The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

doi:10.1016/j.annonc.2024.12.015

Multicenter Study

. 2025 May;36(5):529-542.

doi: 10.1016/j.annonc.2024.12.015. Epub 2025 Jan 13.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

E Rangelova¹, T F Stoop², T M E van Ramshorst³, M Ali⁴, E A van Bodegraven⁵, A A Javed⁶, D Hashimoto⁷, E Steyerberg⁸, A Banerjee⁹, A Jain¹⁰, A Sauvanet¹¹, A Serrablo¹², A Giani¹³, A Giardino¹⁴, A Zerbi¹⁵, A Arshad¹⁶, A G Wijma¹⁷, A Coratti¹⁸, A Zironda¹⁹, A Socratous²⁰, A Rojas²¹, A Halimi²², A Ejaz²³, A Oba²⁴, B Y Patel¹⁶, B Björnsson²⁵, B N Reames²⁶, B Tingstedt²⁷, B K P Goh²⁸, C Payá-Llorente²⁹, C D Del Pozo²⁹, C González-Abós³⁰, C Medin³¹, C H J van Eijck³², C de Ponthaud³³, C Takishita³⁴, C Schwabl³⁵, C Månsson³⁶, C Ricci³⁷, C A Thiels¹⁹, D Douchi³⁸, D L Hughes³⁹, D Kilburn⁴⁰, D Flanking⁴¹, D Kleive⁴², D S Silva⁴³, B H Edil¹⁰, E Pando⁴⁴, E Moltzer⁴⁵, E F Kauffman⁴⁶, E Warren³¹, E Bozkurt⁴⁷, E Sparrelid⁴⁸, E Thoma⁴⁹, E Verkolf³², F Ausania⁵⁰, F Giannone⁵¹, F J Hüttner⁴⁹, F Burdio⁵², F R Souche⁵³, F Berrevoet⁵⁴, F Daams⁴, F Motoi⁵⁵, G Saliba⁴⁸, G Kazemier⁴, G Roeyen⁵⁶, G Nappo¹⁵, G Butturini¹⁴, G Ferrari¹³, G Kito Fusai⁹, G Honda⁵⁷, G Sergeant⁵⁸, H Karteszi⁵⁹, H Takami⁶⁰, H Suto⁶¹, I Matsumoto⁶², I Mora-Oliver⁶³, I Frigerio¹⁴, J M Fabre⁵³, J Chen⁴⁰, J G Sham⁶⁴, J Davide⁴³, J Urdzik³⁶, J de Martino³³, K Nielsen⁶⁵, K Okano⁶¹, K Kamei⁶², K Okada⁶⁶, K Tanaka⁶⁷, K J Labori⁶⁸, K E Goodsell⁶⁹, L Alberici⁷⁰, L Webber⁷¹, L Kirkov⁵³, L de Franco¹⁸, M Miyashita⁷², M Maglione⁷³, M Gramellini¹⁵, M Ramera⁷⁴, M J Amaral⁷⁵, M Ramaekers⁷⁶, M J Truty¹⁹, M A van Dam⁷⁷, M W J Stommel⁴⁵, M Petrikowski⁷⁸, M Imamura⁷⁹, M Hayashi⁶⁰, M D'Hondt⁸⁰, M Brunner⁸¹, M E Hogg²¹, C Zhang²⁶, M Á Suárez-Muñoz⁸², M D Luyer⁷⁶, M Unno³⁸, M Mizuma³⁸, M Janot⁷⁸, M A Sahakyan⁸³, N B Jamieson⁸⁴, O R Busch⁵, O Bilge⁴⁷, O Belyaev⁷⁸, O Franklin⁸⁵, P Sánchez-Velázquez⁵², P Pessaux⁵¹, P S Holka²⁷, P Ghorbani⁴⁸, R Casadei³⁷, R Sartoris⁸⁶, R D Schulick⁸⁷, R Grützmann⁸³, R Sutcliffe⁶⁵, R Mata⁴⁴, R B Patel²³, R Takahashi⁵⁵, S Rodriguez Franco⁸⁷, S S Cabús⁸⁸, S Hirano⁶⁷, S Gaujoux³³, S Festen⁸⁹, S Kozono³⁴, S K Maithel³¹, S M Chai⁹⁰, S Yamaki⁷, S van Laarhoven⁹¹, J S D Mieog⁷⁷, T Murakami⁷⁹, T Codjia⁹², T Sumiyoshi⁶⁶, T M Karsten⁸⁹, T Nakamura⁶⁷, T Sugawara⁹³, U Boggi⁴⁶, V Hartman⁵⁶, V E de Meijer¹⁷, W Bartholomä⁹⁴, W Kwon⁹⁵, Y X Koh²⁸, Y Cho⁹⁵, Y Takeyama⁶², Y Inoue⁷², Y Nagakawa³⁴, Y Kawamoto⁵⁷, Y Ome⁵⁷, Z Soonawalla³⁹, K Uemura⁶⁶, C L Wolfgang⁹⁶, J Y Jang⁹⁵, R Padbury⁴⁰, S Satoi⁹⁷, W Messersmith⁹⁸, J W Wilmink⁹⁹, M Abu Hilal¹⁴, M G Besselink⁵, M Del Chiaro⁸⁷; European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS); International Consortium on Advanced Pancreatic Surgery

Collaborators, Affiliations

Collaborators

C W Michalski⁴⁹, R F de Wilde³², T Tufekci⁴⁷, H Ishida¹⁰⁰, I S Dennahy¹⁰, J A Carter¹⁰¹, J S Olapo¹⁰¹, M Caldera³⁰, M Mazzola¹⁰², M Oshima⁶¹, N Tanaka⁶⁰, S H Choi²¹, S Sato⁷², S Sugawara⁵⁵, T Abadia-Forcen¹², T M Pawlik²³, Y Kimura⁷⁹

Affiliations

¹ Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. Electronic address: t.f.stoop@amsterdamUMC.nl.
² Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA.
³ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Department of Surgery, Fondazione Poliambulanza, Instituto Ospedaliero, Brescia, Italy.
⁴ Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands.
⁵ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands.
⁶ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Department of Surgical Oncology, Department of Surgery, New York University Medical Center, New York, USA.
⁷ Department of Surgery, Kansai Medical University, Osaka, Japan.
⁸ Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
⁹ HPB & Liver Transplant Unit, Royal Free Hospital, London, UK.
¹⁰ Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
¹¹ Department of HPB Surgery and Liver Transplantation, APHP Beaujon Hospital, University of Paris Cité, Clichy, France.
¹² HPB Surgical Division, Miguel Servet University Hospital, Zaragoza, Spain.
¹³ Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
¹⁴ Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy.
¹⁵ Humanitas University, Department of Biomedical Sciences, Milan, Italy; Pancreatic Surgery Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy.
¹⁶ Hepatopancreatobiliary Unit, University Hospitals Southampton NHS Trust, Southampton General Hospital, Southampton, UK.
¹⁷ Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
¹⁸ General and Emergency Surgery Unit, Misericordia Hospital, Azienda USL Toscana Sud-Est, Grosseto, Italy.
¹⁹ Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA.
²⁰ Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
²¹ Department of Surgery, NorthShore University Health System, Evanston, USA.
²² Department of Surgery, Umeå University, Umeå, Sweden; Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
²³ Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, USA.
²⁴ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo; Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan.
²⁵ Department of Surgery, Linköping University Hospital, Linköping, Sweden.
²⁶ Department of Surgery, University of Nebraska Medical Center, Omaha, USA.
²⁷ Department of Clinical Sciences Lund, Surgery, Lund University, Skåne University Hospital, Lund, Sweden.
²⁸ Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.
²⁹ General and Digestive Surgery, Hospital Doctor Peset, Valencia, Spain.
³⁰ Hepatobiliopancreatic Department, Hospital Clinic de Barcelona, Barcelona, Spain.
³¹ Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA.
³² Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
³³ Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
³⁴ Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan.
³⁵ Department of Radiology, Medical University Innsbruck, Innsbruck, Austria.
³⁶ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
³⁷ Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy; Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy.
³⁸ Department of Surgery, Tohoku University, Sendai, Japan.
³⁹ Department of Hepatobiliary and Pancreatic Surgery, Oxford Radcliffe Hospitals NHS Foundation Trust, Oxford, UK.
⁴⁰ Department of Surgery, Flinders Medical Centre, Adelaide, Australia.
⁴¹ Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden.
⁴² Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway.
⁴³ HEBIPA Surgery, Centro Hospitalar Universitário de Santo António, Porto, Portugal.
⁴⁴ Universitat Autónoma de Barcelona, Barcelona, Spain; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
⁴⁵ Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
⁴⁶ Division of General and Transplant Surgery, University of Pisa, Pisa, Italy.
⁴⁷ Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey.
⁴⁸ Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
⁴⁹ Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany.
⁵⁰ Hepatobiliopancreatic Department, Hospital Clinic de Barcelona, Barcelona, Spain; Instituto de Investigaciones Biomédicas August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
⁵¹ Department of Visceral and Digestive Surgery, University Hospital of Strasbourg, Strasbourg, France.
⁵² Department of Surgery, Hepatobiliary and Pancreatic Unit, Hospital del Mar de Barcelona, Barcelona, Spain; Hospital del Mar Research Institute (IMIM), University Pompeu-Fabra, Barcelona, Spain.
⁵³ Oncologic & Minimally-Invasive Digestive Surgery, CHU Montpellier, University of Montpellier, Montpellier, France.
⁵⁴ Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, Ghent, Belgium.
⁵⁵ Department of Surgery, Yamagata University, Yamagata, Japan.
⁵⁶ Department of HPB, Endocrine and Transplantation Surgery, University Hospital Antwerp, Antwerp, Belgium.
⁵⁷ Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
⁵⁸ Department of Abdominal Surgery, Jessa Hospital, Faculty of Medicine and Health Sciences, Universiteit Hasselt, Hasselt, Belgium.
⁵⁹ Department of Radiology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
⁶⁰ Department of Gastroenterological Surgery (Surgery II), Nagoya University, Nagoya, Japan.
⁶¹ Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan.
⁶² Department of Surgery, Kindai University, Osakasayama, Japan.
⁶³ Department of Surgery, Liver and Pancreato-Biliary Unit, Hospital Clínico Universitario Valencia, Biomedical Research Institute, INCLIVA, Valencia, Spain.
⁶⁴ Department of Surgery, University of Washington, Seattle, USA; Fred Hutchinson Cancer Center, Seattle, USA.
⁶⁵ Department of Hepatopancreatobiliary Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
⁶⁶ Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁶⁷ Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Hokkaido, Japan.
⁶⁸ Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁶⁹ Department of Surgery, University of Washington, Seattle, USA.
⁷⁰ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy.
⁷¹ Department of Upper GI Surgery, Fiona Stanley Hospital, Perth, Austria.
⁷² Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan.
⁷³ Department of Visceral, Transplant, and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
⁷⁴ Department of Surgery, Fondazione Poliambulanza, Instituto Ospedaliero, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
⁷⁵ General Surgery Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
⁷⁶ Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.
⁷⁷ Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
⁷⁸ Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
⁷⁹ Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Hokkaido, Japan.
⁸⁰ Department of Digestive and Hepatobiliary-Pancreatic Surgery, Groeninge Hospital, Kortrijk, Belgium.
⁸¹ Department of Surgery, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany.
⁸² HPB Surgical Unit, University Hospital Virgen de la Victoria, Málaga, Spain.
⁸³ The Intervention Center, Oslo University Hospital, Rigshospitalet, Oslo, Norway.
⁸⁴ Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK.
⁸⁵ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Surgery, Umeå University, Umeå, Sweden.
⁸⁶ Department of Radiology, APHP Beaujon Hospital, University of Paris Cité, Clichy, France.
⁸⁷ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA.
⁸⁸ Department of HPB Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁸⁹ Department of Surgery, OLVG, Amsterdam, The Netherlands.
⁹⁰ Department of Anatomical Pathology, PathWest Laboratory Medicine, Perth, Australia.
⁹¹ Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of HPB Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
⁹² Department of Digestive Surgery, Rouen University Hospital, Rouen, France.
⁹³ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo.
⁹⁴ Department of Radiology, Linköping University, Linköping, Sweden.
⁹⁵ Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea.
⁹⁶ Department of Surgical Oncology, Department of Surgery, New York University Medical Center, New York, USA.
⁹⁷ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Surgery, Kansai Medical University, Osaka, Japan.
⁹⁸ Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, USA.
⁹⁹ Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, The Netherlands.
¹⁰⁰ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
¹⁰¹ Department of Surgery, University of Washington, Seattle, Japan.
¹⁰² Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Milan, USA.

PMID: 39814200
DOI: 10.1016/j.annonc.2024.12.015

Free article

Multicenter Study

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

E Rangelova et al. Ann Oncol. 2025 May.

Free article

. 2025 May;36(5):529-542.

doi: 10.1016/j.annonc.2024.12.015. Epub 2025 Jan 13.

Authors

Collaborators

C W Michalski⁴⁹, R F de Wilde³², T Tufekci⁴⁷, H Ishida¹⁰⁰, I S Dennahy¹⁰, J A Carter¹⁰¹, J S Olapo¹⁰¹, M Caldera³⁰, M Mazzola¹⁰², M Oshima⁶¹, N Tanaka⁶⁰, S H Choi²¹, S Sato⁷², S Sugawara⁵⁵, T Abadia-Forcen¹², T M Pawlik²³, Y Kimura⁷⁹

Affiliations

¹ Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. Electronic address: t.f.stoop@amsterdamUMC.nl.
² Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA.
³ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Department of Surgery, Fondazione Poliambulanza, Instituto Ospedaliero, Brescia, Italy.
⁴ Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands.
⁵ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands.
⁶ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Department of Surgical Oncology, Department of Surgery, New York University Medical Center, New York, USA.
⁷ Department of Surgery, Kansai Medical University, Osaka, Japan.
⁸ Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
⁹ HPB & Liver Transplant Unit, Royal Free Hospital, London, UK.
¹⁰ Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
¹¹ Department of HPB Surgery and Liver Transplantation, APHP Beaujon Hospital, University of Paris Cité, Clichy, France.
¹² HPB Surgical Division, Miguel Servet University Hospital, Zaragoza, Spain.
¹³ Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
¹⁴ Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy.
¹⁵ Humanitas University, Department of Biomedical Sciences, Milan, Italy; Pancreatic Surgery Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy.
¹⁶ Hepatopancreatobiliary Unit, University Hospitals Southampton NHS Trust, Southampton General Hospital, Southampton, UK.
¹⁷ Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
¹⁸ General and Emergency Surgery Unit, Misericordia Hospital, Azienda USL Toscana Sud-Est, Grosseto, Italy.
¹⁹ Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA.
²⁰ Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
²¹ Department of Surgery, NorthShore University Health System, Evanston, USA.
²² Department of Surgery, Umeå University, Umeå, Sweden; Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
²³ Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, USA.
²⁴ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo; Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan.
²⁵ Department of Surgery, Linköping University Hospital, Linköping, Sweden.
²⁶ Department of Surgery, University of Nebraska Medical Center, Omaha, USA.
²⁷ Department of Clinical Sciences Lund, Surgery, Lund University, Skåne University Hospital, Lund, Sweden.
²⁸ Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.
²⁹ General and Digestive Surgery, Hospital Doctor Peset, Valencia, Spain.
³⁰ Hepatobiliopancreatic Department, Hospital Clinic de Barcelona, Barcelona, Spain.
³¹ Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA.
³² Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
³³ Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
³⁴ Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan.
³⁵ Department of Radiology, Medical University Innsbruck, Innsbruck, Austria.
³⁶ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
³⁷ Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy; Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy.
³⁸ Department of Surgery, Tohoku University, Sendai, Japan.
³⁹ Department of Hepatobiliary and Pancreatic Surgery, Oxford Radcliffe Hospitals NHS Foundation Trust, Oxford, UK.
⁴⁰ Department of Surgery, Flinders Medical Centre, Adelaide, Australia.
⁴¹ Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden.
⁴² Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway.
⁴³ HEBIPA Surgery, Centro Hospitalar Universitário de Santo António, Porto, Portugal.
⁴⁴ Universitat Autónoma de Barcelona, Barcelona, Spain; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
⁴⁵ Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
⁴⁶ Division of General and Transplant Surgery, University of Pisa, Pisa, Italy.
⁴⁷ Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey.
⁴⁸ Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
⁴⁹ Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany.
⁵⁰ Hepatobiliopancreatic Department, Hospital Clinic de Barcelona, Barcelona, Spain; Instituto de Investigaciones Biomédicas August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
⁵¹ Department of Visceral and Digestive Surgery, University Hospital of Strasbourg, Strasbourg, France.
⁵² Department of Surgery, Hepatobiliary and Pancreatic Unit, Hospital del Mar de Barcelona, Barcelona, Spain; Hospital del Mar Research Institute (IMIM), University Pompeu-Fabra, Barcelona, Spain.
⁵³ Oncologic & Minimally-Invasive Digestive Surgery, CHU Montpellier, University of Montpellier, Montpellier, France.
⁵⁴ Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, Ghent, Belgium.
⁵⁵ Department of Surgery, Yamagata University, Yamagata, Japan.
⁵⁶ Department of HPB, Endocrine and Transplantation Surgery, University Hospital Antwerp, Antwerp, Belgium.
⁵⁷ Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
⁵⁸ Department of Abdominal Surgery, Jessa Hospital, Faculty of Medicine and Health Sciences, Universiteit Hasselt, Hasselt, Belgium.
⁵⁹ Department of Radiology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
⁶⁰ Department of Gastroenterological Surgery (Surgery II), Nagoya University, Nagoya, Japan.
⁶¹ Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan.
⁶² Department of Surgery, Kindai University, Osakasayama, Japan.
⁶³ Department of Surgery, Liver and Pancreato-Biliary Unit, Hospital Clínico Universitario Valencia, Biomedical Research Institute, INCLIVA, Valencia, Spain.
⁶⁴ Department of Surgery, University of Washington, Seattle, USA; Fred Hutchinson Cancer Center, Seattle, USA.
⁶⁵ Department of Hepatopancreatobiliary Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
⁶⁶ Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁶⁷ Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Hokkaido, Japan.
⁶⁸ Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁶⁹ Department of Surgery, University of Washington, Seattle, USA.
⁷⁰ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy.
⁷¹ Department of Upper GI Surgery, Fiona Stanley Hospital, Perth, Austria.
⁷² Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan.
⁷³ Department of Visceral, Transplant, and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
⁷⁴ Department of Surgery, Fondazione Poliambulanza, Instituto Ospedaliero, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
⁷⁵ General Surgery Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
⁷⁶ Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.
⁷⁷ Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
⁷⁸ Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
⁷⁹ Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Hokkaido, Japan.
⁸⁰ Department of Digestive and Hepatobiliary-Pancreatic Surgery, Groeninge Hospital, Kortrijk, Belgium.
⁸¹ Department of Surgery, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany.
⁸² HPB Surgical Unit, University Hospital Virgen de la Victoria, Málaga, Spain.
⁸³ The Intervention Center, Oslo University Hospital, Rigshospitalet, Oslo, Norway.
⁸⁴ Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK.
⁸⁵ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Surgery, Umeå University, Umeå, Sweden.
⁸⁶ Department of Radiology, APHP Beaujon Hospital, University of Paris Cité, Clichy, France.
⁸⁷ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA.
⁸⁸ Department of HPB Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁸⁹ Department of Surgery, OLVG, Amsterdam, The Netherlands.
⁹⁰ Department of Anatomical Pathology, PathWest Laboratory Medicine, Perth, Australia.
⁹¹ Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of HPB Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
⁹² Department of Digestive Surgery, Rouen University Hospital, Rouen, France.
⁹³ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo.
⁹⁴ Department of Radiology, Linköping University, Linköping, Sweden.
⁹⁵ Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea.
⁹⁶ Department of Surgical Oncology, Department of Surgery, New York University Medical Center, New York, USA.
⁹⁷ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Surgery, Kansai Medical University, Osaka, Japan.
⁹⁸ Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, USA.
⁹⁹ Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, The Netherlands.
¹⁰⁰ Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
¹⁰¹ Department of Surgery, University of Washington, Seattle, Japan.
¹⁰² Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Milan, USA.

PMID: 39814200
DOI: 10.1016/j.annonc.2024.12.015

Abstract

Background: Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery.

Patients and methods: This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated.

Results: Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (P_interaction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; P_interaction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (P_interaction = 0.43), splenic vein (P_interaction = 0.30), retroperitoneal (P_interaction = 0.84), and multivisceral (P_interaction = 0.96) involvement.

Conclusions: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

Keywords: CA19-9; neoadjuvant therapy; pancreatic adenocarcinoma; pancreatic body/tail; resectable; tumor size.

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The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

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The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

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