An innovative test for evaluating hepatic reserve may improve clinicians’ ability to predict prognosis and select appropriate therapy for patients with hepatocellular carcinoma (HCC).
A standard step in HCC staging is the assessment of hepatic reserve, or how much of the liver is functional. Since the 1970s, hepatic reserve has been assessed using the Child-Turcotte-Pugh (CTP) score. Five factors make up this score: serum bilirubin level, serum albumin level, prothrombin time, severity of ascites, and severity of encephalopathy.
The CTP score has a major drawback, however, said Ahmed Kaseb, M.D., an associate professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. Ascites and encephalopathy, which are evaluated through imaging and clinical signs and symptoms, can be affected by a number of variables. “Those two parameters are very subjective,” Dr. Kaseb said. “They can also change day to day based on treatment, such as a diuretic. It can be tough to score them.”
Developing a new system
In hopes of improving prognostic accuracy, Dr. Kaseb, who heads the Department of Gastrointestinal Medical Oncology’s HCC program, and his group have been looking for a more objective measure to replace the CTP score’s two subjective parameters. Recognizing that insulin-like growth factor 1 (IGF-1) is synthesized by healthy liver cells, Dr. Kaseb and his colleagues hypothesized that the IGF-1 level, which can be measured in a routine blood test, would work as a substitute for the subjective measures. Plasma IGF-1 levels have been shown to be lower in patients with cirrhosis and/or HCC than in people without liver disease. Dr. Kaseb’s group has now developed a new scoring system, IGF-CTP.
In the standard CTP scoring system, the five parameters are each assigned a score of 1–3, and the total number of points determines the CTP “class.” CTP class A has the best prognosis; CTP class C, the worst. Usually, only patients with CTP class A are considered candidates for active HCC treatment with surgery or tumor ablation. In the new scoring system, four objective parameters—serum bilirubin level, serum albumin level, prothrombin time, and plasma IGF-1 level—are each scored as 1–3, and the total number of points determines the IGF-CTP class.
Testing the new system
Funded by a grant from the National Cancer Institute, Dr. Kaseb’s group compared the score assignments and prognoses between CTP class and IGFCTP class in two sets of patients. The researchers evaluated clinical data and plasma samples for an initial set of 310 HCC patients and determined effective IGF-1 level cutoffs for stratifying patients. These levels were then tested in another set of 155 HCC patients.
The investigators found that patients whose hepatic reserve was scored as CTP class A but IGF-CTP class B had a shorter median overall survival than did patients whose hepatic reserve was scored as class A by both systems (see table). These results suggest that the new system can better select patients with a good prognosis. “These patients might be more likely to benefit from active treatment; they might have fewer adverse effects and longer survival,” Dr. Kaseb said.
The next step is to evaluate the new scoring system in a group of patients who have unresectable HCC with CTP class A hepatic reserve and receive the standard-of-care systemic therapy, sorafenib. After the patients’ times to disease progression and overall survival times have been determined, Dr. Kaseb will calculate patients’ IGF-CTP scores from the blood samples that were used for CTP scoring. Time to disease progression, overall survival time, and rate of adverse events will be compared among IGF-CTP class A, B, and C patients. These data will confirm whether the IGF-CTP score identifies patients who end up doing well and those who end up doing poorly. The same strategy will also be tested in patients undergoing local therapy, such as chemoembolization or radiation, for small HCCs as part of a collaborative study between the departments of Gastrointestinal Medical Oncology and Interventional Radiology.
If further independent and international validation testing confirms the IGF-CTP score’s utility, approval of IGF-1 testing to assess liver function will be sought from the U.S. Food and Drug Administration. (IGF-1 testing is already approved for diagnosing growth hormone deficiency.) “We have to prove that the new score is more valuable than the old one before we recommend it as a standard and use it to prospectively guide therapy decisions,” Dr. Kaseb said.
For more information, contact Dr. Ahmed Kaseb at 713-792-2828.
Kaseb AO, Xiao L, Hassan MM, et al. Development and validation of insulin-like growth factor-1 score to assess hepatic reserve in hepatocellular carcinoma. J Natl Cancer Inst. 2014. doi: 10.1093/jnci/dju088. [Epub ahead of print]
OncoLog, August 2014, Volume 59, Issue 8