Abstract
Objectives
We aimed to evaluate the prognostic value of tumor-to-parenchymal contrast enhancement ratio on portal venous-phase CT (CER on PVP) and compare its prognostic performance to prevailing grading and staging systems in pancreatic neuroendocrine neoplasms (PanNENs).
Methods
In this retrospective study, data on 465 patients (development cohort) who underwent upfront curative-intent resection for PanNEN were used to assess the performance of CER on PVP and tumor size measured by CT (CT-Size) in predicting recurrence-free survival (RFS) using Harrell’s C-index and to determine their optimal cutoffs to stratify RFS using a multi-way partitioning algorithm. External data on 184 patients (test cohort) were used to validate the performance of CER on PVP in predicting RFS and overall survival (OS) and compare its predictive performance with those of CT-Size, 2019 World Health Organization classification system (WHO), and the 8th American Joint Committee on Cancer staging system (AJCC).
Results
In the test cohort, CER on PVP showed C-indexes of 0.83 (95% confidence interval [CI], 0.74–0.91) and 0.84 (95% CI, 0.73–0.95) for predicting RFS and OS, respectively, which were higher than those for the WHO (C-index: 0.73 for RFS [p = .002] and 0.72 for OS [p = .004]) and AJCC (C-index, 0.67 for RFS [p = .002] and 0.58 for OS [p = .002]). CT-Size obtained C-indexes of 0.71 for RFS and 0.61 for OS.
Conclusions
CER on PVP showed superior predictive performance on postoperative survival in PanNEN than current grading and staging systems, indicating its potential as a noninvasive preoperative prognostic tool.
Key Points
• In pancreatic neuroendocrine neoplasms, the tumor-to-parenchymal enhancement ratio on portal venous-phase CT (CER on PVP) showed acceptable predictive performance of postoperative outcomes.
• CER on PVP showed superior predictive performance of postoperative survival over the current WHO classification and AJCC staging system.
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Abbreviations
- AP:
-
Arterial phase
- CER:
-
Contrast enhancement ratio
- HR:
-
Hazard ratio
- IQR:
-
Interquartile range
- NEC:
-
Neuroendocrine carcinoma
- NET:
-
Neuroendocrine tumor
- OS:
-
Overall survival
- PanNEN:
-
Pancreatic neuroendocrine neoplasm
- PVP:
-
Portal venous phase
- RFS:
-
Recurrence-free survival
- ROC:
-
Receiver operating characteristics
References
Fraenkel M, Kim MK, Faggiano A, Valk GD (2012) Epidemiology of gastroenteropancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol 26:691–703
Singhi AD, Klimstra DS (2018) Well-differentiated pancreatic neuroendocrine tumours (PanNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs): concepts, issues and a practical diagnostic approach to high-grade (G3) cases. Histopathology 72:168–177
Lloyd RV, Osamura RY, Klöppel G et al (2017) WHO classification of tumours of endocrine organs, 4th edn. International Agency for Research on Cancer, Lyon
Amin MB, Edge S, Greene F et al (2017) AJCC cancer staging manual. Springer International Publishing, New York
WHO Classification of Tumours Editorial Board (2019) Digestive system tumours, 5th edn. International Agency for Research on Cancer, Lyon
Eo SH, Kang HJ, Hong SM, Cho H (2013) K-adaptive partitioning for survival data, with an application to cancer staging. arXiv:1306.4615v3 [stat.AP]. Available via https://arxiv.org/abs/1306.4615.
Arai T, Kobayashi A, Fujinaga Y et al (2016) Contrast-enhancement ratio on multiphase enhanced computed tomography predicts recurrence of pancreatic neuroendocrine tumor after curative resection. Pancreatology 16:397–402
Kim H, Song KB, Hwang DW, Lee JH, Alshammary S, Kim SC (2019) Time-trend and recurrence analysis of pancreatic neuroendocrine tumors. Endocr Connect 8:1052–1060
Choe J, Kim KW, Kim HJ et al (2019) What Is New in the 2017 World Health Organization Classification and 8th American Joint Committee on Cancer Staging System for Pancreatic Neuroendocrine Neoplasms? Korean J Radiol 20:5–17
Hayes AR, Furnace M, Shah R et al (2021) High-grade gastroenteropancreatic neuroendocrine neoplasms and improved prognostic stratification with the New World Health Organization 2019 Classification: a validation study from a single-institution retrospective analysis. Pancreas 50:516–523
Yang M, Zhang Y, Zeng L et al (2019) Prognostic validity of the american joint committee on cancer eighth edition TNM staging system for surgically treated and well-differentiated pancreatic neuroendocrine tumors: a comprehensive analysis of 254 consecutive patients from a large Chinese institution. Pancreas 48:613–621
Bocchini M, Nicolini F, Severi S et al (2020) Biomarkers for pancreatic neuroendocrine neoplasms (PanNENs) management—an updated review. Front Oncol 10
Lania A, Ferraù F, Rubino M, Modica R, Colao A, Faggiano A (2021) Neoadjuvant therapy for neuroendocrine neoplasms: recent progresses and future approaches. Front Endocrinol (Lausanne) 12:651438
Horiguchi S, Kato H, Shiraha H et al (2017) Dynamic computed tomography is useful for prediction of pathological grade in pancreatic neuroendocrine neoplasm. J Gastroenterol Hepatol 32:925–931
Kim DW, Kim HJ, Kim KW et al (2016) Prognostic value of CT findings to predict survival outcomes in patients with pancreatic neuroendocrine neoplasms: a single institutional study of 161 patients. Eur Radiol 26:1320–1329
Park HJ, Kim HJ, Kim KW et al (2020) Comparison between neuroendocrine carcinomas and well-differentiated neuroendocrine tumors of the pancreas using dynamic enhanced CT. Eur Radiol 30:4772–4782
Kim DW, Kim HJ, Kim KW et al (2015) Neuroendocrine neoplasms of the pancreas at dynamic enhanced CT: comparison between grade 3 neuroendocrine carcinoma and grade 1/2 neuroendocrine tumour. Eur Radiol 25:1375–1383
Takumi K, Fukukura Y, Higashi M et al (2015) Pancreatic neuroendocrine tumors: correlation between the contrast-enhanced computed tomography features and the pathological tumor grade. Eur J Radiol 84:1436–1443
D'Onofrio M, Ciaravino V, Cardobi N et al (2019) CT enhancement and 3D texture analysis of pancreatic neuroendocrine neoplasms. Sci Rep 9:2176
Choi SH, Kim HJ, Kim SY et al (2017) Computed tomography features predictive of lymph node involvement in patients with a nonfunctioning pancreatic neuroendocrine tumor. Pancreas 46:1056–1063
Bonnetain F, Bonsing B, Conroy T et al (2014) Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials). Eur J Cancer 50:2983–2993
Punt CJA, Buyse M, Köhne C-H et al (2007) Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials. J Natl Cancer Inst 99:998–1003
Black WC, Haggstrom DA, Welch HG (2002) All-cause mortality in randomized trials of cancer screening. J Natl Cancer Inst 94:167–173
Harrell FE Jr, Lee KL, Mark DB (1996) Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 15:361–387
Uno H, Cai T, Pencina MJ, D'Agostino RB, Wei LJ (2011) On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data. Stat Med 30:1105–1117
Heagerty PJ, Lumley T, Pepe MS (2000) Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics 56:337–344
Rodallec M, Vilgrain V, Couvelard A et al (2006) Endocrine pancreatic tumours and helical CT: contrast enhancement is correlated with microvascular density, histoprognostic factors and survival. Pancreatology 6:77–85
Okabe H, Hashimoto D, Chikamoto A et al (2017) Shape and enhancement characteristics of pancreatic neuroendocrine tumor on preoperative contrast-enhanced computed tomography may be prognostic indicators. Ann Surg Oncol 24:1399–1405
Kondo H, Kanematsu M, Goshima S et al (2007) MDCT of the pancreas: optimizing scanning delay with a bolus-tracking technique for pancreatic, peripancreatic vascular, and hepatic contrast enhancement. AJR Am J Roentgenol 188:751–756
Almeida RR, Lo GC, Patino M, Bizzo B, Canellas R, Sahani DV (2018) Advances in pancreatic CT imaging. AJR Am J Roentgenol 211:52–66
Fletcher JG, Wiersema MJ, Farrell MA et al (2003) Pancreatic malignancy: value of arterial, pancreatic, and hepatic phase imaging with multi-detector row CT. Radiology 229:81–90
Goshima S, Kanematsu M, Kondo H et al (2006) Pancreas: optimal scan delay for contrast-enhanced multi–detector row CT. Radiology 241:167–174
Liang W, Yang P, Huang R et al (2019) A combined nomogram model to preoperatively predict histologic grade in pancreatic neuroendocrine tumors. Clin Cancer Res 25:584
Couvelard A, O'Toole D, Turley H et al (2005) Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression. Br J Cancer 92:94–101
Marion-Audibert AM, Barel C, Gouysse G et al (2003) Low microvessel density is an unfavorable histoprognostic factor in pancreatic endocrine tumors. Gastroenterology 125:1094–1104
Gao Y, Gao H, Wang G et al (2018) A meta-analysis of prognostic factor of pancreatic neuroendocrine neoplasms. Sci Rep 8:7271
Funding
This study was supported by a grant from the National Research Foundation of Korea (NRF), funded by the Korean government (MSIT) (grant number 2021R1C1C1010138 to Hyo Jung Park). Other authors received no financial support for the work described in this study.
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The scientific guarantor of this publication is Hyoung Jung Kim.
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The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.
Statistics and biometry
We consulted an expert statistician (Jung Bok Lee, Associate Professor, Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea) for this study.
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Written informed consent was waived by the Institutional Review Board.
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Institutional Review Board approval was obtained.
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Study subjects or cohorts have been previously reported in the articles below.
Kim DW, Kim HJ, Kim KW, et al (2015) Neuroendocrine neoplasms of the pancreas at dynamic enhanced CT: comparison between grade 3 neuroendocrine carcinoma and grade 1/2 neuroendocrine tumour. Eur Radiol 25:1375-1383
Kim DW, Kim HJ, Kim KW et al (2016) Prognostic value of CT findings to predict survival outcomes in patients with pancreatic neuroendocrine neoplasms: a single institutional study of 161 patients. Eur Radiol 26:1320-1329
Choi SH, Kim HJ, Kim SY et al (2017) Computed tomography features predictive of lymph node involvement in patients with a nonfunctioning pancreatic neuroendocrine tumor. Pancreas 46:1056-1063
Park HJ, Kim HJ, Kim KW et al (2020) Comparison between neuroendocrine carcinomas and well-differentiated neuroendocrine tumors of the pancreas using dynamic enhanced CT. Eur Radiol 30:4772-4782
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• retrospective
• observational study
• multicenter study
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Park, H.J., Kim, H.J., Kim, J.H. et al. Prognostic value of tumor-to-parenchymal contrast enhancement ratio on portal venous-phase CT in pancreatic neuroendocrine neoplasms. Eur Radiol 33, 2713–2724 (2023). https://doi.org/10.1007/s00330-022-09235-y
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DOI: https://doi.org/10.1007/s00330-022-09235-y