Prognostic analysis of peripheral blood inflammatory markers in 99 nasopharyngeal carcinoma patients with recurrence and metastasis

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in China; furthermore, >80% of cases worldwide occur in South China. This study analyzed the use of peripheral blood inflammatory markers as prognostic factors in patients with local recurrence and distant metastasis after radiochemotherapy for NPC.


INTRODUCTION
Head and neck cancer (HNC) is the most common malignant tumor worldwide, ranking fifth among cancer types, with approximately 600 000 new cases and nearly 300 000 deaths annually. 1,2 Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in HNC, with a large regional distribution; the latest epidemiological results show that 80% of NPC occurs in South China. 3,4 The

5-year recurrence rate of NPC patients after chemoradiotherapy is
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. nearly 15%, and the median overall survival time of patients with local recurrence or distant metastasis is just 20 months. 5,6 In recent years, studies have shown the key role of systemic inflammatory response (SIR) in promoting microvessel regeneration, tumor metastasis, and tumor cell proliferation, in addition to promoting tumor cell differentiation and inhibiting host immune cell activity. [7][8][9] Inflammatory factors in the blood, such as lymphocytes, neutrophils, monocytes, and platelets, show changes in cancer. 10,11 The combinations of these inflammatory factors, such as platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), are also considered prognostic factors for cancers, such as breast, lung, nasopharyngeal, and gastrointestinal and colon cancer. 12,13 However, the effect of inflammatory markers on the prognosis of recurrent NPC is rarely reported. Therefore, the present study collected laboratory data on peripheral blood inflammation indicators before initial NPC treatment to observe the prognostic risk factors affecting local recurrence and distant metastasis, and carried out survival analysis to provide a basis for guiding clinical treatment.

Main grouping criteria
The inclusion criteria for NPC were as follows: (i) before initial treat- and (iii) poor treatment compliance and treatment interruption.

Follow up
The follow-up methods included telephone conversations, short mes-

Statistical analysis
Statistical analysis was carried out using IBM SPSS Statistics for Windows, version 22.0 (Armonk, NY, USA). The Kaplan-Meier method was used to calculate survival rates, log-rank tests were used for univariate prognostic analysis, and a Cox regression model was used for multivariate prognostic analysis to identify independent prognostic factors. An = 0.05 (bilateral) was considered statistically different.

Multivariate analysis
Univariate analysis showed that treatment plan (   Chemoradiotherapy is the main treatment method for NPC, and concurrent chemoradiotherapy plays an important role in the treatment of NPC by improving local control and survival rates. A retrospective study by Palazi et al. showed that improvements in radiotherapy and concurrent chemoradiotherapy could improve the local control and survival rates. 18 Li et al. concluded that chemotherapy was a good prognostic factor for NPC survival without distant metastasis. 19 Lin et al. reported that concurrent chemotherapy could improve local recurrence-free survival and tumor-free survival rates of stage III NPC after radiotherapy. 20 In the present study, seven patients were administered radiotherapy or concurrent chemoradiotherapy combined with adjuvant therapy, with differences in the use and doses of chemotherapeutic drugs before and after radiotherapy; thus, just two groups were compared. The treatment regimens were divided into induction plus radiotherapy and induction plus concurrent chemoradiotherapy groups. The 3-year distant metastasis rates of the two groups were 8% and 25.4%, and the median PFS of the two groups were 13.7 and 23.6 months. The survival curves of the two groups were different, and the difference was statistically significant. The Cox multivariate analysis showed that induction plus radiotherapy was an independent prognostic factor for recurrent and metastatic nasopharyngeal carcinoma. It is concluded that concurrent chemoradiotherapy after induction chemotherapy for NPC is more effective, and can be selected according to the specific conditions and stages of patients, which is consistent with previous studies. Previous studies have confirmed the important role of LDH in predicting the prognosis of malignant lymphoma, multiple myeloma, and malignant germ cell tumors. [21][22][23] Hermes showed worse prognosis after treatment of small-cell lung cancer patients with high serum LDH levels and a significantly higher liver bone metastasis rate of patients with high LDH levels than that of patients with low LDH levels. 24 31 The total survival rate in the high NLR (>2.1) group was significantly lower than that in the low NLR (<2.1) group. There was a significant difference in predicting gastric cancer survival. The present study divided patients into high and low groups based on the median NLR, and observed no significant difference between the two groups. However, the small sample size might have affected these findings.
Previous studies with large numbers of samples have shown the correlation between inflammatory markers and cancer. Inflammatory cells and mediators might produce microenvironments that affect tumor growth, progression, angiogenesis, and metastasis. 7,8,10,11 The present study divided levels of related inflammatory markers into high and low groups, and analyzed their univariate and multivariate prognosis. The final results showed no significant difference in predicting the risk of recurrence and metastasis of NPC between NLR, PLR, and neutrophil count. Because the number of patients who might be included was small and selection bias was possible, it was difficult to separate the survival curves of the two groups; therefore, studies with larger sample sizes are required to provide additional evidence for clinical guidance of NPC treatment. The correlation between SIR and various cancers suggests that the treatment of abnormal inflammation might prevent and treat cancer, and is a simple and easy monitoring index to ultimately guide clinical treatment.