IMPORTANCEThe role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear.OBJECTIVE To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC.DESIGN, SETTING, AND PARTICIPANTS Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months. INTERVENTIONSThe chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m 2 over 120 hours and 100 mg/m 2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy. MAIN OUTCOMES AND MEASURESThe primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety. RESULTSOverall, 126 patients were enrolled (105 men [83.3%] and 21 women [16.7%]; median [IQR] age, 46 [39-52] years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio [HR], 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC.

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Background and aimsThis study aims to examine the mediating effects of insomnia on the associations between problematic Internet use, including Internet addiction (IA) and online social networking addiction (OSNA), and depression among adolescents.MethodsA total of 1,015 secondary school students from Guangzhou in China participated in a cross-sectional survey. Levels of depression, insomnia, IA, and OSNA were assessed using the Center for Epidemiological Studies-Depression Scale, Pittsburgh Sleep Quality Index, Young’s Diagnostic Questionnaire, and Online Social Networking Addiction Scale, respectively. Logistic regression models were fit to test the associations between IA, OSNA, insomnia, and depression. The mediation effects of insomnia were tested using Baron and Kenny’s strategy.ResultsThe prevalence of depression at moderate level or above (CES-D ≥ 21), insomnia, IA, and OSNA were 23.5%, 37.2%, 8.1%, and 25.5%, respectively. IA and OSNA were significantly associated with depression (IA: AOR = 2.79, 95% CI: 1.71, 4.55; OSNA: AOR = 3.27, 95% CI: 2.33, 4.59) and insomnia (IA: AOR = 2.83, 95% CI: 1.72, 4.65; OSNA: AOR = 2.19, 95% CI: 1.61, 2.96), after adjusting for significant background factors. Furthermore, insomnia partially mediated 60.6% of the effect of IA on depression (Sobel Z = 3.562, p < .002) and 44.8% of the effect of OSNA on depression (Sobel Z = 3.919, p < .001), respectively.DiscussionThe high prevalence of IA and OSNA may be associated with increased risk of developing depression among adolescents, both through direct and indirect effects (via insomnia). Findings from this study indicated that it may be effective to develop and implement interventions that jointly consider the problematic Internet use, insomnia, and depression.

Background and aimsThe aim of this study is to estimate the longitudinal associations between online social networking addiction (OSNA) and depression, whether OSNA predicts development of depression, and reversely, whether depression predicts development of OSNA.MethodsA total of 5,365 students from nine secondary schools in Guangzhou, Southern China were surveyed at baseline in March 2014, and followed up 9 months later. Level of OSNA and depression were measured using the validated OSNA scale and CES-D, respectively. Multilevel logistic regression models were applied to estimate the longitudinal associations between OSNA and depression.ResultsAdolescents who were depressed but free of OSNA at baseline had 1.48 times more likely to develop OSNA at follow-up compared with those non-depressed at baseline [adjusted OR (AOR): 1.48, 95% confidence interval (CI): 1.14–1.93]. In addition, compared with those who were not depressed during the follow-up period, adolescents who were persistently depressed or emerging depressed during the follow-up period had increased risk of developing OSNA at follow-up (AOR: 3.45, 95% CI: 2.51–4.75 for persistent depression; AOR: 4.47, 95% CI: 3.33–5.99 for emerging depression). Reversely, among those without depression at baseline, adolescents who were classified as persistent OSNA or emerging OSNA had higher risk of developing depression compared with those who were no OSNA (AOR: 1.65, 95% CI: 1.01–2.69 for persistent OSNA; AOR: 4.29; 95% CI: 3.17–5.81 for emerging OSNA).ConclusionThe findings indicate a bidirectional association between OSNA and depression, meaning that addictive online social networking use is accompanied by increased level of depressive symptoms.