Introduction
Intrahepatic cholangiocarcinoma(ICC)is the second most common malignant tumor of liver. The overall prognosis of ICC is poor due to the malignant and metastatic potential [
1‐
3]. ICC originates from the epithelial cells of the intrahepatic bile duct and the biological behavior is completely different from hepatocellular carcinoma [
4,
5]. In recent years, the morbidity and mortality rates of ICC have increased worldwide [
6‐
8]. The pathogenesis of ICC is complex, and intrahepatic cholangiolithiasis is considered as key factor [
9,
10]. Due to the lack of typical clinical manifestations and early diagnostic methods, a majority of ICC patients are in the advanced stages when first diagnosed, such as distant metastases [
11]. ICC is different from hepatocellular carcinoma and distant cholangiocarcinoma both in terms of biological behavior and treatment strategy [
12]. As for ICC with DM (DM-ICC), comprehensive evaluation of the prognosis based on clinical features including treatment strategies might provide more evidence for clinicians to make the best treatment decisions. Therefore, a prognostic model is urgently needed, while there is currently rear related predictive model for the prognosis of ICC with distant metastasis patients.
The purpose of this study is to establish a prognostic nomogram for predicting the prognosis of ICC with distant metastasis patients. Clinical data from Surveillance, Epidemiology, and End Results (SEER) database were collected and were divided into training and internal validation cohort. Nomogram was constructed based on the training cohort, and were further evaluated based the internal and external validation cohorts. The established nomogram can provide truly individualized prognosis predictions and therefore guide the clinical decisions for ICC with distant metastasis patients.
Discussion
It is necessary and attractive to develop a prognostic prediction model for patients with ICC with distant metastasis. Because it enables specific clinical decisions for different patients. In this study, for the first time, a prognostic prediction nomogram was constructed for patients with ICC with distant metastasis, and the internal validation was performed, and showed good prediction accuracy, which can provide different clinical decisions. Most previous studies [
18‐
20] have constructed nomograms for predicting prognosis of postoperative ICC patients, but all of them included patients who were operable, and excluded patients who were inoperable. Therefore, most of the previous nomograms did not take into account advanced patients, especially those with distant metastasis. For clinicians, all patients cannot give up, and it is necessary and urgent to construct the required nomogram. Under this premise, we constructed a nomogram of patients with ICC of distant metastases with good predictive accuracy.
For most cancer patients, increasing age is an obvious factor affecting the prognosis of patients [
21,
22]. As the patient’s age increases, the resistance to the tumor decreases and the sensitivity to the treatment drug decreases, the patient’s prognosis will show a significant decline, which can also be seen in our nomogram, age is an independent risk factors affecting patient prognosis. In our study of patients with ICC with distant metastasis, age, tumor differentiation, T stage, lymph node metastasis, surgical treatment, chemoradiotherapy, and bone metastasis had a significant impact on survival. As stated in the 8th TNM staging, higher TNM staging means worse prognosis, and in our study as well, higher T staging and patients with lymph node metastasis had worse prognosis. Higher T stage means deeper tumor infiltration, and lymph node metastasis usually affects the postoperative recovery of patients, increases the probability of tumor recurrence, and affects the prognosis of patients [
23]. As in most previous studies [
24,
25], the degree of tumor differentiation also affects patient outcomes. The higher the tumor differentiation, the stronger the malignant behavior of the tumor. Because the degree of differentiation reflects the malignant biological behavior of tumors, the lower the differentiation, the higher the degree of malignancy, and the higher the degree of differentiation, the lower the degree of malignancy. Because tumor cells arise from normal organs, the higher the differentiation, the closer the tumor is to normal cells, and the lower the nature and malignancy. Low or poorly differentiated tumors, especially undifferentiated tumors, indicate that the greater the difference from normal organs, the higher the degree of malignancy.
Until now, there are few studies on surgery for patients with ICC of distant metastases, and even fewer studies on surgery for liver resection and resection of metastases. Therefore, in this study, we included patients who underwent surgical treatment, and the operations performed were liver resection and metastases resection. Due to the large trauma of surgery and the advanced stage of the patient’s tumor, whether or not to perform surgery needs to be considered comprehensively, but surgery is still a means of treatment, which can prolong the survival of patients. Although the prognosis of ICC patients who undergo surgery is much better than that of patients who do not undergo surgery, most patients lose the opportunity for radical surgery at the time of diagnosis due to locally advanced or distant metastases [
26‐
28]. It is more common in patients with ICC of distant metastases, usually accompanied by large blood vessel invasion or multiple metastases when accompanied by distant metastases, so there are fewer opportunities for surgical treatment. At present, radiotherapy, chemotherapy and targeted therapy have been accepted by clinicians as non-surgical treatment methods of tumors, so these treatment methods must be considered in the clinical treatment of tumors. In our study, radiotherapy and chemotherapy were considered as a treatment modality in the treatment of patients with ICC with distant metastasis, and the results showed that both radiotherapy and chemotherapy had the effect of prolonging the prognosis of patients, which was consistent with previous study [
5]. Therefore, radiotherapy and chemotherapy can be used as a treatment for patients with advanced ICC, which can prolong the survival of patients.
At present, there is no prediction model for ICC patients with distant metastasis. However, in the nomogram we constructed, distant metastasis occurs. The prognosis of patients with bone metastases is significantly affected. A previous study [
29] showed that the survival of patients with ICC of bone metastases was lower than with lung metastases and peritoneal metastases, but there was no statistical difference, and our results showed a difference, so far regardless of the proportion of metastases, the overall survival of patients
, period is still low. In conclusion, we constructed a prognostic prediction nomogram for patients with ICC of distant metastases, with good prediction accuracy, high C-index, and calibration defects not far from the actual values. The larger the C index, the more accurate the prognosis prediction to a certain extent [
30]. However, high prognostic prediction accuracy does not necessarily imply good clinical applicability of nomogram [
31]. The decision curve analysis uses an estimated threshold probability distribution and the weighted area under the net benefit curve as a summary metric to judge the clinical utility of the nomogram by the magnitude of the threshold [
14,
32,
33].
Our study is the first to construct a nomogram in a patient with ICC of distant metastases, and external validation was performed. Of course, our study also has some limitations. First, the small number of external validation patients and the single external unit data may affect the validation accuracy of nomogram. Second, there is no relevant serological examination in the SEER database, and these variables will be included in our future studies. Additionally, similar to other retrospective studies, patient inclusion was subject to selection bias. Despite this limitation, we constructed a nomogram with good predictive accuracy and clinical applicability.
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