J Natl Compr Canc Netw. 2015 Aug;13(8):987-94.

Treatment Patterns and Outcomes in Patients with Hepatocellular Carcinoma Stratified by Stage-Guided Treatment Categories


Kuan-Ling Kuo, PhD1; David Stenehjem, PharmD1,2; Frederick Albright, PhD1; Saurabh Ray, Phd3; Diana Brixner, PhD, RPh1,4

1Department of Pharmacotherapy, University of Utah, SLC, Utah; 2Hunstman Cancer Institute, University of Utah Health Care, Salt Lake City, Utah; 3AbbVie Inc, North Chicago, Illinois; 4Univiersity of Utah Program in Personalized Health Care, Salt Lake City, Utah




The purpose of this study was to assess the survival and treatment patterns of hepatocellular carcinoma (HCC) stratified by the NCCN stage-guided treatment categories in the absence of a universally accepted staging system for HCC.


Patients with HCC were identified using ICD-9 codes and inclusion in the Huntsman Cancer Institute tumor registry. Patients were stratified by the NCCN groupings around the time of diagnosis as potentially resectable or operable (RESECT), potentially transplantable (TRANSP), unresectable (UNRESECT), inoperable due to performance status (INOPER), or having metastatic (METAST) disease. Survival and treatment patterns were assessed by NCCN stage-guided treatment categories.


A total of 221 patients (72.9% men) with HCC were identified. At the time of diagnosis, patients were categorized as RESECT (n=28, 12.7%), TRANSP (n=33, 14.9%), UNRESECT (n=77, 34.8%), INOPER (n=40, 18.1%), and METAST (n=38, 17.2%). Staging information was not specified for 5 patients (2.3%) even after chart review. Kaplan-Meier analysis demonstrated significant differences in survival between RESECT and UNRESECT categories, and between UNRESECT and METAST categories. The median survivals in RESECT, TRANSP, UNRESECT, INOPER, and METAST categories were 594, 562, 247, 167, and 44 days, respectively. Patients considered RESECT most frequently underwent resection (61%, n=17) and patients considered TRANSP had the highest use of liver transplants (33.3%, n=11). Use of any treatment was low in the METAST (31.6%, n=12) and INOPER (60.0%, n=24) groups.


Treatment patterns in the NCCN groupings correlated with recommended treatment strategies. Overall, the NCCN groupings have a linear relationship in overall survival.

Copyright © 2015 by the National Comprehensive Cancer Network.

PMID: 26285244



Given the absence of a universally accepted staging or descriptive standard for hepatocellular carcinoma (HCC), the National Comprehensive Cancer Network (NCCN) guidelines (v2.2015) classifies the severity of HCC by treatment groups: potentially resectable or transplantable, unresectable disease, inoperable by performance status or comorbidity with local disease only, and metastatic disease.1

Our research using The Utah Health Sciences enterprise data warehouse (EDW), Utah Population Database (UPDB) and Huntsman Cancer Institute Tumor Registry (HCI-TR) to assess treatment patterns and survival of these NCCN groups. The index date was defined as the date of HCC diagnosis in EDW. Inclusion criteria were as follows: patients greater than or equal to 18 years at the time of diagnosis between 1995 and 2010; at least two International Statistical Classification of Disease (ICD)-9 codes for HCC, i.e., 155.0 with ICD-0 site and histology codes indicative of HCC in the HCI-TR (Figure 1).


kuo fig1

Figure 1 Study Flowchart


HCI-TR provided AJCC TNM staging at diagnosis. All stage IIIB and IIIC patients were classified as unresectable and stage IV (M1) patients were classified as metastatic. All patients classified stage I to IIIa were assessed by chart review to determine if the treating physicians documented the patient as resectable, transplantable, unresectable or inoperable due to performance status around the time of diagnosis. To facilitate chart review, a semi-automated keyword search of the electronic notes was conducted with a specially built text search tool using keywords and Boolean constructs. Treatment patterns were evaluated according to Current Procedure Terminology (CPT) codes within the EDW for ablation, resection, transplant, embolization, and radiation. Chemotherapy utilization was obtained from linked pharmacy records within the EDW.

In summary, through standard review of medical notes, this retrospective observational cohort analysis demonstrates that the NCCN stage-guided treatment categories predict overall survival and treatment utilization (Figure 2). Further validation in a prospective cohort is warranted to reduce the missing clinical data and the accuracy of staging diagnosis. Additionally, due to the small sample size of the current study, future studies could be conducted across cancer centers to obtain the necessary sample size and power to fully validate the NCCN stage-guide treatment categories.


kuo fig2

Figure 2 Kaplan-Meier Curve among Different Treatment Groups



  1. Hepatocellular Carcinoma, NCCN Clinical Practice Guideline in Oncology, 2015 v.2


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