Purpose: To explore the clinical characteristics of bone metastasis (BM) in a large sample of preliminarily diagnosed nasopharyngeal carcinomas (NPCs). Methods: The sample consisted of 1,031 patients diagnosed with NPC at first visitg clinics between October 1989 and June 2012. Several parameters including metastasis locus, T/N staging, diagnosis, therapy and prognosis of BM were analyzed retrospectively. Results: In 70 patients who had been preliminarily diagnosed with BM, the incidence of BM in N0, N1, N2 and N3 stage was 5.7%, 17.2%, 50.2%, and 25.7%, respectively, while the incidence in T0, T1, T2 and T3 stage was 0%, 23.8%, 47.6% and 28.6% respectively. BM occurred in most common in vertebral column, rib, sternum, ilium and femur. Positive rate of Epstein-Barr virus antibody was 77.6%. The median survival time was 12 months. Conclusion: The incidence of BM in NPC preliminarily diagnosed is about 7% and it is related to N classification but not T classification.
Purpose: the study aimed to compare the quality of life (QOL) and radiotherapy complications among Chinese nasopharyngeal carcinoma (NPC) patients at different 3-dimensional conformal radiotherapy (3DCRT) stages adjusting for other variables. Methods: 511 NPC patients at different 3DCRT stages were enrolled. They were interviewed regarding SF-36, complications and socio-demographic variables and cancer- or treatment-related variables. Analysis of covariance (ANCOVA) based on SF-36, complications scores as dependent variables, 3DCRT stages as independent variables, and other variables as covariate were established. Results: The influencing factors of PCS included 3DCRT stages and age group. The influencing factors of MCS included 3DCRT stages and income. Most QOL scores of NPC patients were significantly associated with 3DCRT stage, after accounting for other variables. QOL scores of the patients receiving 3DCRT were the lowest, QOL scores of people after 3DCRT gradually increased. PCS scores of people greater than 5 years after 3DCRT was improved to or even better than the level before 3DCRT. The complications with significantly different scores of patients at different 3DCRT status included xerostomia, throat ache, hypogeusia, caries, hearing loss, snuffles. Conclusions: Clinicians should pay more attention to older NPC patients and patients with lower income. When patients receive 3DCRT, measures should be taken to reduce radiation injury to improve the patients' QOL.
Objective: To make sure the feasibility with $^{18F}FDG$ PET/CT to guided dynamic intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma patients, by dosimetric verification before treatment. Methods: Chose 11 patients in III~IVA nasopharyngeal carcinoma treated with functional image-guided IMRT and absolute and relative dosimetric verification by Varian 23EX LA, ionization chamber, 2DICA of I'mRT Matrixx and IBA detachable phantom. Drawing outline and making treatment plan were by different imaging techniques (CT and $^{18F}FDG$ PET/CT). The dose distributions of the various regional were realized by SMART. Results: The absolute mean errors of interest area were $2.39%{\pm}0.66$ using 0.6cc ice chamber. Results using DTA method, the average relative dose measurements within our protocol (3%, 3 mm) were 87.64% at 300 MU/min in all filed. Conclusions: Dosimetric verification before IMRT is obligatory and necessary. Ionization chamber and 2DICA of I'mRT Matrixx was the effective dosimetric verification tool for primary focal hyper metabolism in functional image-guided dynamic IMRT for nasopharyngeal carcinoma. Our preliminary evidence indicates that functional image-guided dynamic IMRT is feasible.
Purpose: To evaluate acute toxicity in nasopharyngeal cancer (NPC) patients treated with intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) with or without cisplatin-based chemotherapy. Materials and Methods: A total of 45 newly diagnosed, histologically proven non-metastatic NPC patients treated with IMRT between May 2010 and December 2012, were evaluated retrospectively, 37 planned with Eclipse and 8 with Prowess Panther treatment planning system. The doses to the planning target volumes of primary tumor and involved lymph nodes, high risk region, and uninvolved regional nodal areas were 70 Gy, 60 Gy, and 54 Gy respectively and delivered simultaneously over 33 fractions to 39 patients. Another 6 patients irradiated with sequential boost technique. Some 84.4% of patients received chemotherapy. Acute toxicities were graded according to the Radiation Therapy Oncology Group scoring criteria and Common Terminology Criteria for Adverse Events (CTCAE) for chemotherapy side effects. Results: Median age was 43 years (14-79) and all patients were WHO type II. Grade 1 mucositis and dysphagia were observed in 17 (37.8%), and 10 (22.2%) patients, respectively. The incidence of acute grade 2 mucositis and dysphagia was 55.6% and 68.9%, respectively. The most common chemoradiotherapy related acute toxicities were nausea, leucopenia and thrombocytopenia. Grade 3 toxicity was detected in 13 (28.8%) cases. No grade 4 toxicity was occurred. Mean weight loss was 9%. None of the patients required the insertion of percutaneous endoscopic gastrostomy for nutritional support. Radiation therapy was completed without interruption in all patients. Conclusions: IMRT is a safe and effective treatment modality, and well tolerated by patients in the treatment of nasopharyngeal carcinoma. No unexpected side effects were observed.
MicroRNAs (miRNAs) play an essential role in the development and progression of nasopharyngeal carcinomas (NPC). Despite advances in the field of cancer molecular biology and biomarker discovery, the development of clinically validated biomarkers for primary NPC has remained elusive. In this study, we investigated the expression and clinical significance of miRNAs as novel primary NPC diagnostic biomarkers. We used an array containing 2, 500 miRNAs to identify 22 significant miRNAs, and these candidate miRNAs were validated using 67 fresh NPC and 25 normal control tissues via quantitative real-time PCR (qRT-PCR). Expression and correlation analyses were performed with various statistical approaches, in addition to logistic regression and receiver operating characteristic curve analyses to evaluate diagnostic efficacy. qRT-PCR revealed five differentially expressed miRNAs (miR-93-5p, miR-135b-5p, miR-205-5p and miR-183-5p) in NPC tissue samples relative to control samples (p<0.05), with miR-135b-5p and miR-205-5p being of significant diagnostic value (p<0.01). Moreover, comparison of NPC patient clinicopathologic data revealed a negative correlation between miR-93-5p and miR-183-5p expression levels and lymph node status (p<0.05). These findings display an altered expression of many miRNAs in NPC tissues, thus providing information pertinent to pathophysiological and diagnostic research. Ultimately, miR-135b-5p and miR-205-5p may be implicated as novel NPC candidate biomarkers, while miR-93-5p, miR-650 and miR-183-5p may find application as relevant clinical pathology and diagnostic candidate biomarkers.
Background: The purpose of this article is to present preliminary results of simultaneous boost irradiation radiotherapy for locally advanced nasopharyngeal carcinoma (NPC). Methods: Fifty-eight patients who underwent simultaneous boost irradiation radiotherapy for NPC in Cancer Center of Sun Yat-sen University between September 2004 and December 2009 were eligible. Acute and late toxicities were scored weekly according to the Radiation Therapy Oncology Group (RTOG) acute and late radiation morbidity scoring schemes. An especial focus was on evidence of post-radiation brain injury. Also quality of life was analysed according to the EORTC (European Organisation for Research and Treatment of Cancer) recommendations. Discrete variables were compared by ${\chi}^2$ test. The Kaplan-Meier method was used to calculate the survival rates and generate survival curves. Results: A total of 58 patients with a mean follow-up time of 36 months completed clinical trials.Fifty-seven patients (98.3) achieved complete remission in the primary sites and cervical lymph nodes, with only one patient (1.7%) showing partial remission.The most frequently observed acute toxicities during the concurrent chemoradiotherapy were mucositis and leucopenia. Four patients (6.9%) had RTOG grade 3 mucositis, whereas four patients (6.9%) had grade 3 leucopenia. No patient had grade 4 acute toxicity. Three (5.17%) of the patients exhibited injury to the brain on routine MRI examination, with a median observation of 32 months (range, 25-42months). All of them were RTOG grade 0. The 3-year overall, regional-free and distant metastasis-free survival rates were 85%, 94% and 91%, respectively. Conclusion: Simultaneous boost irradiation radiotherapy is feasible in patients with locally advanced nasopharyngeal carcinoma. The results showed excellent local control and overall survival, with no significant increase the incidence of radiation brain injury or the extent of damage. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.
Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor. We here investigated its effects on proliferation and apoptosis of the CNE2 carcinoma cell line, and attempted to establish genome-wide DNA methylation alteration due to differentially histone acetylation status. After cells were treated by TSA, the inhibitory rate of cell proliferation was examined with a CCK8 kit, and cell apoptosis was determined by flow cytometry. Compared to control, TSA inhibited CNE2 cell growth and induced apoptosis. Furthermore, TSA was found to induce genome-wide methylation alteration as assessed by genome-wide methylation array. Overall DNA methylation level of cells treated with TSA was higher than in controls. Function and pathway analysis revealed that many genes with methylation alteration were involved in key biological roles, such as apoptosis and cell proliferation. Three genes (DAP3, HSPB1 and CLDN) were independently confirmed by quantitative real-time PCR. Finally, we conclude that TSA inhibits CNE2 cell growth and induces apoptosis in vitro involving genome-wide DNA methylation alteration, so that it has promising application prospects in treatment of NPC in vivo. Although many unreported hypermethylated/hypomethylated genes should be further analyzed and validated, the pointers to new biomarkers and therapeutic strategies in the treatment of NPC should be stressed.
Nasopharyngeal carcinoma(NPC) is a disease whose primary initial treatment is radiation. Results of radiation therapy in early stage disease is promising; however, in stage IV disease, the best reported five-year survival is only about 30%. In patients with post-radiation recurrent disease, radiation controls only a small portion of patients, as well as being associated with significant radiation injury. In this paper we discuss the use of salvage treatment modalities for post-radiation recurrence. A retrospective chart review and analysis of salvage treatment results were performed for 39 patients with recurrent post-radiation NPC and positive cervical lymph nodes during the period beginning 1985 until 1995. Mean age of these patients was 52.3$\pm$10.37 years and male: female ratio was 1.8 : 1. Twenty patients were treated with salvage treatment, and ten patients were treated by salvage chemotherapy. A total of nine patients underwent surgical salvage treatment, including neck dissection(6), transnasal laser surgery and booster radiotherapy(2), and primary surgery(1). Salvage treatment were effective in reducing patients' pain in twenty patients (51.3%) and prolonging life in nine patients(23.1%); however, recurrence of disease within six months and/or residual disease by clinical or radiologic exam was noted in all patients receiving salvage radiotherapy, chemotherapy, laser surgery with radiotherapy, and primary site surgery. In the group undergoing salvage neck dissection, three patients(50%) were disease free for at least two years. Of the different modalities, radiotherapy was associated with the best quality of life while catastrophic salvage surgery resulting in insignificant prolongation of life was associated with the poorest quality of life. We conclude that salvage surgery is the optimal choice of treatment for regional recurrence such as nodal failure, however palliative salvage therapy could be preferred in other cases with recurrent post-radiation NPC.
Background and Purpose: Cisplatin is the most common chemotherapeutic agent for loco-regionally advanced nasopharyngeal carcinoma (NPC); however, toxicity is a limiting factor for some patients. We retrospectively compared the efficacy and toxicity of weekly docetaxel-based and cisplatin-based concurrent chemoradiotherapy in loco-regionally advanced NPC. Methods and Materials: Eighty-four patients with Stage III and IVA-B NPCs, treated between 2007 and 2008, were retrospectively analyzed. Thirty received weekly docetaxel-based concurrent chemotherapy, and 43 were given weekly cisplatin-based concurrent chemotherapy. Radiotherapy was administered using a conventional technique (seven weeks, 2.0 Gy per fraction, total dose 70-74 Gy) with 6-8 Gy boosts for some patients with locally advanced disease. Results: Median follow-up time was 42.3 months (range, 8.6-50.8 months). There were no significant differences in the 3-year loco-regional failure-free survival (85.6% vs. 92.3%; p=0.264), distant failure-free survival (87.0% vs. 92.5%; p=0.171), progression-free survival (85.7% vs. 88.4%; p=0.411) or overall survival (86.5% vs. 92.5%, p=0.298) of patients treated concurrently with docetaxel or cisplatin. Severe toxicity was not common in either group. Conclusions: Weekly docetaxel-based concurrent chemoradiotherapy is potentially effective and has a tolerable toxicity; however, further investigations are required to determine if docetaxel is superior to cisplatin for advanced stage NPC.
Treatment responses of $N_0$ stage nasopharyngeal carcinoma were firstly analyzed comprehensively to evaluate long term outcomes of patients and identify prognostic factors. A total of 610 patients with $N_0$ NPC, undergoing definitive radiotherapy to their primary lesion and prophylactic radiation to upper neck, were reviewed retrospectively. Concomitant chemotherapy was administrated to 65 out of the 610. Survival rates of the patients were calculated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were identified by the Cox regression model. The study revealed the 5-year and 10-year overall, disease-free, disease-specific, local failure-free, regional failure-free, locoregional failure-free and distant metastasis-free survival rates to be 78.7% and 66.8%, 68.8% and 55.8%, 79.9% and 70.4%, 81.2% and 72.5%, 95.8% and 91.8%, 78.3% and 68.5%, 88.5% and 85.5%, respectively. There were 192 patients experiencing failure (31.5%) after radiotherapy or chemoradiotherapy. Of these, local recurrence, regional relapse and distant metastases as the first event of failure occurred in 100 (100/610, 16.4%), 15(15/610, 2.5%) and 52 (52/610, 8.5%), respectively. Multivariate analysis showed that T stage was the only independent prognostic factor for patients with $N_0$ NPC (P=0.000). Late T stage (P=0.000), male (P=0.039) and anemia (P=0.007) were independently unfavorable factors predicting disease-free survival. After treatment, satisfactory outcome wasgenerally achieved in patients with $N_0$ NPC. Local recurrence represented the predominant mode of treatment failure, while T stage was the only independent prognostic factor for overall survival. Late T stage, male gender, and anemia independently predicted lower possibility of the disease-free survival.
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