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Original Investigation |

Nomograms to Predict Recurrence-Free and Overall Survival After Curative Resection of Adrenocortical Carcinoma

Yuhree Kim, MD, MPH1; Georgios A. Margonis, MD, PhD1; Jason D. Prescott, MD, PhD1; Thuy B. Tran, MD2; Lauren M. Postlewait, MD3; Shishir K. Maithel, MD3; Tracy S. Wang, MD, MPH4; Douglas B. Evans, MD4; Ioannis Hatzaras, MD, MPH5; Rivfka Shenoy, MD5; John E. Phay, MD6; Kara Keplinger, MD6; Ryan C. Fields, MD7; Linda X. Jin, MD7; Sharon M. Weber, MD8; Ahmed I. Salem, MD8; Jason K. Sicklick, MD9; Shady Gad, MD9; Adam C. Yopp, MD10; John C. Mansour, MD10; Quan-Yang Duh, MD11; Natalie Seiser, MD, PhD11; Carmen C. Solorzano, MD12; Colleen M. Kiernan, MD12; Konstantinos I. Votanopoulos, MD13; Edward A. Levine, MD13; George A. Poultsides, MD2; Timothy M. Pawlik, MD, MPH, PhD1
[+] Author Affiliations
1Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
2Department of Surgery, Stanford University School of Medicine, Stanford, California
3Department of Surgery, Emory University, Atlanta, Georgia
4Department of Surgery, Medical College of Wisconsin, Milwaukee
5Department of Surgery, New York University School of Medicine, New York
6Department of Surgery, The Ohio State University, Columbus
7Department of Surgery, Washington University School of Medicine in St Louis, Missouri
8Department of General Surgery, University of Wisconsin School of Medicine and Public Health, Madison
9Department of Surgery, University of California, San Diego
10Department of Surgery, University of Texas Southwestern Medical Center, Dallas
11Department of Surgery, University of California, San Francisco
12Department of Surgery, Vanderbilt University, Nashville, Tennessee
13Department of Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
JAMA Surg. 2016;151(4):365-373. doi:10.1001/jamasurg.2015.4516.
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Importance  Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined.

Objectives  To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction.

Design, Setting, and Participants  Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015.

Main Outcomes and Measures  The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves.

Results  In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63-5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47-15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95-3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27-4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02-3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00-3.17; P = .05), positive nodal status (HR, 5.89; 95% CI, 2.05-16.87; P = .001), and R1 margin (HR, 2.83; 95% CI, 1.51-5.30; P = .001). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.74 for RFS and 0.70 for OS).

Conclusions and Relevance  Independent predictors of survival and recurrence risk after curative-intent surgery for ACC were selected to create nomograms predicting RFS and OS. The nomograms were able to stratify patients into prognostic groups and performed well on internal validation.

Figures in this Article


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Figure 1.
Nomograms Predicting Survival in Patients After Resection of Adrenocortical Carcinoma

The nomogram to predict recurrence-free survival was created based on 5 independent prognostic factors, and the nomogram to predict overall survival was created based on 3 independent prognostic factors (see the Model Specifications and Predictors of RFS and OS subsection of the Methods section).

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Figure 2.
Kaplan-Meier Curves Demonstrating Survival in Patients After Resection for Adrenocortical Carcinoma According to Tertiles of Predicted Survival

P values are by the log-rank test.

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Figure 3.
Calibration Plot Comparing Predicted and Actual Survival Probabilities at 5-y Follow-up

The 30-sample bootstrapped calibration plot for the prediction of 5-y recurrence-free survival and overall survival is shown. The blue line represents the ideal fit; circles represent nomogram-predicted probabilities; triangles represent the bootstrap-corrected estimates; and error bars represent the 95% CIs of these estimates.

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