Prognostic value of cystatin C in patients with nasopharyngeal carcinoma: a retrospective study of 1063 patients

OBJECTIVE: Patients with nasopharyngeal carcinoma experience highly variable outcomes despite receiving similar therapeutic regimens. Identifying biomarkers that predict survival and guide individualized therapy is urgently needed. Cystatin C has been explored as a valuable prognostic marker in several malignancies. We retrospectively assessed the relationship between serum cystatin C levels and nasopharyngeal carcinoma prognosis in a large cohort of nasopharyngeal carcinoma patients receiving long-term follow-up. METHODS: A total of 1063 consecutive patients diagnosed with nasopharyngeal carcinoma from June 2006 to December 2010 were retrospectively analyzed. The serum levels of cystatin C at the time of diagnosis were collected. Receiver operating characteristic curve analysis, the Kaplan-Meier method and multivariate analyses using a Cox regression model were performed to assess the correlation of cystatin C levels with overall survival, progression-free survival, distant metastasis-free survival and loco-regional recurrence-free survival. RESULTS: The median follow-up duration was 68.3 months. The optimal cut-off value of cystatin C levels for predicting death was 0.945 mg/L. Compared with the low cystatin C group, the high cystatin C group experienced significantly shorter overall survival (hazard ratio=1.47, p=0.050), progression-free survival (hazard ratio=1.65, p=0.004), distant metastasis-free survival (hazard ratio=2.37, p<0.001) and loco-regional recurrence-free survival (hazard ratio=2.40, p=0.002). Based on multivariate analysis, a high cystatin C level was identified as a significant and independent negative predictor of overall survival (hazard ratio=1.47, p=0.050), progression-free survival (hazard ratio=1.65, p=0.004), distant metastasis-free survival (hazard ratio=2.37, p<0.001), and loco-regional recurrence-free survival (hazard ratio=2.40, p=0.002). CONCLUSION: Cystatin C levels are associated with the prognosis of nasopharyngeal carcinoma patients. A high cystatin C level is an independent indicator of poor prognosis for nasopharyngeal carcinoma patients.

Serum alkaline phosphatase predicts survival outcomes in patients with skeletal metastatic nasopharyngeal carcinoma

OBJECTIVE: Bone metastasis is frequently associated with nasopharyngeal carcinoma. The diagnosis and follow-up of bone metastatic patients usually relies on skeletal X-ray and bone scintigraphy, which are time-consuming and costly. This study aimed to evaluate whether serum alkaline phosphatase offers clinical value in predicting the clinical response and survival outcome for skeletal metastatic nasopharyngeal carcinoma. METHODS: Serum alkaline phosphatase was measured at baseline and then before each cycle of treatment in 416 nasopharyngeal carcinoma patients with bone metastasis. The correlations between the pre-treatment and post-treatment alkaline phosphatase levels and the treatment efficacy were analyzed using the chi-square test. Survival was analyzed using the Kaplan–Meier method and then compared using the log-rank test. RESULTS: Patients with elevated pre-treatment alkaline phosphatase (>110 IU/L) had significantly worse progression-free survival (P<0.001) and overall survival (P<0.001) than those with a normal level of this marker (≤110 IU/L). Patients with elevated post-treatment alkaline phosphatase had worse progression-free survival (P<0.001) and overall survival (P<0.001) compared with those with a normal level. Patients with normal pre-treatment and post-treatment alkaline phosphatase showed the most favorable prognosis. The Cox multivariate analysis revealed that only the pre-treatment and post-treatment alkaline phosphatase levels were independent prognostic factors for progression-free survival (HR ϝ 1.656, P<0.001; HR ϝ 2.226, P<0.001) and for overall survival (HR ϝ 1.794, P<0.001; HR ϝ 2.657, P<0.001). CONCLUSIONS: Serum alkaline phosphatase appears to be a significant independent prognostic index in patients with skeletal metastatic nasopharyngeal carcinoma, which could reflect the short-term treatment response ...

[Seric soluble interleukin-2 receptor alpha in nasopharyngeal carcinoma in Tunisia. Prospective study about 45 cases]

Soluble interleukin-2 receptor alpha [sIL-2Ralpha is a well-known indicator of T-cell activation noted to be increasing in nasopharyngeal cancer. The aims of this study were to evaluate the importance of the use of this marker in nasopharyngeal carcinoma. Our prospective study interested 45 patients [35M/10F] with a mean age of 49 years [15 to 78], presenting a nasopharyngeal carcinoma histologically confirmed and 61 healthy controls. A blood sample was collected from each patient before any treatment, as well as controls to measure sIL-2Ralpha by immunoenzymatic assay. According to the disease status after a period of follow-up ranging from three to 22 months [median 12 months], patients were divided into two groups: The remission group [n = 28] represented those with favourable evolution and a second group of 15 patients with unfavourable evolution [2 death, 4 cases of persistent primary disease and 9 patients with distance metastasis]. 2 patients were lost to follow-up. serum sIL-2Ralpha levels were significantly higher in patients vs healthy controls [p < 0.0001]. The serum levels correlated with the stage T of NPC [p = 0.01]. Patients having a favourable evolution have lower sIL-2Ralpha levels before treatment vs those with unfavourable evolution without statistical difference. Measurement of serum sIL-2Ralpha provides a good estimation of the nasopharyngeal tumor burden. The usefulness of this marker as a parameter to predict prognosis in NPC should be examined further

Profil serique de la lacticodeshydrogenase et de ses isoenzymes dans le cancer du nasopharynx

Our prospective study included 41 patients, from 13 to 70 years old, and present a nasopharyngeal carcinoma confirmed histologically, during the period going from September 1999 to March 2000, and 45 healthy controls. A blood sample was collected from each patient before any treatment, as well as controls to measure serum LDH and its isoenzymes. Two groups of patients were selected after a period varying from 12 to 37 months with a mean of 29 months: 29 with favourable evolution, 12 with non favourable evolution. The mean serum total LDH and its isoenzymes values were significantly higher in patients than those in controls with values of variable p of 0,001 to 0,05. A significant correlation was found between ganglionnary extension and serum values of total LDH, LDH3 and LDH5. No significant difference were observed between the means serum total LDH before treatment and the clinical evolution of patients. Diagnostic contribution of total LDH is limited, by its ubiquitary character, but could constitute for LDH3 a good marker of the disease progression

Serological analysis of human leukocyte antigens-A and -B antigens in Thai patients with nasopharyngeal carcinoma.

OBJECTIVE: To study the distribution of human leukocyte antigens (HLA) -A and -B antigens by standard microlymphocytotoxicity assay in Thai nasopharyngeal carcinoma (NPC) patients compared to normal controls in order to identify the alleles associated with NPC in Thailand. DESIGN: Retrospective-Analytical study. SUBJECTS: Fifty-three unrelated Thai patients with histologically confirmed NPC diagnosed at King Chulalongkorn Memorial Hospital and 70 healthy unrelated Thai individuals served as controls. METHOD: Lymphocyte separation and HLA typing were performed from freshly drawn blood by standard microlymphocytotoxicity assay. The significance of differences between the two groups was analyzed by the chi-square test. RESULTS: HLA-A2 was observed at a greater frequency in patients being found in 31/53 (58%) NPC patients compared to 27/70 (38%) controls (p = 0.02). An increase in HLA-B46 was also demonstrated. HLA-B46 was present in 16/53 (30%) NPC patients but was observed in 10/70 (14%) in controls (p = 0.03). CONCLUSIONS: This study reported two susceptible, HLA-A2 and HLA-B46 antigens, for NPC in a Thai population.

Soluble interleukin-2 receptor as a clinical parameter for nasopharyngeal carcinoma.

We evaluated whether the serum soluble interleukin-2 receptor (sIL-2R) may be a parameter to monitor the efficacy of treatment for nasopharyngeal carcinoma (NPC). There were 177 NPC patients and 24 healthy controls. The level of sIL-2R was measured with a sandwich ELISA kit. Higher levels of sIL-2R than for controls were found in NPC patients before treatment and in patients with distant metastasis (p < 0.001). There was, however, no difference in sIL-2R levels between controls and NPC patients after radiotherapy in relapse-free or in primary relapse. The sIL-2R levels in sequential testing revealed good correlation with clinical response. The sIL-2R levels were found to be elevated when distant metastasis was detected. Two patients had elevated sIL-2R level up to 5 months before clinical detection of metastasis. These results indicate that serial measurements of sIL-2R levels are worthwhile for NPC patients in their clinical course. The sIL-2R level proved to be an adjunct clinical parameter to monitor the efficacy of treatment of NPC.

Epstein-Barr virus serological markers for nasopharyngeal carcinoma in Thailand.

The present study reports on the prevalence of specific IgA and IgG antibodies to EBV viral capsid antigen in nasopharyngeal carcinoma (NPC) patients with different histological types of carcinoma and their age-matched controls by the indirect immunofluorescence test, using the B-95-8 lymphoblastoid cell line as source of viral capsid antigen. EBV specific IgG was found in almost all the study cases, and antibody titers were significantly higher in the NPC patients than in non-cancer controls. GMT of anti-EBV IgG in NPC patients, patients with other malignant diseases, and those with non-malignant diseases were 371.5, 97.7 and 35.5, respectively. Anti-EBV specific IgA was more specific to NPC than was IgG, and was present in 86.5% (83 of 96) cases of NPC patients, 6.6% (2 of 30) of patients with other cancers, and 3.1% (3 of 97) cases of non-malignant diseases. A weak correlation between level of anti-EBV IgA in NPC patients was observed (r = 0.3). EBV IgA was found in all histological types of NPC, ie, WHO types 1, 2 and 3, but WHO type 1 was rare among NPC patients in Thailand. Use of anti-EBV IgA for monitoring cancer therapy is to be further investigated.

Endogenous tumor necrosis factor-alpha in patients with nasopharyngeal carcinoma.

Serum tumor necrosis factor alpha (TNF) concentration was assayed in 105 patients with nasopharyngeal carcinoma using a sensitive ELISA technique with detection level of 10 pg/ml. The TNF levels were detectable in 45 of 63 (71.4%) patients newly diagnosed for the malignancy and 29 of 42 (69%) patients in remission following treatment with radiotherapy. In 25 normal controls the TNF were less than 10 pg/ml. While TNF may be present in the majority of the patients with the malignant disease, the TNF concentration appeared to have no clinical significance in diagnosis or prognosis of the patients.