Skip to main content
SpringerLink
Log in

CT-based clinico-radiological nomograms for prognosis prediction in patients with intrahepatic mass-forming cholangiocarcinoma: a multi-institutional study

  • Hepatobiliary-Pancreas
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To establish prognostic nomograms based on CT imaging features for predicting the prognosis in patients with intrahepatic mass-forming cholangiocarcinoma (IMCC) before and after surgery.

Methods

Two models were established for overall survival (OS) prediction in a training set (179 IMCC patients underwent surgery at institution 1 from 2009 to 2019): imaging-based nomogram included imaging features and clinical characteristics acquired before surgery; postoperative nomogram included imaging-based score, equal to the linear predictor of the imaging-based nomogram, and pathological parameters. Both prognostic nomograms were validated in an independent external dataset (103 IMCC patients received surgical treatment at two independent institutions from 2009 to 2019). Predictive performance and discrimination were evaluated and compared with the common prognostic models.

Results

The imaging-based nomogram was developed according to preoperative serum carbohydrate antigen 19-9 and four imaging features including multiple nodules, arterial enhancement pattern, CT-reported lymph node (LN) metastasis, and capsular retraction; the postoperative nomogram was built based on the imaging-based score and three pathological parameters including tumor differentiation grade, capsular invasion, and LN status. Both nomograms presented improved prognostic performance and discrimination (concordance index, 0.770–0.812; integrated Brier score, 0.120–0.138) compared with the common prognostic models in the training and external validation datasets. Besides, the nomograms stratified IMCC patients into two risk strata for OS.

Conclusions

Nomograms based on CT imaging features can provide accurate individual survival prediction for IMCC patients before and after surgery, which may help to improve personalized treatment.

Key Points

• Imaging features including multiple nodules, arterial enhancement pattern, CT-reported LN metastasis, and capsular retraction were poor independent prognostic factors for IMCC patients.

• The imaging-based nomograms presented improved prognostic performance and discrimination compared with the common prognostic models.

• The nomograms can provide accurate individual survival prediction for IMCC patients before and after surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

AIC:

Akaike information criteria

AJCC:

American Joint Committee on Cancer

C-index:

Harrel’s concordance index

CA19-9:

Carbohydrate antigen 19-9

IBS:

Integrated Brier score

ICC:

Intrahepatic cholangiocarcinoma

IMCC:

Intrahepatic mass-forming cholangiocarcinoma

LN:

Lymph node

OS:

Overall survival

References

  1. Razumilava N, Gores GJ (2014) Cholangiocarcinoma. Lancet 383:2168–2179

    Article  PubMed  PubMed Central  Google Scholar 

  2. Valle JW, Kelley RK, Nervi B, Oh DY, Zhu AX (2021) Biliary tract cancer. Lancet 30:428–444

    Article  Google Scholar 

  3. Brindley PJ, Bachini M, Ilyas SI et al (2021) Cholangiocarcinoma. Nat Rev Dis Primers 7:65

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  PubMed  Google Scholar 

  5. Aishima S, Oda Y (2015) Pathogenesis and classification of intrahepatic cholangiocarcinoma: different characters of perihilar large duct type versus peripheral small duct type. J Hepatobiliary Pancreat Sci 22:94–100

    Article  PubMed  Google Scholar 

  6. Nakanuma Y, Kakuda Y (2015) Pathologic classification of cholangiocarcinoma: new concepts. Best Pract Res Clin Gastroenterol 29:277–293

    Article  PubMed  Google Scholar 

  7. Vijgen S, Terris B, Rubbia-Brandt L (2017) Pathology of intrahepatic cholangiocarcinoma. Hepatobiliary Surg Nutr 6:22–34

    Article  PubMed  PubMed Central  Google Scholar 

  8. Mazzaferro V, Gorgen A, Roayaie S, Droz Dit Busset M, Sapisochin G (2020) Liver resection and transplantation for intrahepatic cholangiocarcinoma. J Hepatol 72:364–377

    Article  PubMed  Google Scholar 

  9. Tsilimigras DI, Hyer JM, Paredes AZ et al (2021) Tumor burden dictates prognosis among patients undergoing resection of intrahepatic cholangiocarcinoma: a tool to guide post-resection adjuvant chemotherapy? Ann Surg Oncol 28:1970–1978

    Article  PubMed  Google Scholar 

  10. Amin MB, Greene FL, Edge SB et al (2017) The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin 67:93–99

    Article  PubMed  Google Scholar 

  11. Wang Y, Li J, Xia Y et al (2013) Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy. J Clin Oncol 31:1188–1195

    Article  PubMed  Google Scholar 

  12. Hyder O, Marques H, Pulitano C et al (2014) A nomogram to predict long-term survival after resection for intrahepatic cholangiocarcinoma: an Eastern and Western experience. JAMA Surg 149:432–438

    Article  PubMed  Google Scholar 

  13. Raoof M, Dumitra S, Ituarte PHG et al (2017) Development and validation of a prognostic score for intrahepatic cholangiocarcinoma. JAMA Surg 152:e170117

    Article  PubMed  PubMed Central  Google Scholar 

  14. Jiang W, Zeng ZC, Tang ZY et al (2011) A prognostic scoring system based on clinical features of intrahepatic cholangiocarcinoma: the Fudan score. Ann Oncol 22:1644–1652

    Article  CAS  PubMed  Google Scholar 

  15. Koh J, Chung YE, Nahm JH et al (2016) Intrahepatic mass-forming cholangiocarcinoma: prognostic value of preoperative gadoxetic acid-enhanced MRI. Eur Radiol 26:407–416

    Article  PubMed  Google Scholar 

  16. Kim SA, Lee JM, Lee KB et al (2011) Intrahepatic mass-forming cholangiocarcinomas: enhancement patterns at multiphasic CT, with special emphasis on arterial enhancement pattern--correlation with clinicopathologic findings. Radiology 260:148–157

    Article  PubMed  Google Scholar 

  17. Kang Y, Lee JM, Kim SH, Han JK, Choi BI (2012) Intrahepatic mass-forming cholangiocarcinoma: enhancement patterns on gadoxetic acid-enhanced MR images. Radiology 264:751–760

    Article  PubMed  Google Scholar 

  18. Guedj N, Blaise L, Cauchy F, Albuquerque M, Soubrane O, Paradis V (2021) Prognostic value of desmoplastic stroma in intrahepatic cholangiocarcinoma. Mod Pathol 34:408–416

    Article  CAS  PubMed  Google Scholar 

  19. Høgdall D, Lewinska M, Andersen JB (2018) Desmoplastic tumor microenvironment and immunotherapy in cholangiocarcinoma. Trends Cancer 4:239–255

    Article  PubMed  Google Scholar 

  20. Gentilini A, Pastore M, Marra F et al (2018) The role of stroma in cholangiocarcinoma: the intriguing interplay between fibroblastic component, immune cell subsets and tumor epithelium. Int J Mol Sci 19:2885

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gentilini A, Pastore M, Marra F, Raggi C (2017) Tumor reactive stroma in cholangiocarcinoma: the fuel behind cancer aggressiveness. World J Hepatol 9:455–468

    Article  Google Scholar 

  22. Jeong HT, Kim MJ, Chung YE, Choi JY, Park YN, Kim KW (2013) Gadoxetate disodium-enhanced MRI of mass-forming intrahepatic cholangiocarcinomas: imaging-histologic correlation. AJR Am J Roentgenol 201:W603–W611

    Article  PubMed  Google Scholar 

  23. Fujita N, Asayama Y, Nishie A et al (2017) Mass-forming intrahepatic cholangiocarcinoma: enhancement patterns in the arterial phase of dynamic hepatic CT - Correlation with clinicopathological findings. Eur Radiol 27:498–506

    Article  PubMed  Google Scholar 

  24. Balachandran VP, Gonen M, Smith JJ, DeMatteo RP (2015) Nomograms in oncology: more than meets the eye. Lancet Oncol 16:e173–e180

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ji GW, Zhang YD, Zhang H et al (2019) Biliary tract cancer at CT: a radiomics-based model to predict lymph node metastasis and survival outcomes. Radiology 290:90–98

    Article  PubMed  Google Scholar 

  26. Panick CEP, Ward RD, Coppa C, Liu PS (2019) Hepatic capsular retraction: an updated MR imaging review. Eur J Radiol 113:15–23

    Article  PubMed  Google Scholar 

  27. Min JH, Kim YK, Choi SY et al (2019) Intrahepatic mass-forming cholangiocarcinoma: arterial enhancement patterns at MRI and prognosis. Radiology 290:691–699

    Article  PubMed  Google Scholar 

  28. He C, Zhang Y, Song Y et al (2018) Preoperative CEA levels are supplementary to CA19-9 levels in predicting prognosis in patients with resectable intrahepatic cholangiocarcinoma. J Cancer 9:3117–3128

    Article  PubMed  PubMed Central  Google Scholar 

  29. Miwa S, Miyagawa S, Kobayashi A et al (2006) Predictive factors for intrahepatic cholangiocarcinoma recurrence in the liver following surgery. J Gastroenterol 41:893–900

    Article  CAS  PubMed  Google Scholar 

  30. Mavros MN, Economopoulos KP, Alexiou VG, Pawlik TM (2014) Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: systematic review and meta-analysis. JAMA Surg 149:565–574

    Article  PubMed  Google Scholar 

  31. Addeo P, Jedidi I, Locicero A et al (2019) prognostic impact of tumor multinodularity in intrahepatic cholangiocarcinoma. J Gastrointest Surg 23:1801–1809

    Article  PubMed  Google Scholar 

  32. Conci S, Ruzzenente A, Viganò L et al (2018) Patterns of distribution of hepatic nodules (single, satellites or multifocal) in intrahepatic cholangiocarcinoma: prognostic impact after surgery. Ann Surg Oncol 25:3719–3727

    Article  PubMed  Google Scholar 

  33. Tan GX, Miranda R, Sutherland T (2016) Causes of hepatic capsular retraction: a pictorial essay. Insights Imaging 7:831–840

    Article  PubMed  PubMed Central  Google Scholar 

  34. Shroff RT, Kennedy EB, Bachini M et al (2019) Adjuvant therapy for resected biliary tract cancer: ASCO clinical practice guideline. J Clin Oncol 37:1015–1027

    Article  PubMed  Google Scholar 

  35. Mazzaferro V, El-Rayes BF, Droz Dit Busset M et al (2019) Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer 120:165–171

    Article  CAS  PubMed  Google Scholar 

  36. Kim RD, Chung V, Alese OB et al (2020) A phase 2 multi-institutional study of nivolumab for patients with advanced refractory biliary tract cancer. JAMA Oncol 6:888–894

    Article  PubMed  Google Scholar 

Download references

Funding

This study was supported by the National Science Foundation of China (82102150), the Natural Science Foundation of Jiangsu Province (BK20210968), and the Key Research and Development Program of Jiangsu Province (BE2016789).

Author information

Author notes

  1. Chen Yu Jiao and Hui Zhang contributed equally to this work.

Authors and Affiliations

  1. Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, People’s Republic of China

    Chen Yu Jiao, Hui Zhang, Gu Wei Ji, Xue Hao Wang & Xiang Cheng Li

  2. Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, Jiangsu Province, People’s Republic of China

    Chen Yu Jiao, Hui Zhang, Gu Wei Ji, Xue Hao Wang & Xiang Cheng Li

  3. Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China

    Qing Xu & Ming Lu

  4. Department of General Surgery, Yancheng First Hospital, Yancheng, Jiangsu Province, People’s Republic of China

    Biao Zhang

  5. Department of General Surgery, Changzhou First Hospital, Changzhou, Jiangsu Province, People’s Republic of China

    Yue Yang

Authors
  1. Chen Yu Jiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gu Wei Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qing Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ming Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Biao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yue Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xue Hao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiang Cheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Gu Wei Ji, Qing Xu or Xiang Cheng Li.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Xiang Cheng Li.

Conflict of interest

The authors declare that they have no conflict of interest.

Statistics and biometry

One of the authors has significant statistical expertise: Hui Zhang.

Informed consent

Written informed consent was waived by the institutional review board.

Ethical approval

Institutional review board approval was obtained.

Methodology

• retrospective

• diagnostic or prognostic study

• multicenter study

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 4720 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiao, C.Y., Zhang, H., Ji, G.W. et al. CT-based clinico-radiological nomograms for prognosis prediction in patients with intrahepatic mass-forming cholangiocarcinoma: a multi-institutional study. Eur Radiol 32, 8326–8338 (2022). https://doi.org/10.1007/s00330-022-08914-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-022-08914-0

Keywords

Search

Navigation