Demystifying BRAF Mutation Status in Colorectal Liver Metastases
Georgios Margonis
,
Thomas Boerner
(1)
,
Jean-Baptiste Bachet
(2)
,
Stefan Buettner
,
Roberto Moretto
,
Nikolaos Andreatos
,
Andrea Sartore-Bianchi
,
Jane Wang
,
Carsten Kamphues
,
Johan Gagniere
(3, 4)
,
Sara Lonardi
(5)
,
Inger Løes
,
Doris Wagner
(6)
,
Andrea Spallanzani
(7)
,
Kazunari Sasaki
,
Richard Burkhart
,
Filippo Pietrantonio
(8)
,
Emmanouil Pikoulis
,
Timothy Pawlik
,
Stéphanie Truant
(9)
,
Armando Orlandi
,
Anastasia Pikouli
,
Nicoletta Pella
,
Katharina Beyer
,
George Poultsides
,
Hendrik Seeliger
,
Federico Aucejo
,
Peter Kornprat
,
Klaus Kaczirek
,
Per Lønning
,
Martin Kreis
,
Christopher Wolfgang
,
Matthew Weiss
,
Chiara Cremolini
,
Stéphane Benoist
,
Michael D’angelica
1
Department of Experimental Psychology, University of Oxford, Oxford, UK
2 CHU Pitié-Salpêtrière [AP-HP]
3 M2iSH - Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte
4 CIC 1405 - Centre d'Investigation Clinique [CHU Clermont-Ferrand]
5 Veneto Institute of Oncology IOV-IRCCS [Padua, Italy]
6 Department of Biology, University of Pennsylvania
7 Azienda Ospedaleria Universitaria di Modena = University Hospital of Modena
8 Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan]
9 Service de chirurgie hepato-pancreato-biliaire
2 CHU Pitié-Salpêtrière [AP-HP]
3 M2iSH - Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte
4 CIC 1405 - Centre d'Investigation Clinique [CHU Clermont-Ferrand]
5 Veneto Institute of Oncology IOV-IRCCS [Padua, Italy]
6 Department of Biology, University of Pennsylvania
7 Azienda Ospedaleria Universitaria di Modena = University Hospital of Modena
8 Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan]
9 Service de chirurgie hepato-pancreato-biliaire
Georgios Margonis
- Fonction : Auteur
Stefan Buettner
- Fonction : Auteur
Roberto Moretto
- Fonction : Auteur
Nikolaos Andreatos
- Fonction : Auteur
Andrea Sartore-Bianchi
- Fonction : Auteur
Jane Wang
- Fonction : Auteur
Carsten Kamphues
- Fonction : Auteur
Inger Løes
- Fonction : Auteur
Kazunari Sasaki
- Fonction : Auteur
Richard Burkhart
- Fonction : Auteur
Emmanouil Pikoulis
- Fonction : Auteur
Timothy Pawlik
- Fonction : Auteur
Stéphanie Truant
- Fonction : Auteur
- PersonId : 1366649
- IdHAL : stephanie-truant
- ORCID : 0000-0002-2828-4864
Armando Orlandi
- Fonction : Auteur
Anastasia Pikouli
- Fonction : Auteur
Nicoletta Pella
- Fonction : Auteur
Katharina Beyer
- Fonction : Auteur
George Poultsides
- Fonction : Auteur
Hendrik Seeliger
- Fonction : Auteur
Federico Aucejo
- Fonction : Auteur
Peter Kornprat
- Fonction : Auteur
Klaus Kaczirek
- Fonction : Auteur
Per Lønning
- Fonction : Auteur
Martin Kreis
- Fonction : Auteur
Christopher Wolfgang
- Fonction : Auteur
Matthew Weiss
- Fonction : Auteur
Chiara Cremolini
- Fonction : Auteur
Stéphane Benoist
- Fonction : Auteur
Michael D’angelica
- Fonction : Auteur
Résumé
Objective: To investigate the clinical implications of BRAF -mutated (mut BRAF ) colorectal liver metastases (CRLMs). Background: The clinical implications of mut BRAF status in CRLMs are largely unknown. Methods: Patients undergoing resection for mut BRAF CRLM were identified from prospectively maintained registries of the collaborating institutions. Overall survival (OS) and recurrence-free survival (RFS) were compared among patients with V600E versus non-V600E mutations, KRAS/BRAF comutation versus mut BRAF alone, microsatellite stability status (Microsatellite Stable (MSS) vs instable (MSI-high)), upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy versus nonoperative management. Results: A total of 240 patients harboring BRAF -mutated tumors were included. BRAF V600E mutation was associated with shorter OS (30.6 vs 144 mo, P =0.004), but not RFS compared with non-V600E mutations. KRAS/BRAF comutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs 26 mo, P <0.001) but not OS (33.5 vs 41 mo, P =0.3) compared with MSI-high tumors, whereas patients with resected converted disease had slightly worse RFS (8 vs 11 mo, P =0.01) and similar OS (30 vs 40 mo, P =0.4) compared with those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared with those with liver-limited disease (8.8 vs 40 mo, P <0.001). Repeat hepatectomy after intrahepatic recurrence was associated with improved OS compared with nonoperative management (41 vs 18.7 mo, P =0.004). All results continued to hold true in the multivariable OS analysis. Conclusions: Although surgery may be futile in patients with BRAF -mutated CRLM and concurrent extrahepatic disease, resection of converted disease resulted in encouraging survival in the absence of extrahepatic spread. Importantly, second hepatectomy in select patients with recurrence was associated with improved outcomes. Finally, MSI-high status identifies a better prognostic group, with regard to RFS while patients with non-V600E mutations have excellent prognosis.
Domaines
Sciences du Vivant [q-bio]Format du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Demystifying BRAF Mutation Status in Colorectal Liver Metastases
|
Résumé |
en
Objective: To investigate the clinical implications of BRAF -mutated (mut BRAF ) colorectal liver metastases (CRLMs). Background: The clinical implications of mut BRAF status in CRLMs are largely unknown. Methods: Patients undergoing resection for mut BRAF CRLM were identified from prospectively maintained registries of the collaborating institutions. Overall survival (OS) and recurrence-free survival (RFS) were compared among patients with V600E versus non-V600E mutations, KRAS/BRAF comutation versus mut BRAF alone, microsatellite stability status (Microsatellite Stable (MSS) vs instable (MSI-high)), upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy versus nonoperative management. Results: A total of 240 patients harboring BRAF -mutated tumors were included. BRAF V600E mutation was associated with shorter OS (30.6 vs 144 mo, P =0.004), but not RFS compared with non-V600E mutations. KRAS/BRAF comutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs 26 mo, P <0.001) but not OS (33.5 vs 41 mo, P =0.3) compared with MSI-high tumors, whereas patients with resected converted disease had slightly worse RFS (8 vs 11 mo, P =0.01) and similar OS (30 vs 40 mo, P =0.4) compared with those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared with those with liver-limited disease (8.8 vs 40 mo, P <0.001). Repeat hepatectomy after intrahepatic recurrence was associated with improved OS compared with nonoperative management (41 vs 18.7 mo, P =0.004). All results continued to hold true in the multivariable OS analysis. Conclusions: Although surgery may be futile in patients with BRAF -mutated CRLM and concurrent extrahepatic disease, resection of converted disease resulted in encouraging survival in the absence of extrahepatic spread. Importantly, second hepatectomy in select patients with recurrence was associated with improved outcomes. Finally, MSI-high status identifies a better prognostic group, with regard to RFS while patients with non-V600E mutations have excellent prognosis.
|
Auteur(s) |
Georgios Margonis
, Thomas Boerner
1
, Jean-Baptiste Bachet
2
, Stefan Buettner
, Roberto Moretto
, Nikolaos Andreatos
, Andrea Sartore-Bianchi
, Jane Wang
, Carsten Kamphues
, Johan Gagniere
3, 4
, Sara Lonardi
5
, Inger Løes
, Doris Wagner
6
, Andrea Spallanzani
7
, Kazunari Sasaki
, Richard Burkhart
, Filippo Pietrantonio
8
, Emmanouil Pikoulis
, Timothy Pawlik
, Stéphanie Truant
9
, Armando Orlandi
, Anastasia Pikouli
, Nicoletta Pella
, Katharina Beyer
, George Poultsides
, Hendrik Seeliger
, Federico Aucejo
, Peter Kornprat
, Klaus Kaczirek
, Per Lønning
, Martin Kreis
, Christopher Wolfgang
, Matthew Weiss
, Chiara Cremolini
, Stéphane Benoist
, Michael D’angelica
1
Department of Experimental Psychology, University of Oxford, Oxford, UK
( 1052831 )
- Royaume-Uni
2
CHU Pitié-Salpêtrière [AP-HP]
( 353778 )
- 47-83 Boulevard de l'Hôpital, 75013 Paris
- France
3
M2iSH -
Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte
( 1063664 )
- UFR de Médecine et de Pharmacie, 28 Place Henri Dunant, BP 38, 63001 Clermont-Ferrand Cedex
- France
4
CIC 1405 -
Centre d'Investigation Clinique [CHU Clermont-Ferrand]
( 2612 )
- CHU Clermont-Ferrand - Site Gabriel-Montpied, 58 Rue Montalembert, 63000 Clermont-Ferrand
- France
5
Veneto Institute of Oncology IOV-IRCCS [Padua, Italy]
( 533773 )
- Comprehensive Cancer Centre - Via Gattamelata 64 - 35128 Padova.
- Italie
6
Department of Biology, University of Pennsylvania
( 161005 )
- University of Pennsylvania School of Arts and Sciences, Philadelphia, PA 19104
- États-Unis
7
Azienda Ospedaleria Universitaria di Modena = University Hospital of Modena
( 454913 )
- via del Pozzo 71 - 41124 Modena
- Italie
8
Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan]
( 339445 )
- Via Giacomo Venezian, 1, 20133 Milano MI, Italie
- Italie
9
Service de chirurgie hepato-pancreato-biliaire
( 1004993 )
- 100, boulevard du Général Leclerc 92110 Clichy
- France
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Langue du document |
Anglais
|
Nom de la revue |
|
Date de publication |
2023-09-01
|
Volume |
278
|
Numéro |
3
|
Page/Identifiant |
e540-e548
|
Domaine(s) |
|
DOI | 10.1097/sla.0000000000005771 |
Loading...