title: Histological response, pattern of tumor destruction and clinical outcome after neoadjuvant chemotherapy including bevacizumab or cetuximab in patients undergoing liver resection for colorectal liver metastases.
abstract: OBJECTIVE
  We investigated whether the type of antibody [bevacizumab (bev) or cetuximab (cet)] added to neoadjuvant combination chemotherapy before curative liver resection was associated with histological response, the pattern of tumor destruction and clinical outcome in patients with colorectal liver metastases (CLM).
  
  
  METHODS
  We investigated 138 patients with KRAS wild-type status (codon 12, 13 and 61) who received neoadjuvant chemotherapy including bev (n = 101) or cet (n = 37). The primary endpoint was histological response. Secondary endpoints were necrosis and fibrosis of metastases, radiological response, recurrence-free survival (RFS) and overall survival (OS).
  
  
  RESULTS
  Histological response was not significantly different between the two groups (P = 0.19). A significantly higher fraction of patients in the bev group showed necrosis of the metastases of ≥ 50% (P < 0.001), while a higher fraction of patients in the cet group showed fibrosis of ≥ 40% (P = 0.030). Radiological response was not significantly different (P = 0.17). Median RFS was significantly shorter in the cet group in univariable analysis (HR 1.59 (95% CI 1.00, 2.51), P = 0.049), but this difference did not remain significant in multivariable analysis (P = 0.45). The 3-year OS rate was not significantly different (P = 0.73).
  
  
  CONCLUSIONS
  The addition of bevacizumab to combination chemotherapy showed more necrosis but less fibrosis of metastases compared to cetuximab and a trend towards higher histological and radiological response and longer RFS. Further investigations of biological tumor characteristics are required to individualize treatment combinations.
authors: Department of General Surgery, Medical University Vienna, Vienna, Austria.
authors: S
authors: S
authors: Stremitzer
authors: Clinical Institute of Pathology, Medical University Vienna, Vienna, Austria.
authors: J
authors: J
authors: Stift
authors: Department of General Surgery, Medical University Vienna, Vienna, Austria.
authors: J
authors: J
authors: Singh
authors: Department of General Surgery, Medical University Vienna, Vienna, Austria.
authors: P
authors: P
authors: Starlinger
authors: Department of Internal Medicine, St. John of God's Hospital, Vienna, Austria.
authors: B
authors: B
authors: Gruenberger
authors: Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria.
authors: D
authors: D
authors: Tamandl
authors: Department of Surgery I, Rudolfstiftung Hospital, Vienna, Austria. Electronic address: tgruenberger@icloud.com.
authors: T
authors: T
authors: Gruenberger
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008103:Liver Cirrhosis / Q000517:prevention & control; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000517:prevention & control; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin
keywords: Bevacizumab; Cetuximab; Colorectal liver metastases; Histological response; Pattern of tumor destruction; Survival