Skip to main content
Erschienen in: Pathology & Oncology Research 3/2013

01.07.2013 | Research

Bevacizumab Treatment Before Resection of Colorectal Liver Metastases: Safety, Recovery of Liver Function, Pathologic Assesment

verfasst von: K. Dede, T. Mersich, I. Besznyák, A. Zaránd, F. Salamon, Zs. Baranyai, L. Landherr, F. Jakab, A. Bursics

Erschienen in: Pathology & Oncology Research | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Abstract

Patients with metastatic colorectal cancer receive chemotherapy prior liver resection more and more frequently. This preoperative treatment has many effects which have to be analysed, like the safety of liver resection, toxicity, tissue regeneration, radiological and pathological response and survival data. The aim of the study was to evaluate the safety of bevacizumab containing preoperative chemotherapy and functional recovery of the liver after resection for colorectal liver metastases (CLM) and to analyse radiological and pathological data. Data of three groups of 120 consecutive patients—(1) CTX + BV: cytotoxic chemotherapy + bevacizumab, (2) CTX: cytotoxic chemotherapy, (3) NC: no treatment before liver resection—were analysed. Postoperative liver function and complications were compared, clinical, radiological and pathological data were evaluated. Between 01.12.2006 and 31.12.2010 41 resections was performed after chemotherapy + bevacizumab (CTX + BV) and 27 resections was performed after preoperative chemotherapy without bevacizumab (CTX). There were 60 hepatic resections in this period without neoadjuvant treatment (NC). 8 patients had repeated resections. The postoperative complication rate was 40 % but there was no statistical difference between the groups (P = 0.72). Only the type of resection was associated with a significantly higher complication rate (p = 0.03). The subgroup of patients, who received irinotecan had a higher complication rate in the CTX group than in the BV + CTX group (55 % vs 41 %). Preoperative administration of bevacizumab was associated with higher peak postoperative AST, ALT levels but did not affect functional recovery of the liver. The RECIST system was not able to predict the outcome after chemotherapy in every patient and in many cases this system overestimated the effect of chemotherapy. On histopathological examination the presence of necrosis was not associated with chemotherapy or pathological response. Use of chemotherapy before hepatic resection of CLM was not associated with a significant increase in complication rates. The functional recovery of the liver was not affected by the preoperative administration of chemotherapy. The use of combined neoadjuvant chemotherapy is safe before hepatic resection.
Literatur
1.
Zurück zum Zitat Adam R, Delvart V, Pascal G et al (2004) Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 240:644–657PubMedCrossRef Adam R, Delvart V, Pascal G et al (2004) Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 240:644–657PubMedCrossRef
2.
Zurück zum Zitat Kesmodel B, Ellis L et al (2008) Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol 26(32):5224–5260CrossRef Kesmodel B, Ellis L et al (2008) Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol 26(32):5224–5260CrossRef
3.
Zurück zum Zitat Wicherts DA, de Haas RJ, Adam R et al (2011) Impact of bevacizumab on functional recovery and histology of the liver after resection of colorectal metastases. Br J Surg 98(3):399–407PubMedCrossRef Wicherts DA, de Haas RJ, Adam R et al (2011) Impact of bevacizumab on functional recovery and histology of the liver after resection of colorectal metastases. Br J Surg 98(3):399–407PubMedCrossRef
4.
Zurück zum Zitat Folprecht G, Gruenberger T, Bechstein WO et al (2010) Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol 11(1):38–47PubMedCrossRef Folprecht G, Gruenberger T, Bechstein WO et al (2010) Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol 11(1):38–47PubMedCrossRef
5.
Zurück zum Zitat Van Cutsem E, Rivera F, Berry S et al (2009) Safety and efficacy of firstline bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20(11):1842–1847PubMedCrossRef Van Cutsem E, Rivera F, Berry S et al (2009) Safety and efficacy of firstline bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20(11):1842–1847PubMedCrossRef
6.
Zurück zum Zitat Scoggins CR, Campbell ML, Landry CS et al (2009) Preoperative chemotherapy does not increase morbidity or mortality of hepatic resection for colorectal cancer metastases. Ann Surg Oncol 16(1):35–41PubMedCrossRef Scoggins CR, Campbell ML, Landry CS et al (2009) Preoperative chemotherapy does not increase morbidity or mortality of hepatic resection for colorectal cancer metastases. Ann Surg Oncol 16(1):35–41PubMedCrossRef
7.
Zurück zum Zitat Vauthey JN, Pawlik TM, Ribero D et al (2006) Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 24(13):2065–2072PubMedCrossRef Vauthey JN, Pawlik TM, Ribero D et al (2006) Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 24(13):2065–2072PubMedCrossRef
8.
Zurück zum Zitat Ribero D, Wang H, Donadon M et al (2007) Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer 110(12):2761–2767PubMedCrossRef Ribero D, Wang H, Donadon M et al (2007) Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer 110(12):2761–2767PubMedCrossRef
9.
Zurück zum Zitat Klinger M, Eipeldauer S, Hacker S et al (2009) Bevacizumab protects against sinusoidal obstruction syndrome and does not increase response rate in neoadjuvant XELOX/FOLFOX therapy of colorectal cancer liver metastases. Eur J Surg Oncol 35(5):515–520PubMedCrossRef Klinger M, Eipeldauer S, Hacker S et al (2009) Bevacizumab protects against sinusoidal obstruction syndrome and does not increase response rate in neoadjuvant XELOX/FOLFOX therapy of colorectal cancer liver metastases. Eur J Surg Oncol 35(5):515–520PubMedCrossRef
10.
Zurück zum Zitat D’Angelica M, Kornprat P, Gonen M et al (2007) Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: a matched casecontrol study. An Surg Oncol 14:759–765CrossRef D’Angelica M, Kornprat P, Gonen M et al (2007) Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: a matched casecontrol study. An Surg Oncol 14:759–765CrossRef
11.
Zurück zum Zitat Ellis LM, Curley SA et al (2005) Surgical resection after downsizing of colorectal liver metastasis in the era of Bevacizumab. J Clin Oncol 23(22):4853–4855PubMedCrossRef Ellis LM, Curley SA et al (2005) Surgical resection after downsizing of colorectal liver metastasis in the era of Bevacizumab. J Clin Oncol 23(22):4853–4855PubMedCrossRef
12.
Zurück zum Zitat Reddy SK, Morse MA, Hurwitz HI et al (2008) Addition of bevacizumab to irinotecan and oxaliplatin based preoperative chemotherapy regimens does not increase morbidity after resection of colorectal liver metastases. J Am Coll Surg 206:96–106PubMedCrossRef Reddy SK, Morse MA, Hurwitz HI et al (2008) Addition of bevacizumab to irinotecan and oxaliplatin based preoperative chemotherapy regimens does not increase morbidity after resection of colorectal liver metastases. J Am Coll Surg 206:96–106PubMedCrossRef
13.
Zurück zum Zitat Mahfud M, Breitenstein S, El-Badry AM et al (2010) Impact of preoperative bevacizumab on complications after resection of colorectal liver metastases: case-matched control study. World J Surg 34(1):92–100PubMedCrossRef Mahfud M, Breitenstein S, El-Badry AM et al (2010) Impact of preoperative bevacizumab on complications after resection of colorectal liver metastases: case-matched control study. World J Surg 34(1):92–100PubMedCrossRef
14.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment is solid tumors. J Natl Cancer Inst 92:205–216PubMedCrossRef Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment is solid tumors. J Natl Cancer Inst 92:205–216PubMedCrossRef
15.
Zurück zum Zitat Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213PubMedCrossRef Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213PubMedCrossRef
16.
Zurück zum Zitat Dan G, Blazer III, Kishi Y et al (2008) Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol 25(33):5344–5351 Dan G, Blazer III, Kishi Y et al (2008) Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol 25(33):5344–5351
17.
Zurück zum Zitat Nordlinger B, Vauthey J-N, Poston G et al (2010) The timing of chemotherapy and surgery for the treatment of colorectal liver metastases. Clin Colorectal Cancer 9(4):212–218PubMedCrossRef Nordlinger B, Vauthey J-N, Poston G et al (2010) The timing of chemotherapy and surgery for the treatment of colorectal liver metastases. Clin Colorectal Cancer 9(4):212–218PubMedCrossRef
18.
Zurück zum Zitat Spelt L, Andersson B, Nilsson J, Andersson R (2012) Prognostic models for outcome following liver resection for colorectal cancer metastases: a systematic review. EJSO 38:16–24PubMedCrossRef Spelt L, Andersson B, Nilsson J, Andersson R (2012) Prognostic models for outcome following liver resection for colorectal cancer metastases: a systematic review. EJSO 38:16–24PubMedCrossRef
19.
Zurück zum Zitat Gruenberger B, Tamandl D, Schueller J et al (2008) Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol 26(11):1830–1835PubMedCrossRef Gruenberger B, Tamandl D, Schueller J et al (2008) Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol 26(11):1830–1835PubMedCrossRef
20.
Zurück zum Zitat Nordlinger B, Sorbye H, Glimelius B et al (2008) Perioperative chemotherapywith FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomisedcontrolled trial. Lancet 371(9617):1007–1016PubMedCrossRef Nordlinger B, Sorbye H, Glimelius B et al (2008) Perioperative chemotherapywith FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomisedcontrolled trial. Lancet 371(9617):1007–1016PubMedCrossRef
21.
Zurück zum Zitat Chua TC, Saxena A, Liauw A et al (2010) Systematic review of randomized and nonrandomized trials of the clinical response and outcomes of neoadjuvant systemic chemotherapy for resectable colorectal liver metastases. Ann Surg Oncol 17(2):492–501PubMedCrossRef Chua TC, Saxena A, Liauw A et al (2010) Systematic review of randomized and nonrandomized trials of the clinical response and outcomes of neoadjuvant systemic chemotherapy for resectable colorectal liver metastases. Ann Surg Oncol 17(2):492–501PubMedCrossRef
22.
Zurück zum Zitat Nordlinger B, Van Cutsem E, Gruenberger T, European Colorectal Metastases Treatment Group; Sixth International Colorectal Liver Metastases Workshop et al (2009) Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel. Ann Oncol 20(6):985–992PubMedCrossRef Nordlinger B, Van Cutsem E, Gruenberger T, European Colorectal Metastases Treatment Group; Sixth International Colorectal Liver Metastases Workshop et al (2009) Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel. Ann Oncol 20(6):985–992PubMedCrossRef
23.
Zurück zum Zitat Lehmann K, Rickenbacher A, Weber A, Pestalozzi BC, Clavien PA (2012) Chemotherapy before liver resection of colorectal metastases: friend or foe? Ann Surg 255:237–247PubMedCrossRef Lehmann K, Rickenbacher A, Weber A, Pestalozzi BC, Clavien PA (2012) Chemotherapy before liver resection of colorectal metastases: friend or foe? Ann Surg 255:237–247PubMedCrossRef
24.
Zurück zum Zitat Scappaticci FA, Fehrenbacher L, Cartwright T et al (2005) Surgical woundhealing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91:173–180PubMedCrossRef Scappaticci FA, Fehrenbacher L, Cartwright T et al (2005) Surgical woundhealing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91:173–180PubMedCrossRef
25.
Zurück zum Zitat Tamandl D, Gruenberger B, Klinger M et al (2010) Liver resection remains a safe procedure after neoadjuvant chemotherapy including bevacizumab: a case-controlled study. Ann Surg 252(1):124–130PubMedCrossRef Tamandl D, Gruenberger B, Klinger M et al (2010) Liver resection remains a safe procedure after neoadjuvant chemotherapy including bevacizumab: a case-controlled study. Ann Surg 252(1):124–130PubMedCrossRef
26.
Zurück zum Zitat Kishi Y, Zorzi D, Contreras CM et al (2010) Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases. Ann Surg Oncol 17(11):2870–2876PubMedCrossRef Kishi Y, Zorzi D, Contreras CM et al (2010) Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases. Ann Surg Oncol 17(11):2870–2876PubMedCrossRef
27.
Zurück zum Zitat Gordon MS, Margolin K, Talpaz M et al (2001) Phase I safety and pharmacokineticstudy of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 19(3):843–850PubMed Gordon MS, Margolin K, Talpaz M et al (2001) Phase I safety and pharmacokineticstudy of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 19(3):843–850PubMed
28.
Zurück zum Zitat Chun YS, Vauthey JN, Boonsirikamchai P et al (2009) Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal livermetastases. JAMA 302(21):2338–2344PubMedCrossRef Chun YS, Vauthey JN, Boonsirikamchai P et al (2009) Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal livermetastases. JAMA 302(21):2338–2344PubMedCrossRef
29.
Zurück zum Zitat Rubbia-Brandt L, Giostra E, Brezault C et al (2007) Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neoadjuvant chemotherapy followed by liver surgery. Ann Oncol 18:299–304PubMedCrossRef Rubbia-Brandt L, Giostra E, Brezault C et al (2007) Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neoadjuvant chemotherapy followed by liver surgery. Ann Oncol 18:299–304PubMedCrossRef
30.
Zurück zum Zitat Dipen MM, Kopetz S, Boonsirikamchai P et al (2010) Tumor thickness at the tumor-normal interface: a novel pathologic indicator of chemotherapy response in hepatic colorectal metastases. Am J Surg Pathol 34:1287–1294CrossRef Dipen MM, Kopetz S, Boonsirikamchai P et al (2010) Tumor thickness at the tumor-normal interface: a novel pathologic indicator of chemotherapy response in hepatic colorectal metastases. Am J Surg Pathol 34:1287–1294CrossRef
31.
Zurück zum Zitat Li Chang HH, Leeper WR, Chan G, Quan D, Driman DK (2012) Infarct-like necrosis. A distinct form of necrosis seen in colorectal carcinoma liver metastases treated with perioperative chemotherapy. Am J Surg Pathol 36:570–576CrossRef Li Chang HH, Leeper WR, Chan G, Quan D, Driman DK (2012) Infarct-like necrosis. A distinct form of necrosis seen in colorectal carcinoma liver metastases treated with perioperative chemotherapy. Am J Surg Pathol 36:570–576CrossRef
Metadaten
Titel
Bevacizumab Treatment Before Resection of Colorectal Liver Metastases: Safety, Recovery of Liver Function, Pathologic Assesment
verfasst von
K. Dede
T. Mersich
I. Besznyák
A. Zaránd
F. Salamon
Zs. Baranyai
L. Landherr
F. Jakab
A. Bursics
Publikationsdatum
01.07.2013
Verlag
Springer Netherlands
Erschienen in
Pathology & Oncology Research / Ausgabe 3/2013
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-013-9608-2

Weitere Artikel der Ausgabe 3/2013

Pathology & Oncology Research 3/2013 Zur Ausgabe

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

ADT zur Radiatio nach Prostatektomie: Wenn, dann wohl länger

24.05.2024 Prostatakarzinom Nachrichten

Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.

Das sind die führenden Symptome junger Darmkrebspatienten

Darmkrebserkrankungen in jüngeren Jahren sind ein zunehmendes Problem, das häufig längere Zeit übersehen wird, gerade weil die Patienten noch nicht alt sind. Welche Anzeichen Ärzte stutzig machen sollten, hat eine Metaanalyse herausgearbeitet.

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.