Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial

European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS)

doi:10.1016/j.lanepe.2023.100673

Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial

European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS)

Department of Surgery, Fondazione Poliambulanza - Instituto Ospedaliero, Brescia, Italy
Amsterdam UMC
Onze Lieve Vrouwe Gasthuis
Vita-Salute San Raffaele University
Linköping University
University of Pisa
Sahlgrenska University Hospital
Pederzoli Hospital
Humanitas University
IRCCS Istituto Clinico Humanitas - Rozzano (Milano)
IRCCS S. Orsola University Hospital, Bologna, Italy
University of Oslo
Ospedale Policlinico
Erasmus University Rotterdam
Universitätsklinikum Schleswig-Holstein Campus Lübeck
University of Groningen, University Medical Center Groningen
Helsinki University Hospital
Medisch Spectrum Twente
Amsterdam UMC location University of Amsterdam
University Hospital Southampton NHS Foundation Trust
Catharina Hospital
University Hospitals Birmingham NHS Foundation Trust
Amsterdam Public Health
Fondazione Poliambulanza Istituto Ospedaliero
University of Amsterdam
OLVG West
Department of Surgery, Pederzoli Hospital, Peschiera, Italy
Alma Mater University, Bologna, Italy
Oslo University Hospital
University of Groningen
Rikshospitalet-Radiumhospitalet HF
Helsinki University Hospital and University of Helsinki
Medisch Spectrum Twente (MST)
VU University and Amsterdam Public Health Research Institute

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking.

METHODS: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265).

FINDINGS: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group.

INTERPRETATION: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer.

FUNDING: Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society.

Original language	English
Article number	100673
Pages (from-to)	100673
Journal	The Lancet Regional Health - Europe
Volume	31
DOIs	https://doi.org/10.1016/j.lanepe.2023.100673 https://doi.org/10.1016/j.lanepe.2023.100673
Publication status	Published - 1 Aug 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Distal pancreatectomy
Minimally invasive surgery
Pancreatic ductal adenocarcinoma

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European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS) (2023). Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial. The Lancet Regional Health - Europe, 31, 100673. Article 100673. https://doi.org/10.1016/j.lanepe.2023.100673, https://doi.org/10.1016/j.lanepe.2023.100673

@article{0ad27c3390d1401ab82a2d15195b39a5,

title = "Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial",

abstract = "BACKGROUND: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking.METHODS: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7\% was compared with the lower limit of the two-sided 90\% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265).FINDINGS: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73\%) patients in the MIDP group and in 76 (69\%) patients in the ODP group (difference 3.7\%, 90\% CI -6.2 to 13.6\%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41\% vs 38\%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95\% CI 4.5-5.5] vs 5 [95\% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95\% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18\%) of 131 patients in the MIDP group vs 28 (22\%) of 127 patients in the ODP group.INTERPRETATION: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer.FUNDING: Medtronic Covidien AG, Johnson \& Johnson Medical Limited, Dutch Gastroenterology Society.",

keywords = "Distal pancreatectomy, Minimally invasive surgery, Pancreatic ductal adenocarcinoma",

author = "Maarten Korrel and Jones, \{Leia R.\} and \{van Hilst\}, Jony and Gianpaolo Balzano and Bergthor Bj{\"o}rnsson and Ugo Boggi and Bratlie, \{Svein Olav\} and Busch, \{Olivier R.\} and Giovanni Butturini and Giovanni Capretti and Riccardo Casadei and Bj{\o}rn Edwin and Emmen, \{Anouk M. L. H.\} and Alessandro Esposito and Massimo Falconi and \{Groot Koerkamp\}, Bas and Tobias Keck and \{de Kleine\}, \{Ruben H. J.\} and Kleive, \{Dyre B.\} and Arto Kokkola and Lips, \{Daan J.\} and Sanne Lof and Luyer, \{Misha D. P.\} and Alberto Manzoni and Ravi Marudanayagam and \{de Pastena\}, Matteo and Nicol{\`o} Pecorelli and Primrose, \{John N.\} and Claudio Ricci and Roberto Salvia and Per Sandstr{\"o}m and Vissers, \{Frederique L. I. M.\} and Wellner, \{Ulrich F.\} and Alessandro Zerbi and Dijkgraaf, \{Marcel G. W.\} and Besselink, \{Marc G.\} and \{Abu Hilal\}, Mohammad and \{European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS)\} and Adnan Alseidi and Constanza Aquilano and Johanna Arola and Denise Bianchi and Rachel Brown and Daniela Campani and Joanne ChinAleong and Jerome Cros and Lyubomira Dimitrova and Claudio Doglioni and Safi Dokmak and Russell Dorer and Michael Doukas and Fabre, \{Jean Michel\} and Giovanni Ferrari and Viacheslay Grinevich and Stefano Gobbo and Thilo Hackert and \{van den Heuvel\}, Marius and Clement Huijsentruijt and Mar Iglesias and Casper Jansen and Igor Khatkov and David Kooby and Marco Lena and Claudio Luchini and Krishna Menon and Patrick Michenet and Quintus Molenaar and Anna Nedkova and Andrea Pietrabissa and Mihaela Raicu and Rushda Rajak and Branislava Rankovic and Aniko Rendek and Benjamin Riviere and Cunha, \{Antonio Sa\} and Marc, \{Olivier Saint\} and Velazquez, \{Patricia Sanchez\} and Donatella Santini and Aldo Scarpa and Mylene Sebagh and Donald Sears and Mihir Shah and Zahir Soonawalla and Paola Spaggiari and Lars Tharun and Tore Tholfsen and Ales Tomazic and Alessandro Vanoli and Caroline Verbeke and Joanne Verheij and \{von Winterfeld\}, Moritz and \{de Wilde\}, Roeland and Vincent Yip and Yoh Zen",

note = "Funding Information: Medtronic Covidien AG, Johnson \& Johnson Medical Limited, Dutch Gastroenterology Society.Tobias Keck is a member of the advisory board for Olympus, Medtronic, and Dexter. Daan Lips received a proctoring grant by Intuitive Surgical. Marc Besselink and Mohammad Abu Hilal received Investigator Initiated Research grants by Medtronic (DIPLOMA trial), Ethicon (DIPLOMA trial and E-MIPS registry), and Intuitive Surgical (E-MIPS registry) and proctoring grants for Dutch and European training programs in robotic pancreatoduodenectomy by Intuitive Surgical. The other authors have no conflicts of interest. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = aug,

day = "1",

doi = "10.1016/j.lanepe.2023.100673",

language = "English",

volume = "31",

pages = "100673",

journal = "The Lancet Regional Health - Europe",

issn = "2666-7762",

publisher = "Elsevier Ltd",

}

European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS) 2023, 'Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial', The Lancet Regional Health - Europe, vol. 31, 100673, pp. 100673. https://doi.org/10.1016/j.lanepe.2023.100673, https://doi.org/10.1016/j.lanepe.2023.100673

Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial. / European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS).
In: The Lancet Regional Health - Europe, Vol. 31, 100673, 01.08.2023, p. 100673.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA)

T2 - an international randomised non-inferiority trial

AU - Korrel, Maarten

AU - Jones, Leia R.

AU - van Hilst, Jony

AU - Balzano, Gianpaolo

AU - Björnsson, Bergthor

AU - Boggi, Ugo

AU - Bratlie, Svein Olav

AU - Busch, Olivier R.

AU - Butturini, Giovanni

AU - Capretti, Giovanni

AU - Casadei, Riccardo

AU - Edwin, Bjørn

AU - Emmen, Anouk M. L. H.

AU - Esposito, Alessandro

AU - Falconi, Massimo

AU - Groot Koerkamp, Bas

AU - Keck, Tobias

AU - de Kleine, Ruben H. J.

AU - Kleive, Dyre B.

AU - Kokkola, Arto

AU - Lips, Daan J.

AU - Lof, Sanne

AU - Luyer, Misha D. P.

AU - Manzoni, Alberto

AU - Marudanayagam, Ravi

AU - de Pastena, Matteo

AU - Pecorelli, Nicolò

AU - Primrose, John N.

AU - Ricci, Claudio

AU - Salvia, Roberto

AU - Sandström, Per

AU - Vissers, Frederique L. I. M.

AU - Wellner, Ulrich F.

AU - Zerbi, Alessandro

AU - Dijkgraaf, Marcel G. W.

AU - Besselink, Marc G.

AU - Abu Hilal, Mohammad

AU - European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS)

AU - Alseidi, Adnan

AU - Aquilano, Constanza

AU - Arola, Johanna

AU - Bianchi, Denise

AU - Brown, Rachel

AU - Campani, Daniela

AU - ChinAleong, Joanne

AU - Cros, Jerome

AU - Dimitrova, Lyubomira

AU - Doglioni, Claudio

AU - Dokmak, Safi

AU - Dorer, Russell

AU - Doukas, Michael

AU - Fabre, Jean Michel

AU - Ferrari, Giovanni

AU - Grinevich, Viacheslay

AU - Gobbo, Stefano

AU - Hackert, Thilo

AU - van den Heuvel, Marius

AU - Huijsentruijt, Clement

AU - Iglesias, Mar

AU - Jansen, Casper

AU - Khatkov, Igor

AU - Kooby, David

AU - Lena, Marco

AU - Luchini, Claudio

AU - Menon, Krishna

AU - Michenet, Patrick

AU - Molenaar, Quintus

AU - Nedkova, Anna

AU - Pietrabissa, Andrea

AU - Raicu, Mihaela

AU - Rajak, Rushda

AU - Rankovic, Branislava

AU - Rendek, Aniko

AU - Riviere, Benjamin

AU - Cunha, Antonio Sa

AU - Marc, Olivier Saint

AU - Velazquez, Patricia Sanchez

AU - Santini, Donatella

AU - Scarpa, Aldo

AU - Sebagh, Mylene

AU - Sears, Donald

AU - Shah, Mihir

AU - Soonawalla, Zahir

AU - Spaggiari, Paola

AU - Tharun, Lars

AU - Tholfsen, Tore

AU - Tomazic, Ales

AU - Vanoli, Alessandro

AU - Verbeke, Caroline

AU - Verheij, Joanne

AU - von Winterfeld, Moritz

AU - de Wilde, Roeland

AU - Yip, Vincent

AU - Zen, Yoh

N1 - Funding Information: Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society.Tobias Keck is a member of the advisory board for Olympus, Medtronic, and Dexter. Daan Lips received a proctoring grant by Intuitive Surgical. Marc Besselink and Mohammad Abu Hilal received Investigator Initiated Research grants by Medtronic (DIPLOMA trial), Ethicon (DIPLOMA trial and E-MIPS registry), and Intuitive Surgical (E-MIPS registry) and proctoring grants for Dutch and European training programs in robotic pancreatoduodenectomy by Intuitive Surgical. The other authors have no conflicts of interest. Publisher Copyright: © 2023 The Authors

PY - 2023/8/1

Y1 - 2023/8/1

N2 - BACKGROUND: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking.METHODS: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265).FINDINGS: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group.INTERPRETATION: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer.FUNDING: Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society.

AB - BACKGROUND: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking.METHODS: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265).FINDINGS: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group.INTERPRETATION: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer.FUNDING: Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society.

KW - Distal pancreatectomy

KW - Minimally invasive surgery

KW - Pancreatic ductal adenocarcinoma

UR - https://www.scopus.com/pages/publications/85164340899

U2 - 10.1016/j.lanepe.2023.100673

DO - 10.1016/j.lanepe.2023.100673

M3 - Article

C2 - 37457332

SN - 2666-7762

VL - 31

SP - 100673

JO - The Lancet Regional Health - Europe

JF - The Lancet Regional Health - Europe

M1 - 100673

ER -

Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial

Abstract

UN SDGs

Keywords

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