represents the primary cause of mortality in patients with CRC, and the liver is the most common location for distant tumour spread. Up to 25% of patients are found to have synchronous liver metastases at the time of diagnosis and a further 30%-40% will develop metachronous disease in the course of follow-up. It has been suggested that primary tumour location [right side versus left side, primary tumour location (PTL)] can influence oncological outcomes in this patient group and that this should be considered in prognostic models and therapeutic decision-making algorithms. This suggestion is not universally accepted and there have been conflicting reports in the literature to date. AIM To provide a comprehensive summary of the available evidence regarding the impact of PTL on oncological outcomes in patients with colorectal cancer liver metastases (CRCLM). METHODS MEDLINE, EMBASE and COCHRANE were searched for relevant publications using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Data on oncological outcomes was then extracted from full text articles that met the predefined inclusion criteria. RESULTS A total of 41 studies were identified that met predefined inclusion criteria for this review. In 21 out of 38 studies that provided data on overall survival, a statistically significant improvement in overall survival was reported in patients with left sided primary tumours. These studies included a total of 13897 patients compared with 4306 patients in the studies that did not show a significant difference. Eight studies noted a similar trend towards improved disease-free or progression-free survival. Several authors observed distinct patterns of relapse after treatment of hepatic metastases according to PTL; for example hepatic recurrence after treatment of CRCLM appears to occur more aggressively with right-sided CRC. CONCLUSION Taken together, the findings of the present review indicate that PTL may have a role as an independent prognostic factor when determining treatment and disease surveillance strategies in CRC. The mechanisms responsible for this variation remain poorly understood, but are likely to relate to molecular, histological and embryological differences, as well as inherent differences in therapeutic sensitivity.

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Section: Discussionmentioning

confidence: 99%

Impact of primary tumour location on colorectal liver metastases: A systematic review

Bingham¹,

Shetye²,

Suresh³

et al. 2020

WJCO

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“…Adam et al 30 Umeda et al 31 Huang et al 32 Mavros et al 33 Viganò et al 34 Connor et al 35 Eefsen et al 36 Schirripa et al 37 Norén et al 38 Sasaki et al 20 Shindoh et al 39 Amikura et al 40 Creasy et al 22 Dupré et al 41 Liang et al 43 Rhu et al 44 Sultana et al 45 Wang et al 46 Yamashita et al 21 Yamashita et al 21 Goto et al 47 Berardi et al 48 Cremolini et al 49 Engstrand et al 50 Goffredo et al 51 lmai et al 52 Koch et al 53 Laengle et al 54 Ledys et al 55 Liao et al 56 Lionti et al 57 Loosen et al 58 Makowiec et al 59 Margonis et al 60 Marques et al 24 Oshi et al 61 Palkovics et al 62 Shigematsu et al 63 Vallance et al 64 Wang et al 23 Wang et al 65 Zheng et al 66 Prediction interval 0·1 0 ·5 1 2 10…”

Section: Fig 2 Forest Plots Showing Impact Of Primary Tumour Locatiomentioning

confidence: 99%

“…Partelli et al 29 Connor et al 35 Eefsen et al 36 Schirripa et al 37 Sasaki et al 20 Shindoh et al 39 Amikura et al 40 Creasy et al 22 Heise et al 42 Wang et al 46 Yamashita et al 21 Yamashita et al 21 Goto et al 47 Berardi et al 48 Cremolini et al 49 lmai et al 52 Laengle et al 54 Ledys et al 55 Lionti et al 57 Margonis et al 60 Marques et al 24 Oshi et al 61 Shigematsu et al 63 Wang et al 23 Zheng et al 66…”

Section: Referencementioning

confidence: 99%

Meta-analysis of the association between primary tumour location and prognosis after surgical resection of colorectal liver metastases

Wang

Zhang

Wang

et al. 2019

British Journal of Surgery

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Background Primary tumour location is emerging as an important prognostic factor in localized and metastatic colorectal cancers. However, its prognostic role in colorectal liver metastasis (CRLM) after hepatectomy remains controversial. A systematic review and meta‐analysis was undertaken to evaluate its prognostic value. Methods References were identified through searches of PubMed, Embase, Web of Science and the Cochrane Library comparing overall or disease‐free survival after hepatic resection between patients with CRLM originating from right‐ or left‐sided colorectal cancers. Data were pooled using hazard ratios (HRs) and 95 per cent confidence intervals according to a random‐effects model. Meta‐regression and subgroup analyses were conducted to assess the effect of underlying confounding factors on HR estimates and to adjust for this. Results The final analysis included 21 953 patients from 45 study cohorts. Compared with left‐sided primary tumour location, right‐sided location was associated with worse overall survival (HR 1·39, 95 per cent c.i. 1·28 to 1·51; P < 0·001; prediction interval 1·00 to 1·93), and also tended to have a negative impact on disease‐free survival (HR 1·18, 1·06 to 1·32; P = 0·004; prediction interval 0·79 to 1·75). Subgroup analysis showed that the negative effect of right‐sided primary tumour location on overall survival was more prominent in the non‐Asian population (HR 1·47, 1·33 to 1·62) than the Asian population (HR 1·18, 1·05 to 1·32) (P for interaction <0·01). Conclusion This study demonstrated a prognostic role for primary tumour location in patients with CRLM receiving hepatectomy, especially regarding overall survival. Adding primary tumour location may provide important optimization of prognosis prediction models for CRLM in current use.

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“…Currently, some molecular biologic markers are being used to guide therapy and prognostication in patients with CRLM. RAS mutations are found in 15-45% of colorectal cancer patients, and are associated with poor overall survival (OS) and recurrence-free survival (RFS) after liver resection 4 - 6 . A previous study found that the addition of RAS mutation status to create a modified clinical score (m-CS) could outperform the t-CS in predicting survival after resection of CRLM 7 .…”

Section: Introductionmentioning

confidence: 99%

Dynamic monitoring of circulating tumor DNA to predict prognosis and efficacy of adjuvant chemotherapy after resection of colorectal liver metastases

Wang¹,

Yang²,

Liu³

et al. 2021

Theranostics

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Rationale: Hepatectomy and adjuvant chemotherapy after resection of colorectal liver metastases (CRLM) may improve survival, however, patients which may benefit cannot currently be identified. Postoperative circulating tumor DNA (ctDNA) analysis can detect minimal residual disease (MRD) and predict the prognosis and efficacy of adjuvant chemotherapy. Our study aims to determine the impact of serial ctDNA analysis to predict the outcome among patients undergoing resection of CRLM. Methods: Between May 2018 and October 2019, 91 CRLM patients were prospectively enrolled. Whole exome sequencing was performed in 50 primary and 48 metastatic liver tissues. Targeted sequencing of 451 cancer relevant genes was performed in 50 baseline plasma to determine plasma-tissue concordance. We prospectively investigated changes in the amount and constitution of ctDNA in 271 serial plasma samples taken at different time points (baseline, pre-operation, post-operation, post-operative adjuvant chemotherapy (post-ACT) and recurrence) during the treatment of CRLM. Results: Detected molecular alterations were highly consistent among baseline ctDNA, primary and liver metastases tissue. Patients with a higher variant allele frequency (VAF) level at baseline ctDNA represent a higher tumor burden, and decreased ctDNA during pre-operative chemotherapy predicted better tumor response. Patients with detectable post-operative and post-ACT ctDNA were associated with significantly shorter recurrence-free survival (RFS). ROC analysis showed that post-ACT ctDNA status was superior to post-operative ctDNA status in predicting RFS with an AUROC of 0.79. A significant difference in overall recurrence rate was observed in patients with detectable vs undetectable levels of ctDNA after resection of CRLM (79.4% vs 41.7%) and after completion of adjuvant chemotherapy (77.3% vs 40.7%). During adjuvant chemotherapy, patients with decreased ctDNA VAF after adjuvant chemotherapy had a recurrence rate of 63.6%, compared to 92.3% in patients with increased ctDNA VAF. Conclusions: We envision that dynamic ctDNA analysis, especially in a post-ACT setting, might be used to not only reflect MRD but also to determine rational personalized adjuvant therapy after the resection of CRLM.

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The RAS mutation status predicts survival in patients undergoing hepatic resection for colorectal liver metastases: The results from a genetic analysis of all‐RAS

Abstract: Approximately half of CLM patients may have a RAS mutation. CLM patients with RAS mutations had a significantly worse survival rate in comparison to patients with RAS wild-type, regardless of the administration of anti-EGFR antibody therapy.

Cited by 27 publications

References 47 publications

Impact of primary tumour location on colorectal liver metastases: A systematic review

Impact of primary tumour location on colorectal liver metastases: A systematic review

Meta-analysis of the association between primary tumour location and prognosis after surgical resection of colorectal liver metastases

Dynamic monitoring of circulating tumor DNA to predict prognosis and efficacy of adjuvant chemotherapy after resection of colorectal liver metastases

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