title: Perioperative bevacizumab improves survival following lung metastasectomy for colorectal cancer in patients harbouring v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue exon 2 codon 12 mutations†.
abstract: The role of perioperative chemotherapy (POC) and targeted therapies in lung metastasectomy for colorectal cancer (CRC) is still subject to debate. We aimed to evaluate whether POC and targeted therapies were associated with different outcomes according to the mutational status.
  
  
  
  We reviewed data from 223 patients who underwent pulmonary metastasectomy for CRC from 1998 to 2015 and for whom the V-Ki-ras2 Kirsten sarcoma viral oncogene homologue (KRAS) and V-raf Murine sarcoma viral oncogene homologue B1 (BRAF) mutational statuses were known.
  
  
  
  A total of 167 patients (74%) underwent POC: 62 (37%) received neoadjuvant therapy, 59 (35%) were in the adjuvant setting and 46 (28%) were in both the neoadjuvant and adjuvant settings. POC did not significantly influence either the loco-regional recurrence free survival (LRRFS) (P = 0.21) or the overall survival (OS) (P = 0.29). Furthermore, in cases of adjuvant chemotherapy, outcomes were not significantly different in cases of neoadjuvant chemotherapy or both neoadjuvant and adjuvant treatment (P = 0.26 for OS, P = 0.14 for LRRFS). For patients with KRAS mutation, perioperative bevacizumab was associated with a significant improvement in both LRRFS [70 months (41.58–98.42) vs 24 months (1.15–46.86), P = 0.001] and OS [101 vs 55 months (49.77–60.23), P = 0.004]. However, this benefit was only significant in cases of KRAS exon 2 codon 12 mutations [median OS: 101 months (83.97–118.02) vs 60 months (53–66.99), P < 0.001; median LRRFS: 76 months (64.62–87.38) vs 44 months (35.27–52.73), P < 0.001].
  
  
  
  Perioperative bevacizumab appears to be beneficial in patients with exon 2 codon 12 KRAS mutations who have undergone lung metastasectomy for CRC.
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.|Research Unit EA 3430: Tumoral Progression and Microenvironment, Translational and Epidemiological Approaches, Strasbourg University, Strasbourg, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Renaud
authors.affiliation: Biostatistics Department, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Schaeffer
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Falcoz
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Seitlinger
authors.affiliation: Research Unit EA 3430: Tumoral Progression and Microenvironment, Translational and Epidemiological Approaches, Strasbourg University, Strasbourg, France.|Department of General and Digestive Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Romain
authors.affiliation: Department of Molecular Biology, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Voegeli
authors.affiliation: Department of Molecular Biology, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Legrain
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Reeb
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Nicola
authors.initials: N
authors.lastname: Santelmo
authors.affiliation: Department of General and Digestive Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Rohr
authors.affiliation: Department of General and Digestive Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Brigand
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Olland
authors.affiliation: Research Unit EA 3430: Tumoral Progression and Microenvironment, Translational and Epidemiological Approaches, Strasbourg University, Strasbourg, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Guenot
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Massard
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000235:genetics*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary* / Q000628:therapy*; D008297:Male; D059146:Metastasectomy; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D000068258:Bevacizumab; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)