Multi-institutional Development and External Validation of a Nomogram to Predict Recurrence after Curative Resection of Pancreatic Neuroendocrine Tumors

Alessandra Pulvirenti, Ammar A. Javed, Luca Landoni, Nigel B. Jamieson, Joanne F. Chou, Marco Miotto, Jin He, Mithat Gonen, Antonio Pea, Laura H. Tang, Chiara Nessi, Sara Cingarlini, Michael I. D'Angelica, Anthony J. Gill, T. Peter Kingham, Aldo Scarpa, Matthew J. Weiss, Vinod P. Balachandran, Jaswinder S. Samra, John L. CameronWilliam R. Jarnagin, Roberto Salvia, Christopher L. Wolfgang, Peter J. Allen, Claudio Bassi

Research output: Contribution to journalArticle

Abstract

Objective: To develop a nomogram estimating the probability of recurrence free at 5 years after resection for localized grade 1 (G1)/ grade 2 (G2) pancreatic neuroendocrine tumors (PanNETs). Background: Among patients undergoing resection of PanNETs, approximately 17% experience recurrence. It is not established which patients are at risk, with no consensus on optimal follow-up. Method: A multi-institutional database of patients with G1/G2 PanNETs treated at 2 institutions was used to develop a nomogram estimating the rate of freedom from recurrence at 5 years after curative resection. A second cohort of patients from 3 additional institutions was used to validate the nomogram. Prognostic factors were assessed by univariate analysis using Cox regression model. The nomogram was internally validated using bootstrap resampling method and on the external cohort. Performance was assessed by concordance index (c-index) and a calibration curve. Results: The nomogram was constructed using a cohort of 632 patients. Overall, 68% of PanNETs were G1, the median follow-up was 51 months, and we observed 74 recurrences. Variables included in the nomogram were the number of positive nodes, tumor diameter, Ki-67, and vascular/perineural invasion. The model bias-corrected c-index from the internal validation was 0.85, which was higher than European Neuroendocrine Tumors Society/American Joint Committee on Cancer 8th staging scheme (c-index 0.76, P = <0.001). On the external cohort of 328 patients, the nomogram c-index was 0.84 (95% confidence interval 0.79-0.88). Conclusion: Our externally validated nomogram predicts the probability of recurrence-free survival at 5 years after PanNETs curative resection, with improved accuracy over current staging systems. Estimating individual recurrence risk will guide the development of personalized surveillance programs after surgery.

Original languageEnglish (US)
JournalAnnals of surgery
DOIs
StateAccepted/In press - Jan 1 2019

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Nomograms
Neuroendocrine Tumors
Recurrence
Neoplasm Staging
Proportional Hazards Models
Calibration
Blood Vessels
Databases
Confidence Intervals
Survival

Keywords

  • nomogram
  • pancreatic neuroendocrine tumor
  • pancreatic surgery
  • recurrence
  • surveillance
  • well-differentiated

ASJC Scopus subject areas

  • Surgery

Cite this

Multi-institutional Development and External Validation of a Nomogram to Predict Recurrence after Curative Resection of Pancreatic Neuroendocrine Tumors. / Pulvirenti, Alessandra; Javed, Ammar A.; Landoni, Luca; Jamieson, Nigel B.; Chou, Joanne F.; Miotto, Marco; He, Jin; Gonen, Mithat; Pea, Antonio; Tang, Laura H.; Nessi, Chiara; Cingarlini, Sara; D'Angelica, Michael I.; Gill, Anthony J.; Kingham, T. Peter; Scarpa, Aldo; Weiss, Matthew J.; Balachandran, Vinod P.; Samra, Jaswinder S.; Cameron, John L.; Jarnagin, William R.; Salvia, Roberto; Wolfgang, Christopher L.; Allen, Peter J.; Bassi, Claudio.

In: Annals of surgery, 01.01.2019.

Research output: Contribution to journalArticle

Pulvirenti, A, Javed, AA, Landoni, L, Jamieson, NB, Chou, JF, Miotto, M, He, J, Gonen, M, Pea, A, Tang, LH, Nessi, C, Cingarlini, S, D'Angelica, MI, Gill, AJ, Kingham, TP, Scarpa, A, Weiss, MJ, Balachandran, VP, Samra, JS, Cameron, JL, Jarnagin, WR, Salvia, R, Wolfgang, CL, Allen, PJ & Bassi, C 2019, 'Multi-institutional Development and External Validation of a Nomogram to Predict Recurrence after Curative Resection of Pancreatic Neuroendocrine Tumors', Annals of surgery. https://doi.org/10.1097/SLA.0000000000003579
Pulvirenti, Alessandra ; Javed, Ammar A. ; Landoni, Luca ; Jamieson, Nigel B. ; Chou, Joanne F. ; Miotto, Marco ; He, Jin ; Gonen, Mithat ; Pea, Antonio ; Tang, Laura H. ; Nessi, Chiara ; Cingarlini, Sara ; D'Angelica, Michael I. ; Gill, Anthony J. ; Kingham, T. Peter ; Scarpa, Aldo ; Weiss, Matthew J. ; Balachandran, Vinod P. ; Samra, Jaswinder S. ; Cameron, John L. ; Jarnagin, William R. ; Salvia, Roberto ; Wolfgang, Christopher L. ; Allen, Peter J. ; Bassi, Claudio. / Multi-institutional Development and External Validation of a Nomogram to Predict Recurrence after Curative Resection of Pancreatic Neuroendocrine Tumors. In: Annals of surgery. 2019.
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abstract = "Objective: To develop a nomogram estimating the probability of recurrence free at 5 years after resection for localized grade 1 (G1)/ grade 2 (G2) pancreatic neuroendocrine tumors (PanNETs). Background: Among patients undergoing resection of PanNETs, approximately 17{\%} experience recurrence. It is not established which patients are at risk, with no consensus on optimal follow-up. Method: A multi-institutional database of patients with G1/G2 PanNETs treated at 2 institutions was used to develop a nomogram estimating the rate of freedom from recurrence at 5 years after curative resection. A second cohort of patients from 3 additional institutions was used to validate the nomogram. Prognostic factors were assessed by univariate analysis using Cox regression model. The nomogram was internally validated using bootstrap resampling method and on the external cohort. Performance was assessed by concordance index (c-index) and a calibration curve. Results: The nomogram was constructed using a cohort of 632 patients. Overall, 68{\%} of PanNETs were G1, the median follow-up was 51 months, and we observed 74 recurrences. Variables included in the nomogram were the number of positive nodes, tumor diameter, Ki-67, and vascular/perineural invasion. The model bias-corrected c-index from the internal validation was 0.85, which was higher than European Neuroendocrine Tumors Society/American Joint Committee on Cancer 8th staging scheme (c-index 0.76, P = <0.001). On the external cohort of 328 patients, the nomogram c-index was 0.84 (95{\%} confidence interval 0.79-0.88). Conclusion: Our externally validated nomogram predicts the probability of recurrence-free survival at 5 years after PanNETs curative resection, with improved accuracy over current staging systems. Estimating individual recurrence risk will guide the development of personalized surveillance programs after surgery.",
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author = "Alessandra Pulvirenti and Javed, {Ammar A.} and Luca Landoni and Jamieson, {Nigel B.} and Chou, {Joanne F.} and Marco Miotto and Jin He and Mithat Gonen and Antonio Pea and Tang, {Laura H.} and Chiara Nessi and Sara Cingarlini and D'Angelica, {Michael I.} and Gill, {Anthony J.} and Kingham, {T. Peter} and Aldo Scarpa and Weiss, {Matthew J.} and Balachandran, {Vinod P.} and Samra, {Jaswinder S.} and Cameron, {John L.} and Jarnagin, {William R.} and Roberto Salvia and Wolfgang, {Christopher L.} and Allen, {Peter J.} and Claudio Bassi",
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T1 - Multi-institutional Development and External Validation of a Nomogram to Predict Recurrence after Curative Resection of Pancreatic Neuroendocrine Tumors

AU - Pulvirenti, Alessandra

AU - Javed, Ammar A.

AU - Landoni, Luca

AU - Jamieson, Nigel B.

AU - Chou, Joanne F.

AU - Miotto, Marco

AU - He, Jin

AU - Gonen, Mithat

AU - Pea, Antonio

AU - Tang, Laura H.

AU - Nessi, Chiara

AU - Cingarlini, Sara

AU - D'Angelica, Michael I.

AU - Gill, Anthony J.

AU - Kingham, T. Peter

AU - Scarpa, Aldo

AU - Weiss, Matthew J.

AU - Balachandran, Vinod P.

AU - Samra, Jaswinder S.

AU - Cameron, John L.

AU - Jarnagin, William R.

AU - Salvia, Roberto

AU - Wolfgang, Christopher L.

AU - Allen, Peter J.

AU - Bassi, Claudio

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: To develop a nomogram estimating the probability of recurrence free at 5 years after resection for localized grade 1 (G1)/ grade 2 (G2) pancreatic neuroendocrine tumors (PanNETs). Background: Among patients undergoing resection of PanNETs, approximately 17% experience recurrence. It is not established which patients are at risk, with no consensus on optimal follow-up. Method: A multi-institutional database of patients with G1/G2 PanNETs treated at 2 institutions was used to develop a nomogram estimating the rate of freedom from recurrence at 5 years after curative resection. A second cohort of patients from 3 additional institutions was used to validate the nomogram. Prognostic factors were assessed by univariate analysis using Cox regression model. The nomogram was internally validated using bootstrap resampling method and on the external cohort. Performance was assessed by concordance index (c-index) and a calibration curve. Results: The nomogram was constructed using a cohort of 632 patients. Overall, 68% of PanNETs were G1, the median follow-up was 51 months, and we observed 74 recurrences. Variables included in the nomogram were the number of positive nodes, tumor diameter, Ki-67, and vascular/perineural invasion. The model bias-corrected c-index from the internal validation was 0.85, which was higher than European Neuroendocrine Tumors Society/American Joint Committee on Cancer 8th staging scheme (c-index 0.76, P = <0.001). On the external cohort of 328 patients, the nomogram c-index was 0.84 (95% confidence interval 0.79-0.88). Conclusion: Our externally validated nomogram predicts the probability of recurrence-free survival at 5 years after PanNETs curative resection, with improved accuracy over current staging systems. Estimating individual recurrence risk will guide the development of personalized surveillance programs after surgery.

AB - Objective: To develop a nomogram estimating the probability of recurrence free at 5 years after resection for localized grade 1 (G1)/ grade 2 (G2) pancreatic neuroendocrine tumors (PanNETs). Background: Among patients undergoing resection of PanNETs, approximately 17% experience recurrence. It is not established which patients are at risk, with no consensus on optimal follow-up. Method: A multi-institutional database of patients with G1/G2 PanNETs treated at 2 institutions was used to develop a nomogram estimating the rate of freedom from recurrence at 5 years after curative resection. A second cohort of patients from 3 additional institutions was used to validate the nomogram. Prognostic factors were assessed by univariate analysis using Cox regression model. The nomogram was internally validated using bootstrap resampling method and on the external cohort. Performance was assessed by concordance index (c-index) and a calibration curve. Results: The nomogram was constructed using a cohort of 632 patients. Overall, 68% of PanNETs were G1, the median follow-up was 51 months, and we observed 74 recurrences. Variables included in the nomogram were the number of positive nodes, tumor diameter, Ki-67, and vascular/perineural invasion. The model bias-corrected c-index from the internal validation was 0.85, which was higher than European Neuroendocrine Tumors Society/American Joint Committee on Cancer 8th staging scheme (c-index 0.76, P = <0.001). On the external cohort of 328 patients, the nomogram c-index was 0.84 (95% confidence interval 0.79-0.88). Conclusion: Our externally validated nomogram predicts the probability of recurrence-free survival at 5 years after PanNETs curative resection, with improved accuracy over current staging systems. Estimating individual recurrence risk will guide the development of personalized surveillance programs after surgery.

KW - nomogram

KW - pancreatic neuroendocrine tumor

KW - pancreatic surgery

KW - recurrence

KW - surveillance

KW - well-differentiated

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