Is the 1997 AJCC staging system for nasopharyngeal carcinoma prognostically useful for Chinese patient populations?

PURPOSE: The 5th edition of the American Joint Committee on Cancer (AJCC) staging manual defines new rules for classifying nasopharyngeal carcinoma (NPC). The study was conducted to assess its effectiveness in predicting the prognosis for Chinese patient populations. METHODS AND MATERIALS: Between June 1993 and June 1994, 621 consecutively admitted patients with nondisseminated NPC were treated with definitive-intent radiation therapy alone. All had computed tomography of the nasopharynx, skull base, and the upper neck. A computer database containing all information for staging was formed on presentation. The extent of disease of each patient was restaged according to the 1997 AJCC system. RESULTS: Of the 621 patients, The 5-year overall survival (OS) rate was 60%. The 1997 AJCC system creates subgroups (Stages I to IV) that are assigned to 38 (6.1%), 270 (43.5%), 157 (25.3%), and 156 (25.1%) patients, respectively. The incidence of parapharyngeal extension was 74.1% (460/621). Of these patients (460) with parapharyngeal extension, 310 (67.4%) patients were classified as T2b disease. The 1997 AJCC system showed highly significant differences between the overall stages for both OS and relapse-free survival (RFS). The 1997 AJCC T classifications showed significant correlation with local failure, and N classification was accurate in predicting FDM. Multivariate analysis showed that paraoropharyngeal involvement was an independently significant prognostic factor for OS, freedom from local recurrence (FLR), and freedom form distant metastasis (FDM). CONCLUSION: The 1997 AJCC staging system for NPC is prognostically useful for Chinese patient populations. We proposed that subdivision of parapharyngeal extension should be included in future revisions of the staging system.

Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: A prospective randomized trial was performed to evaluate the contribution of neoadjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. PATIENTS AND METHODS: Patients with locoregionally advanced nasopharyngeal carcinoma were treated either with radiotherapy alone (RT group) or neoadjuvant chemotherapy plus radiotherapy (CT/RT group). Neoadjuvant chemotherapy consisting of two to three cycles of cisplatin (100 mg/m(2), day 1), bleomycin (10 mg/m(2), days 1 and 5), and fluorouracil (5-FU; 800 mg/m(2), days 1 through 5, continuous infusion) followed by radiotherapy was given to the CT/RT group. All patients were treated in a uniform fashion by definitive-intent radiation therapy in both groups. RESULTS: Between July 1993 and July 1994, 456 patients were entered onto the study, with 228 patients randomized to each treatment arm, and 449 patients (225 in the RT group and 224 in the CT/RT group) were assessable. All 456 patients were included in survival analysis according to the intent-to-treat principle. The 5-year overall survival (OS) rates were 63% for the CT/RT group and 56% for the RT group (P =.11). The median relapse-free survival (RFS) time was 50 months for the RT group and not reached for the CT/RT group. The 5-year RFS rate was 49% for the RT group versus 59% for the CT/RT group (P =.05). The 5-year freedom from local recurrence rate was 82% for the CT/RT group and 74% for the RT group (P =.04). There was no significant difference in freedom from distant metastasis between the two treatment groups (CT/RT group, 79%; RT group, 75%; P =.40). CONCLUSION: This randomized study failed to demonstrate any significant survival benefit with the addition of neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma. Therefore, neoadjuvant chemotherapy for nasopharyngeal carcinoma should not be used outside of the context of a clinical trial.

A comparison of the Chinese 1992 and fifth-edition International Union Against Cancer staging systems for staging nasopharyngeal carcinoma.

BACKGROUND: The Chinese 1992 staging system for nasopharyngeal carcinoma (NPC) has been widely adopted in mainland China since 1992. The fifth edition of the International Union Against Cancer (UICC) TNM classification defines new rules for classifying NPC. The current study compares the two in predicting NPC prognosis. METHODS: Four hundred eleven NPC patients, most of whom had disease of undifferentiated histologic type and were treated in a constant fashion and with definitive intent with radiation therapy alone, entered this comparative study. The patients were restaged according to the rules of the fifth edition of the UICC staging manual and the Chinese 1992 staging system. RESULTS: In the opinion of the authors, the predictive power of the Chinese 1992 T classification was superior. Conversely, the authors felt that the UICC N classification was more reasonable. The patients were categorized more evenly by the UICC stages than by the Chinese 1992 stages. The 5-year disease specific survival rates for patients in corresponding stages of both systems were almost identical despite differences in the criteria defining T and N classifications. Statistical analysis showed that the agreement rate was 72%. There were some agreement and correlation between the two staging systems. CONCLUSIONS: Both systems are essentially similar. Each system appears to have some subtleties that could improve the outcome prediction of the other system if the two were somehow combined. However, it appeared to the authors that the UICC system was slightly better.

Combination of angiogenesis inhibitor TNP-470 with cytotoxic drugs in experimental therapy of nasopharyngeal carcinoma.

This study was conducted to evaluate the effectiveness of angiogenesis inhibitor 6-O-(N-chloroacetyl-carbamoyl)-fumagillol (TNP-470. AGM-1470) in the treatment of nasopharyngeal carcinoma (NPC) alone and in combination with cytotoxic agents. Forty-two male BALB/c nude mice bearing human NPC cell line CNE-2 were randomized into 6 groups: those treated with saline solution, TNP-470, cisplatin (DDP), fluorouracil (5-FU), TNP-470 + DDP, and TNP-470 + 5-FU, respectively. In every treatment group, tumor growth was suppressed significantly. The combination of 5-FU with TNP-470 showed significant enhancement in antitumor efficacy. TNP-470 also enhanced the inhibitory effect of DDP, although not to statistical significance. All animals gained in body weight, although treatment with 5-FU caused slight, reversible diarrhea of 2 to 3 days' duration. The results showed that TNP-470 suppressed the growth of the human NPC cell line and enhanced the antitumor effect of 5-FU without increasing its toxicity. The combination of angiogenesis inhibitors with conventional cytotoxic agents is promising in the treatment of NPC.

Elevation of serum vascular endothelial growth factor in male patients with metastatic nasopharyngeal carcinoma.

BACKGROUND: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. The authors investigated the correlation between the levels of serum VEGF (S-VEGF) in patients with nasopharyngeal carcinoma (NPC) and disease progression. METHODS: The sera from 65 male patients with nonmetastatic NPC, 22 male patients with metastatic NPC, and 27 healthy male volunteers were obtained. A quantitative enzyme-linked immunosorbent assay was performed to measure the concentrations of S-VEGF in the sera. RESULTS: The mean S-VEGF levels were 371.0 pg/mL(-1) (range, 128.5-691.1 pg/mL(-1)) for healthy controls, 375.6 pg/mL(-1) (range, 72.9-1202.5 pg/mL(-1)) for patients with nonmetastatic NPC, and 958.6 pg/mL(-1) (range, 264.4-3744.9 pg/mL(-1)) for patients with metastatic NPC. The mean S-VEGF level in patients with metastatic NPC was significantly higher than in either patients with nonmetastatic NPC (P < 0.001) or healthy controls (P < 0.001). However, there was no statistical difference between these results for healthy controls and patients with nonmetastatic NPC. At the level of 900 pg/mL(-1), S-VEGF indicated distant dissemination of NPC with a specificity of 95.4%, a sensitivity of 31.8%, a positive predictive value of 70.0%, and a negative predictive value of 80.5%. No significant differences in the levels of S-VEGF were found among various T classifications, N classifications, and clinical stages of nonmetastatic NPC. CONCLUSIONS: The levels of S-VEGF were significantly elevated in male patients with metastatic NPC. These levels did not correlate with locoregional progression of NPC. The usefulness of detecting S-VEGF in the early diagnosis of NPC appears to be limited.

Anti-tumor effect of angiogenesis inhibitor TNP-470 on the human nasopharyngeal carcinoma cell line NPC/HK1.

The efficacy and targeting cells of angiogenesis inhibitor TNP-470 on human squamous cell nasopharyngeal carcinoma (NPC) were investigated. The colorimetric MTT assay was used to evaluate the IC50 values of NPC/HK1 cells and human dermal microvascular endothelial cells (HDMEC) for TNP-470. An NPC human tumor model was built by tumor-bearing nude mice using the NPC cell line of NPC/HK1. TNP-470 (30 mg/kg s.c.) was injected every other day. The results showed that the IC50 of NPC/HK1 cells for TNP-470 was 3.8 times higher than that of HDMEC. A significant difference in tumor volume between control and treatment groups was found after 7 days of treatment and increased thereafter. At the end of the treatment, tumor volume was 773.7 +/- 287.1 mm3 (n = 8) in the control group versus 454.5 +/- 132.8 mm3 (n = 8) in the treatment group (p = 0. 013); the ratio of the mean tumor volume in treated animals to that of control animals was 0.587, resulting a 41.3% decrease in tumor growth. The necrotic area was larger in the treatment group. Physical toxicity did not result from the treatment. These studies suggest that angiogenesis inhibitor TNP-470 is effective in the treatment of squamous cell NPC without obvious toxicity.

nm23-H1 expression in nasopharyngeal carcinoma: correlation with clinical outcome.

The expression levels of nm23-H1 mRNA and its protein in human nasopharyngeal carcinoma (NPC) were detected to clarify the relationship between nm23-H1 and metastasis and prognosis of patients with NPC. nm23-H1 mRNA expression in fresh tissues from 78 patients with NPC was investigated by in situ hybridization and RT-PCR. Routine labeling streptavidin-biotin immuno-histochemistry with the nm23-H1 murine monoclonal antibody was employed to study the expression of nm23-H1 protein in paraffin-embedded specimens from 231 patients with NPC treated in our hospital. The clinical pathologic data and results of follow-up were collected. Comparisons between expression of nm23-H1 protein or mRNA and clinical outcome were performed using the chi2 test. Multivariate prognostic analyses were performed by the Cox regression model. We found that nm23-H1-negative tumors were associated with a higher incidence of lymph-node metastasis (84.2%) than nm23-H1-positive ones (32.8%, p < 0.01). The distant metastasis and loco-regional recurrence rates in the nm23-H1-negative group were 55.8% and 31.68%, respectively but only 17.2% and 11.5%, respectively, in the nm23-H1-positive group (p < 0.01). A significant association was found between expression of nm23-H1 protein and prognosis (p < 0.01). Expression of nm23-H1 protein indicated favorable prognosis, suggesting that the absence of nm23-H1 protein expression was significantly associated with lymph-node metastasis, recurrence and distant metastasis in NPC. Expression of the nm23-H1 gene may be valuable for assessing the prognosis of NPC.

Primary study in experimental antiangiogenic therapy of nasopharyngeal carcinoma with AGM-1470 (TNP-470).

OBJECTIVE: To evaluate the efficacy of the angiogenesis inhibitor AGM-1470 for the experimental treatment of nasopharyngeal carcinoma (NPC). METHODS: A NPC human tumour model was built by tumour-bearing nude mice using the NPC cell line CNE-2. Twenty-one BALB/c nude mice bearing CNE-2 xenografts were randomized into a treatment group and a control group. In the treatment group, AGM-1470 was injected 30 mg/kg subcutaneously every other day; while the vehicle (three per cent ethanol solution in 0.9 per cent saline) was given to the mice in control group. Tumour volumes and animal weights were measured every third day. Autopsy was performed after 18 days of treatment. The tumour tissue as well as the murine tissues of heart, kidney, and liver in each mouse were removed for formalin fixation and routine HE staining. Pathological evaluation was performed in these tissues. RESULTS: There was a significant difference in tumour volume between the two groups at day 9 of treatment and this increased thereafter. At day 15 of treatment, the tumour volume was 4251 +/- 559 mm3 (n = 10) in the control group versus 3122 +/- 967 mm3 (n = 11) in the AGM-1470 treated group (p = 0.004); and T:C ratio (mean tumour volume of treated/mean tumour volume of control) was 0.73, resulting in a 27 per cent decrease in tumour growth. Central necrosis and consequential shrinkage of tumours occurred in both groups at the end of experiment. Physical toxicity and histological toxicity of heart, liver, and kidney did not result from AGM-1470 therapy. CONCLUSIONS: AGM-1470 suppresses the growth of the human NPC cell line CNE-2. Treatment by AGM-1470 has no physical nor histological toxicity. Angiogenesis inhibitors may be effective in the treatment of the local lesion of NPC.

Primary study of neovasculature correlating with metastatic nasopharyngeal carcinoma using computer image analysis.

The significance of neoangiogenesis in the metastasis of nasopharyngeal carcinoma (NPC) was investigated to clarify the role neovascularity in the prognosis of NPC and the probability of antiangiogenesis preventing NPC from distant metastasis. A group of 52 patients presenting with metastatic NPC were selected and strictly paired one-to-one, in sex, age, T stage, and N stage, with another 52 patients with non-metastatic NPC, who had survived for a long time after therapy. The tumor tissues of all 104 patients were retrieved for computer-assisted, immunohistochemical analysis of tumor vasculature. Counts of the microvessels and the relative area of all microvessels per image were significantly higher in metastatic NPC than they were in curable, non-metastatic NPC, while the average area of the microvessels and their average perimeter of in metastatic NPC were smaller than in non-metastatic disease. No significant difference in any microvessel parameter was found among the various types of metastasis. The alterations of microvessel parameters were significantly linked to the metastasis of NPC. Evaluation of neovascularity by computer image analysis may be helpful in estimating the prognosis of NPC and in determining the indicators for aggressive multimodal treatments.

Study of 45 cases of nasopharyngeal carcinoma with dermatomyositis.

The authors have conducted a study of 61 cases of nasopharyngeal carcinoma (NPC) with dermatomyositis (DM) admitted to the hospital between April 1964 and May 1989 and accounting for 0.027% (61/226, 183) of all the malignant tumors at the hospital and 0.086% (61/70,899) of the nasopharyngeal carcinoma cases, during that time period. We have analyzed 45 cases with complete data, using equal number of age-, sex-, and stage-matched cases with only NPC as control. The findings show a 5- and 10-year survival rate and distant metastatic rate of 50.4, 34.5, and 40.5% respectively, for NPC with DM, and 57.8, 55.2, and 56.5% for controls. The results indicated that the radiotherapy with prednisone treatment not only is quite effective but also will not result in a significantly increased rate of distant metastasis.