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Rangelova E, Stoop TF, van Ramshorst TME, Ali M, van Bodegraven EA, Javed AA, Hashimoto D, Steyerberg E, Banerjee A, Jain A, Sauvanet A, Serrablo A, Giani A, Giardino A, Zerbi A, Arshad A, Wijma AG, Coratti A, Zironda A, Socratous A, Rojas A, Halimi A, Ejaz A, Oba A, Patel BY, Björnsson B, Reames BN, Tingstedt B, Goh BKP, Payá-Llorente C, Del Pozo CD, González-Abós C, Medin C, van Eijck CHJ, de Ponthaud C, Takishita C, Schwabl C, Månsson C, Ricci C, Thiels CA, Douchi D, Hughes DL, Kilburn D, Flanking D, Kleive D, Silva DS, Edil BH, Pando E, Moltzer E, Kauffman EF, Warren E, Bozkurt E, Sparrelid E, Thoma E, Verkolf E, Ausania F, Giannone F, Hüttner FJ, Burdio F, Souche FR, Berrevoet F, Daams F, Motoi F, Saliba G, Kazemier G, Roeyen G, Nappo G, Butturini G, Ferrari G, Kito Fusai G, Honda G, Sergeant G, Karteszi H, Takami H, Suto H, Matsumoto I, Mora-Oliver I, Frigerio I, Fabre JM, Chen J, Sham JG, Davide J, Urdzik J, de Martino J, Nielsen K, Okano K, Kamei K, Okada K, Tanaka K, Labori KJ, Goodsell KE, Alberici L, Webber L, Kirkov L, de Franco L, Miyashita M, Maglione M, Gramellini M, Ramera M, Amaral MJ, et alRangelova E, Stoop TF, van Ramshorst TME, Ali M, van Bodegraven EA, Javed AA, Hashimoto D, Steyerberg E, Banerjee A, Jain A, Sauvanet A, Serrablo A, Giani A, Giardino A, Zerbi A, Arshad A, Wijma AG, Coratti A, Zironda A, Socratous A, Rojas A, Halimi A, Ejaz A, Oba A, Patel BY, Björnsson B, Reames BN, Tingstedt B, Goh BKP, Payá-Llorente C, Del Pozo CD, González-Abós C, Medin C, van Eijck CHJ, de Ponthaud C, Takishita C, Schwabl C, Månsson C, Ricci C, Thiels CA, Douchi D, Hughes DL, Kilburn D, Flanking D, Kleive D, Silva DS, Edil BH, Pando E, Moltzer E, Kauffman EF, Warren E, Bozkurt E, Sparrelid E, Thoma E, Verkolf E, Ausania F, Giannone F, Hüttner FJ, Burdio F, Souche FR, Berrevoet F, Daams F, Motoi F, Saliba G, Kazemier G, Roeyen G, Nappo G, Butturini G, Ferrari G, Kito Fusai G, Honda G, Sergeant G, Karteszi H, Takami H, Suto H, Matsumoto I, Mora-Oliver I, Frigerio I, Fabre JM, Chen J, Sham JG, Davide J, Urdzik J, de Martino J, Nielsen K, Okano K, Kamei K, Okada K, Tanaka K, Labori KJ, Goodsell KE, Alberici L, Webber L, Kirkov L, de Franco L, Miyashita M, Maglione M, Gramellini M, Ramera M, Amaral MJ, Ramaekers M, Truty MJ, van Dam MA, Stommel MWJ, Petrikowski M, Imamura M, Hayashi M, D'Hondt M, Brunner M, Hogg ME, Zhang C, Suárez-Muñoz MÁ, Luyer MD, Unno M, Mizuma M, Janot M, Sahakyan MA, Jamieson NB, Busch OR, Bilge O, Belyaev O, Franklin O, Sánchez-Velázquez P, Pessaux P, Holka PS, Ghorbani P, Casadei R, Sartoris R, Schulick RD, Grützmann R, Sutcliffe R, Mata R, Patel RB, Takahashi R, Rodriguez Franco S, Cabús SS, Hirano S, Gaujoux S, Festen S, Kozono S, Maithel SK, Chai SM, Yamaki S, van Laarhoven S, Mieog JSD, Murakami T, Codjia T, Sumiyoshi T, Karsten TM, Nakamura T, Sugawara T, Boggi U, Hartman V, de Meijer VE, Bartholomä W, Kwon W, Koh YX, Cho Y, Takeyama Y, Inoue Y, Nagakawa Y, Kawamoto Y, Ome Y, Soonawalla Z, Uemura K, Wolfgang CL, Jang JY, Padbury R, Satoi S, Messersmith W, Wilmink JW, Abu Hilal M, Besselink MG, Del Chiaro M. The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study. Ann Oncol 2025; 36:529-542. [PMID: 39814200 DOI: 10.1016/j.annonc.2024.12.015] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 10/26/2024] [Accepted: 12/23/2024] [Indexed: 01/18/2025] Open
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 (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 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.
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Affiliation(s)
- E Rangelova
- 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.
| | - T F Stoop
- 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
| | - T M E van Ramshorst
- 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
| | - M Ali
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
| | - E A van Bodegraven
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - A A Javed
- 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
| | - D Hashimoto
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - E Steyerberg
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - A Banerjee
- HPB & Liver Transplant Unit, Royal Free Hospital, London, UK
| | - A Jain
- Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, USA
| | - A Sauvanet
- Department of HPB Surgery and Liver Transplantation, APHP Beaujon Hospital, University of Paris Cité, Clichy, France
| | - A Serrablo
- HPB Surgical Division, Miguel Servet University Hospital, Zaragoza, Spain
| | - A Giani
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - A Giardino
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - A Zerbi
- Humanitas University, Department of Biomedical Sciences, Milan, Italy; Pancreatic Surgery Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - A Arshad
- Hepatopancreatobiliary Unit, University Hospitals Southampton NHS Trust, Southampton General Hospital, Southampton, UK
| | - A G Wijma
- Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - A Coratti
- General and Emergency Surgery Unit, Misericordia Hospital, Azienda USL Toscana Sud-Est, Grosseto, Italy
| | - A Zironda
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA
| | - A Socratous
- 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
| | - A Rojas
- Department of Surgery, NorthShore University Health System, Evanston, USA
| | - A Halimi
- 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
| | - A Ejaz
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, USA
| | - A Oba
- 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
| | - B Y Patel
- Hepatopancreatobiliary Unit, University Hospitals Southampton NHS Trust, Southampton General Hospital, Southampton, UK
| | - B Björnsson
- Department of Surgery, Linköping University Hospital, Linköping, Sweden
| | - B N Reames
- Department of Surgery, University of Nebraska Medical Center, Omaha, USA
| | - B Tingstedt
- Department of Clinical Sciences Lund, Surgery, Lund University, Skåne University Hospital, Lund, Sweden
| | - B K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - C Payá-Llorente
- General and Digestive Surgery, Hospital Doctor Peset, Valencia, Spain
| | - C D Del Pozo
- General and Digestive Surgery, Hospital Doctor Peset, Valencia, Spain
| | - C González-Abós
- Hepatobiliopancreatic Department, Hospital Clinic de Barcelona, Barcelona, Spain
| | - C Medin
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - C H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - C de Ponthaud
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - C Takishita
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - C Schwabl
- Department of Radiology, Medical University Innsbruck, Innsbruck, Austria
| | - C Månsson
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - C Ricci
- 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
| | - C A Thiels
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA
| | - D Douchi
- Department of Surgery, Tohoku University, Sendai, Japan
| | - D L Hughes
- Department of Hepatobiliary and Pancreatic Surgery, Oxford Radcliffe Hospitals NHS Foundation Trust, Oxford, UK
| | - D Kilburn
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - D Flanking
- Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden
| | - D Kleive
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
| | - D S Silva
- HEBIPA Surgery, Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - B H Edil
- Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, USA
| | - E Pando
- Universitat Autónoma de Barcelona, Barcelona, Spain; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - E Moltzer
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - E F Kauffman
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - E Warren
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - E Bozkurt
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - E Sparrelid
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - E Thoma
- Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany
| | - E Verkolf
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - F Ausania
- Hepatobiliopancreatic Department, Hospital Clinic de Barcelona, Barcelona, Spain; Instituto de Investigaciones Biomédicas August Pi I Sunyer (IDIBAPS), Barcelona, Spain
| | - F Giannone
- Department of Visceral and Digestive Surgery, University Hospital of Strasbourg, Strasbourg, France
| | - F J Hüttner
- Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany
| | - F Burdio
- 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
| | - F R Souche
- Oncologic & Minimally-Invasive Digestive Surgery, CHU Montpellier, University of Montpellier, Montpellier, France
| | - F Berrevoet
- Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, Ghent, Belgium
| | - F Daams
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
| | - F Motoi
- Department of Surgery, Yamagata University, Yamagata, Japan
| | - G Saliba
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - G Kazemier
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
| | - G Roeyen
- Department of HPB, Endocrine and Transplantation Surgery, University Hospital Antwerp, Antwerp, Belgium
| | - G Nappo
- Humanitas University, Department of Biomedical Sciences, Milan, Italy; Pancreatic Surgery Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - G Butturini
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - G Ferrari
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - G Kito Fusai
- HPB & Liver Transplant Unit, Royal Free Hospital, London, UK
| | - G Honda
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - G Sergeant
- Department of Abdominal Surgery, Jessa Hospital, Faculty of Medicine and Health Sciences, Universiteit Hasselt, Hasselt, Belgium
| | - H Karteszi
- Department of Radiology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - H Takami
- Department of Gastroenterological Surgery (Surgery II), Nagoya University, Nagoya, Japan
| | - H Suto
- Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan
| | - I Matsumoto
- Department of Surgery, Kindai University, Osakasayama, Japan
| | - I Mora-Oliver
- Department of Surgery, Liver and Pancreato-Biliary Unit, Hospital Clínico Universitario Valencia, Biomedical Research Institute, INCLIVA, Valencia, Spain
| | - I Frigerio
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - J M Fabre
- Oncologic & Minimally-Invasive Digestive Surgery, CHU Montpellier, University of Montpellier, Montpellier, France
| | - J Chen
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - J G Sham
- Department of Surgery, University of Washington, Seattle, USA; Fred Hutchinson Cancer Center, Seattle, USA
| | - J Davide
- HEBIPA Surgery, Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - J Urdzik
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - J de Martino
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - K Nielsen
- Department of Hepatopancreatobiliary Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - K Okano
- Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan
| | - K Kamei
- Department of Surgery, Kindai University, Osakasayama, Japan
| | - K Okada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - K Tanaka
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - K J Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - K E Goodsell
- Department of Surgery, University of Washington, Seattle, USA
| | - L Alberici
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - L Webber
- Department of Upper GI Surgery, Fiona Stanley Hospital, Perth, Austria
| | - L Kirkov
- Oncologic & Minimally-Invasive Digestive Surgery, CHU Montpellier, University of Montpellier, Montpellier, France
| | - L de Franco
- General and Emergency Surgery Unit, Misericordia Hospital, Azienda USL Toscana Sud-Est, Grosseto, Italy
| | - M Miyashita
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - M Maglione
- Department of Visceral, Transplant, and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - M Gramellini
- Humanitas University, Department of Biomedical Sciences, Milan, Italy; Pancreatic Surgery Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - M Ramera
- Department of Surgery, Fondazione Poliambulanza, Instituto Ospedaliero, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - M J Amaral
- General Surgery Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - M Ramaekers
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - M J Truty
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA
| | - M A van Dam
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - M W J Stommel
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - M Petrikowski
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - M Imamura
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Hokkaido, Japan
| | - M Hayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University, Nagoya, Japan
| | - M D'Hondt
- Department of Digestive and Hepatobiliary-Pancreatic Surgery, Groeninge Hospital, Kortrijk, Belgium
| | - M Brunner
- Department of Surgery, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany
| | - M E Hogg
- Department of Surgery, NorthShore University Health System, Evanston, USA
| | - C Zhang
- Department of Surgery, University of Nebraska Medical Center, Omaha, USA
| | - M Á Suárez-Muñoz
- HPB Surgical Unit, University Hospital Virgen de la Victoria, Málaga, Spain
| | - M D Luyer
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - M Unno
- Department of Surgery, Tohoku University, Sendai, Japan
| | - M Mizuma
- Department of Surgery, Tohoku University, Sendai, Japan
| | - M Janot
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - M A Sahakyan
- The Intervention Center, Oslo University Hospital, Rigshospitalet, Oslo, Norway
| | - N B Jamieson
- Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - O R Busch
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - O Bilge
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - O Belyaev
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - O Franklin
- 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
| | - P Sánchez-Velázquez
- 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
| | - P Pessaux
- Department of Visceral and Digestive Surgery, University Hospital of Strasbourg, Strasbourg, France
| | - P S Holka
- Department of Clinical Sciences Lund, Surgery, Lund University, Skåne University Hospital, Lund, Sweden
| | - P Ghorbani
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - R Casadei
- 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
| | - R Sartoris
- Department of Radiology, APHP Beaujon Hospital, University of Paris Cité, Clichy, France
| | - R D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA
| | - R Grützmann
- The Intervention Center, Oslo University Hospital, Rigshospitalet, Oslo, Norway
| | - R Sutcliffe
- Department of Hepatopancreatobiliary Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - R Mata
- Universitat Autónoma de Barcelona, Barcelona, Spain; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - R B Patel
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, USA
| | - R Takahashi
- Department of Surgery, Yamagata University, Yamagata, Japan
| | - S Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA
| | - S S Cabús
- Department of HPB Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - S Hirano
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - S Gaujoux
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - S Festen
- Department of Surgery, OLVG, Amsterdam, The Netherlands
| | - S Kozono
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - S K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - S M Chai
- Department of Anatomical Pathology, PathWest Laboratory Medicine, Perth, Australia
| | - S Yamaki
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - S van Laarhoven
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of HPB Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - J S D Mieog
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - T Murakami
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Hokkaido, Japan
| | - T Codjia
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
| | - T Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - T M Karsten
- Department of Surgery, OLVG, Amsterdam, The Netherlands
| | - T Nakamura
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - T Sugawara
- 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
| | - U Boggi
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - V Hartman
- Department of HPB, Endocrine and Transplantation Surgery, University Hospital Antwerp, Antwerp, Belgium
| | - V E de Meijer
- Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - W Bartholomä
- Department of Radiology, Linköping University, Linköping, Sweden
| | - W Kwon
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Y X Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Y Cho
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Y Takeyama
- Department of Surgery, Kindai University, Osakasayama, Japan
| | - Y Inoue
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Y Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Y Kawamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Y Ome
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Z Soonawalla
- Department of Hepatobiliary and Pancreatic Surgery, Oxford Radcliffe Hospitals NHS Foundation Trust, Oxford, UK
| | - K Uemura
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - C L Wolfgang
- Department of Surgical Oncology, Department of Surgery, New York University Medical Center, New York, USA
| | - J Y Jang
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - R Padbury
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - S Satoi
- 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
| | - W Messersmith
- Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, USA
| | - J W Wilmink
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, The Netherlands
| | - M Abu Hilal
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - M G Besselink
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - M Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA
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Stoop TF, Sugawara T, Oba A, Feld IM, van Roessel S, van Veldhuisen E, Wu YHA, Nishino J, Ali M, Alseidi A, Sauvanet A, Mirabella A, Sa Cunha A, Kokkola A, Groot Koerkamp B, Pietrasz D, Kleive D, Butturini G, Malleo G, van Laarhoven HWM, Frigerio I, Dembinski J, He J, Gagnière J, Kleeff J, Ramia JM, Roberts KJ, Labori KJ, Marino MV, Falconi M, B. Mortensen M, Lesurtel M, Bonds M, Chatzizacharias N, Strobel O, Turrini O, Griffin O, Franklin O, Pfeiffer P, Schulick RD, Salvia R, de Wilde RF, Dokmak S, Rodriguez Franco S, Augustinus S, Burgdorf SK, Crippa S, Hackert T, Tarvainen T, Burns WR, Messersmith W, Wilmink JW, Burkhart RA, Del Chiaro M, Besselink MG. Adjuvant Chemotherapy After Resection of Localized Pancreatic Adenocarcinoma Following Preoperative FOLFIRINOX. JAMA Oncol 2025; 11:276-287. [PMID: 39847363 PMCID: PMC11926629 DOI: 10.1001/jamaoncol.2024.5917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 10/05/2024] [Indexed: 01/24/2025]
Abstract
Importance The effect of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) chemotherapy on overall survival (OS) is unclear because current studies do not account for the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen. Objective To investigate the association of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX with OS, taking into account the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen. Design, Setting, and Participants This retrospective cohort study included patients with localized pancreatic adenocarcinoma treated with 2 to 11 cycles of preoperative (m)FOLFIRINOX followed by resection across 48 centers in 20 countries from 2010 to 2018. Patients who died within 3 months after surgery were excluded (landmark). Data were analyzed from February 1 to December 31, 2023. Exposures Preoperative (m)FOLFIRINOX chemotherapy followed by resection and eventually followed by adjuvant chemotherapy. Main Outcomes and Measures The primary outcome was OS, calculated from the 3-month landmark. Cox regression analysis, including interaction analyses, was performed to investigate the association of adjuvant chemotherapy with OS. Results Overall, 767 patients were included after resection of pancreatic adenocarcinoma (median [IQR] age, 62 [55-67] years; 404 [52.7%] male). Adjuvant chemotherapy was independently associated with prolonged OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87), confirmed by adjusted OS curves. The interaction analysis to assess estimated treatment effect across subgroups was not statistically significant. The forest plot and interaction test suggest that the association of adjuvant chemotherapy was lower among patients receiving 8 or more cycles of preoperative (m)FOLFIRINOX, those who had radiological response, and those with ypN0 disease. Compared to no adjuvant chemotherapy, both adjuvant (m)FOLFIRINOX (HR, 0.57; 95% CI, 0.40-0.80) and other multiagent adjuvant regimens (HR, 0.61; 95% CI, 0.41-0.92) were associated with prolonged OS, whereas single-agent adjuvant chemotherapy was not (HR, 0.75; 95% CI, 0.55-1.03). Conclusions and Relevance In this cohort study, adjuvant (m)FOLFIRINOX and other multiagent chemotherapy regimens were associated with improved OS following resection of localized pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX, whereas single-agent adjuvant chemotherapy was not. The impact of adjuvant chemotherapy on OS may be lower in subgroups such as patients with 8 or more preoperative cycles of (m)FOLFIRINOX, those having radiological response, and those with ypN0.
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Affiliation(s)
- Thomas F. Stoop
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Toshitaka Sugawara
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Atsushi Oba
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Isabel M. Feld
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Stijn van Roessel
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Eran van Veldhuisen
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Y. H. Andrew Wu
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland
| | - Jo Nishino
- Division of Bioinformatics, Research Institute National Cancer Center Japan, Tokyo, Japan
| | - Mahsoem Ali
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Adnan Alseidi
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Alain Sauvanet
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, University Paris Cité, Clichy, France
| | - Antonello Mirabella
- General Surgery Department, Azienda Ospedaliera, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
| | - Antonio Sa Cunha
- Department of Hepato-Biliary-Pancreatic Surgery, Liver Transplant Center, Université Paris-Sud, Université Paris-Saclay, Villejuif, France
| | - Arto Kokkola
- Department of Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Daniel Pietrasz
- Department of Hepato-Biliary-Pancreatic Surgery, Liver Transplant Center, Université Paris-Sud, Université Paris-Saclay, Villejuif, France
| | - Dyre Kleive
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | | | - Giuseppe Malleo
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Hanneke W. M. van Laarhoven
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands
| | | | - Jeanne Dembinski
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, University Paris Cité, Clichy, France
| | - Jin He
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland
| | - Johan Gagnière
- Department of Digestive and Hepatobiliary Surgery-Liver Transplantation, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France
| | - Jörg Kleeff
- Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Halle, Germany
| | - Jose M. Ramia
- Department of Surgery, Hospital General Universitario de Alicante, Alicante, Spain
| | - Keith J. Roberts
- Hepato-Pancreato-Biliary Unit, Department of Surgery, University Hospitals of Birmingham, Birmingham, United Kingdom
| | - Knut J. Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Marco V. Marino
- General Surgery Department, Azienda Ospedaliera, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
| | - Massimo Falconi
- Department of Pancreatic Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milano, Italy
| | - Michael B. Mortensen
- Department of Surgery, Odense Pancreas Center, Odense University Hospital, Odense, Denmark
| | - Mickaël Lesurtel
- Department of Hepato-Biliary-Pancreatic Surgery, Liver Transplant Center, Université Paris-Sud, Université Paris-Saclay, Villejuif, France
| | - Morgan Bonds
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Nikolaos Chatzizacharias
- Hepato-Pancreato-Biliary Unit, Department of Surgery, University Hospitals of Birmingham, Birmingham, United Kingdom
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Olivier Turrini
- Department of Surgical Oncology, Aix-Marseille University, Institut Paoli-Calmettes, CRCM, Marseille, France
| | - Oonagh Griffin
- National Surgical Center for Pancreatic Cancer, St. Vincent’s University Hospital, Dublin, Ireland
| | - Oskar Franklin
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
- Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden
| | - Per Pfeiffer
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Richard D. Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Roeland F. de Wilde
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Safi Dokmak
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, University Paris Cité, Clichy, France
| | - Salvador Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
| | - Simone Augustinus
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Stefan K. Burgdorf
- Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Stefano Crippa
- Department of Pancreatic Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milano, Italy
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Timo Tarvainen
- Department of Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - William R. Burns
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland
| | - Wells Messersmith
- Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora
| | - Johanna W. Wilmink
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands
| | - Richard A. Burkhart
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
| | - Marc G. Besselink
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
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Zhang JZ, Zhang ZW, Guo XY, Zhu DS, Huang XR, Cai M, Guo T, Yu YH. Comparison of clinical characteristics and prognostic factors in two site-specific categories of ampullary cancer. World J Gastroenterol 2024; 30:4281-4294. [PMID: 39492830 PMCID: PMC11525854 DOI: 10.3748/wjg.v30.i39.4281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 09/13/2024] [Accepted: 09/20/2024] [Indexed: 10/12/2024] Open
Abstract
BACKGROUND Ampullary cancer is a relatively rare malignant tumor in the digestive system. Its incidence has increased in recent years. As for now, its biological characteristics have not been fully clarified. Recent studies have primarily focused on the histological classification and genetic changes, but there are fewer investigations into the differences among site-specific subgroups. The clinicopathological characteristics of ampullary cancer occurring in different positions have not been elucidated. Furthermore, the role of adjuvant therapy in the treatment of patients with ampullary cancer remains controversial. AIM To study the clinicopathological features of the two site-specific subgroups of ampullary cancer and explore the factors affecting prognosis. METHODS A total of 356 patients who met the inclusion and exclusion criteria were enrolled. Patients were divided into ampulla of Vater cancer (AVC) and duodenal papilla cancer (DPC) based on the gross and microscopic findings. Baseline data, admission examination results, and perioperative outcomes were collected and analyzed. The Kaplan-Meier curve was used for survival analysis. Univariate and multivariate analysis was performed to explore the independent risk factors affecting the overall survival (OS) of both groups. RESULTS The preoperative total bilirubin level in patients with AVC was significantly higher than those with DPC (P = 0.04). The OS for patients with DPC was 58.90 ± 38.74 months, significantly longer than 44.31 ± 35.90 months for patients with AVC (P < 0.01). The independent risk factors affecting the OS of AVC included: Preoperative albumin level (P = 0.009), total bilirubin level (P = 0.017), and number of positive lymph nodes (P = 0.005). For DPC, risk factors included: Age (P = 0.004), tumor size (P = 0.023), number of positive lymph nodes (P = 0.010) and adjuvant treatment (P = 0.020). Adjuvant therapy significantly improved the OS rate of patients with DPC, but not for those with AVC. CONCLUSION Patients with AVC had a shorter OS compared to those with DPC. The prognosis factors and the role of adjuvant therapy of two groups were different.
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Affiliation(s)
- Jing-Zhao Zhang
- Department of Biliopancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Zhi-Wei Zhang
- Department of Biliopancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Xin-Yi Guo
- Department of Biliopancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Deng-Sheng Zhu
- Department of Biliopancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Xiao-Rui Huang
- Department of Biliopancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Ming Cai
- Department of Biliopancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Tong Guo
- Department of Biliopancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Ya-Hong Yu
- Department of Biliopancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
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Yun WG, Kim D, Lee M, Han Y, Chae YS, Jung HS, Cho YJ, Kwon W, Park JS, Park D, Jang JY. Comparing clinical and genomic features based on the tumor location in patients with resected pancreatic cancer. BMC Cancer 2024; 24:1048. [PMID: 39187784 PMCID: PMC11346014 DOI: 10.1186/s12885-024-12795-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 08/12/2024] [Indexed: 08/28/2024] Open
Abstract
BACKGROUND Pancreatic cancer is anatomically divided into pancreatic head and body/tail cancers, and some studies have reported differences in prognosis. However, whether this discrepancy is induced from the difference of tumor biology is hotly debated. Therefore, we aimed to evaluate the differences in clinical outcomes and tumor biology depending on the tumor location. METHODS In this retrospective cohort study, we identified 800 patients with pancreatic ductal adenocarcinoma who had undergone upfront curative-intent surgery. Cox regression analysis was performed to explore the prognostic impact of the tumor location. Among them, 153 patients with sufficient tumor tissue and blood samples who provided informed consent for next-generation sequencing were selected as the cohort for genomic analysis. RESULTS Out of the 800 patients, 500 (62.5%) had pancreatic head cancer, and 300 (37.5%) had body/tail cancer. Tumor location in the body/tail of the pancreas was not identified as a significant predictor of survival outcomes compared to that in the head in multivariate analysis (hazard ratio, 0.94; 95% confidence interval, 0.77-1.14; P = 0.511). Additionally, in the genomic analyses of 153 patients, there were no significant differences in mutational landscapes, distribution of subtypes based on transcriptomic profiling, and estimated infiltration levels of various immune cells between pancreatic head and body/tail cancers. CONCLUSIONS We could not find differences in prognosis and tumor biology depending on tumor location in pancreatic ductal adenocarcinoma. Discrepancies in prognosis may represent a combination of lead time, selection bias, and clinical differences, including the surgical burden between tumor sites.
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Affiliation(s)
- Won-Gun Yun
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Daeun Kim
- Department of Molecular Science and Technology, Ajou University, Suwon, 16499, Republic of Korea
- Ajou Energy Science Research Center, Ajou University, Suwon, 16499, Republic of Korea
| | - Mirang Lee
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Yoon Soo Chae
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Hye-Sol Jung
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Young Jae Cho
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Joon Seong Park
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Daechan Park
- Department of Molecular Science and Technology, Ajou University, Suwon, 16499, Republic of Korea
- Advanced College of Bio-Convergence Engineering, Ajou University, Suwon, 16499, Republic of Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
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Zhu Y, Liang X, Zhang G, Li F, Xu J, Ma R, Chen X, Ma M, Wang Y, Chen C, Tang H, Li L, Li Z. Microbiota and metabolite alterations in pancreatic head and body/tail cancer patients. Cancer Sci 2024; 115:2738-2750. [PMID: 38888048 PMCID: PMC11309928 DOI: 10.1111/cas.16238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 05/14/2024] [Accepted: 05/22/2024] [Indexed: 06/20/2024] Open
Abstract
Pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) have distinct clinical and biological behaviors. The microbial and metabolic differences in PHC and PBTC have not been studied. The pancreatic microbiota and metabolome of 15 PHC and 8 PBTC tissues and their matched nontumor tissues were characterized using 16S rRNA amplicon sequencing and untargeted metabolomics. At the genus level, Bradyrhizobium was increased while Corynebacterium and Ruminococcus were decreased in the PHC tissues (Head T) compared with the matched nontumor tissues (Head N) significantly. Shuttleworthia, Bacillus, and Bifidobacterium were significantly decreased in the PBTC tissues (Body/Tail T) compared with the matched nontumor tissues (Body/Tail N). Significantly, Ileibacterium was increased whereas Pseudoxanthomonas was decreased in Head T and Body/Tail T, and Lactobacillus was increased in Head T but decreased in Body/Tail T. A total of 102 discriminative metabolites were identified between Head T and Head N, which were scattered through linoleic acid metabolism and purine metabolism pathways. However, there were only four discriminative metabolites between Body/Tail T and Body/Tail N, which were related to glycerophospholipid metabolism and autophagy pathways. The differential metabolites in PHC and PBTC were commonly enriched in alpha-linolenic acid metabolism and choline metabolism in cancer pathways. Eubacterium decreased in Head T was positively correlated with decreased linoleic acid while negatively correlated with increased arachidyl carnitine and stearoylcarnitine. Bacillus decreased in Body/Tail T was negatively correlated with increased L-carnitine. These microbiota and metabolites deserve further investigations to reveal their roles in the pathogenesis of PHC and PBTC, providing clues for future treatments.
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Belfiori G, Crippa S, Pagnanelli M, Gasparini G, Aleotti F, Camisa PR, Partelli S, Pecorelli N, De Stefano F, Schiavo Lena M, Palumbo D, Tamburrino D, Reni M, Falconi M. Very Early Recurrence After Curative Resection for Pancreatic Ductal Adenocarcinoma: Proof of Concept for a "Biological R2 Definition". Ann Surg Oncol 2024; 31:4084-4095. [PMID: 38459416 DOI: 10.1245/s10434-024-15105-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 02/12/2024] [Indexed: 03/10/2024]
Abstract
PURPOSE Very early recurrence after radical surgery for pancreatic ductal adenocarcinoma (PDAC) has been poorly investigated. This study was designed to evaluate this group of patients who developed recurrence, within 12 weeks after surgery, defined as "biological R2 resections (bR2)." METHODS Data from patients who underwent surgical resection as upfront procedure or after neoadjuvant treatment for PDAC between 2015 and 2019 were analyzed. Disease-free, disease-specific survival, and independent predictors of early recurrence were examined. The same analysis was performed separately for upfront and neoadjuvant treated patients. RESULTS Of the 573 patients included in the study, 63 (11%) were classified as bR2. The rate of neoadjuvant treatment was similar in bR2 and in the remaining patients (44 vs. 42%, p = 0.78). After a median follow-up of 27 months, median DFS and DSS for the entire cohort were 17 and 43 months, respectively. Median DSS of bR2 group was 13 months. The only preoperative identifiable independent predictor of very early recurrence was body-tail site lesion, whereas all other were pathological: higher pT (8th classification), G3 differentiation, and high lymph node ratio. These predictors were confirmed for patients undergoing upfront surgery, whereas in the neoadjuvant group the only independent predictor was pT. CONCLUSIONS One of ten patients with "radical" resected PDAC relapses very early after surgery (bR2); hence, imaging must be routinely repeated within 12 weeks. Despite higher biological aggressiveness and worse pathology, this bR2 cluster eludes our preoperative examinations.
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Affiliation(s)
- Giulio Belfiori
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Crippa
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Università Vita Salute San Raffaele, Milan, Italy
| | | | - Giulia Gasparini
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Università Vita Salute San Raffaele, Milan, Italy
| | - Francesca Aleotti
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Stefano Partelli
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Università Vita Salute San Raffaele, Milan, Italy
| | - Nicolò Pecorelli
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Università Vita Salute San Raffaele, Milan, Italy
| | - Federico De Stefano
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Università Vita Salute San Raffaele, Milan, Italy
| | - Marco Schiavo Lena
- Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Diego Palumbo
- Università Vita Salute San Raffaele, Milan, Italy
- Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Domenico Tamburrino
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Michele Reni
- Università Vita Salute San Raffaele, Milan, Italy
- Department of Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
- Università Vita Salute San Raffaele, Milan, Italy.
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Liu J, Zhang YJ, Zhou J, Zhang ZJ, Wen Y. Pancreatic mucinous adenocarcinoma has different clinical characteristics and better prognosis compared to non-specific PDAC: A retrospective observational study. Heliyon 2024; 10:e30268. [PMID: 38720717 PMCID: PMC11076975 DOI: 10.1016/j.heliyon.2024.e30268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 04/11/2024] [Accepted: 04/23/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Pancreatic mucinous adenocarcinoma (PMAC) is a rare malignant tumour, and there is limited understanding of its epidemiology and prognosis. Initially, PMAC was considered a metastatic manifestation of other cancers; however, instances of non-metastatic PMAC have been documented through monitoring, epidemiological studies, and data from the Surveillance, Epidemiology, and End Results (SEER) database. Therefore, it is crucial to investigate the epidemiological characteristics of PMAC and discern the prognostic differences between PMAC and the more prevalent pancreatic ductal adenocarcinoma (PDAC). METHODS The study used data from the SEER database from 2000 to 2018 to identify patients diagnosed with PMAC or PDAC. To ensure comparable demographic characteristics between PDAC and PMAC, propensity score matching was employed. Kaplan-Meier analysis was used to analyse overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were used to determine independent risk factors influencing OS and CSS. Additionally, the construction and validation of risk-scoring models for OS and CSS were achieved through the least absolute shrinkage and selection operator-Cox regression technique. RESULTS The SEER database included 84,857 patients with PDAC and 3345 patients with PMAC. Notably, significant distinctions were observed in the distribution of tumour sites, diagnosis time, use of radiotherapy and chemotherapy, tumour size, grading, and staging between the two groups. The prognosis exhibited notable improvement among married individuals, those receiving acceptable chemotherapy, and those with focal PMAC (p < 0.05). Conversely, patients with elevated log odds of positive lymph node scores or higher pathological grades in the pancreatic tail exhibited a more unfavourable prognosis (p < 0.05). The risk-scoring models for OS or CSS based on prognostic factors indicated a significantly lower prognosis for high-risk patients compared to their low-risk counterparts (area under the curve OS: 0.81-0.82, CSS: 0.80-0.82). CONCLUSION PMAC exhibits distinct clinical characteristics compared to non-specific PDAC. Leveraging these features and pathological classifications allows for accurate prognostication of PMAC or PDAC.
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Affiliation(s)
- Juan Liu
- Clinical Nursing Teaching and Research Section, Second Xiangya Hospital, Central South University, Hunan, China
| | - Yong-jing Zhang
- Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jie Zhou
- Department of Breast and Thyroid Surgery, Yiyang Central Hospital, Yiyang, China
| | - Zi-jian Zhang
- Clinical Nursing Teaching and Research Section, Second Xiangya Hospital, Central South University, Hunan, China
| | - Yu Wen
- Clinical Nursing Teaching and Research Section, Second Xiangya Hospital, Central South University, Hunan, China
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8
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Abdelrahim M, Esmail A, Kasi A, Esnaola NF, Xiu J, Baca Y, Weinberg BA. Comparative molecular profiling of pancreatic ductal adenocarcinoma of the head versus body and tail. NPJ Precis Oncol 2024; 8:85. [PMID: 38582894 PMCID: PMC10998911 DOI: 10.1038/s41698-024-00571-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 02/29/2024] [Indexed: 04/08/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) of the head (H) and body/tail (B/T) differ in embryonic origin, cell composition, blood supply, lymphatic and venous drainage, and innervation. We aimed to compare the molecular and tumor immune microenvironment (TIME) profiles of PDAC of the H vs. B/T. A total of 3499 PDAC samples were analyzed via next-generation sequencing (NGS) of RNA (whole transcriptome, NovaSeq), DNA (NextSeq, 592 genes or NovaSeq, whole exome sequencing), and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). Significance was determined as p values adjusted for multiple corrections (q) of <0.05. Anatomic subsites of PDAC tumors were grouped by primary tumor sites into H (N = 2058) or B/T (N = 1384). There were significantly more metastatic tumors profiled from B/T vs. H (57% vs. 44%, p < 0.001). KRAS mutations (93.8% vs. 90.2%), genomic loss of heterozygosity (12.7% vs. 9.1%), and several copy number alterations (FGF3, FGF4, FGF19, CCND1, ZNF703, FLT4, MUTYH, TNFRS14) trended higher in B/T when compared to H (p < 0.05 but q > 0.05). Expression analysis of immuno-oncology (IO)-related genes showed significantly higher expression of CTLA4 and PDCD1 in H (q < 0.05, fold change 1.2 and 1.3) and IDO1 and PDCD1LG2 expression trended higher in B/T (p < 0.05, fold change 0.95). To our knowledge, this is one of the largest cohorts of PDAC tumors subjected to broad molecular profiling. Differences in IO-related gene expression and TIME cell distribution suggest that response to IO therapies may differ in PDAC arising from H vs. B/T. Subtle differences in the genomic profiles of H vs. B/T tumors were observed.
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Affiliation(s)
- Maen Abdelrahim
- Section of GI Oncology, Houston Methodist Neal Cancer Center and Cockrell Center for Advanced Therapeutics, Houston Methodist Hospital, Houston, TX, USA
| | - Abdullah Esmail
- Section of GI Oncology, Houston Methodist Neal Cancer Center and Cockrell Center for Advanced Therapeutics, Houston Methodist Hospital, Houston, TX, USA
| | - Anup Kasi
- University of Kansas Medical Center, Kansas City, KS, USA
| | - Nestor F Esnaola
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | | | | | - Benjamin A Weinberg
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer, Georgetown University Medical Center, Washington, DC, USA.
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Riner AN, Herremans KM, Vudatha V, Han S, Qu X, Liu J, Mukhopadhyay N, Freudenberger DC, George TJ, Judge SM, Judge AR, Hughes SJ, Trevino JG. Heterogeneity of weight loss and transcriptomic signatures in pancreatic ductal adenocarcinoma. J Cachexia Sarcopenia Muscle 2024; 15:149-158. [PMID: 38123146 PMCID: PMC10834348 DOI: 10.1002/jcsm.13390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 09/27/2023] [Accepted: 11/02/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss. METHODS Treatment naïve patients with PDAC who underwent pancreatectomy at a single institution between 2012 and 2020 were identified retrospectively. Patients with pancreatic head or distal tumours were matched by sex, age, N and T stage. Serologic and anthropometric variables were obtained at the time of diagnosis. Skeletal muscle index (SMI), muscle radiation attenuation (MRA) and adiposity were measured. The primary outcome was presence of significant weight loss [>5% body weight (BW) loss in past 6 months]. Signed rank tests, Cochran Mantel Haenszel tests and Kaplan-Meier survival analysis are presented. RNA-seq of tumours was performed to explore enriched pathways related to cachexia and weight loss. RESULTS Pancreatic head tumours (n = 24) were associated with higher prevalence (70.8% vs. 41.7%, P = 0.081) and degree of weight loss (7.9% vs. 2.5%, P = 0.014) compared to distal tumours (n = 24). BMI (P = 0.642), SMI (P = 0.738) and MRA (P = 0.478) were similar between groups. Combining BW loss, SMI and MRA into a composite score, patients with pancreatic head cancers met more criteria associated with poor prognosis (P = 0.142). Serum albumin (3.9 vs. 4.4 g/dL, P = 0.002) was lower and bilirubin (4.5 vs. 0.4 mg/dL, P < 0.001) were higher with pancreatic head tumours. Survival differed by tumour location (P = 0.014) with numerically higher median overall survival with distal tumours (11.1 vs. 21.8 months; P = 0.066). Transcriptomic analysis revealed inactivation of appetite stimulation, weight regulation and nutrient digestion/metabolism pathways in pancreatic head tumours. CONCLUSIONS Resectable pancreatic head PDAC is associated with higher prevalence of significant weight loss and more poor prognosis features. Pancreaticobiliary obstruction and hypoalbuminemia in patients with head tumours suggests compounding effects of nutrient malabsorption and systemic inflammation on molecular drivers of cachexia, possibly contributing to shorter survival. Therefore, PDAC-associated cachexia is a heterogenous syndrome, which may be influenced by the primary tumour location. Select patients with resectable pancreatic head tumours may benefit from nutritional rehabilitation to improve outcomes.
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Affiliation(s)
- Andrea N. Riner
- Department of SurgeryUniversity of Florida College of MedicineGainesvilleFloridaUSA
| | - Kelly M. Herremans
- Department of SurgeryUniversity of Florida College of MedicineGainesvilleFloridaUSA
| | - Vignesh Vudatha
- Department of SurgeryVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Song Han
- Department of SurgeryUniversity of Florida College of MedicineGainesvilleFloridaUSA
| | - Xufeng Qu
- Department of BiostatisticsVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Jinze Liu
- Department of BiostatisticsVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Nitai Mukhopadhyay
- Department of BiostatisticsVirginia Commonwealth UniversityRichmondVirginiaUSA
| | | | - Thomas J. George
- Department of MedicineUniversity of Florida College of MedicineGainesvilleFloridaUSA
| | - Sarah M. Judge
- Department of Physical TherapyUniversity of Florida Health Science CenterGainesvilleFloridaUSA
| | - Andrew R. Judge
- Department of Physical TherapyUniversity of Florida Health Science CenterGainesvilleFloridaUSA
| | - Steven J. Hughes
- Department of SurgeryUniversity of Florida College of MedicineGainesvilleFloridaUSA
| | - Jose G. Trevino
- Department of SurgeryVirginia Commonwealth UniversityRichmondVirginiaUSA
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Okamoto T, Takeda T, Mie T, Hirai T, Ishitsuka T, Yamada M, Nakagawa H, Furukawa T, Kasuga A, Sasaki T, Ozaka M, Sasahira N. Splenic Hilar Involvement and Sinistral Portal Hypertension in Unresectable Pancreatic Tail Cancer. Cancers (Basel) 2023; 15:5862. [PMID: 38136406 PMCID: PMC10741488 DOI: 10.3390/cancers15245862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 12/10/2023] [Accepted: 12/14/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND Pancreatic tail cancer (PTC) frequently displays splenic hilar involvement (SHI), but its impact on clinical outcomes remains unclear. We investigated the clinical impact of SHI in patients with unresectable PTC. METHODS We retrospectively reviewed all patients with unresectable PTC who received first-line therapy at our institution from 2016 to 2020. RESULTS Of the 111 included patients, 48 had SHI at diagnosis. SHI was significantly associated with younger age, liver metastasis, peritoneal dissemination, larger tumor size, modified Glasgow prognostic score of 1 or more, splenic artery involvement, gastric varices, and splenomegaly. Shorter median overall survival (OS; 9.3 vs. 11.6 months, p = 0.003) and progression-free survival (PFS; 4.3 vs. 6.3 months, p = 0.013) were observed in SHI patients. Poor performance status of 1 or 2, tumor size > 50 mm, hepatic metastasis, mGPS of 1 or 2, and SHI (hazard ratio: 1.65, 95% confidence interval: 1.08-2.52, p = 0.020) were independent predictors of shorter OS. Splenic artery pseudoaneurysm rupture and variceal rupture were rare and only observed in cases with SHI. CONCLUSIONS Splenic hilar involvement is associated with worse outcomes in pancreatic tail cancer.
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Affiliation(s)
- Takeshi Okamoto
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan; (T.T.); (T.M.); (T.H.); (T.I.); (M.Y.); (H.N.); (T.F.); (A.K.); (T.S.); (M.O.); (N.S.)
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11
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Xie T, Xie X, Liu W, Chen L, Liu K, Zhou Z. Prediction of postoperative recurrence in resectable pancreatic body/tail adenocarcinoma: a novel risk stratification approach using a CT-based nomogram. Eur Radiol 2023; 33:7782-7793. [PMID: 37624415 DOI: 10.1007/s00330-023-10047-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 05/28/2023] [Accepted: 06/20/2023] [Indexed: 08/26/2023]
Abstract
OBJECTIVES To identify prognostic CT features that predict recurrence in patients with resectable pancreatic body/tail adenocarcinoma (PBTA) and construct a CT-based nomogram for preoperative risk stratification. METHODS A total of 258 patients with resectable PBTA who underwent upfront surgery were retrospectively enrolled (development cohort, n = 172; validation cohort, n = 86), and their clinical and CT features were analyzed. Stepwise Cox proportional hazard analysis was performed to identify prognostic features and construct a predictive nomogram for recurrence-free survival (RFS). The prognostic performance of the CT-based nomogram was validated and compared to the 8th American Joint Committee on Cancer (AJCC) pathological staging system. RESULTS In the development cohort, the following five CT features for predicting recurrence were identified to construct the nomogram: tumor density in the venous phase, tumor necrosis, adjacent organ invasion, splenic vein invasion, and superior mesenteric vein/portal vein abutment. In the validation cohort, the CT-based nomogram showed a concordance index of 0.65 (95% confidence interval: 0.58-0.73), which was higher than the 8th AJCC staging system. The area under the curves of the nomogram for predicting recurrence at 0.5, 1, and 2 years were 0.66, 0.71, and 0.72, respectively. Patients were categorized into high- and low-risk groups with 1-year recurrence probabilities of 0.73 and 0.43, respectively. CONCLUSIONS The proposed nomogram provided accurate recurrence risk stratification for patients with resectable PBTA in a preoperative setting and may be used to facilitate clinical decision-making. CLINICAL RELEVANCE STATEMENT The proposed CT-based nomogram, based on easily available CT features, may serve as an effective and convenient tool for stratifying further the recurrence risk of patients with pancreatic body/tail adenocarcinoma. KEY POINTS • The CT-based nomogram, incorporating five commonly used CT features, successfully preoperatively stratified patients with resectable PBTA into distinct prognosis groups. • Tumor density in the venous phase, tumor necrosis, splenic vein invasion, adjacent organ invasion, and superior mesenteric vein/portal vein abutment were associated with RFS in patients with resectable PBTA. • The CT-based nomogram exhibited better predictive performance for recurrence than the 8th AJCC staging system.
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Affiliation(s)
- Tiansong Xie
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xuebin Xie
- Medical Imaging Center, Kiang Wu Hospital, Macau, China
| | - Wei Liu
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lei Chen
- Department of Radiology, Fudan University Shanghai Cancer Center (Minhang Campus), Shanghai, China
| | - Kefu Liu
- Department of Radiology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China.
| | - Zhengrong Zhou
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
- Department of Radiology, Fudan University Shanghai Cancer Center (Minhang Campus), Shanghai, China.
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12
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Xia T, Xu P, Mou Y, Zhang X, Song S, Zhou Y, Lu C, Zhu Q, Xu Y, Jin W, Wang Y. Factors predicting recurrence after left‑sided pancreatectomy for pancreatic ductal adenocarcinoma. World J Surg Oncol 2023; 21:191. [PMID: 37349737 DOI: 10.1186/s12957-023-03080-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 06/17/2023] [Indexed: 06/24/2023] Open
Abstract
BACKGROUND Recurrence after resection is the main factor for poor survival. The relationship between clinicopathological factors and recurrence after curative distal pancreatectomy for PDAC has rarely been reported separately. METHODS Patients with PDAC after left‑sided pancreatectomy between May 2015 and August 2021 were retrospectively identified. RESULTS One hundred forty-one patients were included. Recurrence was observed in 97 patients (68.8%), while 44 (31.2%) patients had no recurrence. The median RFS was 8.8 months. The median OS was 24.9 months. Local recurrence was the predominant first detected recurrence site (n = 36, 37.1%), closely followed by liver recurrence (n = 35, 36.1%). Multiple recurrences occurred in 16 (16.5%) patients, peritoneal recurrence in 6 (6.2%) patients, and lung recurrence in 4 (4.1%) patients. High CA19-9 value after surgery, poor differentiation grade, and positive lymph nodes were found to be independently associated with recurrence. The patients receiving adjuvant chemotherapy had a decreased likelihood of recurrence. In the high CA19-9 value cohort, the median PFS and OS of the patients with or without chemotherapy were 8.0 VS. 5.7 months and 15.6 VS. 13.8 months, respectively. In the normal CA19-9 value cohort, there was no significant difference in PFS with or without chemotherapy (11.7 VS. 10.0 months, P = 0.147). However, OS was significantly longer in the patients with chemotherapy (26.4 VS. 13.8 months, P = 0.019). CONCLUSIONS Tumor biologic characteristics, such as T stage, tumor differentiation and positive lymph nodes, affecting CA19-9 value after surgery are associated with patterns and timing of recurrence. Adjuvant chemotherapy significantly reduced recurrence and improved survival. Chemotherapy is strongly recommended in patients with high CA199 after surgery.
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Affiliation(s)
- Tao Xia
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
| | - Peng Xu
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
- Department of Surgery, Qingdao University, Qingdao, China
| | - Yiping Mou
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
- Department of Surgery, Qingdao University, Qingdao, China.
- Department of Surgery, Wenzhou Medical University, Wenzhou, China.
| | - Xizhou Zhang
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Shihao Song
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
- Department of Surgery, Wenzhou Medical University, Wenzhou, China
| | - Yucheng Zhou
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Chao Lu
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Qicong Zhu
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Yunyun Xu
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Weiwei Jin
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Yuanyu Wang
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
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Javed S, Qureshi TA, Gaddam S, Wang L, Azab L, Wachsman AM, Chen W, Asadpour V, Jeon CY, Wu B, Xie Y, Pandol SJ, Li D. Risk prediction of pancreatic cancer using AI analysis of pancreatic subregions in computed tomography images. Front Oncol 2022; 12:1007990. [PMID: 36439445 PMCID: PMC9682250 DOI: 10.3389/fonc.2022.1007990] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 10/24/2022] [Indexed: 10/14/2023] Open
Abstract
Early detection of Pancreatic Ductal Adenocarcinoma (PDAC) is complicated as PDAC remains asymptomatic until cancer advances to late stages when treatment is mostly ineffective. Stratifying the risk of developing PDAC can improve early detection as subsequent screening of high-risk individuals through specialized surveillance systems reduces the chance of misdiagnosis at the initial stage of cancer. Risk stratification is however challenging as PDAC lacks specific predictive biomarkers. Studies reported that the pancreas undergoes local morphological changes in response to underlying biological evolution associated with PDAC development. Accurate identification of these changes can help stratify the risk of PDAC. In this retrospective study, an extensive radiomic analysis of the precancerous pancreatic subregions was performed using abdominal Computed Tomography (CT) scans. The analysis was performed using 324 pancreatic subregions identified in 108 contrast-enhanced abdominal CT scans with equal proportion from healthy control, pre-diagnostic, and diagnostic groups. In a pairwise feature analysis, several textural features were found potentially predictive of PDAC. A machine learning classifier was then trained to perform risk prediction of PDAC by automatically classifying the CT scans into healthy control (low-risk) and pre-diagnostic (high-risk) classes and specifying the subregion(s) likely to develop a tumor. The proposed model was trained on CT scans from multiple phases. Whereas using 42 CT scans from the venous phase, model validation was performed which resulted in ~89.3% classification accuracy on average, with sensitivity and specificity reaching 86% and 93%, respectively, for predicting the development of PDAC (i.e., high-risk). To our knowledge, this is the first model that unveiled microlevel precancerous changes across pancreatic subregions and quantified the risk of developing PDAC. The model demonstrated improved prediction by 3.3% in comparison to the state-of-the-art method that considers the global (whole pancreas) features for PDAC prediction.
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Affiliation(s)
- Sehrish Javed
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Touseef Ahmad Qureshi
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Srinivas Gaddam
- Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Lixia Wang
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Linda Azab
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Ashley Max Wachsman
- Department of Radiology, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Wansu Chen
- Department of Research and Evaluation, Southern California Kaiser Permanente Medical Center, Los Angeles, CA, United States
| | - Vahid Asadpour
- Department of Research and Evaluation, Southern California Kaiser Permanente Medical Center, Los Angeles, CA, United States
| | - Christie Younghae Jeon
- Division of Hematology, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Division of Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Beichien Wu
- Department of Research and Evaluation, Southern California Kaiser Permanente Medical Center, Los Angeles, CA, United States
| | - Yibin Xie
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | | | - Debiao Li
- Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
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Nomogram for Predicting Distant Metastasis of Pancreatic Ductal Adenocarcinoma: A SEER-Based Population Study. Curr Oncol 2022; 29:8146-8159. [PMID: 36354703 PMCID: PMC9689204 DOI: 10.3390/curroncol29110643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 10/22/2022] [Accepted: 10/26/2022] [Indexed: 11/05/2022] Open
Abstract
(1) Background: The aim of this study was to identify risk factors for distant metastasis of pancreatic ductal adenocarcinoma (PDAC) and develop a valid predictive model to guide clinical practice; (2) Methods: We screened 14328 PDAC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Lasso regression analysis combined with logistic regression analysis were used to determine the independent risk factors for PDAC with distant metastasis. A nomogram predicting the risk of distant metastasis in PDAC was constructed. A receiver operating characteristic (ROC) curve and consistency-index (C-index) were used to determine the accuracy and discriminate ability of the nomogram. A calibration curve was used to assess the agreement between the predicted probability of the model and the actual probability. Additionally, decision curve analysis (DCA) and clinical influence curve were employed to assess the clinical utility of the nomogram; (3) Results: Multivariate logistic regression analysis revealed that risk factors for distant metastasis of PDAC included age, primary site, histological grade, and lymph node status. A nomogram was successfully constructed, with an area under the curve (AUC) of 0.871 for ROC and a C-index of 0.871 (95% CI: 0.860-0.882). The calibration curve showed that the predicted probability of the model was in high agreement with the actual predicted probability. The DCA and clinical influence curve showed that the model had great potential clinical utility; (4) Conclusions: The risk model established in this study has a good predictive performance and a promising potential application, which can provide personalized clinical decisions for future clinical work.
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Segmentation of Pancreatic Subregions in Computed Tomography Images. J Imaging 2022; 8:jimaging8070195. [PMID: 35877639 PMCID: PMC9317715 DOI: 10.3390/jimaging8070195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/02/2022] [Accepted: 07/07/2022] [Indexed: 11/16/2022] Open
Abstract
The accurate segmentation of pancreatic subregions (head, body, and tail) in CT images provides an opportunity to examine the local morphological and textural changes in the pancreas. Quantifying such changes aids in understanding the spatial heterogeneity of the pancreas and assists in the diagnosis and treatment planning of pancreatic cancer. Manual outlining of pancreatic subregions is tedious, time-consuming, and prone to subjective inconsistency. This paper presents a multistage anatomy-guided framework for accurate and automatic 3D segmentation of pancreatic subregions in CT images. Using the delineated pancreas, two soft-label maps were estimated for subregional segmentation—one by training a fully supervised naïve Bayes model that considers the length and volumetric proportions of each subregional structure based on their anatomical arrangement, and the other by using the conventional deep learning U-Net architecture for 3D segmentation. The U-Net model then estimates the joint probability of the two maps and performs optimal segmentation of subregions. Model performance was assessed using three datasets of contrast-enhanced abdominal CT scans: one public NIH dataset of the healthy pancreas, and two datasets D1 and D2 (one for each of pre-cancerous and cancerous pancreas). The model demonstrated excellent performance during the multifold cross-validation using the NIH dataset, and external validation using D1 and D2. To the best of our knowledge, this is the first automated model for the segmentation of pancreatic subregions in CT images. A dataset consisting of reference anatomical labels for subregions in all images of the NIH dataset is also established.
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16
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Brock Hewitt D, Aziz H, Pawlik TM. Comment on: "Impact of Tumor Size on the Outcomes of Patients with Resectable Distal Pancreatic Cancer". Ann Surg Oncol 2022; 29:10.1245/s10434-022-11840-6. [PMID: 35499788 DOI: 10.1245/s10434-022-11840-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 03/21/2022] [Indexed: 11/18/2022]
Affiliation(s)
- D Brock Hewitt
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Surgery, Oncology, Health Services Management and Policy, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Hassan Aziz
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Surgery, Oncology, Health Services Management and Policy, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Surgery, Oncology, Health Services Management and Policy, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
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17
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Sun K, Mylavarapu C, Crenshaw A, Zhang Y, Hsu E, Xu J, Niravath M, Jones SL, Ordonez A, Abdelrahim M. Pancreatic head vs pancreatic body/tail cancer: Are they different? World J Gastrointest Oncol 2022; 14:716-723. [PMID: 35321276 PMCID: PMC8919010 DOI: 10.4251/wjgo.v14.i3.716] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 11/16/2021] [Accepted: 01/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The impact of pancreatic tumor location on patient survival has been studied in large national data-based analyses which yielded controversial results.
AIM To explore if pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) have different overall survival (OS), molecular signature and response to chemotherapy.
METHODS We retrospectively queried patient records from July 2016 to June 2020 in our institution. Patient demographics, cancer stage on diagnosis, tumor location, somatic mutations, treatment, and survival are recorded and analyzed. A test is considered statistically significant if the P value was < 0.05.
RESULTS We reviewed 101 patients with complete records, among which 67 (66.34%) were PHC and 34 (33.66%) were PBTC. More PHC were diagnosed at younger age [61.49 vs 68.97, P = 0.010], earlier stages (P = 0.006) and underwent surgical resection (P = 0.025). There were no significant differences among all mutations and pathways studied except for TP53 mutations (37.0% in PHC vs 70.0% in PBTC, P = 0.03). OS was not statistically different between PHC and PBTC (P = 0.636) in the overall population and in subgroups according to surgical resection status or stages. In terms of response to chemotherapy, chemotherapy regimens (FOLFIRINOX-based vs gemcitabine-based) didn’t impact disease free interval in those who had surgical resection in either PHC (P = 0.546) or PBTC (P = 0.654), or the duration of response to first line palliative treatment in those with advanced disease in PHC (P = 0.915) or PBTC (P = 0.524).
CONCLUSION Even though PHC and PBTC have similar poor OS and response to chemotherapy, the different presentations and molecular profiles indicate they are different diseases. Utilization of molecular profiling to develop targeted therapy for individualization of treatment is needed.
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Affiliation(s)
- Kai Sun
- Houston Methodist Cancer Center, Houston Methodist Hospital, Houston, TX 77030, United States
| | - Charisma Mylavarapu
- Department of Internal Medicine, Houston Methodist Hospital, Houston, TX 77030, United States
| | - Aubrey Crenshaw
- Department of Internal Medicine, Houston Methodist Hospital, Houston, TX 77030, United States
| | - Yuqi Zhang
- Department of Internal Medicine, Houston Methodist Hospital, Houston, TX 77030, United States
| | - Enshuo Hsu
- Center for Outcomes Research, Houston Methodist Research Institute, Houston, TX 77030, United States
| | - Jiaqiong Xu
- Center for Outcomes Research, Houston Methodist Research Institute, Houston, TX 77030, United States
| | - Marilyn Niravath
- Center for Outcomes Research, Houston Methodist Research Institute, Houston, TX 77030, United States
| | - Stephen L Jones
- Center for Outcomes Research, Houston Methodist Research Institute, Houston, TX 77030, United States
| | - Adriana Ordonez
- Center for Outcomes Research, Houston Methodist Research Institute, Houston, TX 77030, United States
| | - Maen Abdelrahim
- Houston Methodist Cancer Center, Houston Methodist Hospital, Houston, TX 77030, United States
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18
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Yang Y, Ding Y, Gong Y, Zhao S, Li M, Li X, Song G, Zhai B, Liu J, Shao Y, Zhu L, Pang J, Ma Y, Ou Q, Wu X, Zhang Z. The genetic landscape of pancreatic head ductal adenocarcinoma in China and prognosis stratification. BMC Cancer 2022; 22:186. [PMID: 35180847 PMCID: PMC8855595 DOI: 10.1186/s12885-022-09279-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 02/07/2022] [Indexed: 12/14/2022] Open
Abstract
Background Pancreatic ductal adenocarcinoma (PDAC) is the major subtype of pancreatic cancer and head PDACs show distinct characteristics from body/tail PDACs. With limited studies based on Asian population, the mutational landscape of Asian PDAC remains unclear. Methods One hundred fifty-one Chinese patients with head PDAC were selected and underwent targeted 425-gene sequencing. Genomic alterations, tumor mutational burden, and microsatellite instability were analyzed and compared with a TCGA cohort. Results The genomic landscape of Chinese and Western head PDAC had identical frequently-mutated genes including KRAS, TP53, SMAD4, and CDKN2A. KRAS hotspot in both cohorts was codon 12 but Chinese PDACs containing more G12V but fewer G12R variants. Potentially pathogenic fusions, CHD2-BRAF and KANK1-MET were identified in two KRAS wild-type patients. Serum cancer antigens CA125 and CA19-9 were positively associated with SMAD4 alterations while high CEA was enriched in wild-type CDKN2A subgroup. The probability of vascular invasion was lower in patients with RNF43 alterations. The nomogram developed including histology grade, the mutation status of SMAD4, TGFBR2, and PREX2 could calculate the risk score of prognoses validated by Chinese and TCGA cohort. Conclusions Chinese head PDAC contained more KRAS G12V mutation than Western population. The well-performed nomogram may improve post-operation care in real-world practice. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09279-9.
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Affiliation(s)
- Yefan Yang
- Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Ying Ding
- Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Yuxi Gong
- Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Sha Zhao
- Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Mingna Li
- Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Xiao Li
- Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Guoxin Song
- Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Boya Zhai
- Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Jin Liu
- Clinical Medicine Research Institution, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Yang Shao
- Nanjing Geneseeq Technology Inc, Nanjing, 210032, Jiangsu Province, China
| | - Liuqing Zhu
- Nanjing Geneseeq Technology Inc, Nanjing, 210032, Jiangsu Province, China
| | - Jiaohui Pang
- Nanjing Geneseeq Technology Inc, Nanjing, 210032, Jiangsu Province, China
| | - Yutong Ma
- Nanjing Geneseeq Technology Inc, Nanjing, 210032, Jiangsu Province, China
| | - Qiuxiang Ou
- Nanjing Geneseeq Technology Inc, Nanjing, 210032, Jiangsu Province, China
| | - Xue Wu
- Nanjing Geneseeq Technology Inc, Nanjing, 210032, Jiangsu Province, China
| | - Zhihong Zhang
- Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China.
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19
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Zhang X, Feng S, Wang Q, Huang H, Chen R, Xie Q, Zhang W, Wang A, Zhang S, Wang L, Yao M, Ling Q. Comparative genomic analysis of head and body/tail of pancreatic ductal adenocarcinoma at early and late stages. J Cell Mol Med 2021; 25:1750-1758. [PMID: 33452856 PMCID: PMC7875914 DOI: 10.1111/jcmm.16281] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 12/15/2020] [Accepted: 12/22/2020] [Indexed: 12/11/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers, can be divided into head and body/tail cancers anatomically. We previously reported a prognostic relevance of tumour location in resectable PDAC. This study aimed to further explore the mechanism underlying the molecular diversity between the head and body/tail of PDACs. We detected tumour genomes in 154 resectable (surgery) and non-resectable (biopsy) PDACs using a next-generation sequencing panel. Wilcoxon's rank test or Fisher's exact test was used for evaluating associations between clinical characteristics, mutation frequency and survival probability between the two cohorts. Compared with pancreatic head cancers, pancreatic body/tail cancers showed significantly more enriched genomic alterations in KRAS (97.1% vs 82.4%, P = 0.004) and SMAD4 (42.0% vs 21.2%, P = 0.008). At early stages (I-II), the SMAD4 mutation rate was significantly higher in pancreatic body/tail cancers than pancreatic head cancers (56.0% vs 26.5%, P = 0.021). At late stages (III-IV), pancreatic body/tail cancers presented significantly higher KRAS mutation rate (100.0% vs 75.8%, P = 0.001), higher frequency of MAPK pathway mutation (100% vs 87.8%, P = 0.040) and lower rates of druggable genomic alterations (30.8% vs 57.6%, P = 0.030) than pancreatic head cancers. Our work points out that pancreatic body/tail cancer seems to be more malignant than pancreatic head cancer at late stages.
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Affiliation(s)
- Xueyou Zhang
- Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Shi Feng
- Department of PathologyThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | | | - Haitao Huang
- Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Ruihan Chen
- Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Qinfen Xie
- Department of SurgeryShulan (Hangzhou) HospitalHangzhouChina
| | - Wu Zhang
- Department of SurgeryShulan (Hangzhou) HospitalHangzhouChina
| | | | | | | | | | - Qi Ling
- Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
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