The Predictive Model of Hepatitis B Virus Reactivation Induced by Precise Radiotherapy in Primary Liver Cancer
Wang Shuai1, Wu Guan-peng1, Huang Wei2, Liu Tong-hai2, Yin Yong2, Liu Yi-hui1
1School of Information, Qilu University of Technology, Jinan, China
2Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China
To cite this article:
Wang Shuai, Wu Guan-peng, Huang Wei, Liu Tong-hai, Yin Yong, LiuYi-hui. The Predictive Model of Hepatitis B Virus Reactivation Induced by Precise Radiotherapy in Primary Liver Cancer. Journal of Electrical and Electronic Engineering. Vol. 4, No. 2, 2016, pp. 31-34. doi: 10.11648/j.jeee.20160402.15
Received: March 17, 2016; Accepted: March 31, 2016; Published: April 7, 2016
Abstract: In this paper, to build a predictive model of hepatitis B virus (HBV) reactivation in primary liver cancer (PLC) patients after precise radiotherapy (RT). Logistic regression analysis was adopted to extract the optimal feature subset, TNM, HBV DNA level and outer margin of RT were risk factors for HBV reactivation (P < 0.05). A predictive model of support vector machine (SVM) was established for the optimal feature subset and all of PLC data sets. The experimental results proved that the former obviously improves the classification accuracy, which increased from 74.44% to 78.89%. In this paper, it is concluded that TNM, HBV DNA levels and outer boundary are the risk factor for HBV reactivation (P < 0.05).
Keywords: Primary Liver Cancer, Data Set, Feature Extraction, Support Vector Machine (SVM)
Primary liver cancer (PLC) is one of the most common malignant tumors in China.The clinical discovery of patients with advanced, only about 10% can be resected, and most patients need conservative treatment. In recent year. Conformal radiotherapy three-dimensional (3D-CRT) and modulated radiotherapy intensity (IMRT) have been widely used in clinical practice for the treatment of advanced PLC patients [1-3]. However, the HBV of patients with the primary liver cancer are activated easily after precise radiotherapy [4-6]. The influence factors of HBV reactivation remains to be research, and related prediction model needs to be established.
In 2007 Wu etc  reported 86 cases of PLC patients with 3-DCRT, among of them 1 case combined hepatitis b patients with cirrhosis appears liver atrophy in radiotherapy after 6 months, the amount of HBV DNA exponentially increases continuously and the liver was damaged to death. The author concluded that the cause of death is closely related to HBV reactivation. Huang etc  retrospective analysis of clinical characteristics of 69 cases of HBsAg positive PLC patients with HBV reactivation after precise radiotherapy. They used the statistics of logistic method to evaluate the effects of each index of HBV reactivation, and the result show that the baseline blood HBV DNA levels was the risk factor of HBV reactivation.
At present the intelligent computing technology has been widely used in biomedical field to analysis the complex data. Such as Zhang etc  used the support vector machine (SVM) to predict esophageal squamous carcinoma postoperative survival to provide guidance for clinical diagnosis of thyroid nodules; Gao  described the application of SVM in speech recognition. We use the logistic regression analysis to extract the features of the feature subset in this paper. Firstly we acquire the tumor staging TNM, HBV DNA level and outer boundary were the risk factors for HBV virus activation (P < 0.05). Then we use the SVM to establish the classification prediction model of the optimal feature subset after feature extraction and all primary liver cancer data sets.
2. Data and Feature Extraction
We select Shandong province tumor hospital treated 90 liver cancer patients after precise radiotherapy as the research object, namely 90 samples, and each sample has the 30 characteristics. The matrix is the 90*30. All cases had complete record by clinical examination, B ultrasonic examination, abdominal CT or pathological examination, and the diagnosis is the primary liver after that. There are 52 males and 38 females. The range of the age is 30 to 74 years old, the average age is 56.1 years old. In the 90 patiens, there are 20 patiens of HBV reactivation and 70 patiens of HBV without activation.
2.2. Feature Extraction
We use the SPSS 17.0 software to screen the risk factors by the single factor logistic method, then use the Binarys logistic regression method to analyze many factors. Putting the statistically significant single factor into logistic regression analysis .
2.2.1. Independent Sample T-test
Independent samples t-test was performed on the various influencing factors of primary liver cancer data set. Independent sample means there is no connection between two samples each other. Two independent samples accept the same measurements respectively.
2.2.2. Rank Sum Test
Rank sum test is a nonparametric statistics. It is needn’t to consider the distribution of the data. We use the rank-sum test with comparing the multiple samples in this article.
2.2.3. Chi Square Analysis
Chi-square analysis is a kind of widely used hypothesis test method. It is suitable for data classification of variables (measurement data).
2.2.4. Multiple Factors Analysis
Each variable turns into logistic regression analysis follow the effect from high to low. Every time introducing an independent variable, we will take a significance test on the role of each independent variable in the regression equation. We just select significant meaning of the independent variables.
3. Support Vector Machine
The SVM is a linear separable cases surface theory which is mainly based on the optimal classification. optimal classification is able to rightly separate the two different categories (that is, to achieve the training error rate is 0) while the classification interval is enough far. SVM classification is ensure the both sides of the blank area (margin) reach maximum . Figure 1 for the optimal classification plane.
In the figure, black and white points represent different types of samples. H is the optimal classification on the surface of the straight line. H1 and H2 are respectively classification line H recent samples in a straight line.
4. Experimental Analysis
We use SVM classification to classify the original data and the feature data after statistical analysis respectively. The matrix size of the original data set is 90*30. The matrix size of feature data set is 90*3.
4.1. Cross Validation
Cross validation is a commonly used machine learning method in data sampling, it has many different forms. We uses the K fold cross validation (k-fold cross-validation) in this article. The basic process is that the samples were divided into K sets equally. The k-1 sets is used to training sample and leaving set is used to test samples. This process is repeated K times, and putting average value of the test error in the K times process as generalization error .
4.2. Feature Extraction
4.2.1. Independent Samples T-test
The table 1 data takes independent sample T test method, the result as follows. We concluded that there is a significant relationship between external boundary and HBV reactivation (P < 0.05). While to the age, there is no significant relationship between liver with such factors as the maximum dose and HBV virus reactivation.
|Factors (units)||average||standard deviation||p-values|
|Total dose radiation (Gy)||57.929||7.1907||0.917|
|Equivalent biometric (Gy)||69.969||8.1987||0.891|
|Number of radiotherapy (time)||28.48||5.484||0.871|
|GTV volume (cm3)||179.59||228.768||0.441|
|PTV volume (cm3)||392.0676||318.933||0.891|
|Maximum dose (Gy)||6902.56||1160.37||0.562|
|The average dose (Gy)||1597.09||623.795||0.689|
4.2.2. Rank Sum Test
The table 2 data takes rank sum test, the result as follows. We concluded that HBV DNA levels, put a boundary encoding, outside the two classification of encoding has significant relationship with HBV reactivation (P < 0.05).The P value of TNM is close to 0.05. So we think that TNM is related to the HBV reactivation.
|Mann - Whitney U||Wilcoxon W||Z||p-values|
|HBV baseline three categories||416.000||2901.000||-2.938||0.003|
|Outside the boundary encoding||446.500||2931.500||-2.594||0.009|
|The outer boundary are two classification and coding||480.000||2965.000||-2.475||0.013|
4.2.3. Chi-square Analysis
The table 3 data takes chi-square analysis method, the result as follows. We conclude that there is no significant relationship between the table 3 data with HBV reactivation.
|factor||case number||reactivation||chi-square value||p-values|
|TACE times before radiotherapy|
4.2.4. Multivariate Analysis
The table 4 data takes multivariate analysis method, the result as follows. We found that the baseline serum HBV DNA levels, outer boundary, TNM is the risk factor for HBV reactivation.
|Outside the boundary encoding||-1.206||1.308||.356||0.299|
|The outer boundary are two classification and coding||1.702||1.463||.245||5.488|
4.3. Support Vector Machine (SVM) Results
We use SVM classification to classify the original data and the feature data after statistical analysis, we use K fold cross validation to get the classification. Results are shown in the following table.
The matrix size of the original data set is 90*30. The SVM use 10 fold cross-validation, we concluded that the accuracy is 72.22%, sensitivity is 76.06%, specificity is 57.89%. The SVM use 5 fold cross-validation, we concluded that the accuracy is 71.11%, sensitivity is 76.06%, specificity is 52.63%. The SVM use 3 fold cross-validation, we concluded that the accuracy is 71.11%, sensitivity is 76.06%, specificity is 52.63%.
The matrix size of feature data set is 90*30. The SVM use 10 fold cross-validation, we concluded that the accuracy is 72.22%, sensitivity is 77.46%, specificity is 52.63%. The SVM use 5 fold cross-validation, we concluded that the accuracy is 72.22%, sensitivity is 76.06%, specificity is 57.89%. The SVM use 3 fold cross-validation, we concluded that the accuracy is 78.89%, sensitivity is 80.28%, specificity is 68.42%.
In this paper, we concluded that TNM, HBV DNA levels and outer boundary are the risk factor for HBV reactivation (P < 0.05). The data set after feature extraction had the highest accuracy, sensitivity and specificity by using the support vector machine (SVM) and 3 fold cross-validation. The accuracy is 78.89%, sensitivity is 80.28%, specificity is 68.42%.
The research work is supported by the National Natural Science Foundation of China (Grant No. 61375013, 81402538), and Natural Science Foundation of Shandong Province (ZR2013FM020), China.
At the end, I am appreciated my teacher and teammate Wu Guanpeng, they gave me a lot of help in this research. I have learned much from them and it is very helpful to me.