The Relationship between Neutrophil on Lymphocyte Ratio with Clinical Stage of Nasopharyngeal Carcinoma Patients

Conclusions: Based on statistical analysis of the data, this study did not find a significant relationship between the neutrophil-lymphocyte ratio and the clinical stage of nasopharyngeal carcinoma (P = 0.252), even after correcting for sex. carcinoma before treatment describes a worse prognosis and survival compared to the neutrophil ratio value. -low lymphocytes. 48.49


Neutrophil to Lymphocyte Ratio with Clinical Stage in Nasopharyngeal Carcinoma
Patients at RSUP Dr. Wahidin Sudirohusodo Period July 2018 -July 2019.

METHODS
The target population in this study were all patients with nasopharyngeal carcinoma. The affordable population is all patients with nasopharyngeal carcinoma who are undergoing treatment at. RSUP. Dr Wahidin Sudirohusodo for the period July 2018 to July 2019. The research sample includes the entire affordable population that meets the inclusion and exclusion criteria. The sampling method in this research is using the total sampling technique. Of the 33 research subjects included in the study, it was found that most of the research subjects were male, and the rest were female. This study is an analytical observational study with a cross-sectional approach, which is the best way to get the prevalence of a condition. Data analysis was carried out, namely univariate and bivariate data analysis. Univariate analysis was carried out descriptively of each variable with a frequency distribution table accompanied by an explanation.

Characteristics of Research Subjects
The population studied in this study were all patients with nasopharyngeal carcinoma who were treated at RSUP Dr. Wahidin Sudirohusodo, Makassar, South Sulawesi in July 2018 to July 2019 through. This study succeeded in obtaining 33 research subjects through the total sampling method , where the data were completely obtained through the patient's medical record in the form of secondary data. Based on the data obtained, information was obtained that 60.6% of the research subjects were male, while the remaining 39.4% were female (see Table  3.1). Based on the age distribution, it was found that the subjects in this study had an average age of 46.61 ± 14.63 years (see Table 3.2). The age range of the study population was 55 years (15 to 70 years). * There are several modes, the smallest mode is shown

Neutrophil-Lymphocyte Ratio
The neutrophil-lymphocyte ratio (neutrophil-to-lymphocyte ratio/NLR ) in this study is the result of a calculation obtained by dividing the value of the percentage of neutrophils by the value of the percentage of lymphocytes examined from the same sample. The variables of neutrophil count, lymphocyte count, and neutrophil-lymphocyte ratio were assessed on a numerical scale. The distribution of these three variables can be seen in Table 3.3. This study found that the average NLR value in this study was 10.28 ± 14.31. After testing the normality of the data on these three variables, it was found that these three variables were not normally distributed (see Table 3.4). The conclusion of this normality test was taken using the Shapiro-Wilk test because the number of samples in this study was relatively small (n = 33).

Nasopharyngeal Carcinoma Clinical Stage
Based on the data obtained from the medical records of the research subjects, it was found that most of the patients with nasopharyngeal carcinoma were at stage IVA, as many as 13 subjects (39.4%). This proportion was followed by stage II and stage III both having 7 subjects (21.2%), and stage IVB as many as 6 subjects (18.2%). This study did not find any patients with nasopharyngeal carcinoma who were still in stage I. In more detail, the proportion of nasopharyngeal carcinoma stages found in this study can be seen in Table 3.5. The staging of nasopharyngeal carcinoma used in this study uses the latest classification from the AJCC eighth edition in 2018. The proportion of each nasopharyngeal carcinoma stage parameter, namely T (tumor), N (node) and M (distant metastases) in this study can be seen in Table 3.6. From this study, it can be obtained data that the most staging parameters of nasopharyngeal carcinoma in research subjects are T2 and T4, respectively 9 subjects (27.3%) for tumor parameters, N2 as many as 11 subjects (33.3%) for node parameters, and M0 for 27 subjects (81.8%) for distant metastases.

Relationship between Neutrophil-Lymphocyte Ratio with Clinical Stage of Nasopharyngeal Carcinoma
The relationship between the neutrophil-lymphocyte ratio and the clinical stage of nasopharyngeal carcinoma was performed on a tabular basis and statistically to see a trend and/or a statistically significant relationship between the two variables. The tabular analysis which can be seen in Table 3.7 shows that the highest mean neutrophil-lymphocyte ratio was found at stage IVA (14.15 ± 20.32) and the lowest at stage III (5.85 ± 5.04). The neutrophil-lymphocyte ratio is a numerical variable that is not normally distributed, so a comparative bivariate analysis was performed using a non-parametric test, namely the Kruskal-Wallis test. From this test, it was found that there was no significant relationship between the neutrophil-lymphocyte ratio and the stage of nasopharyngeal carcinoma (P = 0.497). After merging the variable categories of nasopharyngeal carcinoma stage IVA and IVB into a single stage category IV, the Kruskal-Wallis test was performed again and there was no significant relationship between the neutrophil-lymphocyte ratio and the stage of nasopharyngeal carcinoma (P = 0.356). The merging of categories was carried out one step further, namely by combining the categories of nasopharyngeal carcinoma stages I, II, and III into stage I-III categories. This modified variable was then tested using the Mann-Whitney test (see Table 3.8), but found that there was no significant relationship between the neutrophil-lymphocyte ratio and the stage of nasopharyngeal carcinoma (P = 0.252). A significant relationship between the neutrophil-lymphocyte ratio and the stage of nasopharyngeal carcinoma was not found even though it was corrected for sex (P = 0.791 for males and P = 0.217 for females). A more detailed analysis was also carried out on the parameters of clinical staging of nasopharyngeal carcinoma, namely the T (tumor), N (nodal), and M (distant metastases) components. Analysis of these three parameters found that there was no significant relationship between the neutrophil-lymphocyte ratio and the clinical stage parameters of nasopharyngeal carcinoma, with P = 0.133 for the T parameter, P = 0.414 for the N parameter, and P = 0.963 for the M parameter.

DISCUSSIONS
Based on statistical analysis of the data, no significant relationship was found between the neutrophil-lymphocyte ratio variable and the clinical stage of nasopharyngeal carcinoma (P = 0.497). The statistical test used to see whether or not there is a relationship between these two variables is the Kruskal-Wallis test, which was chosen because it is a non-parametric comparative test for variables with more than two categories.
This study seeks to find out the possibility of a statistically significant relationship between these two variables by combining the categories of the clinical stage variables of nasopharyngeal carcinoma. ) and advanced stages (III-IV). However, after combining and performing statistical tests with non-parametric comparative tests for variables with two categories (Mann-Whitney test), no significant relationship was found between the neutrophil-lymphocyte ratio and the clinical stage of nasopharyngeal carcinoma (P = 0.252). Even after correction for both sexes, there was still no significant relationship between the neutrophil-lymphocyte ratio and the clinical stage of nasopharyngeal carcinoma, with P values of 0.791 for males and 0.217 for females.
Further analysis was carried out on the parameters of the clinical staging determinants of nasopharyngeal carcinoma, namely the T (tumor), N (nodal), and M (distant metastases) components. Analysis of these three parameters found that there was no significant relationship between the neutrophil-lymphocyte ratio and the clinical stage parameters of nasopharyngeal carcinoma, with P = 0.133 for the T parameter, P = 0.414 for the N parameter, and P = 0.963 for the M parameter.
The results of this study are not in accordance with the hypothesis, namely that the neutrophil-lymphocyte ratio can be used as a biological marker ( biomarker ) to determine the level of disease progression which is characterized by the clinical stage of nasopharyngeal carcinoma. The relationship between neutrophil-lymphocyte ratio and malignancy was proposed by Sambasivaiah K, et al in 2005 in India, where the study found that the value of the neutrophil-lymphocyte ratio was found to be higher in cancer at an advanced stage compared to an early stage. However, this study used all cancer patients regardless of the location of the malignancy, where only 2.8% of the study subjects were patients with head and neck malignancies. 45 Another study conducted by Kartika, et al in 2019 in Bandung, Indonesia also found a relationship between the value of the neutrophil-lymphocyte ratio and the clinical stage of squamous cell cancer in the head and neck, where the higher the neutrophillymphocyte ratio value, the higher the clinical stage. of his violence. However, this difference could be due to the non-specificity of the location of the malignancy studied by the study, where only 4.3% of the study group had nasopharyngeal carcinoma. 46 Although the two studies suggesting an association between the neutrophillymphocyte ratio and clinical stage of malignancy did not specifically examine nasopharyngeal carcinoma, the possibility that this relationship exists is significant still cannot be ruled out with certainty, because theoretically the host response to increased cancer progression should be cause a systemic inflammatory reaction that can be seen by increasing the value of the neutrophil-lymphocyte ratio. However, the absence of this finding in this study could be due to the relatively small sample size in this study which did not allow this study to be generalized to a larger population. 47 Another possibility why no relationship was found between the neutrophillymphocyte ratio and the clinical stage of nasopharyngeal carcinoma is that in a specific malignancy, in this case nasopharyngeal carcinoma, the neutrophil-lymphocyte ratio does not directly describe disease progression, but rather describes the prognostic value of the malignancy. Research conducted by Yin J, et al in 2017 and Yao JJ, et al in 2019 suggested the same thing, namely that a high neutrophil-lymphocyte ratio value in nasopharyngeal carcinoma before treatment describes a worse prognosis and survival compared to the neutrophil ratio value. -low lymphocytes. 48.49

CONCLUSION
Based on statistical analysis of the data, this study did not find a significant relationship between the neutrophil-lymphocyte ratio and the clinical stage of nasopharyngeal carcinoma (P = 0.252), even after correcting for sex. Statistical tests were used to see whether or not there was a relationship. between these two variables is the Kruskal-Wallis test, which was chosen because it is a non-parametric comparative test for variables with more than two categories.