Adjuvant therapy after resection of colorectal liver metastases: the predictive value of the MSKCC clinical risk score in the era of modern chemotherapy

BMC Cancer

Moritz Koch¹  Jürgen Weitz¹  Markus W Büchler³  Dirk Jäger²  Henning Schulze-Bergkamen²  Christoph Reissfelder¹  Nuh N Rahbari¹ 

[1]Department of Visceral-, Thoracic and Vascular Surgery University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstr. 74, D-01307 Dresden, Germany

[2]Department of Medical Oncology, National Center of Tumor Diseases, University of Heidelberg, Heidelberg, Germany

[3]Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

关键词: Liver resection;    Leucovorin;    5-FU;    FOLFIRI;    FOLFOX;    Colorectal cancer;   

Others  :  858982
DOI  :  10.1186/1471-2407-14-174

 received in 2013-08-03, accepted in 2014-02-19,  发布年份 2014

【 摘 要 】

Background

Despite introduction of effective chemotherapy protocols, it has remained uncertain, if patients with colorectal cancer (CRC) liver metastases should receive adjuvant therapy. Clinical or molecular predictors may help to select patients at high risk for disease recurrence and death who obtain a survival advantage by adjuvant chemotherapy.

Methods

A total of 297 patients with potentially curative resection of CRC liver metastases were analyzed. These patients had no neoadjuvant therapy, no extrahepatic disease and negative resection margins. The primary endpoint was overall survival. Patients’ risk status was evaluated using the Memorial Sloan-Kettering Cancer Center clinical risk score (MSKCC-CRS). Multivariable analyses were performed using Cox proportional hazard models.

Results

A total of 137 (43%) patients had a MSKCC-CRS > 2. Adjuvant chemotherapy was administered to 116 (37%) patients. Patients who received adjuvant chemotherapy were of younger age (p = 0.03) with no significant difference in the presence of multiple metastases (p = 0.72) or bilobar metastases (p = 0.08). On multivariate analysis adjuvant chemotherapy was associated with improved survival in the entire cohort (Hazard ratio 0.69; 95% confidence interval 0.69–0.98). It improved survival markedly in high-risk patients with a MSKCC-CRS > 2 (HR 0.40; 95% CI 0.23–0.69), whereas it was of no benefit in patients with a MSKCC-CRS ≤ 2 (HR 0.90; 95% CI 0.57–1.43).

Conclusions

The MSKCC-CRS offers a tool to select patients for adjuvant therapy after resection of CRC liver metastases. Validation in independent patient cohorts is required.

【 授权许可】

   
2014 Rahbari et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]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(11):1241-1246.
• [2]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(3):309-318. discussion 318–321
• [3]Reissfelder C, Rahbari NN, Koch M, Ulrich A, Pfeilschifter I, Waltert A, Muller SA, Schemmer P, Buchler MW, Weitz J: Validation of prognostic scoring systems for patients undergoing resection of colorectal cancer liver metastases. Ann Surg Oncol 2009, 16(12):3279-3288.
• [4]Francini G, Petrioli R, Lorenzini L, Mancini S, Armenio S, Tanzini G, Marsili S, Aquino A, Marzocca G, Civitelli S: Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer. Gastroenterology 1994, 106(4):899-906.
• [5]O'Connell MJ, Mailliard JA, Kahn MJ, Macdonald JS, Haller DG, Mayer RJ, Wieand HS: Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol 1997, 15(1):246-250.
• [6]André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A: Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009, 27(19):3109-3116.
• [7]Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, Nitti D, Torri V, Elias D, O'Callaghan C, Langer B, Martignoni G, Bouché O, Lazorthes F, Van Cutsem E, Bedenne L, Moore MJ, Rougier P: Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol 2008, 26(30):4906-4911.
• [8]Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T: 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):1007-1016.
• [9]Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T: 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(12):1208-1215.
• [10]Merkel S, Bialecki D, Meyer T, Muller V, Papadopoulos T, Hohenberger W: Comparison of clinical risk scores predicting prognosis after resection of colorectal liver metastases. J Surg Oncol 2009, 100(5):349-357.
• [11]Zakaria S, Donohue JH, Que FG, Farnell MB, Schleck CD, Ilstrup DM, Nagorney DM: Hepatic resection for colorectal metastases: value for risk scoring systems? Ann Surg 2007, 246(2):183-191.
• [12]Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH, D'Angelica M: Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol 2007, 25(29):4575-4580.
• [13]Sobin LH, Gospodarowicz MK, Wittekind C: UICC: TNM classification of malignant tumours. Volume 7. New York: Wiley & Sons; 2009.
• [14]Rahbari NN, Zimmermann JB, Koch M, Bruckner T, Schmidt T, Elbers H, Reissfelder C, Weigand MA, Buchler MW, Weitz J: IVC CLAMP: infrahepatic inferior vena cava clamping during hepatectomy–a randomised controlled trial in an interdisciplinary setting. Trials 2009, 10:94. BioMed Central Full Text
• [15]Reissfelder C, Rahbari NN, Koch M, Kofler B, Sutedja N, Elbers H, Buchler MW, Weitz J: Postoperative course and clinical significance of biochemical blood tests following hepatic resection. Br J Surg 2011, 98(6):836-844.
• [16]Rahbari NN, Reissfelder C, Koch M, Elbers H, Striebel F, Buchler MW, Weitz J: The predictive value of postoperative clinical risk scores for outcome after hepatic resection: a validation analysis in 807 patients. Ann Surg Oncol 2011, 18(13):3640-3649.
• [17]Rahbari NN, Koch M, Schmidt T, Motschall E, Bruckner T, Weidmann K, Mehrabi A, Buchler MW, Weitz J: Meta-analysis of the clamp-crushing technique for transection of the parenchyma in elective hepatic resection: back to where we started? Ann Surg Oncol 2009, 16(3):630-639.
• [18]Rahbari NN, Wente MN, Schemmer P, Diener MK, Hoffmann K, Motschall E, Schmidt J, Weitz J, Buchler MW: Systematic review and meta-analysis of the effect of portal triad clamping on outcome after hepatic resection. Br J Surg 2008, 95(4):424-432.
• [19]Weh HJ, Wilke HJ, Dierlamm J, Klaassen U, Siegmund R, Illiger HJ, Schalhorn A, Kreuser ED, Hilgenfeld U, Steinke B: Weekly therapy with folinic acid (FA) and high-dose 5-fluorouracil (5-FU) 24-hour infusion in pretreated patients with metastatic colorectal carcinoma. A multicenter study by the Association of Medical Oncology of the German Cancer Society (AIO). Ann Oncol 1994, 5(3):233-237.
• [20]André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004, 350(23):2343-2351.
• [21]André T, Louvet C, Maindrault-Goebel F, Couteau C, Mabro M, Lotz JP, Gilles-Amar V, Krulik M, Carola E, Izrael V, de Gramont A: CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur J Cancer 1999, 35(9):1343-1347.
• [22]O'Connell MJ, Adson MA, Schutt AJ, Rubin J, Moertel CG, Ilstrup DM: Clinical trial of adjuvant chemotherapy after surgical resection of colorectal cancer metastatic to the liver. Mayo Clin Proc 1985, 60(8):517-520.
• [23]Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, Nitti D, Torri V, Elias D, O'Callaghan C, Langer B, Martignoni G, Bouché O, Lazorthes F, Van Cutsem E, Bedenne L, Moore MJ, Rougier : 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 Amer Soc Clin Oncol 2002, 21(149a):592.
• [24]Lopez-Ladron A, Salvador J, Bernabe R: Observation versus postoperative chemotherapy after resection of liver metastases in patients with advanced colorectal cancer. Proc Amer Soc Clin Oncol 2003, 22(373):1497.
• [25]Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J, Belghiti J, Piedbois P, Guimbaud R, Nordlinger B, Bugat R, Lazorthes F, Bedenne L: 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(31):4976-4982.
• [26]André T, Bensmaine MA, Louvet C, François E, Lucas V, Desseigne F, Beerblock K, Bouché O, Carola E, Merrouche Y, Morvan F, Dupont-André G, de Gramont A: Multicenter phase II study of bimonthly high-dose leucovorin, fluorouracil infusion, and oxaliplatin for metastatic colorectal cancer resistant to the same leucovorin and fluorouracil regimen. J Clin Oncol 1999, 17(11):3560-3568.
• [27]Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, Chollet P, Llory JF, Letourneau Y, Coudert B, Bertheaut-Cvitkovic F, Larregain-Fournier D, Le Rol A, Walter S, Adam R, Misset JL, Lévi F: Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 2000, 18(1):136-147.
• [28]Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Alberts SR: A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004, 22(1):23-30.
• [29]Rougier P, Van Cutsem E, Bajetta E, Niederle N, Possinger K, Labianca R, Navarro M, Morant R, Bleiberg H, Wils J, Awad L, Herait P, Jacques C: Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet 1998, 352(9138):1407-1412.
• [30]Köhne CH, van Cutsem E, Wils J, Bokemeyer C, El-Serafi M, Lutz MP, Lorenz M, Reichardt P, Ruckle-Lanz H, Frickhofen N, Fuchs R, Mergenthaler HG, Langenbuch T, Vanhoefer U, Rougier P, Voigtmann R, Müller L, Genicot B, Anak O, Nordlinger B: Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European organisation for research and treatment of cancer gastrointestinal group study 40986. J Clin Oncol 2005, 23(22):4856-4865.
• [31]Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL: Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 2000, 343(13):905-914.
• [32]Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Gilberg F, Rittweger K, Schmoll HJ: Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 2011, 29(11):1465-1471.
• [33]Ychou M, Hohenberger W, Thezenas S, Navarro M, Maurel J, Bokemeyer C, Shacham-Shmueli E, Rivera F, Kwok-Keung Choi C, Santoro A: A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol 2009, 20(12):1964-1970.
• [34]Parks R, Gonen M, Kemeny N, Jarnagin W, D'Angelica M, DeMatteo R, Garden OJ, Blumgart LH, Fong Y: Adjuvant chemotherapy improves survival after resection of hepatic colorectal metastases: analysis of data from two continents. J Am Coll Surg 2007, 204(5):753-761. discussion 761–753
• [35]Adam R, Bhangui P, Poston G, Mirza D, Nuzzo G, Barroso E, Ijzermans J, Hubert C, Ruers T, Capussotti L, Ouellet JF, Laurent C, Cugat E, Colombo PE, Milicevic M: Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg 2010, 252(5):774-787.
• [36]Maithel SK, Gonen M, Ito H, Dematteo RP, Allen PJ, Fong Y, Blumgart LH, Jarnagin WR, D'Angelica MI: Improving the clinical risk score: an analysis of molecular biomarkers in the era of modern chemotherapy for resectable hepatic colorectal cancer metastases. Surgery 2012, 151(2):162-170.
• [37]Fritzmann J, Morkel M, Besser D, Budczies J, Kosel F, Brembeck FH, Stein U, Fichtner I, Schlag PM, Birchmeier W: A colorectal cancer expression profile that includes transforming growth factor beta inhibitor BAMBI predicts metastatic potential. Gastroenterology 2009, 137(1):165-175.
• [38]Rahbari NN, Aigner M, Thorlund K, Mollberg N, Motschall E, Jensen K, Diener MK, Buchler MW, Koch M, Weitz J: Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology 2010, 138(5):1714-1726.
• [39]Kahlert C, Klupp F, Brand K, Lasitschka F, Diederichs S, Kirchberg J, Rahbari N, Dutta S, Bork U, Fritzmann J, Reissfelder C, Koch M, Weitz J: Invasion front-specific expression and prognostic significance of microRNA in colorectal liver metastases. Cancer Sci 2011, 102(10):1799-1807.
• [40]Nash GM, Gimbel M, Shia J, Nathanson DR, Ndubuisi MI, Zeng ZS, Kemeny N, Paty PB: KRAS mutation correlates with accelerated metastatic progression in patients with colorectal liver metastases. Ann Surg Oncol 2010, 17(2):572-578.
• [41]Yopp AC, Shia J, Butte JM, Allen PJ, Fong Y, Jarnagin WR, Dematteo RP, D'Angelica MI: CXCR4 Expression predicts patient outcome and recurrence patterns after hepatic resection for colorectal liver metastases. Ann Surg Oncol 2011, 19(Suppl 3):S339-S346.
• [42]Rahbari NN, Bork U, Motschall E, Thorlund K, Buchler MW, Koch M, Weitz J: Molecular detection of tumor cells in regional lymph nodes is associated with disease recurrence and poor survival in node-negative colorectal cancer: a systematic review and meta-analysis. J Clin Oncol 2012, 30(1):60-70.
• [43]Rahbari NN, Reissfelder C, Muhlbayer M, Weidmann K, Kahlert C, Buchler MW, Weitz J, Koch M: Correlation of circulating angiogenic factors with circulating tumor cells and disease recurrence in patients undergoing curative resection for colorectal liver metastases. Ann Surg Oncol 2011, 18(8):2182-2191.
• [44]Yoon SS, Kim SH, Gonen M, Heffernan NM, Detwiller KY, Jarnagin WR, D'Angelica M, Blumgart LH, Tanabe KK, Dematteo RP: Profile of plasma angiogenic factors before and after hepatectomy for colorectal cancer liver metastases. Ann Surg Oncol 2006, 13(3):353-362.