Development and Validation of a Multi-institutional Preoperative Nomogram for Predicting Grade of Dysplasia in Intraductal Papillary Mucinous Neoplasms (IPMNs) of the Pancreas

Marc A. Attiyeh, Carlos Fernández-Del Castillo, Mohammad Al Efishat, Anne A. Eaton, Mithat Gönen, Ruqayyah Batts, Ilaria Pergolini, Neda Rezaee, Keith D. Lillemoe, Cristina R. Ferrone, Mari Mino-Kenudson, Matthew J. Weiss, John L. Cameron, Ralph H. Hruban, Michael I. D'Angelica, Ronald P. Dematteo, T. Peter Kingham, William R. Jarnagin, Christopher L. Wolfgang, Peter J. Allen

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35 Scopus citations

Abstract

Objective: Previous nomogram models for patients undergoing resection of intraductal papillary mucinous neoplasms (IPMNs) have been relatively small single-institutional series. Our objective was to improve upon these studies by developing and independently validating a new model using a large multiinstitutional dataset. Summary Background Data: IPMNs represent the most common radiographically identifiable precursor lesions of pancreatic cancer. They are a heterogenous group of neoplasms in which more accurate markers of high-grade dysplasia or early invasive carcinoma could help avoid unnecessary surgery in 1 case and support potentially curative intervention (resection) in another. Methods: Prospectively maintained databases from 3 institutions were queried for patients who had undergone resection of IPMNs between 2005 and 2015. Patients were separated into main duct [main and mixed-type (MD)] and branch duct (BD) types based on preoperative imaging. Logistic regression modeling was used on a training subset to develop 2 independent nomograms (MD and BD) to predict low-risk (low-or intermediate-grade dysplasia) or high-risk (high-grade dysplasia or invasive carcinoma) disease. Model performance was then evaluated using an independent validation set. Results: We identified 1028 patients who underwent resection for IPMNs [MD: N = 454 (44%), BD: N = 574 (56%)] during the 10-year study period. High-risk disease was present in 487 patients (47%). Patients with high-risk disease comprised 71% and 29% of MD and BD groups, respectively (P <0.0001). MD and BD nomograms were developed on the training set [70% of total (n = 720); MD: N = 318, BD: N = 402] and validated on the test set [30% (n = 308); MD: N = 136, BD: N = 172]. The presence of jaundice was almost exclusively associated with high-risk disease (57 of 58 patients, 98%). Cyst size >3.0cm, solid component/mural nodule, pain symptoms, and weight loss were significantly associated with high-risk disease. C-indices were 0.82 and 0.81 on training and independent validation sets, respectively; Brier scores were 0.173 and 0.175, respectively. Conclusions: For patients with suspected IPMNs, we present an independently validated model for the prediction of high-risk disease.

Original languageEnglish (US)
Pages (from-to)157-163
Number of pages7
JournalAnnals of surgery
Volume267
Issue number1
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Bibliographical note

Funding Information:
Objective: Previous nomogram models for patients undergoing resection of intraductal papillary mucinous neoplasms (IPMNs) have been relatively small single-institutional series. Our objective was to improve upon these studies by developing and independently validating a new model using a large multi-institutional dataset. Summary Background Data: IPMNs represent the most common radiographically identifiable precursor lesions of pancreatic cancer. They are a heterogenous group of neoplasms in which more accurate markers of high-grade dysplasia or early invasive carcinoma could help avoid unnecessary surgery in 1 case and support potentially curative intervention (resection) in another. Methods: Prospectively maintained databases from 3 institutions were queried for patients who had undergone resection of IPMNs between 2005 and 2015. Patients were separated into main duct [main and mixed-type (MD)] and branch duct (BD) types based on preoperative imaging. Logistic regression modeling was used on a training subset to develop 2 independent nomograms (MD and BD) to predict low-risk (low-or intermediate-grade dysplasia) or high-risk (high-grade dysplasia or invasive carcinoma) disease. Model performance was then evaluated using an independent validation set. Results: We identified 1028 patients who underwent resection for IPMNs [MD: n = 454 (44%), BD: n = 574 (56%)] during the 10-year study period. High-risk disease was present in 487 patients (47%). Patients with high-risk From the *Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; †Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA; zDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY; §Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD; ôDepartment of Pathology, Massachusetts General Hospital, Boston, MA; and ||Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Uni-versity School of Medicine, Baltimore, MD. The work presented in this paper was supported in part by NIH funding (R01 CA182076). Study conception and design: MAA, CF-dC, MAE, AAE, MG, RB, KDL, CRF, MM-K, MJW, JLC, RHH, MID, RPD, TPK, WRJ, CLW, PJA. Acquisition of data: MAA, MAE, RB, IP, NR. Analysis and interpretation of data: MAA, MAE, AAE, MG, PJA. Drafting of the manuscript: MAA, PJA. Critical revision: MAA, CF-dC, MAE, AAE, MG, IP, NR, KDL, CRF, MM-K, MJW, JLC, RHH, MID, RPD, TPK, WRJ, CLW, PJA. The authors report no conflicts of interest. Reprints: Peter J. Allen, MD, Department of Surgery, C896, Memorial Sloan Kettering Cancer Center, New York, NY 10021. E-mail: allenp@mskcc.org. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0003-4932/16/26701-0157 DOI: 10.1097/SLA.0000000000002015 disease comprised 71% and 29% of MD and BD groups, respectively (P <0.0001). MD and BD nomograms were developed on the training set [70% of total (n = 720); MD: n = 318, BD: n = 402] and validated on the test set [30% (n = 308); MD: n = 136, BD: n = 172]. The presence of jaundice was almost exclusively associated with high-risk disease (57 of 58 patients, 98%). Cyst size >3.0 cm, solid component/mural nodule, pain symptoms, and weight loss were significantly associated with high-risk disease. C-indices were 0.82 and 0.81 on training and independent validation sets, respectively; Brier scores were 0.173 and 0.175, respectively. Conclusions: For patients with suspected IPMNs, we present an independently validated model for the prediction of high-risk disease.

Keywords

  • IPMN
  • cancer
  • dysplasia
  • intraductal papillary mucinous neoplasm
  • nomogram
  • pancreas
  • the pancreatic surgery consortium

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