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Multicenter Study
. 2021 Dec 1;274(6):1051-1057.
doi: 10.1097/SLA.0000000000003579.

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

Alessandra Pulvirenti  1   2 , Ammar A Javed  3 , Luca Landoni  2 , Nigel B Jamieson  4   5 , Joanne F Chou  6 , Marco Miotto  2 , Jin He  3 , Mithat Gonen  6 , Antonio Pea  2 , Laura H Tang  7 , Chiara Nessi  2 , Sara Cingarlini  8 , Michael I D'Angelica  1 , Anthony J Gill  9 , T Peter Kingham  1 , Aldo Scarpa  10 , Matthew J Weiss  3 , Vinod P Balachandran  1 , Jaswinder S Samra  5 , John L Cameron  3 , William R Jarnagin  1 , Roberto Salvia  2 , Christopher L Wolfgang  3 , Peter J Allen  11 , Claudio Bassiy  2
Affiliations
Multicenter Study

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

Alessandra Pulvirenti et al. Ann Surg. .

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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Conflict of interest statement

The authors declare no conflict of interests.

Figures

FIGURE 1.
FIGURE 1.
Nomogram predicting the probability of 5-year recurrence-free survival. Points are assigned for number of positive lymph nodes, Ki-67, tumor diameter, presence of vascular invasion or perineural invasion, by drawing a line upward from the corresponding values to the “Points” line. The sum of these 3 points, plotted on the “Total points” line, corresponds to predictions of 5-year recurrence-free probabilities.
FIGURE 2.
FIGURE 2.
Time to recurrence by (A) ENETS/AJCC 8th staging system for PanNET and (B) AJCC 8th ed. staging system for PanNEC.
FIGURE 3.
FIGURE 3.
Calibration plot for predction of of 5-year recurrence-free survival on external cohort. The x-axis represents the nomogram-predicted probability of RFS and the y-axis represents the observed fraction with evidence of RFS. Perfect prediction corresponds to the 45° line. Points estimated below the 45° line correspond to nomogram overall prediction whereas points situated above the 45° line correspond to nomogram under prediction.
See this image and copyright information in PMC

References

    1. Pulvirenti A, Marchegiani G, Pea A, et al. Clinical implications of the 2016 International Study Group on pancreatic surgery definition and grading of postoperative pancreatic fistula on 775 consecutive pancreatic resections. Ann Surg. 2018;268:1069–1075. - PubMed
    1. Strosberg JR, Cheema A, Weber JM, et al. Relapse-free survival in patients with nonmetastatic, surgically resected pancreatic neuroendocrine tumors. Ann Surg. 2012;256:321–325. - PubMed
    1. Ricci C, Casadei R, Taffurelli G, et al. Is radical surgery always curative in pancreatic neuroendocrine tumors? A cure model survival analysis. Pancreatology. 2018;1–5. - PubMed
    1. Landoni L, Marchegiani G, Pollini T, et al. The evolution of surgical strategies for pancreatic neuroendocrine tumors (Pan-NENs). Ann Surg. 2019;269: 725–732. - PubMed
    1. The International Agency for Research on Cancer. In: Bosman FT, Carneiro F, Hruban RH, Theise N, eds. WHO Classification of Tumours of the Digestive System. 4th ed, World Health Organization; 2010:418.