Hepatectomy versus systemic therapy for liver-limited BRAF V600E-mutated colorectal liver metastases: multicentre retrospective study

Author:

Margonis Georgios Antonios1ORCID,Wang Jaeyun Jane2,Boerner Thomas1,Moretto Roberto3,Buettner Stefan2,Andreatos Nikolaos4,Gagnière Johan5,Wagner Doris6,Løes Inger Marie7,Bergamo Francesca8,Pietrantonio Filippo9ORCID,Scartozzi Mario10,Spallanzani Andrea11,Vincenzi Bruno12,Antoniou Efstathios13,Pikoulis Emmanouil13,Sartore-Bianchi Andrea141516,Stasinos Georgios17,Sasaki Kazunari18,Pawlik Timothy M19ORCID,Orlandi Armando20,Pella Nicoletta21,Fitschek Fabian22,Kaczirek Klaus22,Dupré Aurélien23ORCID,Pozios Ioannis24,Beyer Katharina24,Kornprat Peter6,Aucejo Federico N4,Burkhart Richard2,Weiss Matthew J25,Lønning Per Eystein7ORCID,Poultsides George17,Cremolini Chiara3ORCID,Kreis Martin E24,D’Angelica Michael1

Affiliation:

1. Department of Surgery, Memorial Sloan Kettering Cancer Center , New York, New York , USA

2. Department of Surgery, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA

3. Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, University of Pisa , Pisa , Italy

4. Department of General Surgery, Digestive Disease Institute, Cleveland Clinic , Cleveland, Ohio , USA

5. Department of Digestive and Hepatobiliary Surgery—Liver Transplantation U1071 Inserm/Clermont-Auvergne University Hospital of Clermont-Ferrand , Clermont-Ferrand , France

6. Department of General Surgery, Medical University of Graz , Graz , Austria

7. Department of Clinical Science, University of Bergen, Department of Oncology, Haukeland University Hospital , Bergen , Norway

8. Unit of Medical Oncology 1, Department of Oncology, Veneto Institute of Oncology, IRCCS , Padua , Italy

9. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy

10. Medical Oncology, University Hospital of Cagliari , Cagliari , Italy

11. Department of Oncology and Haematology, Division of Oncology, University Hospital of Modena , Modena , Italy

12. Department of Medical Oncology, Campus Bio-Medico, Università di Roma , Rome , Italy

13. Third Department of Surgery, School of Medicine, National and Kapodistrian University of Athens, ‘Attikon’ University General Hospital , Athens , Greece

14. Department of Oncology and Hemato-Oncology, Università degli Studi di Milano , Milan , Italy

15. Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda , Milan , Italy

16. Division of Clinical Research and Innovation, Grande Ospedale Metropolitano Niguarda, Milan, Italy

17. Technical Chamber of Greece , Athens , Greece

18. Department of Surgery, Stanford University School of Medicine , Stanford, California , USA

19. Department of Surgery, Ohio State University Wexner Medical Center , Columbus, Ohio , USA

20. Comprehensive Cancer Centre, Medical Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS , Rome , Italy

21. Department of Oncology, ASUFC University Hospital of Udine , Udine , Italy

22. Department of General Surgery, Medical University of Vienna , Vienna , Austria

23. Department of Surgery, Léon Bérard Cancer Centre Lyon , Lyon , France

24. Department of General and Visceral Surgery, Charité Campus Benjamin Franklin , Berlin , Germany

25. Northwell Health Cancer Institute, Zucker School of Medicine at Hofstra , New York, New York , USA

Abstract

Abstract Background To date, only two studies have compared the outcomes of patients with liver-limited BRAF V600E-mutated colorectal liver metastases (CRLMs) managed with resection versus systemic therapy alone, and these have reported contradictory findings. Methods In this observational, international, multicentre study, patients with liver-limited BRAF V600E-mutated CRLMs treated with resection or systemic therapy alone were identified from institutional databases. Patterns of recurrence/progression and overall survival were compared using multivariable analyses of the entire cohort and a propensity score-matched cohort. Results Of 170 patients included, 119 underwent hepatectomy and 51 received systemic treatment. Surgically treated patients had a more favourable pattern of recurrence with most recurrences limited to a single site, whereas diffuse progression was more common among patients who received systemic treatment (19 versus 44%; P = 0.002). Surgically treated patients had longer median overall survival (35 versus 20 months; P < 0.001). Hepatectomy was independently associated with better OS than systemic treatment alone (HR 0.37, 95% c.i. 0.21 to 0.65). In the propensity score-matched cohort, surgically treated patients had longer median overall survival (28 versus 20 months; P < 0.001); hepatectomy was independently associated with better overall survival (HR 0.47, 0.25 to 0.88). Conclusion BRAF V600E mutation should not be considered a contraindication to surgery for patients with resectable, liver-only CRLMs.

Funder

National Cancer Institute

Italian Ministry of Health

Publisher

Oxford University Press (OUP)

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