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. 2022 Sep;247(18):1657-1669.
doi: 10.1177/15353702221113828. Epub 2022 Aug 10.

Diagnostic and prognostic nomograms for newly diagnosed intrahepatic cholangiocarcinoma with brain metastasis: A population-based analysis

Zhili Liu  1   2   3   4 , Jianying Yi  5 , Jie Yang  1   2   3   4 , Xingxin Zhang  6 , Lu Wang  7 , Shuye Liu  1   2   3   4
Affiliations

Diagnostic and prognostic nomograms for newly diagnosed intrahepatic cholangiocarcinoma with brain metastasis: A population-based analysis

Zhili Liu et al. Exp Biol Med (Maywood). 2022 Sep.

Abstract

Brain metastasis (BM) is one of the rare metastatic sites of intrahepatic cholangiocarcinoma (ICC). ICC with BM can seriously affect the quality of life of patients and lead to a poor prognosis. The aim of this study was to establish two nomograms to estimate the risk of BM in ICC patients and the prognosis of ICC patients with BM. Data on 19,166 individuals diagnosed with ICC were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent risk factors and prognostic factors were identified by the logistic and the Cox regression, respectively. Next, two nomograms were developed, and their discrimination was estimated by concordance index (C-index) and calibration plots, while the clinical benefits of the prognostic nomogram were evaluated using the receiver operating characteristic (ROC) curves, the decision curve analysis (DCA), and the Kaplan-Meier analyses. The independent risk factors for BM were T stage, N stage, surgery, alpha-fetoprotein (AFP) level, and tumor size. T stage, surgery, radiotherapy, and bone metastasis were prognostic factors for overall survival (OS). For the prognostic nomogram, the C-index was 0.759 (95% confidence interval (CI) = 0.745-0.773) and 0.764 (95% CI = 0.747-0.781) in the training and the validation cohort, respectively. The calibration curves revealed a robust agreement between predictions and actual observations probability. The area under curves (AUCs) for the 3-, 6-, and 9-month OS were 0.721, 0.727, and 0.790 in the training cohort and 0.702, 0.777, and 0.853 in the validation cohort, respectively. The DCA curves yielded remarkable positive net benefits over a wide range of threshold probabilities. The Kaplan-Meier analysis illustrated that the nomogram could significantly distinguish the population with different survival risks. We successfully established the two nomograms for predicting the incidence of BM and the prognosis of ICC patients with BM, which may assist clinicians in choosing more effective treatment strategies.

Keywords: Epidemiology; Intrahepatic cholangiocarcinoma; Surveillance; and End Results; brain metastasis; diagnosis; nomogram; prognosis.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
The flow diagram of the study.
Figure 2.
Figure 2.
Diagnostic nomogram for predicting BM among ICC patients. When using the nomogram for an individual ICC patient, each risk factor is assigned a point value by drawing a vertical line from the corresponding value to the first point line. The total points are calculated by adding the individual points of the corresponding predictors, and each total point corresponds to a probability of brain metastasis among ICC patients in the bottom row. (A color version of this figure is available in the online journal.) BM: brain metastasis; ICC: intrahepatic cholangiocarcinoma.
Figure 3.
Figure 3.
The calibration curves in the training cohort (A) and the validation cohort (B).
Figure 4.
Figure 4.
Prognostic nomogram for predicting the 3-, 6-, and 9-month overall survival of ICC patients with BM. When using the nomogram for an individual ICC patient with brain metastasis, each prognostic factor is assigned a point value by drawing a vertical line from the corresponding value to the first point line. The total points are calculated by adding the individual points of the corresponding predictors, and each total point corresponds to the 3-, 6-, and 9-month survival probabilities in the bottom row. (A color version of this figure is available in the online journal.) ICC: intrahepatic cholangiocarcinoma; BM: brain metastasis.
Figure 5.
Figure 5.
The calibration curves of the nomogram for the (A) 3-, (B) 6-, and (C) 9-month OS prediction in the training cohort. The calibration curves of the nomogram for predicting the (D) 3-, (E) 6-, and (F) 9-month OS in the validation cohort. (A color version of this figure is available in the online journal.) OS: overall survival.
Figure 6.
Figure 6.
The receiver operating characteristic curves for the 3-, 6-, and 9-month OS in (A) the training cohort and (B) the validation cohort. (A color version of this figure is available in the online journal.) OS: overall survival.
Figure 7.
Figure 7.
The receiver operating characteristic curves of the prognostic nomogram and each independent indicator at (A) 3-, (B) 6-, and (C) 9-month points in the training cohort and at (D) 3-, (E) 6-, and (F) 9-month points in the validation cohort. (A color version of this figure is available in the online journal.) Surgery: surgery of the primary site.
Figure 8.
Figure 8.
The decision curve analysis of the nomogram for the (A) 3-, (B) 6-, and (C) 9-month OS prediction in the training cohort. The decision curve analysis of the nomogram for predicting the (D) 3-, (E) 6-, and (F) 9-month OS in the validation cohort. OS: overall survival.
Figure 9.
Figure 9.
Kaplan–Meier curves for patients in the low-risk (blue) and high-risk (red) clusters: (A) training cohort and (B) validation cohort. (A color version of this figure is available in the online journal.)
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