Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study

G. Rindi; C. Klersy; L. Albarello; E. Baudin; A. Bianchi; M.W. Buchler; M. Caplin; A. Couvelard; J. Cros; W.W. de Herder; G. Delle Fave; C. Doglioni; B. Federspiel; L. Fischer; G. Fusai; F. Gavazzi; C.P. Hansen; F. Inzani; H. Jann; P. Komminoth; U.P. Knigge; L. Landoni; S. La Rosa; R.T. Lawlor; T.V. Luong; I. Marinoni; F. Panzuto; U.-F. Pape; S. Partelli; A. Perren; M. Rinzivillo; C. Rubini; P. Ruszniewski; A. Scarpa; A. Schmitt; G. Schinzari; J.-Y. Scoazec; F. Sessa; E. Solcia; P. Spaggiari; C. Toumpanakis; A. Vanoli; B. Wiedenmann; G. Zamboni; W.T. Zandee; A. Zerbi; M. Falconi

doi:10.1159/000494355

Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study

G. Rindi, C. Klersy, L. Albarello, E. Baudin, A. Bianchi, M.W. Buchler, M. Caplin, A. Couvelard, J. Cros, W.W. de Herder, G. Delle Fave, C. Doglioni, B. Federspiel, L. Fischer, G. Fusai, F. Gavazzi, C.P. Hansen, F. Inzani, H. Jann, P. KomminothU.P. Knigge, L. Landoni, S. La Rosa, R.T. Lawlor, T.V. Luong, I. Marinoni, F. Panzuto, U.-F. Pape, S. Partelli, A. Perren, M. Rinzivillo, C. Rubini, P. Ruszniewski, A. Scarpa, A. Schmitt, G. Schinzari, J.-Y. Scoazec, F. Sessa, E. Solcia, P. Spaggiari, C. Toumpanakis, A. Vanoli, B. Wiedenmann, G. Zamboni, W.T. Zandee, A. Zerbi, M. Falconi

Research output: Contribution to journal › Article

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 language	English
Pages (from-to)	375-386
Number of pages	12
Journal	Neuroendocrinology
Volume	107
Issue number	4
DOIs	https://doi.org/10.1159/000494355
Publication status	Published - 2018

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Rindi, G., Klersy, C., Albarello, L., Baudin, E., Bianchi, A., Buchler, M. W., Caplin, M., Couvelard, A., Cros, J., de Herder, W. W., Delle Fave, G., Doglioni, C., Federspiel, B., Fischer, L., Fusai, G., Gavazzi, F., Hansen, C. P., Inzani, F., Jann, H., ... Falconi, M. (2018). Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study. Neuroendocrinology, 107(4), 375-386. https://doi.org/10.1159/000494355

Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study. / Rindi, G.; Klersy, C.; Albarello, L.; Baudin, E.; Bianchi, A.; Buchler, M.W.; Caplin, M.; Couvelard, A.; Cros, J.; de Herder, W.W.; Delle Fave, G.; Doglioni, C.; Federspiel, B.; Fischer, L.; Fusai, G.; Gavazzi, F.; Hansen, C.P.; Inzani, F.; Jann, H.; Komminoth, P.; Knigge, U.P.; Landoni, L.; La Rosa, S.; Lawlor, R.T.; Luong, T.V.; Marinoni, I.; Panzuto, F.; Pape, U.-F.; Partelli, S.; Perren, A.; Rinzivillo, M.; Rubini, C.; Ruszniewski, P.; Scarpa, A.; Schmitt, A.; Schinzari, G.; Scoazec, J.-Y.; Sessa, F.; Solcia, E.; Spaggiari, P.; Toumpanakis, C.; Vanoli, A.; Wiedenmann, B.; Zamboni, G.; Zandee, W.T.; Zerbi, A.; Falconi, M.

In: Neuroendocrinology, Vol. 107, No. 4, 2018, p. 375-386.

Research output: Contribution to journal › Article

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, U-F, Partelli, S, Perren, A, Rinzivillo, M, Rubini, C, Ruszniewski, P, Scarpa, A, Schmitt, A, Schinzari, G, Scoazec, J-Y, Sessa, F, Solcia, E , Spaggiari, P, Toumpanakis, C, Vanoli, A, Wiedenmann, B, Zamboni, G, Zandee, WT, Zerbi, A & Falconi, M 2018, '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, G. ; Klersy, C. ; Albarello, L. ; Baudin, E. ; Bianchi, A. ; Buchler, M.W. ; Caplin, M. ; Couvelard, A. ; Cros, J. ; de Herder, W.W. ; Delle Fave, G. ; Doglioni, C. ; Federspiel, B. ; Fischer, L. ; Fusai, G. ; Gavazzi, F. ; Hansen, C.P. ; Inzani, F. ; Jann, H. ; Komminoth, P. ; Knigge, U.P. ; Landoni, L. ; La Rosa, S. ; Lawlor, R.T. ; Luong, T.V. ; Marinoni, I. ; Panzuto, F. ; Pape, U.-F. ; Partelli, S. ; Perren, A. ; Rinzivillo, M. ; Rubini, C. ; Ruszniewski, P. ; Scarpa, A. ; Schmitt, A. ; Schinzari, G. ; Scoazec, J.-Y. ; Sessa, F. ; Solcia, E. ; Spaggiari, P. ; Toumpanakis, C. ; Vanoli, A. ; Wiedenmann, B. ; Zamboni, G. ; Zandee, W.T. ; Zerbi, A. ; Falconi, M. / Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study. In: Neuroendocrinology. 2018 ; Vol. 107, No. 4. pp. 375-386.

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title = "Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study",

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{\textquoteright}s C statistics, and Royston{\textquoteright}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.",

author = "G. Rindi and C. Klersy and L. Albarello and E. Baudin and A. Bianchi and M.W. Buchler and M. Caplin and A. Couvelard and J. Cros and W.W. de Herder and G. Delle Fave and C. Doglioni and B. Federspiel and L. Fischer and G. Fusai and F. Gavazzi and C.P. Hansen and F. Inzani and H. Jann and P. Komminoth and U.P. Knigge and L. Landoni and S. La Rosa and R.T. Lawlor and T.V. Luong and I. Marinoni and F. Panzuto and U.-F. Pape and S. Partelli and A. Perren and M. Rinzivillo and C. Rubini and P. Ruszniewski and A. Scarpa and A. Schmitt and G. Schinzari and J.-Y. Scoazec and F. Sessa and E. Solcia and P. Spaggiari and C. Toumpanakis and A. Vanoli and B. Wiedenmann and G. Zamboni and W.T. Zandee and A. Zerbi and M. Falconi",

year = "2018",

doi = "10.1159/000494355",

language = "English",

volume = "107",

pages = "375--386",

journal = "Neuroendocrinology",

issn = "0028-3835",

publisher = "S. Karger AG",

number = "4",

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TY - JOUR

T1 - Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study

AU - Rindi, G.

AU - Klersy, C.

AU - Albarello, L.

AU - Baudin, E.

AU - Bianchi, A.

AU - Buchler, M.W.

AU - Caplin, M.

AU - Couvelard, A.

AU - Cros, J.

AU - de Herder, W.W.

AU - Delle Fave, G.

AU - Doglioni, C.

AU - Federspiel, B.

AU - Fischer, L.

AU - Fusai, G.

AU - Gavazzi, F.

AU - Hansen, C.P.

AU - Inzani, F.

AU - Jann, H.

AU - Komminoth, P.

AU - Knigge, U.P.

AU - Landoni, L.

AU - La Rosa, S.

AU - Lawlor, R.T.

AU - Luong, T.V.

AU - Marinoni, I.

AU - Panzuto, F.

AU - Pape, U.-F.

AU - Partelli, S.

AU - Perren, A.

AU - Rinzivillo, M.

AU - Rubini, C.

AU - Ruszniewski, P.

AU - Scarpa, A.

AU - Schmitt, A.

AU - Schinzari, G.

AU - Scoazec, J.-Y.

AU - Sessa, F.

AU - Solcia, E.

AU - Spaggiari, P.

AU - Toumpanakis, C.

AU - Vanoli, A.

AU - Wiedenmann, B.

AU - Zamboni, G.

AU - Zandee, W.T.

AU - Zerbi, A.

AU - Falconi, M.

PY - 2018

Y1 - 2018

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.

U2 - 10.1159/000494355

DO - 10.1159/000494355

M3 - Article

VL - 107

SP - 375

EP - 386

JO - Neuroendocrinology

JF - Neuroendocrinology

SN - 0028-3835

IS - 4

ER -