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Original Investigation |

A Nomogram to Predict Long-term Survival After Resection for Intrahepatic Cholangiocarcinoma:  An Eastern and Western Experience

Omar Hyder, MD1; Hugo Marques, MD2; Carlo Pulitano, MD3; J. Wallis Marsh, MD4; Sorin Alexandrescu, MD5; Todd W. Bauer, MD6; T. Clark Gamblin, MD, MS7; Georgios C. Sotiropoulos, MD, PhD8; Andreas Paul, MD8; Eduardo Barroso, MD2; Bryan M. Clary, MD9; Luca Aldrighetti, MD3; Cristina R. Ferrone, MD10; Andrew X. Zhu, MD10; Irinel Popescu, MD5; Jean-Francois Gigot, MD, PhD11; Gilles Mentha, MD12; Shen Feng, MD13; Timothy M. Pawlik, MD, MPH, PhD1
[+] Author Affiliations
1Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
2Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
3Department of Surgery, Ospedale San Raffaele, Milan, Italy
4Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
5Department of Surgery, Fundeni Institute, Bucharest, Romania
6Department of Surgery, University of Virginia, Charlottesville
7Department of Surgery, Medical College of Wisconsin, Milwaukee
8Department of Surgery, University Hospital Essen, Essen, Germany
9Department of Surgery, Duke Medical Center, Durham, North Carolina
10Department of Surgery, Massachusetts General Hospital, Boston
11Department of Surgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium
12Department of Surgery, Hôpitaux Universitaires de Genève, Geneva, Switzerland
13Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
JAMA Surg. 2014;149(5):432-438. doi:10.1001/jamasurg.2013.5168.
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Importance  Intrahepatic cholangiocarcinoma (ICC) is a primary cancer of the liver that is increasing in incidence, and the prognostic factors associated with outcome after surgery remain poorly defined.

Objective  To combine clinicopathologic variables associated with overall survival after resection of ICC into a prediction nomogram.

Design, Setting, and Participants  We performed an international multicenter study of 514 patients who underwent resection for ICC at 13 major hepatobiliary centers in the United States, Europe, and Asia from May 1, 1990, through December 31, 2011. Multivariate Cox proportional hazards regression modeling with backward selection using the Akaike information criteria was used to select variables for construction of the nomogram. Discrimination and calibration were performed using Kaplan-Meier curves and calibration plots.

Interventions  Surgical resection of ICC at a participating hospital.

Main Outcomes and Measures  Long-term survival, effect of potential prognostic factors, and performance of proposed nomogram.

Results  Median patient age was 59.2 years, and 53.1% of the patients were male. Most patients (74.7%) had a solitary tumor, and median tumor size was 6.0 cm. Patients were treated with an extended hepatectomy (202 [39.3%]), a hemihepatectomy (180 [35.0%]), or a minor liver resection (<3 segments) (132 [25.7%]). Most patients underwent R0 resection (87.9%), and 35.7% of patients had N1 disease. Using the backward selection of clinically relevant variables, we found that age at diagnosis (hazard ratio [HR], 1.31; P < .001), tumor size (HR, 1.50; P < .001), multiple tumors (HR, 1.58; P < .001), cirrhosis (HR, 1.51; P = .08), lymph node metastasis (HR, 1.78; P = .01), and macrovascular invasion (HR, 2.10; P < .001) were selected as factors predictive of survival. On the basis of these factors, a nomogram was created to predict survival of ICC after resection. Discrimination using Kaplan-Meier curves, calibration curves, and bootstrap cross-validation revealed good predictive abilities (C index, 0.692).

Conclusions and Relevance  On the basis of an Eastern and Western experience, a nomogram was developed to predict overall survival after resection for ICC. Validation revealed good discrimination and calibration, suggesting clinical utility to improve individualized predictions of survival for patients undergoing resection of ICC.

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Figure 1.
Transformation of Continuous Variables in Univariate Analysis Using Restricted Cubic Splines
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Figure 2.
A Nomogram for Predicting Postsurgery Survival of Patients With Resectable Intrahepatic Cholangiocarcinoma

To calculate predicted survival, the patient’s age is located on the row labeled “Age, y” and a straight line is drawn up to the row labeled “Points” to determine the corresponding points. This process is repeated for each of the remaining factors by drawing a straight line to the “Points” row to determine the points associated with each factor. After summing the total points, one locates the appropriate total point number and draws a straight line from this to the rows labeled “3-Year Survival, %” and “5-Year Survival, %” to determine the patient’s predicted survival probability.

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Figure 3.
Kaplan-Meier Survival Curves and Patients at Risk at Each Year According to Quartiles of the Predicted Survival
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Figure 4.
Calibration Plot Comparing Predicted and Actual Survival Probabilities at 5 Years of Follow-up

Thin gray line represents the reference line.

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