Irradiation-induced nasopharyngeal necrosis (INN) in newly diagnosed nasopharyngeal carcinoma treated by intensity-modulated radiation therapy: clinical characteristics and the influence of treatment strategies.

PURPOSE: To define the clinical characteristics of irradiation-induced nasopharyngeal necrosis (INN) after intensity-modulated radiotherapy (IMRT) and identify the influence of treatment strategies on INN in primary nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: From 2008 to 2019, NPC patients pathologically diagnosed with INN after primary IMRT were reviewed. Those patients were matched with propensity scores for patients without INN in our center. The impact of treatment strategies on INN occurrence was assessed using univariate and multivariate logistic regression analysis. RESULTS: The incidence rate of INN was 1.9% among the primary NPC population, and 53 patients with INN were enrolled. Headache and foul odor were the main symptoms, and 71.7% of cases had pseudomembrane during or at the end of radiotherapy. All patients were in early or middle stage INN, and no one presented with skull-based osteoradionecrosis. Then 212 non-INN patients were included based on propensity scores match. Overall survival (p = 0.248) and progression-free survival (p = 0.266) curves were similar between the INN and non-INN groups. Treatment strategies including combining chemotherapy or molecular targeted therapy with radiotherapy were not associated with INN occurrence, while boost dose (OR 7.360; 95% CI 2.301-23.547; p = 0.001) was a predictor factor for it. However, the optimal threshold for an accumulated dose to predict INN's occurrence was failed to determine. CONCLUSION: In the IMRT era, the severity of INN in primary NPC patients is lessened. This study showed that treatment strategies contributed little to develop INN, while the accumulated dose of radiation may relate to its occurrence.

Influence of computed tomographic dimensions of the nasopharynx on middle ear effusion and inflammation in pugs and French bulldogs with brachycephalic airway syndrome.

OBJECTIVE: To compare the prevalence of middle ear abnormalities in pugs and in French bulldogs and evaluate the influence of nasopharyngeal dimensions on middle ear effusion. STUDY DESIGN: Retrospective study. ANIMALS: Thirty pugs and 30 French bulldogs with brachycephalic airway syndrome and no known history of ear disease. METHODS: Computed tomographic (CT) studies were reviewed for middle ear effusion, mucosal contrast enhancement, signs of osteitis, and tympanic wall thickness. Soft palate thickness and cross-sectional areas of the nasopharynx at the opening of the auditory tube were measured and normalized to each individual's skull index before statistical comparison between breeds. Statistical dependence of middle ear abnormalities and nasopharyngeal dimensions was assessed by using Spearman's rank correlation tests. RESULTS: Middle ear effusion was observed in 17 of 30 (56.7%) French bulldogs and five of 30 (16.7%) pugs. Contrast enhancement of the tympanic bulla was noted in 25 of 60 (41.6%) French bulldog ears and three of 60 (5.0%) pug ears. The cross-sectional airway dimensions (difference [Δ] = 0.31 cm2 , P < .0001) and soft palate thickness (Δ = 0.44 cm, P < .0001) were reduced in pugs compared with in French bulldogs. Weak correlations were detected between soft palate thickness and nasopharyngeal dimensions and presence of tympanic bulla effusion (r = 0.324 and r = 0.198, respectively) or contrast enhancement (r = 0.270 and r = 0.199, respectively). CONCLUSION: Middle ear effusion and inflammation were more common in French bulldogs than in pugs and did not seem related to nasopharyngeal dimensions. CLINICAL SIGNIFICANCE: French bulldogs with brachycephalic airway syndrome seem predisposed to middle ear effusion and inflammation.

Radiation Therapy-Induced Changes of the Nasopharyngeal Commensal Microbiome in Nasopharyngeal Carcinoma Patients.

PURPOSE: The human commensal microbiome has been suggested to be involved in the regulation of response to anticancer therapies. However, little is known regarding changes in commensal microbes in patients with cancer during radiation therapy. We conducted a prospective, longitudinal proof-of-concept cohort study with patients with newly diagnosed nasopharyngeal carcinoma (NPC) who underwent radiation therapy-based treatment. METHODS AND MATERIALS: Nasopharyngeal swabs were collected before radiation therapy, twice per week during radiation therapy, and after radiation therapy. The nasopharyngeal microbiome was assessed using 16S rRNA amplicon sequencing. A patient's response to treatment was measured 3 months after the completion of radiation therapy as a short-term clinical outcome. In total, 39 NPC patients with 445 nasopharyngeal samples were analyzed. RESULTS: There was stable temporal change in the community structure of the nasopharyngeal microbiome among patients with NPC during treatment (P = .0005). Among 73 abundant amplicon sequence variants (ASVs), 7 ASVs assigned to genus Corynebacterium decreased significantly during the treatment (W-statistic >80%); 23 ASVs showed statistically significant changes in the ratio of abundance between early and late responders during treatment (false discovery rate <0.05). CONCLUSIONS: This study addressed stable temporal change in the nasopharyngeal microbiome among patients with NPC during radiation therapy-based treatment and provided preliminary evidence of an association with a short-term clinical outcome.

Dosimetric parameters predict radiation-induced choanal stenosis in patients with nasopharyngeal carcinoma.

BACKGROUND: Radiation-induced choanal stenosis (RICS) severely decreases life quality of patients with nasopharyngeal carcinoma (NPC) and originates from nasal mucositis, which depends on radiation dose. This self-controlled study aimed to find the correlations between dosimetric parameters and RICS. METHODS: Totally 49 NPC patients treated with intensity-modulated radiotherapy from May 2010 to Aug. 2013 and diagnosed with RICS during follow-up were enrolled into this study. Minimum point dose, maximum point dose, mean dose (Dmean), dose covering ≥33% volume (D33), dose covering ≥66% volume (D66), and volume receiving ≥60 Gy (V60) were compared between the nasal cavities with and without RICS, through paired t-test. The parameters with difference would enter receiver operating characteristic analysis to determine their cutoff values. Then predicting abilities of the cutoff values were tested by Chi-square test. RESULT: The nasal cavities with RICS appeared to have higher Dmean, D33, D66 and V60, compared with those without RICS (P values were 0.014, 0.003, 0.006 and 0.010). Dmean ≥54.22 Gy, D33 ≥ 61.96 Gy, D66 ≥ 46.50 Gy and V60 ≥ 48.13% were demonstrated to be related with a higher risk of RICS. CONCLUSION: Dmean, D33, D66 and V60 of nasal cavity might be used as predictors of RICS. Their values needed to be controlled whenever possible, for ameliorating life quality of NPC patients.

Microbial etiology, susceptibility profile of postradiation nasopharyngeal necrosis patients with nasopharyngeal carcinoma.

OBJECTIVE: Postradiation nasopharyngeal necrosis (PRNN) is a notorious complication after radiotherapy that affects prognosis in patients with nasopharyngeal carcinoma (NPC). It is important for clinical doctors to realize this problem in order to cope with this severe clinical situation. The aim of our study was to assess the bacteriology of PRNN and to demonstrate the antimicrobial susceptibility pattern that should guide the clinicians towards more appropriate antibiotic use. METHODS: Sixty-nine NPC patients with PRNN in our department between March 2013 and December 2017 were retrospectively enrolled. Pathogenic culture and drug sensitivity test were performed in these 69 NPC patients with PRNN. The infection rate of Pathogens and the sensitivity of the drugs were analyzed based on these results. RESULTS: Sixty-nine NPC patients with PRNN were enrolled in our study. Pathogens were identified in 58 (84%) patients. Of the 58 patients, Staphylococcus aureus was isolated in 34 (58.6%) patients. And the second most common group of bacterial isolates was Pseudomonas aeruginosa. Antibiotic sensitivity showed that Levofloxacin was the highest (88.5%), followed by Ciprofloxacin (85.2%) and Gentamicin (80.3%). The only pathologic fungus was Candidaalbicans, about 6.8%. The positive rates of bacterial and fungal culture in PRNN patients were not significantly different from the patients' gender, age, stage, number of radiotherapy courses (P>0.05), but the cure rate was statistically higher in culture-negative patients in comparison with culture-positive patients (63.6% vs 20.7%, P=0.011). CONCLUSION: Our results provide an overall picture of the microbiology and drug susceptibility patterns for NPC patients with PRNN and could help implement guidelines for more rational treatment and improve therapeutic outcome.

Hopkins criteria for residual disease assessment after definitive radiotherapy in nasopharyngeal carcinoma.

OBJECTIVES: Assessment of viable tumor residue after definitive radiotherapy is essential in patients with nasopharyngeal carcinoma (NPC). This study aimed to investigate the use of Hopkins criteria on positron emission tomography/computed tomography (PET/CT) for posttreatment response evaluation and whether plasma Epstein-Barr virus (EBV) DNA could bring additional value. MATERIALS AND METHODS: NPC patients who underwent FDG-PET/CT scan within 26 weeks after definitive radiotherapy were retrospectively reviewed. Residual disease was evaluated by Hopkins 5-point score. Accuracy of Hopkins criteria before and after incorporating EBV DNA was calculated. Prognostic value for locoregional failure-free survival (LRFFS) and disease-free survival (DFS) was analyzed. RESULTS: One hundred and sixteen patients were evaluated. Median follow-up time was 28.3 months (range 3.3-92.0 months). Residual disease was found in 19 (16.4%) patients. Overall, Hopkins criteria had high specificity (86.6%; 95% CI, 78.2%-92.7%) and negative prognostic value (NPV) (94.4%; 95% CI, 88.7%-97.3%), while sensitivity and positive prognostic value (PPV) was 73.7% (95% CI, 48.8%-90.9%), 51.9% (95% CI, 37.8%-65.6%), respectively. Posttreatment plasma EBV DNA was not predictive of residual tumor (P = .272). PPV and accuracy were 50.0% (95% CI, 32.1%-67.9%) and 83.0% (95% CI, 73.8%-90.0%) after incorporating detectable EBV DNA into the scoring system. Positive PET/CT results were significantly correlated with inferior 3-year LRFFS (95.7% vs 79.5%, P = .043) and 3-year DFS (84.6% vs 54.4%, P = .028). CONCLUSIONS: The Hopkins criteria demonstrated high NPV and specificity in posttreatment assessment, with the potential to be a reliable prognostic indicator for locoregional failure. Combining EBV DNA with PET/CT did not improve diagnostic accuracies. PET/CT should not be performed less than 12 weeks after treatment.

Comparison of multi-institutional pre-treatment verification for VMAT of nasopharynx with delivery errors.

PURPOSE: Measurement-based pre-treatment verification with phantoms frequently uses gamma analysis to assess acceptable delivery accuracy. This study evaluates the sensitivity of a commercial system to simulated machine errors for three different institutions' Volumetric Modulated Arc Therapy (VMAT) planning approaches. METHODS: VMAT plans were generated for ten patients at three institutions using each institution's own protocol (manually-planned at institution 1; auto-planned at institutions 2 and 3). Errors in Multi-Leaf Collimator (MLC) field size (FS), MLC shift (S), and collimator angle (C) of -5, -2, -1, 1, 2 and 5 mm or degrees were introduced. Dose metric constraints discriminated which error magnitudes were considered unacceptable. The smallest magnitude error treatment plans deemed clinically unacceptable (typically for a 5% dose change) were delivered to the ArcCHECK for all institutions, and with a high-dose point ion chamber measurement in 2 institutions. Error detection for different gamma analysis criteria was compared. RESULTS: Not all deliberately introduced VMAT plan errors were detected using a typical 3D 3%/3 mm global gamma pass rate of 95%. Considering all institutions, gamma analysis was least sensitive to negative FS errors. The most sensitive was a 2%/2 mm global analysis for institution 1, whilst for institution 2 it was 3%/3 mm global analysis. The majority of errors (58/59 for institution 1, 54/60 for institution 3) were detected using ArcCHECK and ion chamber measurements combined. CONCLUSIONS: Not all clinically unacceptable errors are detected. Combining ion chamber measurements with gamma analysis improved sensitivity and is recommended. Optimum gamma settings varied across institutions.

miR-206 enhances nasopharyngeal carcinoma radiosensitivity by targeting IGF1.

Radioresistance remains a major problem in nasopharyngeal carcinoma (NPC) treatment. However, the underlying molecular mechanisms of NPC radioresistance remain poorly understood. The present study aimed to investigate the potential role and mechanism of miR-206 in NPC radioresistance. We observed that miR-206 was down-regulated in radioresistant NPC cells. Furthermore, restoration of miR-206 in CNE2-IR cells suppressed enhanced radiosensitivity of NPC cells. In contrast, inhibition of miR-206 in CNE2 cells reduced the radiosensitivity. We also found that miR-206 directly targeted IGF1 and inhibited the PI3K/AKT pathway. Our data demonstrate that miR-206 sensitizes NPC cell to irradiation by targeting IGF1, highlighting the therapeutic potential of miR-206 in NPC radiosensitization.

A retrospective study of 606 cases of nasopharyngeal carcinoma with or without oropharyngeal candidiasis during radiotherapy.

BACKGROUND: To evaluate the clinical characteristics, treatment-related toxicities and survival in patients with nasopharyngeal carcinoma (NPC) with or without oropharyngealcandidiasis (OPC) during radiotherapy. METHODS: The current study was conducted with NPC patients undergoing radiotherapy at Sun Yat-Sen University Cancer Center between June 2011 and May 2012. A clinical diagnosis of candidiasis was determined on the basis of a positive potassium hydroxide (KOH) test and the presence of pseudomembranous (white) form of candidal overgrowth. The Cox proportional hazard regression model was used to test the association of OPC and related survival rates. RESULTS: Compared with the non-OPC group, the OPC group had significantly increased occurrence rates of grade 3-4 mucositis (14.5% vs. 7.4%, P = 0.049), anaemia (11.3% vs. 4.4%, P = 0.020), hepatotoxicity (4.8% vs. 1.1%, P = 0.021) and critical weight loss (85.5% vs. 56.6%, P<0.001) during radiotherapy. The OPC group had a significantly lower disease-free survival (DFS) (70.9% vs. 82.6%, P = 0.012), mainly as a result of a reduction in locoregional relapse-free survival (LRFS) (87.0%vs. 94.9%, P = 0.025). After stratification by T stage, the 5-year DFS in T3-4 patients were 82.0% and 68.8% in non-OPC and OPC groups, respectively (P = 0.022). Multivariate analyses indicated that OPC was a prognostic factor for LRFS and DFS. CONCLUSIONS: OPC during radiotherapy may worsen the nutritional status of NPC patients according to weight loss and anaemia, leading to a negative impact on 5-year locoregional relapse-free survival and disease-specific survival. Further investigations are needed to explore whether prevention and treatment of OPC during radiotherapy will be useful.

Nasopharyngeal radium irradiation: The lessons of history.

In the Netherlands, nasopharyngeal radium irradiation was started in 1945. The indications included refractory symptoms of otitis media with effusion and other adenoid-related disorders after adenoidectomy. It was considered a safe and effective therapy. Its use decreased sharply in 1958, following a worldwide media avalanche around the dramatic events in the treatment of a 5-year-old child in Utrecht, enhancing the widespread fear of radioactivity. This case history illustrates the powerful role of the media in medical decision-making.

A model to predict the risk of lethal nasopharyngeal necrosis after re-irradiation with intensity-modulated radiotherapy in nasopharyngeal carcinoma patients.

BACKGROUND: For patients with nasopharyngeal carcinoma (NPC) who undergo re-irradiation with intensity-modulated radiotherapy (IMRT), lethal nasopharyngeal necrosis (LNN) is a severe late adverse event. The purpose of this study was to identify risk factors for LNN and develop a model to predict LNN after radical re-irradiation with IMRT in patients with recurrent NPC. METHODS: Patients who underwent radical re-irradiation with IMRT for locally recurrent NPC between March 2001 and December 2011 and who had no evidence of distant metastasis were included in this study. Clinical characteristics, including recurrent carcinoma conditions and dosimetric features, were evaluated as candidate risk factors for LNN. Logistic regression analysis was used to identify independent risk factors and construct the predictive scoring model. RESULTS: Among 228 patients enrolled in this study, 204 were at risk of developing LNN based on risk analysis. Of the 204 patients treated, 31 (15.2%) developed LNN. Logistic regression analysis showed that female sex (P = 0.008), necrosis before re-irradiation (P = 0.008), accumulated total prescription dose to the gross tumor volume (GTV) ≥145.5 Gy (P = 0.043), and recurrent tumor volume ≥25.38 cm(3) (P = 0.009) were independent risk factors for LNN. A model to predict LNN was then constructed that included these four independent risk factors. CONCLUSIONS: A model that includes sex, necrosis before re-irradiation, accumulated total prescription dose to GTV, and recurrent tumor volume can effectively predict the risk of developing LNN in NPC patients who undergo radical re-irradiation with IMRT.

Salivary Anionic Changes after Radiotherapy for Nasopharyngeal Carcinoma: A 1-Year Prospective Study.

OBJECTIVES: To investigate the salivary anionic changes of patients with nasopharyngeal carcinoma (NPC) treated by radiotherapy. MATERIAL AND METHODS: Thirty-eight patients with T1-4, N0-2, M0 NPC received conventional radiotherapy. Stimulated whole saliva was collected at baseline and 2, 6 and 12 months after radiotherapy. Salivary anions levels were measured using ion chromatography. RESULTS: A reduction in stimulated saliva flow and salivary pH was accompanied by sustained changes in anionic composition. At 2 months following radiotherapy, there was a significant increase in chloride, sulphate, lactate and formate levels while significant reductions in nitrate and thiocyanate levels were found. No further changes in these anion levels were observed at 6 and 12 months. No significant changes were found in phosphate, acetate, or propionate levels throughout the study period. CONCLUSIONS: Conventional radiotherapy has a significant and prolonged impact on certain anionic species, likely contributing to increased cariogenic properties and reduced antimicrobial capacities of saliva in NPC patients post-radiotherapy.

Comparison of Calculated Radiation Delivery Versus Actual Radiation Delivery in Military Macaws (Ara militaris).

The skin and oral cavity are common sites of neoplasia in avian species. Radiation therapy has been described for the treatment of these tumors in birds; however, its observed effectiveness has been variable. One possible explanation for this variability when radiation is used to treat the head is the unique anatomy of the avian skull, which contains an elaborate set of sinuses not found in mammalian species. To compare a calculated dose of radiation intended to be administered and the actual amount of radiation delivered to the target area of the choana in 3 adult military macaws (Ara militaris), computed tomography scans were obtained and the monitor unit was calculated to deliver 100 cGy (1Gy) by using radiation planning software. The birds received 3-4 radiation treatments each from a megavoltage radiation therapy unit. A thermoluminescent dosimetry chip (TLD) placed in the choana of the birds was used to measure the amount of ionizing radiation delivered at each treatment. The TLDs were kept in place using Play-Doh as a tissue analog. The actual dose of radiation delivered was lower than the 100-cGy calculated dose, with the 95% confidence limits of predicted bias values between 2.35 and 5.39 (radiation dose from 94.61 to 97.65 cGy). A significant difference was identified between the actual amount of radiation delivered and the calculated radiation goal (P < .001). None of the TLDs received the intended dose of 100 cGy of radiation. The results revealed that the amount of radiation delivered did not reach intended levels. Because the combination of the significance of this discrepancy and the standard dose inhomogeneity could lead to greater than 10% dose inhomogeneity, future investigation is warranted for accurate dose calculation and efficacy of radiation therapy for neoplasia at the lumen of the choana in birds.

Parotid area lymph node metastases from preliminarily diagnosed patients with nasopharyngeal carcinoma: report on tumor characteristics and oncologic outcomes.

The parotid area lymph node (PLN) is an uncommon site of metastasis originating from nasopharyngeal carcinoma (NPC). The study aimed to investigate clinical characteristics and outcomes of patients with preliminarily diagnosed NPC with PLN metastases. Here we retrospectively reviewed Magnetic resonance imaging (MRI) scans of 2221 patients with untreated nonmetastatic NPC who received intensity-modulated radiation therapy (IMRT). Finally, 64 (2.9%) patients were identified with PLN metastases, of which, 34 received PLN-sparing IMRT and 30 received PLN-radical IMRT. We also found that 42.2% had N3 disease and 95.3% had stages III-IVb. PLN metastases on MRI were characterized by ipsilateral retropharyngeal lymph node (RLN) or level II nodal extracapsular spread (ECS), ipsilateral giant cervical nodes, ipsilateral parapharyngeal extension, or solitary parotid metastasis. The 5-year overall survival, distant metastasis-free survival, regional relapse-free survival, and parotid relapse-free survival rates were 70.4%, 64.3%, 76.7%, and 87.9%, respectively. Distant metastases were the main cause of treatment failure and death. Using PLN-sparing IMRT, sparing PLN with minimal axial diameter of <10 mm, could increase the risk of parotid recurrence. However, it was not an independent prognostic factor. N classification and concurrent-based chemotherapy were almost statistically significant for distant failure and death. Overall, we demonstrated that the PLN metastases might be derived from RLN or level II nodal ECS, giant cervical nodes in a retrograde fashion, or parapharyngeal extension. Sparing PLN of <10 mm by IMRT should consider the risk of parotid recurrence. Distant metastases remained the dominant treatment failure. Further effective systemic chemotherapy should be explored.

MiR-205 promotes proliferation, migration and invasion of nasopharyngeal carcinoma cells by activation of AKT signalling.

OBJECTIVE: To examine the role of microRNA (miR)-205 in proliferation, migration and invasion of nasopharyngeal carcinoma (NPC). METHODS: The human NPC cell line CNE2 was transfected with miR-205 mimic, anti-miR-205 inhibitor or scrambled oligonucleotide (control). Cell proliferation was assessed via MTT assay. Cell migration and invasion were evaluated by transwell migration and Matrigel® invasion assay, respectively. Radiation induced apoptosis was quantified via Caspase-Glo3/7 assay. Apoptotic proteins and epithelial-mesenchymal transition (EMT) proteins were semiquantified by Western blot analysis. RESULTS: Overexpression of miR-205 increased the proliferation, migration and invasion of CNE2 cells, and decreased radiation-induced apoptosis compared with control cells. MiR-205 overexpression downregulated E-cadherin and upregulated Snail expression via downregulation of PTEN and upregulation of AKT. CONCLUSION: MiR-205 plays vital roles in tumourigenesis and tumour progression in NPC, and may be a potential treatment target.

MicroRNA-9 suppresses the sensitivity of CNE2 cells to ultraviolet radiation.

MicroRNA (miR)-9 has been demonstrated to regulate the radiosensitivity of tumor cells. In the present study, the mechanism by which miR-9 modulates the sensitivity of nasopharyngeal carcinoma (NPC) cells to ultraviolet (UV) radiation was investigated. The results demonstrated that exposure of NPC cells to UV light resulted in a significant increase in the expression of miR-9, and that CNE2 cells overexpressing miR-9 exhibited reduced levels of DNA damage and increased levels of total glutathione upon UV exposure. Accordingly, the inhibition of the expression of miR-9 promoted UV-induced DNA damage and apoptosis. Although miR-9 inhibited the expression of E-cadherin in the CNE2 cells and increased their resistance to UV radiation, the use of small interfering RNA to inhibit the expression of E-cadherin was not sufficient to decrease the radiosensitivity of the NPC cells. These data demonstrated that miR-9 did not modulate the sensitivity of the CNE2 cells to UV radiation through E-cadherin, but suggested that miR-9 regulated radiosensitivity through its effects on glutathione. These findings suggest that miR-9 may be a potential target for modulating the radiosensitivity of NPC cells.

Prognostic factors on overall survival of newly diagnosed metastatic nasopharyngeal carcinoma.

BACKGROUND: To investigate factors associated with overall survival in patients with newly diagnosed metastatic nasopharyngeal carcinoma. MATERIALS AND METHODS: Two hundred and two consecutive patients with pathologically confirmed nasopharyngeal carcinoma with distant metastasis at diagnosis seen between December 2007 and May 2011 were reviewed. Patient, tumor and treatment factors were analyzed for their significance regarding overall survival. RESULTS: The median follow-up time was 22 months. At the time of this report, 116 patients had died. For 112 patients, cause of death was nasopharyngeal carcinoma. The 1, 2, 3, and 4-year overall survival rates were 75.6%, 50.2%, 39.2%, and 28.2%, respectively. Cox regression multivariate analysis showed that T-stage (p=0.045), N-stage (p=0.014), metastasis number (p<0.001) and radiotherapy for nasopharynx and neck (p<0.001) were significant factors for overall survival. CONCLUSIONS: Early T-stage and N-stage, solitary metastasis in a single organ were good prognostic factors for patients with newly diagnosed metastatic nasopharyngeal carcinoma. Radiotherapy should be strongly recommended in systemic treatment.

Clinical findings and imaging features of 67 nasopharyngeal carcinoma patients with postradiation nasopharyngeal necrosis.

Postradiation nasopharyngeal necrosis is an important late effect of radiotherapy that affects prognosis in patients with nasopharyngeal carcinoma. In the present study, we reviewed the clinical and imaging features of 67 patients with pathologically diagnosed postradiation nasopharyngeal necrosis who were treated at Sun Yat-sen University Cancer Center between June 2006 and January 2010. Their clinical manifestations, endoscopic findings, and imaging features were analyzed. Early nasopharyngeal necrosis was limited to a local site in the nasopharyngeal region, and the tissue defect was not obvious, whereas deep parapharyngeal ulcer or signs of osteoradionecrosis in the basilar region was observed in serious cases. Those with osteoradionecrosis and/or exposed carotid artery had a high mortality. In conclusion, Postradiation nasopharyngeal necrosis has characteristic magnetic resonance imaging appearances, which associate well with clinical findings, but pathologic examination is essential to make the diagnosis.

Epstein-Barr virus DNA load in nasopharyngeal brushings and whole blood in nasopharyngeal carcinoma patients before and after treatment.

PURPOSE: Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) and highly prevalent in Indonesia. EBV-DNA load can be used for early diagnosis and may have prognostic value. In this study, EBV-DNA load was evaluated in minimal invasive nasopharyngeal (NP) brushings and whole blood for initial diagnosis and therapy assessment against the standard-of-care diagnosis by biopsy with EBV-RISH and standard EBV-IgA serology. EXPERIMENTAL DESIGN: NP brushings and blood samples were collected from 289 consecutive ENT patients suspected of NPCs and 53 local healthy controls. EBV-DNA load was quantified by real-time PCR and serology by peptide-based EBV-IgA ELISA. Tissue biopsies were examined by routine histochemistry and by EBER RNA in situ hybridization. RESULTS: Repeated NP brushing was well tolerated by patients and revealed high viral load in the 228 NPC cases at diagnosis than 61 non-NPC cancer cases and healthy controls (P < 0.001). The diagnostic value of EBV-DNA load in blood and EBV-IgA serology was inferior to the NP brush results. The level of EBV-DNA load in brushes of patients with NPC was not related to T, N, or M stage, whereas elevated EBV-DNA load in blood correlated with N and M stage. EBV-DNA levels in brushings and whole blood showed a significant reduction at 2 months after treatment (P = 0.001 and P = 0.005, respectively), which was not reflected in EBV-IgA serology. CONCLUSIONS: NP brush sampling combined with EBV-DNA load analysis is a minimal invasive and well-tolerated diagnostic procedure, suited for initial diagnosis and follow-up monitoring of NPCs.

Pretreatment body mass index as an independent prognostic factor in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy: findings from a randomised trial.

OBJECTIVE: To investigate the relationship between the pretreatment body mass index (BMI) and the clinical outcomes in patients with locoregionally advanced nasopharyngeal carcinoma treated with combination of chemotherapy and radiotherapy. METHODS: From August 2002 to April 2005, 400 patients with stage III or stage IVa nasopharyngeal carcinoma were recruited for a randomised clinical trial of induction chemotherapy combined with radiotherapy or concurrent chemoradiotherapy. The patients were divided into four groups of underweight (BMI<18.5kg/m(2)), normal weight (BMI 18.5-22.9kg/m(2)), overweight (BMI 23.0-27.4kg/m(2)) or obese (BMI≥27.5kg/m(2)) according to the World Health Organization classifications for Asian populations. The differences in the long-term survival, of these four BMI groups were analysed. RESULTS: The 5-year failure-free survival rates for the underweight, normal weight, overweight and obese groups were 44%, 61%, 68% and 73%, respectively (p=0.014), and the 5-year overall survival rates were 51%, 68%, 80% and 72% (p=0.001), respectively. BMI was a strongly favoured prognostic factor of overall survival and failure-free survival in a Cox regression model. CONCLUSIONS: Pretreatment body mass index was a simple, reliable independent prognostic factor for patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.