Early-stage Nasopharyngeal Carcinoma Patients Research Articles

Nasopharyngeal Carcinoma: Clinical Achievements and Considerations Among Treatment Options.

Nasopharyngeal carcinoma (NPC) is a severe malignancy arising from the nasopharyngeal epithelium and is southern China’s third most common cancer. With the advancement of treatment methods, early-stage NPC patients usually have a better prognosis and more prolonged survival period than those with other malignant tumors. Most treatment failures are due to distant metastasis or a locally advanced stage of NPC in the initial diagnosis. In addition, approximately 10% of patients develop local recurrence, and 10%–20% of patients experience distant metastasis after treatment. These patients have a poor prognosis, with a median survival of only approximately 10–15 months. In the rapid development of treatment options, the efficacy and safety of some treatments have been validated and approved for first-line treatment, while those of other treatments remain unclear. The present study aims to provide a comprehensive overview of recent advances in NPC treatment and explain the various therapeutic possibilities in treating locally advanced, recurrent, and metastatic NPC patients.

Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing

BackgroundEarly diagnosis of nasopharyngeal carcinoma (NPC) is vital to improve the prognosis of these patients. However, early diagnosis of NPC is typically challenging. Therefore, we explored the pathogenetic roles and associated mechanisms of exosomes in plasma of patients with early-stage NPC.MethodsExosomes in plasma were extracted by ultra-high-speed centrifugation. Western blot and transmission electron microscopy (TEM) were used to verify the purity of exosomes. The sequencing data (6 plasma samples from healthy volunteers vs. 6 NPC plasma samples) were analyzed by principal component analysis (PCA), DESeq2, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and TargetScan. The differentially expressed miRNAs (DEmiRNAs) were obtained from the dataset (GSE118720) downloaded from the Gene Expression Omnibus (GEO) repository. Additionally, the datasets downloaded from the GEO database (GSE12452, GSE13597, GSE53819, GSE64634) were used to predict the target genes and functions of hsa-miR-1301-3p. qPCR was applied to verify the differences in the expressions of hsa-miR-1301-3p between 10 normal plasma and 10 NPC plasma samples.ResultsWestern blot, TEM, and Nanoparticle Tracking Analysis showed adequate purity of the extracted exosomes. RNA-seq analysis revealed 21 upregulated miRNAs, and 10 downregulated miRNAs in plasma exosomes of early-stage NPC patients. GO analysis showed that the target genes of DEmiRNAs were mainly enriched in DNA synthesis and transcription regulation. KEGG analysis revealed that DEmiRNAs were mainly enriched in PI3K-Akt and MAPK signaling pathways. Moreover, the expression of hsa-mir-1301-3p was verified to be significantly upregulated in enlarged samples of plasma exosomes.ConclusionsWe identified several DEmiRNAs extracted from tumor-derived exosomes between normal plasma and early-stage NPC plasma. Bioinformatics analyses indicated that these DEmiRNAs may be related to NPC development. Our study may provide novel insights into underlying biomarkers and mechanisms of plasma exosomes in early-stage NPC.

A Randomized Controlled Trial on Evaluation of Plasma Epstein-Barr Virus Biomarker for Early Diagnosis in Patients With Nasopharyngeal Carcinoma.

Early diagnosis of nasopharyngeal carcinoma (NPC) remains a major problem in Southern China. Epstein-Barr virus (EBV) biomarkers have been widely used in NPC screening. This study aims to evaluate the early diagnostic performances of individual EBV biomarkers in NPC. The levels of EBV biomarkers-IgA antibodies against EBV nuclear antigen 1 (EBNA1-IgA), EBV capsid antigen (VCA-IgA), EBV early antigen (EA-IgA), EBV BZLF1 transcription activator protein (Zta-IgA) and IgG antibodies against EBV BRLF1 transcription activator protein (Rta-IgG)-from 106 NPC patients (stage I and II) and 150 normal subjects were measured. VCA-IgA and EA-IgA were detected by immunofluorescence assay (IFA), EBNA1-IgA, Rta-IgG and Zta-IgA were measure by enzyme-linked immunosorbent assay (ELISA), and EBV DNA was detected by qPCR. Statistical analyses of a single index were conducted to evaluate the significance of NPC early diagnosis and TNM classification. The level of EBNA1-IgA, EBV DNA, VCA-IgA, EA-IgA, Rta-IgG and Zta-IgA in early-stage NPC was significantly higher than in healthy controls (all P < 0.001). EBNA1-IgA yielded the biggest area under the curve (AUC) of 0.962 in distinguishing early-stage NPC patients from the normal subjects, with a sensitivity of 91.5% and a specificity of 98.7%. However, EBV biomarker levels were not associated with tumor size (all P > 0.050), whereas four biomarker levels (EBNA1-IgA, EBV DNA, VCA-IgA, EA-IgA) were related to lymph node metastasis (N0 and N1-2), among which EBNA1-IgA and EBV DNA showed good performance. Finally, high correlation was found between VCA-IgA and EA-IgA (r > 0.800). A single EBNA1-IgA exhibits excellent discrimination performance in early diagnosis of NPC and could become a promising marker for NPC screening.

Abstract A02: The feedback loop among miR-449b-3p/ADAM17/NF-κB promotes metastasis in nasopharyngeal carcinoma

Abstract Emerging pieces of evidence have proved an important role of miRNAs in tumorigenesis and progression. However, the function of miRNAs in nasopharyngeal carcinoma (NPC) development remains poorly elucidated. Quantitative reverse transcription-polymerase chain was used to detect the expression level of miR-449b-3p in NPC cell lines and tissues. We performed cell viability assay, colony formation, flow cytometric, transwell assay, and wound-healing assay to assess the ability of cell proliferation, apoptosis, invasion, and migration in vitro, respectively. NPC xenograft tumor and lymph node metastatic mice model were conducted to validate the function of miR-449b-3p in vivo. Luciferase reporter assay, ChIP assay, and Western blot analysis were actualized to explore the mechanism underlying the miR-449b-3p on NPC metastasis. Here we showed that miR-449b-3p was downregulated in NPC specimens (p&amp;lt;0.001) and cells (p&amp;lt;0.05), and most of the patients with advanced-stage NPC had an impaired expression of miR-449b-3p, on the contrary, early-stage NPC patients had a high level of miR-449b-3p (p&amp;lt;0.001). Moreover, miR-449b-3p inhibited NPC metastasis both in vitro and in vivo. Further investigation revealed that a disintegrin and metalloproteinase 17 (ADAM17) was the direct target of miR-449b-3p. Rescue experiments suggested that the downregulation of ADAM17 in miR-449b-3p inhibited cells partially reversed the inhibition of cell invasion and migration. We also found that ADAM17 could conversely suppress the promoter activity and expression of miR-449b-3p via inducing NF-κB transcriptional activity. In conclusion, our study provides new insights into the mechanism underlying the invasion and metastasis in NPC. The novel miR-449b-3p/ADAM17/NF-κB feedback loop in NPC could potentially be a target for clinical treatment in NPC. Citation Format: Qian Fei, Ming-Yu Du, Ning Jiang, Li Yin, Xia He. The feedback loop among miR-449b-3p/ADAM17/NF-κB promotes metastasis in nasopharyngeal carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A02.

Rac1: A potential radiosensitization target of human nasopharyngeal carcinoma CNE2 cells

Radiotherapy has a high cure rate for early nasopharyngeal carcinoma(NPC). However, the radiation resistance of poorly differentiated NPC cells impacts the effectiveness of treatment of early-stage NPC patients. Here, we explored the relationship between Ras-related C3 botulinum toxin substrate 1(Rac1) expression and NPC radiosensitivity. In vitro and in vivo studies revealed that upregulation of Rac1, when combined with X-ray treatment, increased growth inhibition and induced remarkable morphological changes and apoptosis in CNE2 cells. Furthermore, rupturing of the cell and nuclear membranes, degeneration of the cristae and significant swelling of the mitochondria were observed, which were consistent with the high apoptotic rate. The Rac1(+) cells exhibited approximately 50% more migration compared with that of the NC and Rac1(-) cells. The overexpression of Rac1 can increase the radiation sensitivity of NPC CNE2 cells, and the mechanism may be closely related to the oxidative damage of mitochondria. Rac1 might be a potential target for radiosensitization in poorly differentiated NPC.

Neck skin dose planning for early-stage nasopharyngeal carcinoma: a comparative study of three radiotherapy methods

Objective To compare the neck skin dose between fixed-field dynamic intensity-modulated radiation therapy (dIMRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT) in the treatment of early-stage nasopharyngeal carcinoma. Methods A total of 16 early-stage nasopharyngeal carcinoma patients undergoing radiotherapy were enrolled as subjects. The neck skin was delineated by contraction of the outer edge of neck by 3 mm. Dose planning was made by the traditional method (TP group) and a new method (NP group), in which the neck skin was considered as the organ at risk. Dmean and V5-V70 for the neck skin were recorded. The paired t-test was used to analyze the differences between two plans in each radiotherapy method. An analysis of variance was used to compare the same plan between the three radiotherapy methods. Results The HT group had significantly higher Dmean and V5-V70 for the neck skin than the dIMRT group and the VMAT group (P=0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.02). Using dIMRT, the Dmean and V10-V60 for the neck skin were reduced by 7%, 8%, 22%, 25%, 38%, 59%, and 85% in the NP group than in the TP group (P=0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00). Using VMAT, the Dmean and V20-V40 for the neck skin were reduced by 4%, 19%, 29%, and 34% in the NP group than in the TP group (P=0.02, 0.01, 0.02, 0.01). Using HT, the V30-V60 for the neck skin were reduced by 20%, 29%, 50%, and 67% in the NP group than in the TP group (P=0.00, 0.00, 0.00, 0.00, 0.03). Conclusions In the treatment of early-stage nasopharyngeal carcinoma, HT causes a higher radiation dose to the neck skin than dIMRT and VMAT, while dIMRT and VMAT have similar neck skin doses. The neck skin dose can be significantly reduced with the neck skin as the organ at risk. Key words: Nasopharyngeal neoplasms/dynamic intensity-modulated radiation therapy; Nasopharyngeal neoplasms/volumetric modulated arc therapy; Nasopharyngeal neoplasms/helical tomotherapy; Skin dose

Chemokine CCL27 is a novel plasma biomarker for identification the nasopharyngeal carcinoma patients from the Epstein-Barr virus capsid antigen-specific IgA seropositive population

BackgroundTo investigate the predictive value of chemokine CCL27 for identifying early stage nasopharyngeal carcinoma (NPC) patients within a population seropositive for Epstein-Barr virus (EBV) capsid antigen-specific IgA (VCA-IgA).MethodsCCL27 in plasma samples from 104 NPC patients, 112 VCA-IgA–positive healthy donors, and 140 VCA-IgA–negative normal subjects was measured by ELISA. Expression of CCL27 in nasopharyngeal tissue from 20 VCA-IgA–positive healthy donors and 20 NPC patients was examined by immunohistochemical staining.ResultsLevels of CCL27 in the plasma of VCA-IgA–positive healthy donors (607.33 ± 218.81 pg/ml) were significantly higher than the levels in all NPC patients (437.09 ± 217.74, P = < 0.0001) and in the subset of patients with early stage NPC (463.85 ± 226.17, P = 0.0126). Plasma CCL27 levels were significantly lower in the VCA-IgA–negative normal subjects (358.22 ± 133.15 pg/ml) than in either the VCA-IgA–positive healthy donors (P < 0.0001) or the NPC patients (P = 0.0113). CCL27 protein was detected in 16 of 20 (80%) nasopharyngeal tissue samples from VCA-IgA–positive healthy donors and in 3 of 20 (15%) tumor tissue samples from NPC patients. There was no relationship between CCL27 levels and VCA-IgA titers or plasma EBV DNA content. Receiver operating characteristic (ROC) curves demonstrated that plasma CCL27 levels had a sensitivity of 67.00%, a specificity of 73.10%, and an area under the ROC of 0.725 (95% confidence interval [CI]: 0.657–0.793) for distinguishing between NPC patients and VCA-IgA–positive healthy donors. Further analysis showed that CCL27 levels could distinguish between early stage NPC patients and VCA-IgA–positive healthy donors with an area under the ROC of 0.712 (95% CI: 0.560–0.865), a sensitivity of 59.80%, and a specificity of 84.60%.ConclusionsChemokine CCL27 could successfully identify NPC patients within a VCA-IgA–positive population.

Label-Free Classification of a Nasopharyngeal Carcinoma Tissue Test at Different Stages Based on Raman Spectroscopy.

Raman spectroscopy (RS) of nasopharyngeal carcinoma (NPC) tissue provides substantial biomolecular information and various biomedicine features for tissue at different stages of cancer development. This study suggested an automatic and quick method for the classification of Raman spectra at different stages of NPC by multivariate statistical analysis. During RS measurement, Raman spectra were acquired from all NPC tissues in two groups of samples: 30 early-stage NPC patients (stages I and II) and 46 advanced-stage NPC patients (stages III and IV). In addition, a tentative diagnostic algorithm comprising principal components analysis and support vector machine was used to effectively classify multivariate data from the Raman spectra to yield sensitivities (70%; 21 of 30 samples) and specificities (91%; 42 of 46 samples) by the leave-one-out cross-validation method. Meaningful chemical compositions in the classification process were then deduced by analyzing the classified mathematical model. This beneficial work provides a great potential clinical method for the automatic classification of NPC stages and the speculation of the chemical compositions for NPC staging.

Distinctive microRNA expression in early stage nasopharyngeal carcinoma patients

The goal of this study was to investigate microRNAs (miRs) expression at different stages of nasopharyngeal carcinoma (NPC). MiR expression profiling at various stages of NPC was performed by miR array and further verified using quantitative real‐time RT‐PCR. Pathway enrichment analysis was carried out to identify the functional pathways regulated by the miRs. The expression of a selected group of identified miRs was verified in stage I NPC by in situ hybridization (ISH). A total of 449 miRs were identified with significantly different expressions between NPC tissues and normal pharyngeal tissues. Eighty‐four miRs were dysregulated only in stage I NPC, among which 45 miRs were up‐regulated and the other 39 were down‐regulated. Pathway enrichment assay revleaed that three significantly down‐regulated and three significantly up‐regulated miRs involved in 12 pathways associating with tumour formation and progression. Quantitative RT‐PCR confirmed the miR array result. In addition, the low expression levels of hsa‐miR‐4324, hsa‐miR‐203a and hsa‐miR‐199b‐5p were further validated in stage I NPC by ISH. This present study identifed the miR signature in stage I NPC, providing the basis for early detection and treatment of NPC.

Abstract 4773: Aberrant methylation at chromosome 6p as novel biomarkers for diagnosis and prognosis of nasopharyngeal carcinoma

Abstract Background: Nasopharyngeal carcinoma (NPC) has the highest incidence in Guangdong province and Hong Kong in Southern China. Early detection of NPC is necessary to improve patient survival. Although aberrant methylation at promoter region of the tumour suppressors were often reported in NPC, genome-wide methylation changes have not been comprehensively investigated. Aim: We aimed to examine the methylation profile of NPC patient tumours using a high-throughput approach to discover candidate biomarkers for early detection of NPC. Methods: We systematically analyzed methylome data in the primary tumours and matched normal adjacent tissues from 25 NPC patients collected by Area of Excellence (AoE) NPC Tissue Bank using the Illumina HumanMethylation450 BeadChip platform. Comparatively, methylome data of solid tumours including prostate cancer, invasive breast cancer, pancreatic cancer, kidney cancer, thyroid cancer, liver cancer, rectal cancer, colon cancer, head and neck cancer, lung adenocarcinoma and lung squamous cell carcinoma collected by The Cancer Genome Atlas (TCGA) were examined. A quantitative method, bisulfite pyrosequencing, was applied to evaluate the aberrant methylation in an independent NPC patient cohort. Results: In NPC, the hypermethylation pattern was more dominant than hypomethylation, where over 90% of the differentially methylated loci were hypermethylated within or close to CpG islands in tumours. The comparative methylome analysis reveals aberrant methylation at chromosome 6p frequently occurred in NPC (FDR = 1.33×10-9), but was rare in other types of solid tumours. Evident enrichment of the repressive mark H3K27me3 was found at this region, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation. Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort, and 76.9% of the early-stage NPC patients can be detected by aberrant methylation on 6p. Furthermore, aberrant methylation at this region was observed in NPC recurrent tumours and matched metastatic lymph nodes, indicating the potential use of genes in this region for prognosis. Conclusion: Our study highlights the importance of epigenetic deregulation in NPC. A novel genomic region on 6p with aberrant methylation was identified. This region contains several important genes that have great potential to be used as biomarkers for NPC early detection. The global genome-wide unbiased approach is useful to discover potential biomarkers for early diagnosis and prognosis in cancers. Acknowledgements: NPC AoE funding was provided by the Hong Kong Research Grants Council (AoE/M-06/08) to MLL and HKU Small Project Funding to WD. Citation Format: Wei Dai, Arthur Kwok Leung Cheung, Josephine Mun Yee Ko, Hong Zheng, Yue Cheng, Roger Kai Cheong Ngan, Wai Tong Ng, Anne Wing Mui Lee, Chun Chung Yau, Victor Ho Fu Lee, Maria Li Lung. Aberrant methylation at chromosome 6p as novel biomarkers for diagnosis and prognosis of nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4773. doi:10.1158/1538-7445.AM2015-4773

Combination of autoantibodies against NY-ESO-1 and viral capsid antigen immunoglobulin A for improved detection of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China and Southeast Asia, and early detection remains a challenge. Autoantibodies have been found to precede the manifestations of symptomatic cancer by several months to years, making their identification of particular relevance for early detection. In the present study, the diagnostic value of serum autoantibodies against NY-ESO-1 in NPC patients was evaluated. The study included 112 patients with NPC and 138 normal controls. Serum levels of autoantibodies against NY-ESO-1 and classical Epstein-Barr virus marker, viral capsid antigen immunoglobulin A (VCA-IgA), were measured by enzyme-linked immunosorbent assay. Measurement of autoantibodies against NY-ESO-1 and VCA-IgA demonstrated a sensitivity/specificity of 42.9/94.9% [95% confidence interval (CI), 33.7–52.6/89.4–97.8%] and 55.4/95.7% (95% CI, 45.7–64.7/90.4–98.2%), respectively. The area under receiver operating characteristic curve for autoantibodies against NY-ESO-1 (0.821; 95% CI, 0.771–0.871) was marginally lower than that for VCA-IgA (0.860; 95% CI, 0.810–0.910) in NPC. The combination of autoantibodies against NY-ESO-1 and VCA-IgA yielded an enhanced sensitivity of 80.4% (95% CI, 71.6–87.0%) and a specificity of 90.6% (95% CI, 84.1–94.7%). Moreover, detection of autoantibodies against NY-ESO-1 could differentiate early-stage NPC patients from normal controls. Our results suggest that autoantibodies against NY-ESO-1 may serve as a potential biomarker, as a supplement to VCA-IgA, for the screening and diagnosis of NPC.

Intensity-modulated radiotherapy combined with chemotherapy for early-stage nasopharyngeal carcinoma patients in northwest China

Objective To evaluate the therapeutic efficacy and prognostic factors of intensity-modulated radiotherapy combined with chemotherapy for early-stage nasopharyngeal carcinoma patients in northwest China. Methods From January 2006 to December 2009,58 patients with early-stage nasopharyngeal carcinoma were treated with IMRT in Xijing hospital,the clinical data were analyzed retrospectively.Survival rates was calculated by the Kaplan-Meier method and the differences was compared by the Logrank test.Univariate analysis method was use to identify all significant factors.Results The follow-up rate was 100％.The follow-up time of 46 patients was more than 3 years.The 1-,2 and 3-year survival were 98％,94％ and 91％,respectively.The 3-year overall survival (OS),local recurrence-free survival (LRFS),distant metastasis-free surv ival (DMFS) for T1N0-1,T2N0 and T2N1 stage were 100％,100％,100％ and 74 ％,81％,87 ％,respectively ( x2 =5.74,P =0.01 ; x2 =4.95,P =0.03 ; x2 =4.24,P=0.04).The 3-year OS,LRFS,DMFS for IMRT combined with chemotherapy and IMRT alone were 100％,100％,100％ and 85％,85％,88％ respectively ( x2 =4.02,P =0.04; x2 =4.12,P =0.03 ; x2 =4.84,P =0.02).In T2N1 stage,IMRT combined with chemotherapy and IMRT alone were 100％,100％,100％ and 79％,79％,80％ respectively (x2 =5.28,P =0.03 ;x2 =4.84,P =0.04;x2 =4.72,P =0.04).In univariate analysis,N stage,clinical stage,IMRT combined with chemotherapy were significantly associated with the survival ( x2 =5.39,P =0.02 ; x2 =5.74,P =0.01 ; x2 =4.02,P =0.04).Conclusions In all early-stage nasopharyngeal carcinoma,T2N1 stage is a sub-group of high risk of distant metastasis.Combination of IMRT and chemotherapy may improve the LRFS,DMFS and OS in those patients. Key words: Nasopharyngeal neoplasms in northwest China; Nasopharyngeal neoplasms/intensity-modulated radiotherapy; Nasopharyngeal neoplasms/chemotherapy; Prognosis

Establishment of VCA and EBNA1 IgA‐based combination by enzyme‐linked immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a two‐stage design with a preliminary performance study and a mass screening in southern China

A two-stage study was conducted in southern China to determine and validate an optimal combination of Epstein-Barr virus (EBV)-related seromarkers for nasopharyngeal carcinoma (NPC) screening. In the first stage, six seromarkers [VCA-IgA, EA-IgA, Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA), EBNA1-IgG, Zta-IgA and Rta-IgG] were detected by enzyme-linked immunosorbent assay (ELISA) and two traditional NPC screening seromarkers (VCA-IgA and EA-IgA) were detected by immunofluorescence assay (IFA) in serum samples from 191 NPC patients and 337 controls. An optimal combination of seromarkers for NPC diagnosis was selected using logistic regression models. Results showed that the diagnostic performances of VCA-IgA and EA-IgA tested by ELISA were superior to the performances of the same seromarkers by IFA. VCA-IgA combined with EBNA1-IgA by ELISA was identified as the optimal combination, with an area under the receiver operating characteristic (ROC) curve (AUC) up to 0.97, a sensitivity of 95.3% and a specificity of 94.1% for classification of NPCs vs. controls. In the second stage, 5,481 participants aged 30-59 years and without clinical evidence of NPC were recruited into a population-based NPC screening program from May 2008 to February 2009 in Sihui City, China. Their sera were tested simultaneously by both the new and the traditional screening schemes and eight early stage NPC patients were subsequently histopathologically confirmed. The traditional and the new screening schemes had comparable specificity (estimated as 98.5%), but the sensitivity of the new scheme (75.0%) was significantly higher than that of the traditional one (25.0%). The combination of VCA-IgA and EBNA1-IgA by ELISA outperforms the traditional NPC screening scheme and could become the preferred serodiagnostic strategy for NPC screening in high-incidence areas.

Treatment outcomes for different subgroups of nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy

Although many studies have investigated intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), sample sizes in the reported studies are usually small and different in outcomes in different T and N subgroups are seldom analyzed. Herein, we evaluated the outcomes of NPC patients treated with IMRT and further explored treatment strategy to improve such outcome. We collected clinical data of 865 NPC patients treated with IMRT alone or in combination with chemotherapy, and classified all cases into the following prognostic categories according to different TNM stages: early stage group (T1–2N0–1M0), advanced local disease group (T3–4N0–1M0), advanced nodal disease group (T1–2N2–3M0), and advanced locoregional disease group (T3–4N2–3M0). The 5-year overall survival (OS), local relapse-free survival (LRFS), and distant metastases-free survival (DMFS) were 83.0%, 90.4%, and 84.0% respectively. The early disease group had the lowest treatment failure rate, with a 5-year OS of 95.6%. The advanced local disease group and advanced nodal disease group had similar failure pattern and treatment outcomes as well as similar hazard ratios for death (4.230 and 4.625, respectively). The advanced locoregional disease group had the highest incidence of relapse and death, with a 5-year DMFS and OS of 62.3% and 62.2%, respectively, and a hazard ratio for death of 10.402. Comparing with IMRT alone, IMRT in combination with chemotherapy provided no significant benefit to locoregionally advanced NPC. Our results suggest that the decision of treatment strategy for NPC patients should consider combinations of T and N stages, and that IMRT alone for early stage NPC patients can produce satisfactory results. However, for advanced local, nodal, and locoregional disease groups, a combination of chemotherapy and radiotherapy is recommended.

Long-Term Outcomes of Early-Stage Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiotherapy Alone

Reports of intensity-modulated radiotherapy (IMRT) for early-stage nasopharyngeal carcinoma (NPC) have been limited. The present study evaluated the long-term survival outcomes and toxicity of early-stage NPC patients treated with IMRT alone. Between February 2001 and January 2008, 198 early-stage (T1-T2bN0-N1M0) NPC patients had undergone IMRT alone. The data from these patients were retrospectively analyzed. The patients were treated to 68 Gy at 2.27 Gy/fraction prescribed to the planning target volume of the primary nasopharygeal gross tumor volume. The Radiation Therapy Oncology Group scoring system was used to assess the toxicity. At a median follow-up of 50.9 months (range, 12-104), the 5-year estimated disease-specific survival, local recurrence-free survival, and distant metastasis-free survival rate was 97.3%, 97.7%, and 97.8%, respectively. The 5-year local recurrence-free survival rate was 100% for those with Stage T1 and T2a and 94.2% for those with Stage T2b lesions (p = 0.252). The 5-year distant metastasis-free survival rate for Stage T1N0, T2N0, T1N1, and T2N1 patients was 100%, 98.8%, 100%, and 93.8%, respectively (p = .073). All local recurrence occurred in patients with T2b lesions. Five patients developed distant metastasis. Of these 5 patients, 4 had had Stage T2bN1 disease and 1 had had Stage T2bN0 disease with retropharyngeal lymph node involvement. The most common acute toxicities were mainly Grade 1 or 2. At 24 months after IMRT, no Grade 3 or 4 xerostomia had developed, and 62 (96.9%) of 64 evaluated patients were free of trismus; only 2 patients (3.1%) had Grade 1 trismus. Radiation encephalopathy and cranial nerve injury were not observed. IMRT alone for Stage T1N0, T2N0, T1N1, and T2N1 yielded satisfactory survival outcomes with acceptable toxicity, and no differences were found in survival outcomes among these four subgroups. Patients with Stage T2b lesions might have relatively greater risk of local recurrence and those with T2bN1 disease mighth have a greater risk of distant metastasis.

Treatment Outcomes for Radiotherapy Alone are Comparable With Neoadjuvant Chemotherapy Followed by Radiotherapy in Early‐Stage Nasopharyngeal Carcinoma

To analyze the impact of neoadjuvant chemotherapy (CT) on the treatment of early-stage nasopharyngeal carcinoma (NPC) as compared with radiotherapy (RT) alone. We analyzed retrospectively the outcome of 60 previously untreated and histologically confirmed early-stage NPC patients treated with either RT alone or with neoadjuvant CT followed by RT (CT/RT) at the Seoul National University Hospital between 1986 and 2004. Neoadjuvant CT consisted of three cycles with 5-fluourouracil and cisplatin. RT was given to the nasopharynx and neck nodes. The median dose to the primary site, involved nodes, and elective nodes was 70.2 Gy, 63 Gy, and 45 Gy, respectively. According to the 1997 American Joint Committee on Cancer staging system, 9 patients had stage I or IIA disease, and 22 patients had stage IIB disease in the RT group. For the CT/RT group, 8 patients had stage I or IIA disease, and 21 patients had stage IIB disease. The median follow-up for all patients was 124.5 (range, 5-239) months. The 5-year locoregional failure-free (LRFF), distant metastasis-free (DMF), disease-free survival (DFS), and overall survival (OS) rate was 84%, 93%, 81%, and 84% for the RT group and 77%, 86%, 71%, and 79% for the CT/RT group, respectively. There were no significant differences in LRFF (P = .728), DMF (P = .433), DFS (P = .562), and OS (P = .625) rates between the RT and CT/RT groups. Multivariate analysis revealed that delaying RT for more than 81 days was significantly associated with an increased risk of locoregional failure in the subgroup of patients with stage IIB disease (P = .044). In our retrospective analysis, the use of neoadjuvant CT showed no additional benefit to treatment with RT alone. Neoadjuvant CT may cause deleterious effect on stage IIB disease by delaying RT.