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Erschienen in: Annals of Surgical Oncology 4/2020

12.11.2019 | Hepatobiliary Tumors

KRAS Mutation Predicted More Mirometastases and Closer Resection Margins in Patients with Colorectal Cancer Liver Metastases

verfasst von: Qiongyan Zhang, MD, Junjie Peng, PhD, MD, Min Ye, MD, Weiwei Weng, PhD, MD, Cong Tan, MD, Shujuan Ni, PhD, MD, Dan Huang, PhD, MD, Weiqi Sheng, PhD, MD, Lei Wang, PhD, MD

Erschienen in: Annals of Surgical Oncology | Ausgabe 4/2020

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Abstract

Background

The presence of micrometastases is a source of recurrence after surgical resection of colorectal liver metastases (CRLM). The KRAS mutation is common in colorectal cancer, however the correlation between KRAS status and micrometastases has not been thoroughly clarified.

Methods

We enrolled a cohort of 251 consecutive CRLM patients who received complete liver surgery with known KRAS mutation status, and collected clinicopathological information, including micrometastases, margin status, preoperative chemotherapy, and liver recurrence-free survival (LRFS) and overall survival (OS) rates.

Results

KRAS-mutant (mutKRAS) patients had a higher incidence (60.3 vs. 40.8%; p = 0.002) and higher number of micrometastases [2.0 (range 0–38.0) vs. 0 (range 0–15.0); p < 0.001] than KRAS wild-type (wtKRAS) patients. The micrometastases in the mutKRAS group were more distant than those in the wtKRAS group [0.7 (range 0.1–9.0) vs. 0.6 (range 0.2–5.0) mm; p = 0.018). The mutKRAS group had more involved margin resections (21.5 vs. 9.2%; p = 0.07) and narrower margin widths [2.0 (range 0–40.0) vs. 4.3 (0–50.0) mm; p = 0.002] than the wtKRAS group. In addition, preoperative chemotherapy was associated with a lower rate of micrometastases in mutKRAS CRLM tumors (p < 0.05). mutKRAS status, positive margins, and micrometastases were all related to worse LRFS and OS (p < 0.05); however, micrometastases were not significantly correlated with OS in the multivariate analysis (p = 0.106).

Conclusions

mutKRAS patients had more micrometastases, increased R1 resections, and narrower margins. The presence of micrometastases may have led to the narrow margin width observed in these cases.
Literatur
1.
Zurück zum Zitat Chen W, Zheng R, Baade P, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.CrossRef Chen W, Zheng R, Baade P, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.CrossRef
2.
Zurück zum Zitat Van Cutsem E, Cervantes A, Nordlinger B, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25 Suppl 3:iii1–9.PubMed Van Cutsem E, Cervantes A, Nordlinger B, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25 Suppl 3:iii1–9.PubMed
3.
Zurück zum Zitat Viganò L, Russolillo N, Ferrero A, et al. Evolution of long-term outcome of liver resection for colorectal metastases: analysis of actual 5-year survival rates over two decades. Ann Surg Oncol. 2012;19:2035–44.CrossRef Viganò L, Russolillo N, Ferrero A, et al. Evolution of long-term outcome of liver resection for colorectal metastases: analysis of actual 5-year survival rates over two decades. Ann Surg Oncol. 2012;19:2035–44.CrossRef
4.
Zurück zum Zitat Creasy J, Sadot E, Koerkamp B, et al. Actual 10-year survival after hepatic resection of colorectal liver metastases: what factors preclude cure? Surgery 2018;163:1238–44.CrossRef Creasy J, Sadot E, Koerkamp B, et al. Actual 10-year survival after hepatic resection of colorectal liver metastases: what factors preclude cure? Surgery 2018;163:1238–44.CrossRef
5.
Zurück zum Zitat Hamady Z, Lodge J, Welsh F, et al. One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach. Ann Surg. 2014;259:543–8.CrossRef Hamady Z, Lodge J, Welsh F, et al. One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach. Ann Surg. 2014;259:543–8.CrossRef
6.
Zurück zum Zitat Wakai T, Shirai Y, Sakata J, et al. Appraisal of 1 cm hepatectomy margins for intrahepatic micrometastases in patients with colorectal carcinoma liver metastasis. Ann Surg Oncol. 2008;15:2472–81.CrossRef Wakai T, Shirai Y, Sakata J, et al. Appraisal of 1 cm hepatectomy margins for intrahepatic micrometastases in patients with colorectal carcinoma liver metastasis. Ann Surg Oncol. 2008;15:2472–81.CrossRef
7.
Zurück zum Zitat Margonis G, Sergentanis T, Ntanasis-Stathopoulos I, et al. Impact of surgical margin width on recurrence and overall survival following R0 hepatic resection of colorectal metastases: a systematic review and meta-analysis. Ann Surg. 2018;267:1047–55.CrossRef Margonis G, Sergentanis T, Ntanasis-Stathopoulos I, et al. Impact of surgical margin width on recurrence and overall survival following R0 hepatic resection of colorectal metastases: a systematic review and meta-analysis. Ann Surg. 2018;267:1047–55.CrossRef
8.
Zurück zum Zitat Yokoyama N, Shirai Y, Ajioka Y, et al. Immunohistochemically detected hepatic micrometastases predict a high risk of intrahepatic recurrence after resection of colorectal carcinoma liver metastases. Cancer 2002;94:1642–7.CrossRef Yokoyama N, Shirai Y, Ajioka Y, et al. Immunohistochemically detected hepatic micrometastases predict a high risk of intrahepatic recurrence after resection of colorectal carcinoma liver metastases. Cancer 2002;94:1642–7.CrossRef
9.
Zurück zum Zitat Wakai T, Shirai Y, Sakata J, et al. Histologic evaluation of intrahepatic micrometastases in patients treated with or without neoadjuvant chemotherapy for colorectal carcinoma liver metastasis. Int J Clin Exp Pathol. 2012;5:308–14.PubMedPubMedCentral Wakai T, Shirai Y, Sakata J, et al. Histologic evaluation of intrahepatic micrometastases in patients treated with or without neoadjuvant chemotherapy for colorectal carcinoma liver metastasis. Int J Clin Exp Pathol. 2012;5:308–14.PubMedPubMedCentral
10.
Zurück zum Zitat Nanko M, Shimada H, Yamaoka H, et al. Micrometastatic colorectal cancer lesions in the liver. Surg Today 1998;28:707–13.CrossRef Nanko M, Shimada H, Yamaoka H, et al. Micrometastatic colorectal cancer lesions in the liver. Surg Today 1998;28:707–13.CrossRef
11.
Zurück zum Zitat Karagkounis G, Torbenson M, Daniel H, et al. Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. Cancer. 2013;119:4137–44.CrossRef Karagkounis G, Torbenson M, Daniel H, et al. Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. Cancer. 2013;119:4137–44.CrossRef
12.
Zurück zum Zitat Okuno M, Goumard C, Kopetz S, et al. RAS mutation is associated with unsalvageable recurrence following hepatectomy for colorectal cancer liver metastases. Ann Surg Oncol. 2018;25:2457–66.CrossRef Okuno M, Goumard C, Kopetz S, et al. RAS mutation is associated with unsalvageable recurrence following hepatectomy for colorectal cancer liver metastases. Ann Surg Oncol. 2018;25:2457–66.CrossRef
13.
Zurück zum Zitat Taieb J, Zaanan A, Le Malicot K, et al. Prognostic effect of BRAF and KRAS mutations in patients with stage III colon cancer treated with leucovorin, fluorouracil, and oxaliplatin with or without cetuximab: a post hoc analysis of the PETACC-8 trial. JAMA Oncol. 2016;2(5):643–53.CrossRef Taieb J, Zaanan A, Le Malicot K, et al. Prognostic effect of BRAF and KRAS mutations in patients with stage III colon cancer treated with leucovorin, fluorouracil, and oxaliplatin with or without cetuximab: a post hoc analysis of the PETACC-8 trial. JAMA Oncol. 2016;2(5):643–53.CrossRef
14.
Zurück zum Zitat Odisio B, Yamashita S, Huang S, et al. Local tumour progression after percutaneous ablation of colorectal liver metastases according to RAS mutation status. Br J Surg. 2017;104:760–68.CrossRef Odisio B, Yamashita S, Huang S, et al. Local tumour progression after percutaneous ablation of colorectal liver metastases according to RAS mutation status. Br J Surg. 2017;104:760–68.CrossRef
15.
Zurück zum Zitat Zimmitti G, Shindoh J, Mise Y, et al. RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy before resection of colorectal liver metastases. Ann Surg Oncol. 2015;22:834–42.CrossRef Zimmitti G, Shindoh J, Mise Y, et al. RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy before resection of colorectal liver metastases. Ann Surg Oncol. 2015;22:834–42.CrossRef
16.
Zurück zum Zitat Brudvik K, Mise Y, Chung M, et al. RAS mutation predicts positive resection margins and narrower resection margins in patients undergoing resection of colorectal liver metastases. Ann Surg Oncol. 2016;23:2635–43.CrossRef Brudvik K, Mise Y, Chung M, et al. RAS mutation predicts positive resection margins and narrower resection margins in patients undergoing resection of colorectal liver metastases. Ann Surg Oncol. 2016;23:2635–43.CrossRef
17.
Zurück zum Zitat Adam R, de Gramont A, Figueras J, et al. Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus. Cancer Treat Rev. 2015;41:729–41.CrossRef Adam R, de Gramont A, Figueras J, et al. Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus. Cancer Treat Rev. 2015;41:729–41.CrossRef
18.
Zurück zum Zitat Nishioka Y, Shindoh J, Yoshioka R, et al. Clinical impact of preoperative chemotherapy on microscopic cancer spread surrounding colorectal liver metastases. Ann Surg Oncol. 2017;24:2326–333.CrossRef Nishioka Y, Shindoh J, Yoshioka R, et al. Clinical impact of preoperative chemotherapy on microscopic cancer spread surrounding colorectal liver metastases. Ann Surg Oncol. 2017;24:2326–333.CrossRef
19.
Zurück zum Zitat Sasaki K, Margonis GA, Wilson A, et al. Prognostic implication of KRAS status after hepatectomy for colorectal liver metastases varies according to primary colorectal tumor location. Ann Surg Oncol. 2016;23:3736–43.CrossRef Sasaki K, Margonis GA, Wilson A, et al. Prognostic implication of KRAS status after hepatectomy for colorectal liver metastases varies according to primary colorectal tumor location. Ann Surg Oncol. 2016;23:3736–43.CrossRef
20.
Zurück zum Zitat Oshi M, Margonis GA, Sawada Y, et al. Higher tumor burden neutralizes negative margin status in hepatectomy for colorectal cancer liver metastasis. Ann Surg Oncol. 2019;26(2):593–603.CrossRef Oshi M, Margonis GA, Sawada Y, et al. Higher tumor burden neutralizes negative margin status in hepatectomy for colorectal cancer liver metastasis. Ann Surg Oncol. 2019;26(2):593–603.CrossRef
21.
Zurück zum Zitat Viganò L, Capussotti L, De Rosa G, et al. Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival. Ann Surg. 2013;258:731–40 (discussion 741–2).CrossRef Viganò L, Capussotti L, De Rosa G, et al. Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival. Ann Surg. 2013;258:731–40 (discussion 741–2).CrossRef
22.
Zurück zum Zitat Dhir M, Lyden E, Wang A, et al. Influence of margins on overall survival after hepatic resection for colorectal metastasis: a meta-analysis. Ann Surg. 2011;254:234–42.CrossRef Dhir M, Lyden E, Wang A, et al. Influence of margins on overall survival after hepatic resection for colorectal metastasis: a meta-analysis. Ann Surg. 2011;254:234–42.CrossRef
23.
Zurück zum Zitat Are C, Gonen M, Zazzali K, et al. The impact of margins on outcome after hepatic resection for colorectal metastasis. Ann Surg. 2007;246:295–300.CrossRef Are C, Gonen M, Zazzali K, et al. The impact of margins on outcome after hepatic resection for colorectal metastasis. Ann Surg. 2007;246:295–300.CrossRef
24.
Zurück zum Zitat Sadot E, Groot Koerkamp B, Leal J, et al. Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate? Ann Surg. 2015;262:476–85 (discussion 483–5).CrossRef Sadot E, Groot Koerkamp B, Leal J, et al. Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate? Ann Surg. 2015;262:476–85 (discussion 483–5).CrossRef
25.
Zurück zum Zitat Holdhoff M, Schmidt K, Diehl F, et al. Detection of tumor DNA at the margins of colorectal cancer liver metastasis. Clin Cancer Res. 2011;17:3551–7.CrossRef Holdhoff M, Schmidt K, Diehl F, et al. Detection of tumor DNA at the margins of colorectal cancer liver metastasis. Clin Cancer Res. 2011;17:3551–7.CrossRef
26.
Zurück zum Zitat Vauthey J, Zimmitti G, Kopetz S, et al. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg. 2013;258:619–26 (discussion 626–7).CrossRef Vauthey J, Zimmitti G, Kopetz S, et al. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg. 2013;258:619–26 (discussion 626–7).CrossRef
27.
Zurück zum Zitat Løes I, Immervoll H, Sorbye H, et al. Impact of KRAS, BRAF, PIK3CA, TP53 status and intraindividual mutation heterogeneity on outcome after liver resection for colorectal cancer metastases. Int J Cancer. 2016;139:647–56.CrossRef Løes I, Immervoll H, Sorbye H, et al. Impact of KRAS, BRAF, PIK3CA, TP53 status and intraindividual mutation heterogeneity on outcome after liver resection for colorectal cancer metastases. Int J Cancer. 2016;139:647–56.CrossRef
28.
Zurück zum Zitat Margonis G, Sasaki K, Andreatos N, et al. KRAS mutation status dictates optimal surgical margin width in patients undergoing resection of colorectal liver metastases. Ann Surg Oncol. 2017;24:264–71.CrossRef Margonis G, Sasaki K, Andreatos N, et al. KRAS mutation status dictates optimal surgical margin width in patients undergoing resection of colorectal liver metastases. Ann Surg Oncol. 2017;24:264–71.CrossRef
29.
Zurück zum Zitat Lehmann K, Rickenbacher A, Weber A, et al. Chemotherapy before liver resection of colorectal metastases: friend or foe? Ann Surg. 2012;255:237–47.CrossRef Lehmann K, Rickenbacher A, Weber A, et al. Chemotherapy before liver resection of colorectal metastases: friend or foe? Ann Surg. 2012;255:237–47.CrossRef
30.
Zurück zum Zitat Shindoh J, Loyer E, Kopetz S, et al. Optimal morphologic response to preoperative chemotherapy: an alternate outcome end point before resection of hepatic colorectal metastases. J Clin Oncol. 2012;30:4566–72.CrossRef Shindoh J, Loyer E, Kopetz S, et al. Optimal morphologic response to preoperative chemotherapy: an alternate outcome end point before resection of hepatic colorectal metastases. J Clin Oncol. 2012;30:4566–72.CrossRef
31.
Zurück zum Zitat Folprecht G, Gruenberger T, Bechstein W, et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010;11:38–47.CrossRef Folprecht G, Gruenberger T, Bechstein W, et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010;11:38–47.CrossRef
32.
Zurück zum Zitat Andreou A, Aloia T, Brouquet A, et al. Margin status remains an important determinant of survival after surgical resection of colorectal liver metastases in the era of modern chemotherapy. Ann Surg. 2013;257:1079–88.CrossRef Andreou A, Aloia T, Brouquet A, et al. Margin status remains an important determinant of survival after surgical resection of colorectal liver metastases in the era of modern chemotherapy. Ann Surg. 2013;257:1079–88.CrossRef
Metadaten
Titel
KRAS Mutation Predicted More Mirometastases and Closer Resection Margins in Patients with Colorectal Cancer Liver Metastases
verfasst von
Qiongyan Zhang, MD
Junjie Peng, PhD, MD
Min Ye, MD
Weiwei Weng, PhD, MD
Cong Tan, MD
Shujuan Ni, PhD, MD
Dan Huang, PhD, MD
Weiqi Sheng, PhD, MD
Lei Wang, PhD, MD
Publikationsdatum
12.11.2019
Verlag
Springer International Publishing
Erschienen in
Annals of Surgical Oncology / Ausgabe 4/2020
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-08065-5

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