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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 5/2012

Open Access 01-05-2012 | Hepatobiliary Tumors

Outcome of Microscopic Incomplete Resection (R1) of Colorectal Liver Metastases in the Era of Neoadjuvant Chemotherapy

Authors: Ninos Ayez, MD, Zarina S. Lalmahomed, MD, Alexander M. M. Eggermont, MD, PhD, Jan N. M. Ijzermans, MD, PhD, Jeroen de Jonge, MD, PhD, Kees van Montfort, PhD, Cornelis Verhoef, MD, PhD

Published in: Annals of Surgical Oncology | Issue 5/2012

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Abstract

Background

Data from patients with colorectal liver metastases (CRLM) who received neoadjuvant chemotherapy before resection were reviewed and evaluated to see whether neoadjuvant chemotherapy influences the predictive outcome of R1 resections (margin is 0 mm) in patients with CRLM.

Methods

Between January 2000 and December 2008, all consecutive patients undergoing liver resection for CRLM were analyzed. Patients were divided into those who did and did not receive neoadjuvant chemotherapy. The outcome after R0 (tumor-free margin >0 mm) and R1 (tumor-free margin 0 mm) resection was compared.

Results

A total of 264 were eligible for analysis. Median follow-up was 34 months. Patients without chemotherapy showed a significant difference in median disease-free survival (DFS) after R0 or R1 resection: 17 [95% confidence interval (CI) 10–24] months versus 8 (95% CI 4–12) months (P < 0.001), whereas in patients with neoadjuvant chemotherapy the difference in DFS between R0 and R1 resection was not significant: 18 (95% CI 10–26) months versus 9 (95% CI 0–20) months (P = 0.303). Patients without chemotherapy showed a significant difference in median overall survival (OS) after R0 or R1 resection: 53 (95% CI 40–66) months versus 30 (95% CI 13–47) months (P < 0.001). In patients with neoadjuvant chemotherapy, the median OS showed no significant difference: 65 (95% CI 39–92) months for the R0 group versus the R1 group, in whom the median OS was not reached (P = 0.645).

Conclusions

In patients treated with neoadjuvant chemotherapy, R1 resection was of no predictive value for DFS and OS.
Literature
1.
Bengmark S, Hafstrom L. The natural history of primary and secondary malignant tumors of the liver. I. The prognosis for patients with hepatic metastases from colonic and rectal carcinoma by laparotomy. Cancer. 1969;23:198–202.PubMedCrossRef
2.
Simmonds PC. Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group. BMJ. 2000;321(7260):531–5.PubMedCrossRef
3.
Seymour MT, Stenning SP, Cassidy J. Attitudes and practice in the management of metastatic colorectal cancer in Britain. Colorectal Cancer Working Party of the UK Medical Research Council. Clin Oncol (R Coll Radiol). 1997;9:248–51.CrossRef
4.
Adam R. Chemotherapy and surgery: new perspectives on the treatment of unresectable liver metastases. Ann Oncol. 2003;14(Suppl. 2):ii13–6.PubMed
5.
Scheele J, Stangl R, Altendorf-Hofmann A. Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg. 1990;77:1241–6.PubMedCrossRef
6.
Scheele J, Altendorf-Hofmann A. Resection of colorectal liver metastases. Langenbecks Arch Surg. 1999;384:313–27.PubMedCrossRef
7.
Adam R, Avisar E, Ariche A, et al. Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. Ann Surg Oncol. 2001;8:347–53.PubMedCrossRef
8.
Nordlinger B, Guiguet M, Vaillant JC, et al. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Francaise de Chirurgie. Cancer. 1996;77:1254–62.PubMedCrossRef
9.
Giacchetti S, Itzhaki M, Gruia G, et al. Long-term survival of patients with unresectable colorectal cancer liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery. Ann Oncol. 1999;10:663–9.PubMedCrossRef
10.
Nikfarjam M, Shereef S, Kimchi ET, et al. Survival outcomes of patients with colorectal liver metastases following hepatic resection or ablation in the era of effective chemotherapy. Ann Surg Oncol. 2009;16:1860–7.PubMedCrossRef
11.
Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230:309–18.PubMedCrossRef
12.
Iwatsuki S, Dvorchik I, Madariaga JR, et al. Hepatic resection for metastatic colorectal adenocarcinoma: a proposal of a prognostic scoring system. J Am Coll Surg. 1999;189:291–9.PubMedCrossRef
13.
Nagashima I, Takada T, Nagawa H, et al. Proposal of a new and simple staging system of colorectal liver metastasis. World J Gastroenterol. 2006;12:6961–5.PubMed
14.
Konopke R, Kersting S, Distler M, et al. Prognostic factors and evaluation of a clinical score for predicting survival after resection of colorectal liver metastases. Liver Int. 2009;29:89–102.PubMedCrossRef
15.
Rees M, Tekkis PP, Welsh FK, et al. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg. 2008;247:125–35.PubMedCrossRef
16.
Lise M, Bacchetti S, Da Pian P, et al. Patterns of recurrence after resection of colorectal liver metastases: prediction by models of outcome analysis. World J Surg. 2001;25:638–44.PubMedCrossRef
17.
Schindl M, Wigmore SJ, Currie EJ, et al. Prognostic scoring in colorectal cancer liver metastases: development and validation. Arch Surg. 2005;140:183–9.PubMedCrossRef
18.
Cady B, Jenkins RL, Steele GD, Jr., et al. Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome. Ann Surg. 1998;227:566–71.PubMedCrossRef
19.
Scheele J, Stang R, Altendorf-Hofmann A, et al. Resection of colorectal liver metastases. World J Surg. 1995;19:59–71.PubMedCrossRef
20.
Shirabe K, Takenaka K, Gion T, et al. Analysis of prognostic risk factors in hepatic resection for metastatic colorectal carcinoma with special reference to the surgical margin. Br J Surg. 1997;84:1077–80.PubMedCrossRef
21.
Pawlik TM, Scoggins CR, Zorzi D, et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg. 2005;241:715–22.PubMedCrossRef
22.
Figueras J, Burdio F, Ramos E, et al. Effect of subcentimeter nonpositive resection margin on hepatic recurrence in patients undergoing hepatectomy for colorectal liver metastases. Evidences from 663 liver resections. Ann Oncol. 2007;18:1190–5.PubMedCrossRef
23.
Elias D, Cavalcanti A, Sabourin JC, et al. Resection of liver metastases from colorectal cancer: the real impact of the surgical margin. Eur J Surg Oncol. 1998;24:174–9.PubMedCrossRef
24.
Elias D, Cavalcanti A, Sabourin JC, et al. Results of 136 curative hepatectomies with a safety margin of less than 10 mm for colorectal metastases. J Surg Oncol. 1998;69:88–93.PubMedCrossRef
25.
Bodingbauer M, Tamandl D, Schmid K, et al. Size of surgical margin does not influence recurrence rates after curative liver resection for colorectal cancer liver metastases. Br J Surg. 2007;94:1133–8.PubMedCrossRef
26.
de Haas RJ, Wicherts DA, Flores E, et al. R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg. 2008;248:626–37.PubMed
27.
Choti MA, Sitzmann JV, Tiburi MF, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg. 2002;235:759–66.PubMedCrossRef
28.
Nuzzo G, Giuliante F, Ardito F, et al. Influence of surgical margin on type of recurrence after liver resection for colorectal metastases: a single-center experience. Surgery. 2008;143:384–93.PubMedCrossRef
29.
Poultsides GA, Schulick RD, Pawlik TM. Hepatic resection for colorectal metastases: the impact of surgical margin status on outcome. HPB (Oxford). 2010;12:43–9.CrossRef
30.
Cady B, McDermott WV. Major hepatic resection for metachronous metastases from colon cancer. Ann Surg. 1985;201:204–9.PubMedCrossRef
31.
Ekberg H, Tranberg KG, Andersson R, et al. Determinants of survival in liver resection for colorectal secondaries. Br J Surg. 1986;73:727–31.PubMedCrossRef
32.
Pawlik TM, Vauthey JN. Surgical margins during hepatic surgery for colorectal liver metastases: complete resection not millimeters defines outcome. Ann Surg Oncol. 2008;15:677–9.PubMedCrossRef
33.
Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol. 1997;15:938–46.PubMed
34.
Petrelli NJ. Perioperative or adjuvant therapy for resectable colorectal hepatic metastases. J Clin Oncol. 2008;26:4862–3.PubMedCrossRef
35.
Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371(9617):1007–16.PubMedCrossRef
36.
Adam R, Bhangui P, Poston G, et al. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg. 2010;252:774–87.PubMedCrossRef
37.
Langer B, Bleiberg H, Labianca R, Shepherd L, Nitti D, Marsoni S, Tu D, Sargeant A-M, Fields A. Fluorouracil (FU) plus l-leucovorin (l-LV) versus observation after potentially curative resection of liver or lung metastases from colorectal cancer (CRC): results of the ENG (EORTC/NCIC CTG/GIVIO) randomized trial. Proc Am Soc Clin Oncol. 2002;21:592.
38.
O’Connell MJ, Adson MA, Schutt AJ, et al. Clinical trial of adjuvant chemotherapy after surgical resection of colorectal cancer metastatic to the liver. Mayo Clin Proc. 1985;60:517–20.PubMed
39.
Lopez-Ladron A, Salvador AJ, Bernabe R, Bernardos A, Arriola E, Serrano J, Reina JJ, Gomez MA, Barneto I, Moreno-Nogueira JA Observation versus postoperative chemotherapy after resection of liver metastases in patients with advanced colorectal cancer. Proc Am Soc Clin Oncol. 2003;22:1497.
40.
Portier G, Elias D, Bouche O, et al. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol. 2006;24:4976–82.PubMedCrossRef
41.
Mitry E, Fields AL, Bleiberg H, et al. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008;26:4906–11.PubMedCrossRef
42.
Taylor I. Adjuvant chemotherapy after resection of liver metastases from colorectal cancer. Eur J Cancer. 2008;44:1198–201.PubMedCrossRef
43.
Hou RM, Chu F, Zhao J, et al. The effects of surgical margin and edge cryotherapy after liver resection for colorectal cancer metastases. HPB (Oxford). 2007;9:201–7.CrossRef
44.
Yan TD, Padang R, Xia H, et al. Management of involved or close resection margins in 120 patients with colorectal liver metastases: edge cryotherapy can achieve long-term survival. Am J Surg. 2006;191:735–42.PubMedCrossRef
45.
Nanko M, Shimada H, Yamaoka H, et al. Micrometastatic colorectal cancer lesions in the liver. Surg Today. 1998;28:707–13.PubMedCrossRef
46.
Kokudo N, Miki Y, Sugai S, et al. Genetic and histological assessment of surgical margins in resected liver metastases from colorectal carcinoma: minimum surgical margins for successful resection. Arch Surg. 2002;137:833–40.PubMedCrossRef
47.
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.PubMedCrossRef
48.
Ng JK, Urbanski SJ, Mangat N, et al. Colorectal liver metastases contract centripetally with a response to chemotherapy: a histomorphologic study. Cancer. 2008;112:362–71.PubMedCrossRef
49.
Yamamoto J, Sugihara K, Kosuge T, et al. Pathologic support for limited hepatectomy in the treatment of liver metastases from colorectal cancer. Ann Surg. 1995;221:74–8.PubMedCrossRef
50.
Mentha G, Majno PE, Andres A, et al. Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary. Br J Surg. 2006;93:872–8.PubMedCrossRef
51.
Klinger M, Tamandl D, Eipeldauer S, et al. Bevacizumab improves pathological response of colorectal cancer liver metastases treated with XELOX/FOLFOX. Ann Surg Oncol. 2010;17:2059–65.PubMedCrossRef
52.
Burger JW, de Graaf EJ, Doornebosch PG, et al. Local excision of rectal cancer after chemoradiation: feasibility depends on the primary stage. Int J Colorectal Dis. 2010;25:1141–2.PubMedCrossRef
53.
Brouquet A, Abdalla EK, Kopetz S, et al. High survival rate after two-stage resection of advanced colorectal liver metastases: response-based selection and complete resection define outcome. J Clin Oncol. 2011;29:1083–90.PubMedCrossRef
54.
Benoist S, Brouquet A, Penna C, et al. Complete response of colorectal liver metastases after chemotherapy: does it mean cure? J Clin Oncol. 2006;24:3939–45.PubMedCrossRef
55.
Karoui M, Penna C, Amin-Hashem M, et al. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg. 2006;243:1–7.PubMedCrossRef
56.
Allen PJ, Kemeny N, Jarnagin W, et al. Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases. J Gastrointest Surg. 2003;7:109–15; discussion 116–7.PubMedCrossRef
57.
Hamady ZZ, Cameron IC, Wyatt J, et al. Resection margin in patients undergoing hepatectomy for colorectal liver metastasis: a critical appraisal of the 1 cm rule. Eur J Surg Oncol. 2006;32:557–63.PubMedCrossRef
58.
Okano K, Yamamoto J, Kosuge T, et al. Fibrous pseudocapsule of metastatic liver tumors from colorectal carcinoma. Clinicopathologic study of 152 first resection cases. Cancer. 2000;89:267–75.PubMedCrossRef
Metadata
Title
Outcome of Microscopic Incomplete Resection (R1) of Colorectal Liver Metastases in the Era of Neoadjuvant Chemotherapy
Authors
Ninos Ayez, MD
Zarina S. Lalmahomed, MD
Alexander M. M. Eggermont, MD, PhD
Jan N. M. Ijzermans, MD, PhD
Jeroen de Jonge, MD, PhD
Kees van Montfort, PhD
Cornelis Verhoef, MD, PhD
Publication date
01-05-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 5/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-2114-4

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