Competitive testing of the WHO 2010 versus the WHO 2017 grading of pancreatic neuroendocrine neoplasms: Data from a large international cohort study

Guido Rindi, Catherine Klersy, Luca Albarello, Eric Baudin, Antonio Bianchi, Markus W. Buchler, Martyn Caplin, Anne Couvelard, Jérôme Cros, Wouter W. De Herder, Gianfranco Delle Fave, Claudio Doglioni, Birgitte Federspiel, Lars Fischer, Giuseppe Fusai, Francesca Gavazzi, Carsten P. Hansen, Frediano Inzani, Henning Jann, Paul KomminothUlrich P. Knigge, Luca Landoni, Stefano La Rosa, Rita T. Lawlor, Tu V. Luong, Ilaria Marinoni, F. Panzuto, Ulrich Frank Pape, Stefano Partelli, Aurel Perren, Maria Rinzivillo, Corrado Rubini, Philippe Ruszniewski, Aldo Scarpa, Anja Schmitt, Giovanni Schinzari, Jean Yves Scoazec, Fausto Sessa, Enrico Solcia, Paola Spaggiari, Christos Toumpanakis, Alessandro Vanoli, Bertram Wiedenmann, Giuseppe Zamboni, Wouter T. Zandee, Alessandro Zerbi, Massimo Falconi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). Objectives: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. Method: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. Results: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. Conclusions: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

Original languageEnglish
Pages (from-to)375-386
Number of pages12
JournalNeuroendocrinology
Volume107
Issue number4
DOIs
Publication statusPublished - Jan 1 2019

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Pancreatic Neoplasms
Cohort Studies
Joints
Neoplasms
Regression Analysis
Age Groups
Observation
Survival

Keywords

  • Grading
  • Neuroendocrine neoplasm
  • Pancreas
  • Personalized medicine
  • Staging
  • Tailored therapy
  • WHO

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Competitive testing of the WHO 2010 versus the WHO 2017 grading of pancreatic neuroendocrine neoplasms : Data from a large international cohort study. / Rindi, Guido; Klersy, Catherine; Albarello, Luca; Baudin, Eric; Bianchi, Antonio; Buchler, Markus W.; Caplin, Martyn; Couvelard, Anne; Cros, Jérôme; De Herder, Wouter W.; Delle Fave, Gianfranco; Doglioni, Claudio; Federspiel, Birgitte; Fischer, Lars; Fusai, Giuseppe; Gavazzi, Francesca; Hansen, Carsten P.; Inzani, Frediano; Jann, Henning; Komminoth, Paul; Knigge, Ulrich P.; Landoni, Luca; La Rosa, Stefano; Lawlor, Rita T.; Luong, Tu V.; Marinoni, Ilaria; Panzuto, F.; Pape, Ulrich Frank; Partelli, Stefano; Perren, Aurel; Rinzivillo, Maria; Rubini, Corrado; Ruszniewski, Philippe; Scarpa, Aldo; Schmitt, Anja; Schinzari, Giovanni; Scoazec, Jean Yves; Sessa, Fausto; Solcia, Enrico; Spaggiari, Paola; Toumpanakis, Christos; Vanoli, Alessandro; Wiedenmann, Bertram; Zamboni, Giuseppe; Zandee, Wouter T.; Zerbi, Alessandro; Falconi, Massimo.

In: Neuroendocrinology, Vol. 107, No. 4, 01.01.2019, p. 375-386.

Research output: Contribution to journalArticle

Rindi, G, Klersy, C, Albarello, L, Baudin, E, Bianchi, A, Buchler, MW, Caplin, M, Couvelard, A, Cros, J, De Herder, WW, Delle Fave, G, Doglioni, C, Federspiel, B, Fischer, L, Fusai, G, Gavazzi, F, Hansen, CP, Inzani, F, Jann, H, Komminoth, P, Knigge, UP, Landoni, L, La Rosa, S, Lawlor, RT, Luong, TV, Marinoni, I, Panzuto, F, Pape, UF, Partelli, S, Perren, A, Rinzivillo, M, Rubini, C, Ruszniewski, P, Scarpa, A, Schmitt, A, Schinzari, G, Scoazec, JY, Sessa, F, Solcia, E, Spaggiari, P, Toumpanakis, C, Vanoli, A, Wiedenmann, B, Zamboni, G, Zandee, WT, Zerbi, A & Falconi, M 2019, 'Competitive testing of the WHO 2010 versus the WHO 2017 grading of pancreatic neuroendocrine neoplasms: Data from a large international cohort study', Neuroendocrinology, vol. 107, no. 4, pp. 375-386. https://doi.org/10.1159/000494355
Rindi, Guido ; Klersy, Catherine ; Albarello, Luca ; Baudin, Eric ; Bianchi, Antonio ; Buchler, Markus W. ; Caplin, Martyn ; Couvelard, Anne ; Cros, Jérôme ; De Herder, Wouter W. ; Delle Fave, Gianfranco ; Doglioni, Claudio ; Federspiel, Birgitte ; Fischer, Lars ; Fusai, Giuseppe ; Gavazzi, Francesca ; Hansen, Carsten P. ; Inzani, Frediano ; Jann, Henning ; Komminoth, Paul ; Knigge, Ulrich P. ; Landoni, Luca ; La Rosa, Stefano ; Lawlor, Rita T. ; Luong, Tu V. ; Marinoni, Ilaria ; Panzuto, F. ; Pape, Ulrich Frank ; Partelli, Stefano ; Perren, Aurel ; Rinzivillo, Maria ; Rubini, Corrado ; Ruszniewski, Philippe ; Scarpa, Aldo ; Schmitt, Anja ; Schinzari, Giovanni ; Scoazec, Jean Yves ; Sessa, Fausto ; Solcia, Enrico ; Spaggiari, Paola ; Toumpanakis, Christos ; Vanoli, Alessandro ; Wiedenmann, Bertram ; Zamboni, Giuseppe ; Zandee, Wouter T. ; Zerbi, Alessandro ; Falconi, Massimo. / Competitive testing of the WHO 2010 versus the WHO 2017 grading of pancreatic neuroendocrine neoplasms : Data from a large international cohort study. In: Neuroendocrinology. 2019 ; Vol. 107, No. 4. pp. 375-386.
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abstract = "Background: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). Objectives: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. Method: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. Results: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. Conclusions: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.",
keywords = "Grading, Neuroendocrine neoplasm, Pancreas, Personalized medicine, Staging, Tailored therapy, WHO",
author = "Guido Rindi and Catherine Klersy and Luca Albarello and Eric Baudin and Antonio Bianchi and Buchler, {Markus W.} and Martyn Caplin and Anne Couvelard and J{\'e}r{\^o}me Cros and {De Herder}, {Wouter W.} and {Delle Fave}, Gianfranco and Claudio Doglioni and Birgitte Federspiel and Lars Fischer and Giuseppe Fusai and Francesca Gavazzi and Hansen, {Carsten P.} and Frediano Inzani and Henning Jann and Paul Komminoth and Knigge, {Ulrich P.} and Luca Landoni and {La Rosa}, Stefano and Lawlor, {Rita T.} and Luong, {Tu V.} and Ilaria Marinoni and F. Panzuto and Pape, {Ulrich Frank} and Stefano Partelli and Aurel Perren and Maria Rinzivillo and Corrado Rubini and Philippe Ruszniewski and Aldo Scarpa and Anja Schmitt and Giovanni Schinzari and Scoazec, {Jean Yves} and Fausto Sessa and Enrico Solcia and Paola Spaggiari and Christos Toumpanakis and Alessandro Vanoli and Bertram Wiedenmann and Giuseppe Zamboni and Zandee, {Wouter T.} and Alessandro Zerbi and Massimo Falconi",
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T1 - Competitive testing of the WHO 2010 versus the WHO 2017 grading of pancreatic neuroendocrine neoplasms

T2 - Data from a large international cohort study

AU - Rindi, Guido

AU - Klersy, Catherine

AU - Albarello, Luca

AU - Baudin, Eric

AU - Bianchi, Antonio

AU - Buchler, Markus W.

AU - Caplin, Martyn

AU - Couvelard, Anne

AU - Cros, Jérôme

AU - De Herder, Wouter W.

AU - Delle Fave, Gianfranco

AU - Doglioni, Claudio

AU - Federspiel, Birgitte

AU - Fischer, Lars

AU - Fusai, Giuseppe

AU - Gavazzi, Francesca

AU - Hansen, Carsten P.

AU - Inzani, Frediano

AU - Jann, Henning

AU - Komminoth, Paul

AU - Knigge, Ulrich P.

AU - Landoni, Luca

AU - La Rosa, Stefano

AU - Lawlor, Rita T.

AU - Luong, Tu V.

AU - Marinoni, Ilaria

AU - Panzuto, F.

AU - Pape, Ulrich Frank

AU - Partelli, Stefano

AU - Perren, Aurel

AU - Rinzivillo, Maria

AU - Rubini, Corrado

AU - Ruszniewski, Philippe

AU - Scarpa, Aldo

AU - Schmitt, Anja

AU - Schinzari, Giovanni

AU - Scoazec, Jean Yves

AU - Sessa, Fausto

AU - Solcia, Enrico

AU - Spaggiari, Paola

AU - Toumpanakis, Christos

AU - Vanoli, Alessandro

AU - Wiedenmann, Bertram

AU - Zamboni, Giuseppe

AU - Zandee, Wouter T.

AU - Zerbi, Alessandro

AU - Falconi, Massimo

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). Objectives: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. Method: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. Results: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. Conclusions: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

AB - Background: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). Objectives: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. Method: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. Results: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. Conclusions: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

KW - Grading

KW - Neuroendocrine neoplasm

KW - Pancreas

KW - Personalized medicine

KW - Staging

KW - Tailored therapy

KW - WHO

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