The prognostic value of weight loss during radiotherapy among patients with nasopharyngeal carcinoma: a large-scale cohort study.

BACKGROUND: We aim to investigate the prognostic value of weight loss during radiotherapy (RT) among patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 1149 NPC patients who received radical RT were retrospectively analyzed. Patients' weight were measured at initiation of RT (WPre-RT) and every week during RT (WRT1,2,3,4,5,6,7). Percentage of weight loss (PWL) at 1st, 2nd, 3rd, 4th, 5th, 6th, and 7th week of RT (RT-PWL1,2,3,4,5,6,7) were calculated using the following equation: (WPre-RT -WRT1,2,3,4,5,6,7)/WPre-RT × 100%. The optimal threshold of RT-PWL7 was determined by recursive partitioning analyses (RPAs). Our endpoints included disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS). RESULTS: The median RT-PWLs were 0, 0, 1.5, 2.9, 4.1, 5.5, 6.6% at 1st, 2nd, 3rd, 4th, 5th, 6th, and 7th week of RT, respectively. RT-PWL7 optimal threshold with respect to DFS was 5.3% based on RPAs. Therefore, a consistent threshold of 5% (<5% vs > ≥5%) was selected to classify NPC patients into low RT-PWL7 and high RT-PWL7 groups for survival analysis. Compared to high RT-PWL7 (≥5%), patients with low RT-PWL7 (< 5%) had significantly better ten-year DFS (61.2% vs 78.8%; P < 0.001), OS (70.1% vs 86.6%; P < 0.001), and DMFS (80.2% vs 88.5%; P = 0.007). However, no difference was observed between LRRFS groups (91.7% vs 94.3%; P = 0.173). In multivariate analysis, high RT-PWL7 was an independent risk factor for DFS (HR, 1.56; 95%CI, 1.19-2.03; P = 0.001), OS (HR, 1.54; 95%CI, 1.11-2.15; P = 0.011), and DMFS (HR, 1.47; 95%CI, 1.03-2.10; P = 0.033) in patients with NPC. In addition, treatment strategy, plasma Epstein-Barr virus DNA, and N stage were associated with weight loss. CONCLUSIONS: High RT-PWL7 was significantly associated with decreased DFS, OS, and DMFS for NPC patients. Clinicians should continuously inform patients on the health impact of minimizing RT-PWL7 under 5% during radiotherapy.

Combining pretreatment plasma Epstein-Barr virus DNA level and cervical node necrosis improves prognostic stratification in patients with nasopharyngeal carcinoma: A cohort study.

This study aimed to evaluate the prognostic value of combining pretreatment Epstein-Barr virus (EBV) DNA level and cervical node necrosis (CNN) for patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT). A total of 607 incident nonmetastatic NPC patients treated with IMRT ± chemotherapy were reviewed. Patients were divided into four groups based on EBV DNA level and CNN status. The primary endpoint was progression-free survival (PFS). Kaplan-Meier curves with log-rank test were applied to compare survival outcomes and the Cox proportional model was used to identify independent prognostic factors. Pretreatment EBV DNA level and CNN status were independent prognostic factors. Patients in the low-level EBV DNA group or non-CNN group had significantly better 5-year PFS. Multivariate analyses demonstrated that CNN was an independent prognostic factor for overall survival (OS) (HR = 1.927, 95% CI: 1.129-3.290, P = .016), PFS (HR = 1.492, 95% CI: 1.005-2.214, P = .047), distant metastasis-free survival (DMFS) (HR = 1.661, 95% CI: 1.044-2.644, P = .032), but not locoregional relapse-free survival. EBV DNA levels correlated significantly with CNN with a correlation coefficient of .324 (P < .001). Compared with low-level EBV DNA and non-CNN grouping, high-level EBV DNA and CNN grouping had poor PFS. The combined classification was an independent prognostic factor for OS (P < .001), PFS (P = .001), and DMFS (P = .018). Pretreatment plasma EBV DNA level and CNN status both closely correlated with prognosis of NPC patients in the IMRT era. Combined EBV DNA level and CNN status improves risk stratification and prognostic value.

The Characteristics and Survival Outcomes in Patients Aged 70 Years and Older with Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era.

PURPOSE: We aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era. METHODS AND MATERIALS: From 2006 to 2013, 126 non-metastatic NPC patients aged ≥ 70 years who were treated with IMRT +/‒ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS)were calculatedwith the Kaplan-Meier method, and differenceswere compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses. RESULTS: For the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p < 0.001). Multivariate analyses showed ACE-27 score 0-1 was significantly associated with superior OS (hazard ratio [HR], 3.02; 95% CI, 1.64 to 5.55; p < 0.001). In addition, the rate of OS was higher for stage I-III than that of stage IV, with borderline significance (HR, 1.67; 95% CI, 0.99 to 2.82; p=0.053). But no significant advantage was observed in OS when chemotherapy was used (p > 0.05). CONCLUSION: Our findings suggest IMRT +/- chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged ≥ 70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.

Plasma Epstein-Barr Viral Deoxyribonucleic Acid Predicts Worse Outcomes in Pediatric Nonmetastatic Nasopharyngeal Carcinoma Patients: An Observational Study of 89 Cases in an Endemic Area.

To evaluate the clinical significance of pretreatment levels of plasma Epstein-Barr virus DNA (pEBV DNA) on prognoses in pediatric nasopharyngeal carcinoma (NPC) patients. Eighty-nine patients aged 21 years old or younger with nonmetastatic NPC were evaluated to determine the effect of pEBV DNA levels on progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS). Survival probabilities in patient groups that were segregated by clinical stage or pEBV DNA load (low or high) were compared. The median pretreatment concentrations of pEBV DNA were 3440 copies/mL in 35 patients with stage III disease and 14,900 copies/mL in 50 patients with stage IV disease (P = 0.059). The median concentration of pEBV DNA was 34,500 copies/mL in 17 patients with relapse, which was higher than the concentration in 72 patients without relapse, who had a median level of 4985 copies/mL (P = 0.057). Further study showed that pretreatment pEBV DNA load was an independent prognostic indicator in pediatric NPC patients. High pEBV DNA was associated with adverse clinical outcomes, including PFS [3-year PFS rate = 80.5% versus 95.8%, hazard ratio (HR) = 5.00, 95% confidence interval (CI) = 1.00-25.00; P = 0.050], DMFS (3-year DMFS rate = 80.5% versus 95.8%, HR = 5.20, 95% CI = 1.04-26.00; P = 0.045), and OS (3-year OS rate = 82.9% versus 95.8%, HR = 5.41, 95% CI = 1.08-27.22; P = 0.040). Pretreatment pEBV DNA load was an independent prognostic indicator for PFS, DMFS, and OS in pediatric patients with NPC. Prospective studies, however, are needed to validate these results.

Effect of Prolonged Radiotherapy Treatment Time on Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma.

PURPOSE: To estimate the influence of prolonged radiation treatment time (RTT) on survival outcomes in nasopharyngeal carcinoma after continuous intensity-modulated radiation therapy. METHODS AND MATERIALS: Retrospectively review 321 patients with NPC treated between October 2009 and December 2010 and all of them underwent simultaneous accelerated intensity-modulated radiation therapy. The fractionated dose was 2-2.47 Gy/F (median 2.27 Gy), and the total dose for nasopharyngeal region was 64-74 Gy/ 28-33 fractions. The association of prolonged RTT and treatment interruption with PFS, LRFS and DFFS were assessed by univariate analysis and multivariate analysis. Survival analyses were carried out using Kaplan-Meier methodology and the log-rank test was used to assess the difference. The Cox regression proportional hazard model was used for multivariate analyses and evaluating the prognostic parameters for PFS, LRFS and DFFS. RESULTS: Univariate analysis revealed no significant associations between prolonged RTT and PFS, LRFS, DFFS when dichotomized using various cut-off values (all P>0.05). In multivariate analysis, RTT (range, 36-63 days) as a continuous variable, had no influence on any survival outcome as well (P>0.05). T and N classification were independent prognostic factors for PFS, LRFS and DFFS (all P<0.05, except T classification for LRFS, P = 0.057). Age was an independent prognostic factor for PFS (hazard ratio [HR], 1.033; P = 0.008) and DFFS (HR, 1.032; P = 0.043). CONCLUSION: We conclude that no such association between survival outcomes and radiation treatment duration (range: 36-63 days) can be found in the present retrospective study, however, we have to remind that prolongation in treatment should be limited in clinical application and interruptions caused by any reason should be minimized as much as possible.

Different prognostic values of plasma Epstein-Barr virus DNA and maximal standardized uptake value of 18F-FDG PET/CT for nasopharyngeal carcinoma patients with recurrence.

PURPOSE: To evaluate and compare the prognostic value of Epstein-Barr virus (EBV) DNA and maximal standard uptake values (SUVmax ) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) in subgroups of nasopharyngeal carcinoma (NPC) patients with locoregional or distant recurrence. PATIENTS AND METHODS: A total of 194 patients with recurrent NPC (locoregional recurrence: 107, distant recurrence: 87) were enrolled. Patients took evidence of recurrence performed with 18F-FDG-PET and an EBV DNA test before salvage treatment. Clinical parameters, the status of EBV DNA and the value of SUVmax were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards regression model. RESULTS: In the subgroup of patients with locoregional recurrence, patients with SUVmax<8.65 had significantly better overall survival (OS) (P=0.005) compared with the patients with SUVmax ≥8.65. However, both elevated EBV DNA load (≥21,100 copies/ml) and distant SUVmax (≥13.55) were significantly associated with worse OS compared with the patients with EBV DNA <21,100 copies/ml or distant SUVmax <13.55 for the subgroup with distant recurrence (P=0.015 and P=0.006, respectively). The predictive ability of EBV DNA was superior to that of SUVmax (P=0.062). Multivariate analysis showed that SUVmax was only an independent prognostic factor for OS in patients with locoregional recurrence (P=0.042), whereas EBV DNA independently predicted OS for the patients with distant recurrence (P=0.007). For those patients with undetectable EBV DNA, SUVmax<8.65 was still an independent favorable prognostic factor (P=0.038). CONCLUSIONS: SUVmax is a useful biomarker for predicting OS in nasopharyngeal carcinoma patients with locoregional recurrence or with undetectable EBV DNA. Both distant SUVmax and EBV DNA appear to be independent predictors of OS in patients with distant recurrence; however, the predictive ability of EBV DNA was superior to that of SUVmax.

Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development.

Dexamethasone (Dex) has anti-inflammatory and immunomodulatory properties against many conditions. There is a potential teratogenic risk, however, for pregnant women receiving Dex treatment. It has been claimed that Dex exposure during pregnancy could affect osteogenesis in the developing embryo, which still remains highly controversial. In this study, we employed chick embryos to investigate the effects of Dex exposure on skeletal development using combined in vivo and in vitro approach. First, we demonstrated that Dex (10(-8)-10(-6)µmol/egg) exposure resulted in a shortening of the developing long bones of chick embryos, and it accelerated the deposition of calcium salts. Secondly, histological analysis of chick embryo phalanxes exhibited Dex exposure inhibited the proliferation of chondrocytes, increased apoptosis of chondrocytes and osteocytes, and led to atypical arranged hypertrophic chondrocytes. The expression of genes related to skeletogenesis was also analyzed by semi-quantitative RT-PCR. The expression of ALP, Col1a2 and Col2a1 was decreased in the Dex treated phalanxes. A detectable increase was observed in Runx-2 and Mmp-13 expression. We next examined how Dex affected the different stages of skeletogenesis in vitro. Utilizing limb bud mesenchyme micromass cultures, we determined that Dex exposure exerted no effect on apoptosis but impaired chondrogenic cell proliferation. Interestingly, low dose of Dex moderately prompted nodule formation as revealed by alcian blue staining, but higher doses of Dex significantly inhibited similar chondrogenic differentiation. Dex exposure did not induce apoptosis when the chondrogenic precursors were still at the mesenchymal stage, however, cell viability was suppressed when the mesenchyme differentiated into chondrocytes. Alizarin red staining revealed that the capacity to form mineralized bone nodules was correspondingly enhanced as Dex concentrations increased. The mRNA level of Sox-9 was slightly increased in mesenchymal cell mass treated by low concentration of Dex. Mmp-13 expression was obviously up-regulated by Dex in both mesenchymal cells and primary chondrocyte cultures. And Col10a1 expression was also increased by Dex exposure in chondrocyte. In summary, we have revealed that different concentrations of Dex exposure during early gestation could exert a biphasic effect on vertebrate skeletal development.