Top

World Journal of Surgical Oncology

Published in:

Open Access 01-12-2015 | Research

Predictive factors for time to recurrence, treatment and post-recurrence survival in patients with initially resected colorectal liver metastases

Authors: Jon-Helge Angelsen, Asgaut Viste, Inger Marie Løes, Geir Egil Eide, Dag Hoem, Halfdan Sorbye, Arild Horn

Published in: World Journal of Surgical Oncology | Issue 1/2015

Abstract

Background

Despite progress in resection for colorectal liver metastases (CLM), the majority of patients experience recurrence. We aimed to evaluate factors influencing time to recurrence (TTR), treatment and post-recurrence survival (PRS) related to site of recurrence.

Methods

This is a retrospective population-based cohort study (1998–2012) of consecutive patients without extrahepatic disease treated with resection for CLM in a referral centre.

Results

A total of 311 patients underwent resection for CLM. After a median follow-up of 4.2 years (range 1.2–15.2), 209 (67.4 %) patients developed recurrence, hepatic 90, extrahepatic 59 and both 60. Median TTR was 14.0 months, and 5-year recurrence-free status was 25.7 %. Five- and 10-year overall survival (OS) was 38.8 and 22.0 %, respectively. Median OS was 45 months. A multivariate analysis displayed synchronous disease (hazard ratio (HR) 1.50), American Society of Anaesthesiologists (ASA) score (HR 1.40), increasing number (HR 1.24) and size of metastases (HR 1.08) to shorten TTR (all p < 0.05). Perioperative chemotherapy (n = 59) increased overall TTR (HR 0.63) and overall survival (OS; HR 0.55). Hepatic TTR was correlated to synchronous disease (HR 2.07), number of lesions (HR 1.20), R1 resection (HR 2.00) and ASA score (HR 1.69), whereas extrahepatic TTR was correlated to N stage of the primary (HR 1.79), number (HR 1.27) and size of metastases (HR 1.16). Single-site recurrence was most common (135 of 209, 64.5 %), while 58 patients had double- and 16 triple-site relapses. Median PRS was 24.3 months. There was a difference in median PRS (months) according to site of relapse: liver 30.5, lung 32.3, abdominal 22.0, liver and lung 14.3, others 14.8 (p = 0.002). Repeated liver resections were performed in n = 57 patients resulting in 40.6 months median OS and 36.8 % 5-year OS.

Conclusions

An adverse overall TTR was correlated to number and size of metastases, ASA score and synchronous disease. Perioperative chemotherapy increased TTR and OS after surgery for CLM. Patients with solitary post-resection relapse in the liver or lungs had the potential for longevity due to multimodal treatment.

Dunne DF, Yip VS, Jones RP, McChesney EA, Lythgoe DT, Psarelli EE, et al. Enhanced recovery in the resection of colorectal liver metastases. J Surg Oncol. 2014;110:197.CrossRefPubMed

Adam R, Bhangui P, Poston G, Mirza D, Nuzzo G, Barroso E, et al. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg. 2010;252:774–85.CrossRefPubMed

Wei AC, Greig PD, Grant D, Taylor B, Langer B, Gallinger S. Survival after hepatic resection for colorectal metastases: a 10-year experience. Ann Surg Oncol. 2006;13:668–76.CrossRefPubMed

Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy—a model to predict long-term survival. Ann Surg. 2004;240:644–57.PubMedCentralCrossRefPubMed

Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, 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;371:1007–16.PubMedCentralCrossRefPubMed

Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, 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.CrossRefPubMed

de Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Schulick RD, et al. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250:440–8.PubMed

Pawlik TM, Scoggins CR, Zorzi D, Abdalla EK, Andres A, Eng C, et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg. 2005;241:715–24.PubMedCentralCrossRefPubMed

D’Angelica M, Kornprat P, Gonen M, DeMatteo RP, Fong Y, Blumgart LH, et al. Effect on outcome of recurrence patterns after hepatectomy for colorectal metastases. Ann Surg Oncol. 2011;18:1096–103.CrossRefPubMed

10.

Mise Y, Imamura H, Hashimoto T, Seyama Y, Aoki T, Hasegawa K, et al. Cohort study of the survival benefit of resection for recurrent hepatic and/or pulmonary metastases after primary hepatectomy for colorectal metastases. Ann Surg. 2010;251:902–9.CrossRefPubMed

11.

Assumpcao L, Choti MA, Gleisner AL, Schulick RD, Swartz M, Herman J, et al. Patterns of recurrence following liver resection for colorectal metastases: effect of primary rectal tumor site. Arch Surg. 2008;143:743–9. discussion 749–750.PubMedCentralCrossRefPubMed

12.

Adair RA, Young AL, Cockbain AJ, Malde D, Prasad KR, Lodge JP, et al. Repeat hepatic resection for colorectal liver metastases. Br J Surg. 2012;99:1278–83.CrossRefPubMed

13.

Kulik U, Bektas H, Klempnauer J, Lehner F. Repeat liver resection for colorectal metastases. Br J Surg. 2013;100:926–32.CrossRefPubMed

14.

Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–37.CrossRefPubMed

15.

Glimelius B, Sorbye H, Balteskard L, Bystrom P, Pfeiffer P, Tveit K, et al. A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer. Ann Oncol. 2008;19:909–14.CrossRefPubMed

16.

Ruers T, Punt C, Van Coevorden F, Pierie JP, Borel-Rinkes I, Ledermann JA, et al. Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol. 2012;23:2619–26.PubMedCentralCrossRefPubMed

17.

Nozawa H, Sunami E, Nakajima J, Nagawa H, Kitayama J. Synchronous and metachronous lung metastases in patients with colorectal cancer: a 20-year monocentric experience. Exp Ther Med. 2012;3:449–56.PubMedCentralPubMed

18.

Clavien PA, Sanabria JR, Strasberg SM. Proposed classification of complications of surgery with examples of utility in cholecystectomy. Surgery. 1992;111:518–26.PubMed

19.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed

20.

Sorbye H, Glimelius B, Berglund A, Fokstuen T, Tveit KM, Braendengen M, et al. Multicenter phase II study of Nordic fluorouracil and folinic acid bolus schedule combined with oxaliplatin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2004;22:31–8.CrossRefPubMed

21.

Punt CJA, Buyse M, Kohne C-H, Hohenberger P, Labianca R, Schmoll HJ, et al. Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials. J Natl Cancer Inst. 2007;99:998.CrossRefPubMed

22.

Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer—analysis of 1001 consecutive cases. Ann Surg. 1999;230:309–18.PubMedCentralCrossRefPubMed

23.

Kaplan EL, Meier P. Nonparametric-estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.CrossRef

24.

Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966;50:163–70.PubMed

25.

Cox DR. Regression models and life-tables. J R Stat Society Ser B-Stat Methodol. 1972;34:187.

26.

Angelsen JH, Horn A, Eide GE, Viste A. Surgery for colorectal liver metastases: the impact of resection margins on recurrence and overall survival. World J Surg Oncol. 2014;12:127.PubMedCentralCrossRefPubMed

27.

Sahani DV, Kalva SP, Fischman AJ, Kadavigere R, Blake M, Hahn PF, et al. Detection of liver metastases from adenocarcinoma of the colon and pancreas: comparison of mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET. AJR Am J Roentgenol. 2005;185:239–46.CrossRefPubMed

28.

Ward J, Robinson PJ, Guthrie JA, Downing S, Wilson D, Lodge JP, et al. Liver metastases in candidates for hepatic resection: comparison of helical CT and gadolinium- and SPIO-enhanced MR imaging. Radiology. 2005;237:170–80.CrossRefPubMed

29.

Sahani DV, Bajwa MA, Andrabi Y, Bajpai S, Cusack JC. Current status of imaging and emerging techniques to evaluate liver metastases from colorectal carcinoma. Ann Surg. 2014;259:861–72.CrossRefPubMed

30.

Auer RC, White RR, Kemeny NE, Schwartz LH, Shia J, Blumgart LH, et al. Predictors of a true complete response among disappearing liver metastases from colorectal cancer after chemotherapy. Cancer. 2010;116:1502–9.CrossRefPubMed

31.

Lee H, Choi DW, Cho YB, Yun SH, Kim HC, Lee WY, et al. Recurrence pattern depends on the location of colon cancer in the patients with synchronous colorectal liver metastasis. Ann Surg Oncol. 2014;21:1641–6.CrossRefPubMed

32.

Nigri G, Petrucciani N, Ferla F, La Torre M, Aurello P, Ramacciato G. Neoadjuvant chemotherapy for resectable colorectal liver metastases: what is the evidence? Results of a systematic review of comparative studies. Surgeon. 2015;13:83.CrossRefPubMed

33.

Sorbye H, Mauer M, Gruenberger T, Glimelius B, Poston GJ, Schlag PM, et al. Predictive factors for the benefit of perioperative FOLFOX for resectable liver metastasis in colorectal cancer patients (EORTC Intergroup Trial 40983). Ann Surg. 2012;255:534.CrossRefPubMed

34.

Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14:1208–15.CrossRefPubMed

35.

Sorbye H. Recurrence patterns after resection of liver metastases from colorectal cancer. Recent Results Cancer Res. 2014;203:243–52.CrossRefPubMed

36.

Ng JKS, Urbanski SJ, Mangat N, McKay A, Sutherland FR, Dixon E, et al. Colorectal liver metastases contract centripetally with a response to chemotherapy—a histomorphologic study. Cancer. 2008;112:362–71.CrossRefPubMed

37.

Zhu D, Zhong Y, Wei Y, Ye L, Lin Q, Ren L, et al. Effect of neoadjuvant chemotherapy in patients with resectable colorectal liver metastases. PLoS One. 2014;9:e86543.PubMedCentralCrossRefPubMed

38.

Scoggins CR, Campbell ML, Landry CS, Slomiany BA, Woodall CE, McMasters KM, et al. Preoperative chemotherapy does not increase morbidity or mortality of hepatic resection for colorectal cancer metastases. Ann Surg Oncol. 2009;16:35–41.CrossRefPubMed

39.

Adam R, Pascal G, Castaing D, Azoulay D, Delvart V, Paule B, et al. Tumor progression while on chemotherapy—a contraindication to liver resection for multiple colorectal metastases? Ann Surg. 2004;240:1052–64.PubMedCentralCrossRefPubMed

40.

Wicherts DA, de Haas RJ, Salloum C, Andreani P, Pascal G, Sotirov D, et al. Repeat hepatectomy for recurrent colorectal metastases. Br J Surg. 2013;100:808–18.CrossRefPubMed

41.

Hwang M, Jayakrishnan TT, Green DE, George B, Thomas JP, Groeschl RT, et al. Systematic review of outcomes of patients undergoing resection for colorectal liver metastases in the setting of extra hepatic disease. Eur J Cancer. 2014;50:1747–57.CrossRefPubMed

Title: Predictive factors for time to recurrence, treatment and post-recurrence survival in patients with initially resected colorectal liver metastases
Authors: Jon-Helge Angelsen
Asgaut Viste
Inger Marie Løes
Geir Egil Eide
Dag Hoem
Halfdan Sorbye
Arild Horn
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2015
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/s12957-015-0738-8

At a glance: The STEP trials

Springer Medicine

Predictive factors for time to recurrence, treatment and post-recurrence survival in patients with initially resected colorectal liver metastases

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2015

The role of 18F-FDG uptake features in the differential diagnosis of solitary pulmonary lesions with PET/CT

Primary anorectal malignant melanoma: a rare but aggressive tumor: report of a case

Chemoresponse after non-curative gastrectomy for M1 gastric cancer

Clinicopathological characteristics, diagnosis, treatment, and outcomes of primary gastric adenosquamous carcinoma

Unexpected esophageal diseases appeared in thyroid resections

Postoperative recurrence of desmoid tumors: clinical and pathological perspectives