The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma.


Journal

Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354

Informations de publication

Date de publication:
03 2019
Historique:
pubmed: 27 10 2017
medline: 18 12 2019
entrez: 26 10 2017
Statut: ppublish

Résumé

Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies. Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial. There were 1151 patients, of whom 505 (43.9%) had an R1 resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative (R0 >1 mm) tumors, 25.4 (21.6-30.4) months for 146 (12.7%) patients with R1<1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥1, maximum tumor size, and R1-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status, WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence. R1-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.

Sections du résumé

OBJECTIVE AND BACKGROUND
Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies.
METHODS
Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial.
RESULTS
There were 1151 patients, of whom 505 (43.9%) had an R1 resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative (R0 >1 mm) tumors, 25.4 (21.6-30.4) months for 146 (12.7%) patients with R1<1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥1, maximum tumor size, and R1-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status, WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence.
CONCLUSIONS
R1-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.

Identifiants

pubmed: 29068800
doi: 10.1097/SLA.0000000000002557
doi:

Substances chimiques

Antineoplastic Agents 0
Deoxycytidine 0W860991D6
Leucovorin Q573I9DVLP
Fluorouracil U3P01618RT
Gemcitabine 0

Banques de données

ClinicalTrials.gov
['NCT00058201']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

520-529

Subventions

Organisme : Cancer Research UK
ID : SP2590/0101
Pays : United Kingdom
Organisme : Cancer Research UK
ID : SP1984/0204
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 8968
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C245/A 15957
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 11883
Pays : United Kingdom
Organisme : Department of Health
ID : 08/29/02
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Auteurs

Paula Ghaneh (P)

Liverpool Cancer Research U.K. Cancer Trials Unit, University of Liverpool, Liverpool, United Kingdom University of Liverpool, Liverpool, UK.
The Department of Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.

Jorg Kleeff (J)

The Department of Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.

Christopher M Halloran (CM)

The Department of Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.

Michael Raraty (M)

The Department of Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.

Richard Jackson (R)

Liverpool Cancer Research U.K. Cancer Trials Unit, University of Liverpool, Liverpool, United Kingdom University of Liverpool, Liverpool, UK.

James Melling (J)

The Department of Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.

Owain Jones (O)

The Department of Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.

Daniel H Palmer (DH)

Liverpool Cancer Research U.K. Cancer Trials Unit, University of Liverpool, Liverpool, United Kingdom University of Liverpool, Liverpool, UK.

Trevor F Cox (TF)

Liverpool Cancer Research U.K. Cancer Trials Unit, University of Liverpool, Liverpool, United Kingdom University of Liverpool, Liverpool, UK.

Chloe J Smith (CJ)

Liverpool Cancer Research U.K. Cancer Trials Unit, University of Liverpool, Liverpool, United Kingdom University of Liverpool, Liverpool, UK.

Derek A O'Reilly (DA)

Department of Surgery, Manchester Royal Infirmary, Manchester, UK.

Jakob R Izbicki (JR)

Department of Surgery, University of Hamburg Medical institutions UKE, Hamburg, Germany.

Andrew G Scarfe (AG)

Department of Oncology Division of Medical Oncology 2228 Cross Cancer Institute and University of Alberta, Canada.

Juan W Valle (JW)

Department of Medical Oncology , The Christie, Manchester, UK.

Alexander C McDonald (AC)

Department of Medical Oncology, The Beatson West of Scotland Cancer Centre, Glasgow, Scotland, UK.

Ross Carter (R)

Department of Surgery, Glasgow Royal Infirmary, Glasgow, Scotland, UK.

Niall C Tebbutt (NC)

Department of Medical Oncology, Austin Health, Melbourne, Australia.

David Goldstein (D)

Department of Medical Oncology, Prince of Wales hospital and Clinical School University of New South Wales, Australia.

Robert Padbury (R)

Department of Surgery, Flinders Medical Centre, Adelaide, South Australia.

Jennifer Shannon (J)

Department of Medical Oncology, Nepean Cancer Centre and University of Sydney, Australia.

Christos Dervenis (C)

Department of Surgery, The Agia Olga Hospital, Athens, Greece.

Bengt Glimelius (B)

Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology, Uppsala Clinical Research Center, Uppsala, Sweden.

Mark Deakin (M)

Department of Surgery, University Hospital, North Staffordshire, UK.

Alan Anthoney (A)

Division of Oncology at the University of Leeds, St James's University Hospital, Leeds, UK.

Markus M Lerch (MM)

Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.

Julia Mayerle (J)

Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.

Attila Oláh (A)

Department of Surgery, The Petz Aladar Hospital, Gyor, Hungary.

Charlotte L Rawcliffe (CL)

Liverpool Cancer Research U.K. Cancer Trials Unit, University of Liverpool, Liverpool, United Kingdom University of Liverpool, Liverpool, UK.

Fiona Campbell (F)

Department of Pathology, The Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.

Oliver Strobel (O)

The Department of Surgery, University of Heidelberg, Heidelberg, Germany.

Markus W Büchler (MW)

The Department of Surgery, University of Heidelberg, Heidelberg, Germany.

John P Neoptolemos (JP)

Liverpool Cancer Research U.K. Cancer Trials Unit, University of Liverpool, Liverpool, United Kingdom University of Liverpool, Liverpool, UK.
The Department of Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.

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Classifications MeSH