Qiaojuan Guo

A Comparison Between the Chinese 2008 and the 7th Edition Ajcc Staging Systems for Nasopharyngeal Carcinoma

Objectives:The Chinese 1992 staging system for nasopharyngeal carcinoma (NPC) was revised in 2008 and was renamed as the Chinese 2008 staging system. The seventh edition of the American Joint Committee on Cancer (AJCC) staging manual also defined new rules for classifying NPC in 2010. The purpose of the current study is to compare the 2 in terms of patient distribution and efficacy in predicting prognosis. Methods:A total of 816 patients with untreated nondisseminated NPC who underwent magnetic resonance imaging scan of the nasopharynx and neck were studied retrospectively. All magnetic resonance imaging scans were reevaluated independently by 2 radiologists specialized in head and neck cancers. All patients were restaged according to the Chinese 2008 staging system and the AJCC staging system of NPC. Results:Using the 2 staging systems, the consistency for patient distributions in T, N, and overall stages was found to be moderate, with the &kgr; value of 0.65, 0.54, and 0.46, respectively. According to the Chinese 2008 and the AJCC staging systems, the proportion of patients in stages I, II, III, and IV accounted for 2.3% versus 2.3%, 11.0% versus 23.7%, 39.4% versus 49.1%, and 47.3% versus 24.9%, respectively. The AJCC T classification was better in predicting the 5-year local relapse-free survival, whereas the Chinese 2008 N classification was superior in predicting the 5-year distant metastasis-free survival. However, survival curves for the 5-year overall survival were comparable in both systems. Conclusions:We revealed a slightly better patient distribution of overall stage with AJCC comparing with the Chinese 2008 staging system. The prognostic value of AJCC T classification was considered to be better, whereas that of Chinese 2008 N classification was superior.

Survival analyses correlate stanniocalcin 2 overexpression to poor prognosis of nasopharyngeal carcinomas.

BackgroundStanniocalcin 2 (STC2) is overexpressed in several types of human cancers, and its overexpression positively correlates to tumor progression and poor prognosis. However, the clinical significance of STC2 overexpression in nasopharyngeal carcinomas (NPC) has not been investigated. This study examined STC2 expression in a cohort of 94 NPC samples, and explored its value in clinical diagnosis and prognosis.MethodsTumor samples from 94 patients diagnosed in 2008 were studied. All samples were obtained prior to treatment start. All cases were clinically diagnosed and pathologically confirmed to be poorly differentiated or undifferentiated NPC without distant metastasis, and have been treated with radical radiation therapy and followed-up for five years. Survival analyses were performed.ResultsOf the 94 NPC samples, STC2 overexpression (STC2+) was detected in 65 samples (69.1%). Overall survival rate of STC2 (+) patients is significantly lower than that of patients with normal STC2 levels (72.2% vs. 96.4%, respectively, P = 0.049). Moreover, STC2 (+) is also strongly predictive of a low progression-free survival and distant metastasis-free survival (63.0% vs 92.9%. P = 0.007; and 77.0% vs 96.4%. P = 0.028). Of the 54 patients treated with IMRT, residual tumors were found in 54.8% of STC2 positive patients (17/31), but only in 17.4% of STC2 negative ones (4/23), suggesting STC2 overexpression predicts a higher risk of residual tumors after IMRT.ConclusionsSTC2 overexpression correlates to poor prognosis for NPC and may be useful as a novel biomarker to predict NPC responses to radiation. Whether STC2 promotes NPC progression and metastasis remains to be investigated.

Suggestions for lymph node classification of UICC/AJCC staging system: a retrospective study based on 1197 nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy.

AbstractThis article provides suggestions for N classification of Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system of nasopharyngeal carcinoma (NPC), purely based on magnetic resonance imaging (MRI) in intensity-modulated radiation therapy (IMRT) era.A total of 1197 nonmetastatic NPC patients treated with IMRT were enrolled, and all were scanned by MRI at nasopharynx and neck before treatment. MRI-based nodal variables including level, laterality, maximal axial diameter (MAD), extracapsular spread (ECS), and necrosis were analyzed as potential prognostic factors. Modifications of N classification were then proposed and verified.Only nodal level and laterality were considered to be significant variables affecting the treatment outcome. N classification was thus proposed accordingly: N0, no regional lymph node (LN) metastasis; N1, retropharyngeal LNs involvement (regardless of laterality), and/or unilateral levels I, II, III, and/or Va involvement; N2, bilateral levels I, II, III, and/or Va involvement; and N3, levels IV, Vb, and Vc involvement. This proposal showed significant predicting value in multivariate analysis. N3 patients indicated relatively inferior overall survival (OS) and distant metastasis-free survival (DMFS) than N2 patients; however, the difference showed no statistical significance (P = 0.673 and 0.265 for OS and DMFS, respectively), and this was considered to be correlated with the small sample sizes of N3 patients (79 patients, 6.6%).Nodal level and laterality, but not MAD, ECS, and necrosis, were considered to be significant predicting factors for NPC. The proposed N classification was proved to be powerfully predictive in our cohort; however, treatment outcome of the proposed N2 and N3 patients could not differ significantly from each other. This insignificance may be because of the small sample sizes of N3 patients. Our results are based on a single-center data, to develop a new N classification that is universally acceptable; further verification by data from multicenter is warranted.

Long-term survival of nasopharyngeal carcinoma patients with Stage II in intensity-modulated radiation therapy era

OBJECTIVES To evaluate the long-term survival and the role of chemotherapy in nasopharyngeal carcinoma (NPC) patients in Stage II treated by intensity-modulated radiation therapy (IMRT). METHODS Three hundred and eleven NPC patients in Stage II were reviewed. All were treated with IMRT with or without chemotherapy, with 191, 20 and 100 patients being defined as T1N1M0, T2N0M0 and T2N1M0 stage, respectively. RESULTS At a median follow-up of 57 months, the 5-year overall survival, disease-specific survival, distant metastasis-free survival, loco-regional relapse-free survival (LRRFS) and progression-free survival were 91.1, 93.5, 90.6, 95.9 and 87.6%, respectively. T2N1 patients had significant poorer survival outcomes than T1N1 patients, with T2N0 patients in between. Further analysis showed that the addition of chemotherapy could only improve LRRFS [hazard ratio (HR) 0.263, 95% confidence interval (CI) 0.083-0.839, P = 0.024], especially for T1N1 patients (HR 0.209, 95% CI 0.046-0.954, P = 0.043). For those in the T2N1M0 group, chemotherapy, as used in our series, added no benefit to any endpoint. CONCLUSIONS IMRT in NPC patients in Stage II was quite therapeutic; however, different subgroups have distinct survival outcomes. Distant metastasis was the main failure pattern, especially for those with T2N1 disease, and the chemotherapy currently in use failed to treat subclinical metastatic foci effectively. Further prospective study is warranted to find out the role and the optimal schedule of chemotherapy in this subgroup of patients.

Locoregionally advanced nasopharyngeal carcinoma in childhood and adolescence: Analysis of 95 patients treated with combined chemotherapy and intensity-modulated radiotherapy.

The purpose of this study was to evaluate the treatment outcomes and toxicities of intensity‐modulated radiation therapy (IMRT) for children and adolescents with locoregionally advanced nasopharyngeal carcinoma (NPC).

The Correlation Between the Comprehensive Nutrition Index and Quality of Life of Patients with Nasopharyngeal Carcinoma Treated by Intensity-Modulated Radiotherapy

The purpose of this study was to compare the changing tendency of nutrition with 54 nasopharyngeal carcinoma patients during intensity-modulated radiation therapy (IMRT), and to investigate the correlation between comprehensive nutritional status and quality of life (QoL), which was assessed by the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire. The nutritional index, including body mass index, ideal body weight percentage, usual body weight percentage, albumin, hemoglobin, and total lymphocyte count (TLC), was evaluated at 2 time points: within 48 h after admission (T1) and at the end of treatment with IMRT (T2). A statistically significant downgrade of every index was observed during IMRT. A comprehensive nutritional model was established by principal components analysis at T2. QoL scores of functional (P = 0.002) and the global QoL scales (P = 0.001) existed a positive correlation with comprehensive nutritional status. QoL scores of symptom scales (P = 0.002) and 6 single items (P = 0.005) had a negative correlation with it. The scores of global QoL scales in comprehensive nutrition of normal (20.4%), moderate (55.6%), and severe malnutrition (24.1%) were 69.70 ± 17.98, 48.33 ± 19.25, and 37.18 ± 24.67, respectively. Patients with different nutritional status had different QoL (B = 10.405, SE = 2.828, t = 3.680, P = 0.001). Multiaspect nutritional supports should be enhanced to improve patients’ comprehensive nutritional status during treatment.

Decreased expression of the NKG2D ligand ULBP4 may be an indicator of poor prognosis in patients with nasopharyngeal carcinoma

U16-binding protein 4 (ULBP4), a human ligand for natural killer group 2, member D (NKG2D) receptor on NK cells and subsets of T cells, is thought to activate anticancer immune responses. However, the expression pattern and prognostic effect of ULBP4 in nasopharyngeal carcinoma (NPC) has not been investigated. We first compared ULBP4 expression between archival 15 NPC tissues and 8 normal nasopharynx (NP) tissues using qPCR. Then ULBP4 expression among 111 NPC specimens was validated on immunohistochemical examination. In addition, the association of ULBP4 expression with clinical characteristics and survival outcomes was analyzed. Furthermore, the impact of ULBP4 expression in NPC cells on the cytotoxic activity of NK cells was investigated. Both mRNA and protein ULBP4 expressions of NPC tissues were significantly lower than those in normal NP tissues. However, no association of ULBP4 expression with clinical characteristics was observed. Patients with NPC having decreased expression of UBLP4 had significantly poorer overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) than those with preserved levels of ULBP4. On multivariate analyses, low expression of ULBP4 was of borderline significance for OS, PFS, and DMFS (P = 0.060, 0.053, and 0.076, respectively). Further, LDH analysis demonstrated that the cytotoxic activitity of NK cells against C666-1 or 5-8F NPC cells with lenti-ULBP4 was considerably increased as compared to those with lenti-vector at various E/T ratios. Hence, restoration of ULBP4 expression may be a novel therapeutic strategy for treatment of NPC. However, further study is required to confirm these findings.

Prognostic effect of parotid area lymph node metastases after preliminary diagnosis of nasopharyngeal carcinoma: a propensity score matching study

Parotid area lymph node (PLN) metastasis in nasopharyngeal carcinoma (NPC) is rare, and its prognosis remains largely unknown. Our study aimed to investigate the prognostic value and staging categories of PLN metastasis in patients with NPC and treated with intensity‐modulated radiation therapy (IMRT), to provide a reference for clinical treatment for NPC with PLN metastasis. Records for 1616 untreated NPC patients without distant metastasis was retrospectively reviewed. All patients underwent magnetic resonance imaging (MRI) examination prior to treatment and then received IMRT as their primary treatment. Forty‐five NPC patients (2.8%) showed initial PLN metastasis on follow‐up MRI. PLN metastasis was significantly associated with the N classification and clinical stage. Univariate analysis showed that PLN metastasis had an unfavorable influence on overall survival (OS), progression‐free survival (PFS), distant metastasis‐free survival (DMFS), and regional relapse‐free survival (RRFS) in NPC patients. Using propensity score matching (PSM) to calibrate selection bias and confounding bias, it was observed that PLN metastasis remained an adverse prognostic factor for OS, PFS, DMFS, and RRFS. Furthermore, the 5‐year DMFS and RRFS curves for PLN metastasis were significantly separated from that for N2 disease but crossed that for N3 disease. Therefore, PLN metastasis was found to be an adverse prognostic factor for NPC and to be associated with the same DMFS as N3 disease. Therefore, more aggressive therapeutic strategies consistent with those for N3 disease are recommended for NPC with PLN metastasis to reduce distant metastasis.

Evolution of the Chinese staging system for nasopharyngeal carcinoma

The clinical treatment of nasopharyngeal carcinoma (NPC) in China started in 1940s is based on our own clinical staging system. In 1965, we established the first TNM staging system for NPC. Advances in technology and therapy led to continuous updates in clinical staging. Currently, the Chinese staging system of 2008 is commonly used in China. Compared with the 7th edition of the American Joint Committee on Cancer (AJCC) staging system, which is widely used internationally, the N classification was based on magnetic resonance imaging (MRI) as well as the lymph node criteria of the Radiation Therapy Oncology Group (RTOG) consensus guidelines. However, several studies showed that these two staging systems were associated with limitations. Additional international studies from different cancer centers are needed to improve and evolve a universally accepted staging system for NPC.

Pretreatment Serum Lactate Dehydrogenase Level as an Independent Prognostic Factor of Nasopharyngeal Carcinoma in the Intensity-Modulated Radiation Therapy Era

Background The aims of this study were to analyze the prognostic value of baseline lactate dehydrogenase (LDH) among nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT), and to evaluate the potential application of LDH in monitoring treatment efficacy dynamically. Material/Methods From June 2005 to December 2010, 1188 patients with non-metastatic NPC who underwent IMRT with or without chemotherapy were reviewed. Univariate and multivariate analyses were performed to evaluate the predictive value of baseline LDH. Wilcoxon signed-rank test was used to analyze the difference between baseline and post-radiotherapy LDH, and to compare post-radiotherapy LDH with the LDH in cases of distant failure. Results Patients with elevated LDH had significant inferior survival rates, in terms of overall survival (70.0% vs. 83.2%, p=0.010), disease-specific survival (71.1% vs. 85.7%, p=0.002), and distant metastasis-free survival (71.1% vs. 83.4%, p=0.009), but not correlated with locoregional relapse-free survival (p=0.275) or progression-free survival (p=0.104). Subgroup analysis demonstrated that this predictive effect was more significant with advanced stage. Sixty-five post-radiotherapy LDH levels were available from the 90 patients with high LDH at initial diagnosis, and these levels fell in 65 patients, with 62 cases (95.4%) falling within the normal range. Of the 208 patients who experienced distant metastasis, 87 had an available LDH level at that time. Among them, 69 cases (79.3%) had an increased level compared with the post-radiotherapy LDH level. Conclusions Pretreatment LDH is a simple, cost-effective biomarker that could predict survival rates and might be used in individualized treatment. It is also a potential biomarker that might reflect tumor burden and be used to monitor therapy efficacy.