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The Number of Lymph Nodes Examined is Associated with Survival Outcomes of Neuroendocrine Tumors of the Jejunum and Ileum (siNET): Development and Validation of a Prognostic Model Based on SEER Database

  • Original Article
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Journal of Gastrointestinal Surgery

Abstract

Purpose

The number of  neuroendocrine tumors (NETs) is gradually increasing worldwide, and those located in the small intestine (siNETs) are the most common. As some biological and clinical characteristics of tumors of the jejunum and the ileum differ, there is a need to assess the prognosis of individuals with siNETs of the jejunum and ileum separately. We generated a predictive nomogram by assessing individuals with siNETs from the Surveillance, Epidemiology, and End Results (SEER) database.

Methods

We used univariate Cox regression analysis to determine both the overall survival (OS) and the cancer-specific survival (CSS) of 2501 patients with a pathological confirmation of siNETs of the jejunum and ileum. To predict 3-, 5-, and 10-year OS of siNETs, a nomogram was generated based on a training cohort and validated with an external cohort. Accuracy and clinical practicability were evaluated separately by Harrell’s C-indices, calibration plots, and decision curves. The correlation was examined between dissected lymph nodes and positive lymph nodes.

Results

Dissection of 7 or more lymph nodes significantly improved patient OS and was found to be a protective factor for patients with siNETs. In Cox regression analyses, age, primary site, tumor size, N stage, M stage, and regional lymph node examination were significant predictors in the nomogram. A significant positive correlation was found between dissected lymph nodes and positive lymph nodes.

Conclusions

Patients with 7 or more dissected lymph nodes showed an accurate tumor stage and a better prognosis. Our nomogram accurately predicted the OS of patients with siNETs.

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Data Availability

The datasets used and/or analyzed during the current study are available from the Surveillance, Epidemiology, and End Results (SEER) database (http://seer.cancer.gov/data/sample-dua.html).

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Acknowledgements

We thank all patients, investigators, and institutions involved in this study, especially the SEER database for providing platforms and valuable data sets.

Author information

Author notes

  1. Peng Wang and Erlin Chen contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Peng Wang, Erlin Chen, Mingjie Xie, Zhou Zhou, Yuanjie Niu, Wei Song, Qingfeng Ni & Jianwei Zhu

  2. Department of Urinary Surgery, The 2nd Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Wei Xu

  3. Department of Gynecology and Obstetrics, Tumor Hospital Affiliated to Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Chaoyang Ou

Authors
  1. Peng Wang
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Contributions

Peng Wang, Erlin Chen, Qingfeng Ni, and Jianwei Zhu carried out the design of this study, analyses of statistics, and draft the manuscript. Mingjie Xie, Wei Xu, Chaoyang Ou, Zhou Zhou, Yuanjie Niu, and Wei Song carried out collection of the statistics and prepared the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Qingfeng Ni or Jianwei Zhu.

Ethics declarations

Ethics Approval and Consent to Participate

Because the patients in the SEER database could not be identified, the analyses and reporting of the data in our study were exempt from review by the Ethics Board of Affiliated Hospital of Nantong University. The requirement for written informed consent to participate was waived. We were permitted to have Internet access to the database after our signed data-use agreement (http://seer.cancer.gov/data/sample-dua.html ) was approved by the SEER administration.

Competing Interest

The authors declare no competing interests.

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Supplementary information

Below is the link to the electronic supplementary material.

Supplementary Figure 1.

Flow diagram for selecting patients with neuroendocrine tumors of the jejunum and ileum from SEER database into this study. (PNG 320 kb)

High Resolution Image (TIF 1072 kb)

Supplementary Figure 2.

OS for patients with siNET stratified by (A) LNR (the ratio between positive and dissected lymph nodes); CSS for patients with siNET stratified by (B) LNR (C) age, (D) 8th AJCC T stage; (E) 8th AJCC N stage; (F) 8th AJCC M stage. (PNG 245 kb)

High Resolution Image (TIF 2739 kb)

Supplementary Figure 3.

CSS for patients with siNET stratified by (A)Grade, (B) tumor size; (C)primary site; (D)sex; (E) Chemotherapy; (F) Radiotherapy. (PNG 295 kb)

High Resolution Image (TIF 2764 kb)

Supplementary Figure 4.

External validation of the prognostic nomogram for siNET. (A) ROC curves for 3-/5-/10- year OS in external validation cohort. (B) Calibration plots for 3-/5-/10- year OS in external validation cohort. (C) DCA curve for 3-/5-/10- year OS in external validation cohort. (PNG 402 kb)

High Resolution Image (TIF 1899 kb)

Supplementary Figure 5.

time-dependent C -index ROC curves for siNET predicted by our new nomogram (red line) and the 8th AJCC staging system (blue line) in (A) the validation cohort, (B) external validation cohort. (PNG 171 kb)

High Resolution Image (TIF 567 kb)

Supplementary Table 1.

Clinical, pathological and treatment information of external validation cohort from Affiliated Hospital of Nantong University, the 2nd affiliated Hospital of Nantong University and Tumor Hospital Affiliated to Nantong University. Abbreviations: AJCC, American Joint Committee on Cancer staging system.; LNR: the ratio between positive and dissected lymph nodes; Tumor size: Postoperative pathological measured. (DOCX 26 kb)

Supplementary Table 2.

ICMJE DISCLOSURE FORM. (DOCX 103 kb)

Supplementary File 1.

TRIPOD statement. (PDF 139 kb)

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Wang, P., Chen, E., Xie, M. et al. The Number of Lymph Nodes Examined is Associated with Survival Outcomes of Neuroendocrine Tumors of the Jejunum and Ileum (siNET): Development and Validation of a Prognostic Model Based on SEER Database. J Gastrointest Surg 26, 1917–1929 (2022). https://doi.org/10.1007/s11605-022-05359-0

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