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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported significantly improved failure-free survival using gemcitabine plus cisplatin induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized trial, patients were assigned to be treated with concurrent chemoradiotherapy alone (standard therapy, n = 238) or gemcitabine and cisplatin induction chemotherapy before concurrent chemoradiotherapy (n = 242). With a median follow-up of 69.8 months, the induction chemotherapy group had a significantly higher 5-year OS (87.9% v 78.8%, hazard ratio, 0.51 [95% CI 0.34 to 0.78]; P = .001) and a comparable risk of late toxicities (≥ grade 3, 11.3% v 11.4%). Notably, the depth of the tumor response to induction chemotherapy correlated significantly and positively with survival (complete response v partial response v stable/progressive disease, 5-year OS, 100% v 88.4% v 61.5%, P = .005). Besides, patients with a low pretreatment cell-free Epstein-Barr virus DNA load (< 4,000 copies/mL) might not benefit from induction chemotherapy (5-year OS, 90.6% v 91.4%, P = .77). In conclusion, induction chemotherapy before concurrent chemoradiotherapy improved OS significantly in patients with locally advanced nasopharyngeal carcinoma, without increasing the risk of late toxicities. Tumor response to induction chemotherapy and pretreatment cell-free Epstein-Barr virus DNA might be useful to guide individualized treatment.

Objective: To investigate the self-efficacy and mental health of elderly patients with coronary heart disease (CHD) in rural Hebei Province as well as to analyze the relationship between them. Methods: From June 2021 to December 2021, 480 elderly patients with CHD from rural areas, who had been discharged by the Department of Cardiology from three tertiary hospitals in three cities with different economic levels in Hebei Province for more than a year, were selected as the research subjects. The general self-efficacy scale (GSES) and symptom self-rating scale (SCL-90) were used to investigate the self-efficacy and mental health of these patients. SPSS 25.0 was used for data analysis. Results: The total mean self-efficacy score of elderly patients with CHD in rural Hebei Province was 17.18 ± 4.68, which is lower than the international norm (t = -32.067, P = 0.000) and the national norm (t = -28.783, P = 0.000) ; the total average SCL-90 score was 148.64 ± 55.13, which is higher than the national norm for adults and the reference norm for ordinary elderly people; except for hostility and psychosis, the other dimensions were significantly higher than the national norm for adults (P < 0.05); except for psychosis, the other dimensions were significantly higher than the reference norm for ordinary elderly people (P < 0.05); the self-efficacy score was found to be negatively correlated with the total SCL-90 score and the score for each dimension (P < 0.05). Conclusion: Elderly CHD patients with higher self-efficacy in rural Hebei Province have higher mental health level. It is suggested that the mental health of elderly patients with CHD in rural areas can be improved by improving their self-efficacy.

Objective: To analyze the independent risk factors and establish a risk prediction model by investigating the readmission of elderly patients with coronary heart disease (CHD) within 1 year after discharge. Methods: A total of 480 CHD patients, who were hospitalized in the Affiliated Hospital of Hebei University from October 2019 to December 2020, were included in this study. A general data scale, mental health status scale, the Clinical Frailty Scale, Pittsburgh Sleep Quality Index, as well as the Family Adaptability and Cohesion Evaluation Scale were used to collect data. According to the number of readmissions due to CHD within 1 year after discharge, the patients were divided into two groups: the readmission group (n = 212) and the no readmission group (n = 268). General data, laboratory examination indicators, frailty, mental health status, sleep status, as well as family intimacy and adaptability were compared between the two groups. Logistic regression was used to analyze the independent risk factors for the readmission of these patients, and R software was used to construct a line diagram model for predicting readmission of elderly patients with CHD. Results: Five factors including body mass index (OR = 1.045), low density lipoprotein (OR = 1.123), frailty (OR = 1.946), mental health (OR = 1.099), as well as family intimacy and adaptability (OR = 0.928) were included to construct the risk prediction model for the readmission of elderly patients with CHD within 1 year after discharge. The ROC curve showed that the area under the curve for predicting readmission of elderly patients with CHD was 0.816; Hosmer-Lemeshow goodness of fit test showed X2 = 1.456 and P = 0.989; the maximum Youden index corresponding to the predicted value of risk was 0.526. The results showed that the model could accurately predict the risk of readmission in elderly patients with CHD within 1 year after discharge. Conclusion: This study constructed a line diagram model based on five independent risk factors of the readmission of elderly patients with CHD: body mass index, low density lipoprotein, frailty, mental health status, as well as family intimacy and adaptability. This model has good discrimination, accuracy, and predictive efficiency, providing reference for the early prevention and intervention of readmission in elderly patients with CHD recurrence.

We propose a magnetic laser in a subwavelength system consisting of a high-refractive-index dielectric cavity and an active medium formed by magnetic quantum emitters. Stimulated emissions of magnetic quantum emitters induced by their coherent interactions with quantized magnetic fields of a cavity are theoretically considered. The condition to archive such a magnetic laser is obtained. Numerical results show that magnetic lasers are feasible in some realistic systems, for example, a silicon disk of high-quality whispering gallery modes with embedded emitters. Furthermore, the competitions between the electric interaction and magnetic one in terms of their Purcell factors are also considered in some magnetic laser achievable systems. In a wavelength-scale silicon block of a high-order magnetic mode, the ratio of magnetic Purcell factor to the electric one can reach more than ~10^3 large. Our results open up ways to enhanced magnetic light-matter interactions., 21 pages, 5 figures

Upper-neck irradiation (UNI) at the uninvolved neck has shown similar regional relapse-free survival as standard whole-neck irradiation (WNI) in N0-1 nasopharyngeal carcinoma patients. However, whether UNI at the contralateral uninvolved neck is feasible in unilateral N3 disease, defined as6 cm and/or below the caudal border of the cricoid cartilage, remains unclear.Data for 291 nasopharyngeal carcinoma patients with unilateral N3 disease, who were treated with intensity-modulated radiotherapy from 2009 to 2015, were retrospectively analyzed. Among them, 190 received bilateral WNI (WNI group); the remaining 101 received WNI at the involved neck and UNI at the contralateral uninvolved neck (UNI group). Survival rates were estimated using the Kaplan-Meier method and difference between groups were compared using the log rank tests.The median follow-up was 79.4 months (interquartile range, 56.0-89.3). Twenty-five patients had regional lymph node relapses (UNI: 10.9%, 11/101 vs. WNI: 7.4%, 14/190, p=0.31). Of these, 23 patients relapsed within the previously involved neck regions, while only two patients had relapses in the contralateral uninvolved neck (one each in the UNI and WNI groups). Five-year regional relapse-free survival rates were similar between groups (89.7% vs. 92.7%, p=0.29). Similar between-group findings were also observed for 5-year overall survival (76.1% vs. 80.4%, p=0.40), distant metastasis-free survival (74.9% vs. 79.2%, p=0.44), and local relapse-free survival (95.6% vs. 94.7%, p=0.64). Furthermore, oncologic outcomes in subgroup and multivariable analyses were similar between groups.Regional control and survival outcomes were comparable in UNI at the contralateral uninvolved neck and standard WNI in nasopharyngeal carcinoma patients with unilateral N3 disease. Our findings provide evidence for future radiotherapy guidelines of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.

The interaction of magnetic dipole (MD) emitters and common photonic cavities is usually weak, which is partially due to the low magnetic near field enhancements of the cavities. Here, we show that whispering gallery modes (WGMs) of a subwavelength dielectric cavity can not only greatly boost the emission rate of a MD emitter but also bring efficient couplings between coherent MD emitters. In a WGM cavity, the maximal emission rate ({\gamma}max) of a single emitter occurs at an antinode of the field pattern. The emission of the MD emitter can also be greatly affected by another coherent one depending on the magnetic field response of the WGM. The maximal contribution can also reach {\gamma}max. Notably, the cooperative emission rate of the coherent MD emitters does not decay with distance in the considered range due to the high-quality feature of a WGM. In contrast to the emission, the absorption of an emitter is hardly affected by the coherent couplings between emitters mediated by a WGM. The difference between the performances of emission and absorption is highly related to the excitation behaviors of WGMs. Our results are important for enhanced magnetic light-matter interactions., Comment: 26 pages, 6 figures

Based on its excellent visible light absorption and photoelectric response capabilities, SbSI has attracted significant research attention for a wide range of applications. Despite the fact that interesting physical properties can be induced from the sophisticated band structures of SbSI, that is, either with direct or indirect band gaps, its nonlinear optical (NLO) properties are not yet fully explored. In the present work, the NLO response of SbSI nanorods is investigated by the combination of open-aperture (OA) Z-scan, pump–probe, and spatial self-phase modulation (SSPM). It is found that the synthesized SbSI nanorods possess a relatively large nonlinear absorption coefficient and a small saturable optical intensity at a wavelength of 400 nm, compared to those of other materials. More importantly, the OA Z-scan experiments suggest that the direct band gap of SbSI plays a dominant role on the NLO effects, which is further verified by the SSPM experiments. The present work suggests that the SbSI nanorods may have great potentials for optical switches and saturable absorbers.

Background: Disability is an important problem in aging societies globally. However, the research findings of the prevalence of disability have been inconsistent. This study aims to estimate the prevalence of disability and its influencing factors among the Chinese older population from 1979 to 31 July 2021. Methods: A systematic review and meta-analysis were conducted using both international (PubMed, Web of Science, CBMdisc, PsycINFO, the Cochrane Library, and EMBASE) and Chinese (CNKI, CQVIP, and WanFang) databases. Meta-analysis was performed using a random-effects model to account for heterogeneity. Subgroup analyses were also done. Results: The pooled prevalence of disability across all 97 studies was 26.2% (95% CI: 23.7–28.6%). The estimates varied according to the types of activities of daily living (ADL), gender, age, and region. Studies based on the identification of cases by using the complete ADL scale showed a higher prevalence than those using the basic ADL scale. The prevalence was slightly higher among female older individuals than among male older individuals. The highest rates were seen in older individuals aged 80 years or older. Elders in central China, southwest China, and northwest China were more likely to be BADL-disabled. Conclusion: Prevalence of disability among the Chinese older population is high, around 26%. Using standardized diagnostic systems to correctly estimate the prevalence of disability would be helpful for public health professionals in China.

Here we theoretically investigate the coherent interactions between the quantum emitters with magnetic dipole transitions and subwavelength all-dielectric resonators of whispering gallery modes (WGMs). We extend a semi-analytical method which can efficiently calculate the far-field spectrum of a general hybrid system. Then, a subwavelength sphere with refractive index around n = 3.5 is chosen as the dielectric resonator. Due to the high magnetic field enhancements of the WGMs of the sphere, strong couplings between magnetic quantum emitters and subwavelength WGMs can occur, where a clear Rabi splitting appears on the extinction spectrum of the hybrid system. The match between the relaxation times of the WGMs and emitters are important to efficiently achieve a strong enough coupling. The other parameters including the order of a WGM, the radius, the refractive index, the transition dipole moment and excitation intensity are also important factors that can affect the couplings. Our results pave the way for strong interactions between light and magnetic emitters mediated by subwavelength all-dielectric resonators.

Reaching strong coupling between a single molecule and a plasmonic nanocavity (PNC) at ambient conditions is important for many nanophotonic applications. Many efforts have been devoted towards such a goal. Here, we develop a semi-analytical method which can efficiently calculate the extinction spectrum of a general coupled system of a single molecule and a PNC. The field enhancement and the enhancement efficiency of a PNC are found to be crucial to obtain a clear large Rabi splitting. The bound for the coupling strength can be obtained correspondingly. Specifically, we find that a plasmonic raindrop dimer with a gap size of 1.5 nm can achieve strong coupling with a single common molecule of a transition dipole moment of \ensuremath{\sim}3.8 Debye. The raindrop dimer shows a better performance than the other common experimentally feasible plasmonic nanocavities. The case of a special nonlinear coupling where an additional peak appears at the Rabi splitting dip is also discussed. Our results pave the way for single-emitter quantum optics at ambient conditions.

Background The impact of radiotherapy interruption due to the Spring Festival holidays in China on the survival of patients with nasopharyngeal carcinoma (NPC) is unclear. Methods Nontrial patients with locoregionally advanced NPC receiving radiotherapy plus induction chemotherapy (IC) and/or concurrent chemotherapy (CC) were included (N = 5035) and divided into two groups based on the Spring Festival-induced radiotherapy interruption. Kaplan–Meier curves for overall survival (OS) and failure-free survival (FFS) were compared between rival groups. Impact of the timing of radiotherapy interruption (during or outside the Spring Festival) on survival was investigated in a propensity score-matched dataset. We adopted ordination correspondence analysis to determine the cut-off of radiotherapy prolongation for prognostic prediction, and accordingly performed subgroup analysis based on delayed days and chemotherapy details. Individual patient data of three phase III NPC trials (NCT00677118, NCT01245959, NCT01872962) were used for validation (N = 1465). Results Radiotherapy interruption was most frequently observed between December to January of the following year. Significantly lower OS and FFS were associated with the Spring Festival-induced interruption of radiotherapy (P = 0.009 and 0.033, respectively), but not that interruption of IC. In two matched comparison groups, the timing of radiotherapy interruption during the Spring Festival was more likely to lead to a decrease in FFS than outside the Spring Festival (P = 0.046), which was not observed in the validation using clinical trial data or in the subgroup analysis based on the 5-day delayed time. The absence of CC and the accumulated dose of cisplatin P = 0.002) and OS (P = 0.010), respectively. Conclusions The poor survival of patients with NPC is associated with the Spring Festival-induced interruption of radiotherapy. We recommend that these patients receive adequate doses of cisplatin concurrently with radiotherapy.

Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials.In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety.A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group.Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).

Objective In cancer trials, prior cancer is a common exclusion criterion. We evaluated the characteristics of prior cancer exclusion criteria in nasopharyngeal carcinoma (NPC) trials and determined its prognostic effect on patients with NPC. Methods We reviewed NPC trials for prior cancer exclusion criteria. Then we estimated the effect of prior cancer among NPC patients using the Surveillance, Epidemiology, and End Results database. Propensity score-matching was used to compensate for differences in baseline characteristics between patients with and without prior cancer. Results There were 109 clinical trials involving 10,437 patients; 49 trials (45%) excluded patients with prior cancer. Prior cancer exclusion was more common in recent or phase III trials. We identified 10,195 NPC patients; 6.2% had prior cancer. More than 70% of these cancers were in situ/localized/regional and diagnosed relatively close to the NPC diagnosis (median 3.3 years). Patients with certain prior cancer type (prostate, breast, gynecological, hematological), time of diagnosis (>5 years ago), or stage (in situ/localized) did not have inferior survival compared with patients with no prior cancer. We tested one form of prior cancer exclusion criteria in an NPC cohort resembling a modern trial population: it did not adversely affect overall and NPC-specific survival. Conclusions Many NPC trials excluded patients with prior cancer, which impacts trial accrual and generalizability. Our findings suggest that broader inclusion in trials of patients with NPC with prior cancer might not affect trial outcomes. More research is needed to understand the appropriateness of this exclusion policy across cancer types and trials.

Background and Aim: Approximately 60% of glioblastoma multiforme (GBM) patients possess an unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) gene, which confers a limited response to standard-of-care treatment with temozolomide (TMZ), resulting in a lower survival. Dianhydrogalactitol (VAL-083) is a novel bi-functional DNA-targeting agent that induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated repair of the O6 guanine alkylator TMZ. A Phase 2 study has been initiated for VAL-083 in newly diagnosed MGMT unmethylated GBM. Subjects and Methods: The study has two parts: part 1 is a dose–escalation and induction format to enroll up to ten patients in which they received VAL-083 at 20, 30, or 40 mg/m2 per day for 3 days every 21 days concurrently with standard radiation treatment and VAL-083 for up to eight additional cycles. Part 2 comprises an expansion phase to enroll up to twenty additional patients. This study was performed with approval by the Institutional Review Board of Sun Yat-sen University Cancer Center (B2016-058-01) on January 13, 2017, and registered with the ClinicalTrials.gov (NCT03050736) on February 13, 2017. Results: After completion of dose escalation, VAL-083, 30 mg/m2 per day, in combination with radiation therapy, was generally safe and well tolerated. At the cutoff date, 23 patients had been enrolled, 14 of whom had been treated in the expansion phase. Consistent with prior studies, myelosuppression was the most common adverse event. Pharmacokinetic assessment indicated that the levels of VAL-083 were as high in the cerebrospinal fluid as in plasma, 2 h postinfusion. Of the 22 patients who had reached their four precycle magnetic resonance imaging assessments, 12 were assessed with disease progression, with a median progression-free survival of 9.9 (95% confidence interval 7.3–12.0) months for all the patients studied. Conclusion: These preliminary data support VAL-083 as a potentially valuable treatment option for newly diagnosed GBM.

Background: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) antibody that has shown preclinical and clinical anticancer activity in cerebral glioblastoma multiforme (GBM). We conducted a phase II, single-arm, multicenter clinical trial to evaluate the benefit of adding nimotuzumab to current standard chemo-radiotherapy for patients with GBM with positive EGFR expression. Methods: Newly diagnosed patients with histologically proven single supratentorial GBM and epidermal growth factor receptor (EGFR) positive expressions were recruited. All patients were treated with nimotuzumab, administered once a week intravenously for 6 weeks in addition to radiotherapy with concomitant and adjuvant temozolomide after surgery. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary objectives included objective response rate (ORR) and toxicity. Results: A total of 39 patients were enrolled and 36 patients were evaluated for efficacy. The ORR at the end of RT was 72.2%. Median OS and PFS were 24.5 and 11.9 months. The 1-year OS and PFS rates were 83.3% and 49.3%. The 2-year OS and PFS rates were 51.1% and 29.0%. O (6)-methylquanine DNA methyl-tranferase (MGMT) expression is known to affect the efficacy of chemotherapy and status of its expression is examined. No significant correlation between treatment outcomes and MGMT status was found. Most frequent treatment-related toxicities were mild to moderate and included constipation, anorexia, fatigue, nausea, vomiting, and leucopenia. Conclusions: Our study show that nimotuzumab in addition to standard treatment is well tolerable and has increased survival in newly diagnosed GBM patients with EGFR positive expression.

IMPORTANCE: Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). OBJECTIVE: To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes

Key Points Question What are the associations of cancer stage at time of diagnosis, treatment, and marital status with cancer-specific survival? Findings This cohort study of 1.7 million adults with cancer found that stage at diagnosis mediated the association of marriage with cancer-specific survival in breast, colorectal, and endometrial cancers as well as melanoma; receiving surgery mediated the association in lung, pancreatic, and prostate cancers; and receiving chemotherapy mediated the association in lung and pancreatic cancers. Meaning These findings suggest that promoting the early diagnosis of breast, colorectal, and endometrial cancers and melanoma and providing definitive treatment for lung, pancreatic, and prostate cancers could improve cancer-specific survival among unmarried patients with cancer., This cohort study evaluates the extent to which marriage is associated with cancer-specific survival, stage at diagnosis, and treatment among patients with 9 common solid cancers and recommends methods for reducing the survival gap., Importance Married patients with cancer have better cancer-specific survival than unmarried patients. Increasing the early diagnosis and definitive treatment of cancer among unmarried patients may reduce the survival gap. Objectives To evaluate the extent to which marriage is associated with cancer-specific survival, stage at diagnosis, and treatment among patients with 9 common solid cancers and to recommend methods for reducing the survival gap. Design, Setting, and Participants This retrospective, population-based cohort study included patients older than 18 years who were diagnosed with 1 of 9 common cancers between January 1, 2007, and December 31, 2016. Patient data were retrieved from the Surveillance, Epidemiology, and End Results Program. Statistical analyses were performed from August 1 to October 1, 2020. Exposures Marital status, classified as married and unmarried (including single, separated, divorced, widowed, and unmarried patients or domestic partners). Main Outcomes and Measures The primary outcome was the time ratio (TR) of cancer-specific survival (married vs unmarried). Mediation analyses were conducted to determine the extent to which the association of marriage with cancer-specific survival was mediated by stage at diagnosis and treatment. Results This study included 1 733 906 patients (894 379 [51.6%] women; 1 067 726 [61.6%] married; mean [SD] age, 63.76 [12.60] years). Multivariate analyses found that those who were married were associated with better cancer-specific survival than unmarried patients (TR, 1.36; 95% CI, 1.35-1.37). Early diagnosis in breast cancer, colorectal cancer, endometrial cancer, and melanoma mediated the association between marital status and cancer-specific survival (breast cancer: proportion mediated [PM], 11.4%; 95% CI, 11.2%-11.6%; colorectal cancer: PM, 10.9%; 95% CI, 10.7%-11.2%; endometrial cancer: PM, 12.9%; 95% CI, 12.5%-13.3%; melanoma: PM, 12.0%; 95% CI, 11.7-12.4%). Surgery mediated the association between marital status and cancer-specific survival in lung (PM, 52.2%; 95% CI, 51.9%-52.4%), pancreatic (PM, 28.9%; 95% CI, 28.6%-29.3%), and prostate (PM, 39.3%; 95% CI, 39.0%-39.6%) cancers. Chemotherapy mediated the association of marital status with cancer-specific survival in lung (PM, 37.7%; 95% CI, 37.6%-37.9%) and pancreatic (PM, 28.6%; 95% CI, 28.4%-28.9%) cancers. Improved cancer-specific survival associated with marriage was greater among men than women (men: TR, 1.27; 95% CI, 1.25-1.28; women: TR, 1.20; 95% CI, 1.19-1.21). The contribution of receiving an early diagnosis and treatment with surgery or chemotherapy to the association between marital status and cancer-specific survival was greater among men than women (early diagnosis: PM, 21.7% [95% CI, 21.5%-21.9%] vs PM, 20.3% [95% CI, 20.2%-20.4%]; surgery: PM, 26.6% [95% CI, 26.4%-26.7%] vs PM, 11.1% [95% CI, 11.0%-11.2%]; chemotherapy: PM, 6.8% [95% CI, 6.7%-6.8%] vs PM, 5.1% [95% CI, 5.0%-5.2%]). Conclusions and Relevance In this study, survival disparities associated with marital status were attributable to early diagnosis in breast, colorectal, and endometrial cancers as well as melanoma and to treatment-related variables in lung, pancreatic, and prostate cancers. The findings also suggest that marriage may play a greater protective role in the cancer-specific survival of men than of women.

BACKGROUND The prognosis of patients who have Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without EBV-related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV-related NPC by incorporating the measurement of plasma EBV DNA. METHODS In total, 979 patients with NPC who received intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT. RESULTS The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression-free survival and overall survival in univariate analysis (all P 2000 copies/mL; T1-T3N2, EBV DNA ≤2000 copies/mL), stage RIII (T1-T3N2, EBV DNA >2000 copies/mL; T4N0-N2), and stage RIVA (any T and N3). In the validation cohort, the 5-year progression-free survival rate was 100%, 87.9%, 76.7%, 68.7%, and 50.4% for proposed stage RI, RIIA, RIIB, RIII, and RIV NPC, respectively (P < .001). Compared with the eighth edition TNM stage groupings, the proposed stage groupings incorporating EBV DNA provided better hazard consistency, hazard discrimination, outcome prediction, and sample size balance. CONCLUSIONS The proposed stage groupings have better prognostic performance than the eighth edition of the TNM staging system. EBV DNA titers should be included in the TNM staging system to assess patients who have EBV-related NPC.

Purpose: Epigenetic alterations play important roles in metastasis and drug resistance through gene regulation. However, the functional features and molecular mechanisms of epigenetic changes remain largely unclear in nasopharyngeal carcinoma (NPC) metastasis. Experimental Design: Gene regulatory network analysis was used to identify metastatic-specific dysregulated genes between normal and NPC tissues and the expression was validated in published Gene-Expression Omnibus data set. The regulatory and functional role of RAB37 downregulation was examined in NPC and was validated in vitro and in vivo, and downstream target of RAB37 was explored. The clinical value of RAB37 methylation was evaluated in NPC metastasis and chemosensitivity. Results: We identified RAB37 as a specific hypermethylated gene that is most commonly downregulated in NPC. Moreover, RAB37 downregulation was attributed to hypermethylation of its promoter and was significantly associated with metastasis- and docetaxel chemoresistance-related features in NPC. Ectopic RAB37 overexpression suppressed NPC cell metastasis and enhanced chemosensitivity to docetaxel. Mechanistically, RAB37 colocalized with TIMP2, regulated TIMP2 secretion, inhibited downstream MMP2 activity, and consequently altered NPC cell metastasis. Furthermore, RAB37 hypermethylation was correlated with poor clinical outcomes in patients with NPC. We developed a prognostic model based on RAB37 methylation and N stage that effectively predicted an increased risk of distant metastasis and a favorable response to docetaxel-containing induction chemotherapy (IC) in NPC patients. Conclusions: This study shows that RAB37 hypermethylation is involved in NPC metastasis and chemoresistance, and that our prognostic model can identify patients who are at a high risk of distant metastasis and might benefit from for docetaxel IC.

Background The purpose of this study was to verify 10-year results of survival and late toxicities and assess the ultimate therapeutic ratio of intensity-modulated radiotherapy (IMRT) versus two-dimensional radiotherapy (2DRT) in patients with nasopharyngeal carcinoma (NPC). Materials and Methods We retrospectively reviewed the data from 1,276 patients with nonmetastatic NPC who received IMRT or 2DRT from January 2003 to December 2006. Results Of the 1,276 patients, 512 were treated with IMRT and 764 with 2DRT. Median follow-up was 115 months. At 10 years, the IMRT group demonstrated significantly better results than the 2DRT group in local failure-free survival (L-FFS; 90% vs. 84%; hazard ratio [HR], 0.57, 95% confidence interval [CI], 0.40–0.81; p = .001), failure-free survival (FFS; 69% vs. 58%; HR, 0.69, 95% CI, 0.57–0.83; p Conclusion IMRT demonstrated an improved ultimate therapeutic ratio compared with 2DRT in patients with NPC after a 10-year follow-up, with significant improvement of L-FFS, FFS, and OS and decrease in most late toxicities. Implications for Practice The ultimate therapeutic ratio of intensity-modulated radiotherapy versus two-dimensional radiotherapy in patients with nasopharyngeal carcinoma is unclear. In this retrospective study of 1,276 patients with nonmetastatic nasopharyngeal carcinoma with a follow-up of 115 months, intensity-modulated radiotherapy demonstrated an improved ultimate therapeutic ratio compared with two-dimensional radiotherapy, with significant improvement of local failure-free survival, failure-free survival, and overall survival and decrease in most late toxicities and noncancer deaths. However, distant control remains insufficient with this treatment modality.

Background: The changes in the risk of disease failure over time in nasopharyngeal carcinoma (NPC) remains unknown. Methods: We analyzed 749 patients treated with intensity-modulated radiotherapy in a single center. The annual hazard rates of disease failure (recurrence or death from any cause) were estimated using the life-table method. Results: In total, 41 (5.5%), 22 (2.9%) and 129 (17.2%) patients developed local, regional and distant recurrences, respectively; 149 (19.9%) patients died. Of the 600 patients who were alive at the last follow-up, 496 (82.7%) had follow-up times longer than 6 years. The 6-year failure-free survival rate was 74.8%. Older age (> 50 years) and advanced stage (Ⅲ-ⅣB) were independent risk factors for disease failure in multivariate analysis. The hazard curve for failure risk in the whole cohort showed a sharp peak at 2 years, changed to a gradually decreasing plateau between years 3 and 5 and then declined sharply. Subgroup analyses revealed similar hazard curves in both sexes. However, the patterns of hazard curve significantly differed between high-risk (> 50 years or stage Ⅲ-ⅣB) and low-risk (≤ 50 years or stage Ⅰ-Ⅱ) patients. Interpretation: The failure hazard rate in NPC didn't decline in a linear manner, but displayed a sharp peak at 2 years. The patterns of hazard function significantly differed between patients with different age and stage. Further studies are warranted to confirm our results.

Background The purpose of this study was to determine the predictive value of pretreatment serum uric acid (SUA) for metastasis in locally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy. Methods This retrospective study examined 1063 patients with locally advanced NPC. Multivariate survival analysis was used. Results High pretreatment SUA level (>353.4 μmol/L) independently predicted distant metastasis-free survival (p = .013) and was associated with high white blood cell (p = .005), lymphocyte counts (p < .001), and male sex (p < 0.001). In addition, SUA levels were significantly elevated in patients with T1 to T3 classification (p = .042). For patients with subsequent lung metastases after treatment, markedly higher pretreatment SUA levels were detected compared with patients who had other distant metastases (p =.012) and patients without distant metastasis (p = .024). Conclusion Pretreatment SUA may be a useful biomarker for evaluating treatment options for patients with locally advanced NPC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 492–497, 2017

Anapole modes of all-dielectric nanostructures hold great promise for many nanophotonic applications. However, anapole modes can hardly couple to other modes through far-field interactions, and their near-field enhancements are dispersed widely inside the nanostructures. These facts bring challenges to the further increasing of the response of an anapole mode. Here, we theoretically show that an anapole mode response in a dielectric nanostructure can be boosted through electromagnetic interactions with the coupling distance of a wavelength scale, which is beyond both the near-field and far-field limits. The all-dielectric nanostructure consists of a disk holding an anapole mode and a ring. Both analytical calculations and numerical simulations are carried out to investigate the electromagnetic interactions in the system. It is found that the electric dipoles associated with the fields of the anapole mode on the disk undergo retardation-related interactions with the electric dipoles associated with the ring, leading to the efficiently enhanced response of the anapole mode. The corresponding near field enhancement on the disk can reaches more than 90 times for a slotted silicon disk-ring nanostructure, where the width of the slot is 10 nm. This enhancement is about 5 times larger than that of an individual slotted disk. Our results reveal the greatly enhanced anapole mode through electromagnetic couplings in all-dielectric nanostructures, and the corresponding large field enhancement could find important applications for enhanced nonlinear photonics, near-field enhanced spectroscopies, and strong photon–exciton couplings.

Background: The optimal treatment for early-stage nasopharyngeal carcinoma (NPC) remains controversial. Identification of prognostic factors for metastasis and tumor progression is urgently required to improve clinical decision-making for patients with American Joint Committee on Cancer (AJCC) 2009 stage II NPC from the endemic area. Methods: Consecutive newly-diagnosed patients (n=296) with non-disseminated, biopsy-proven stage II NPC were retrospectively reviewed; all patients received intensity-modulated radiotherapy and MRI follow-up. Plasma EBV DNA level, serum lactate dehydrogenase, serum albumin, serum globulin and leukocyte counts were measured before therapy. Survival rates were analyzed using the Kaplan-Meier method and log-rank test and multivariate Cox proportional hazards model. Results: Median follow-up was 50.2 months (range, 8-69.5 months). Multivariate analysis demonstrated a plasma Epstein-Barr virus (EBV) DNA level ≥ 4000 copies/mL, maximal axial diameter (MAD) of the cervical lymph nodes ≥ 30 mm and serum globulin level < 29.5 g/L were independent predictors of poor DMFS (P = 0.018; P = 0.019; P = 0.006, respectively). On the basis of these parameters, a prognostic model was developed as follows: 1) patients with no risk factors; 2) one risk factor; and 3) two or three risk factors. The 3-year distant metastasis-free survival rates for groups 1, 2 and 3 were 100%, 94.6% and 84.3%, respectively (P = 0.001). Conclusion: The prognostic model based on EBV DNA, serum globulin and nodal size may facilitate individualized treatment of patients with stage II NPC at high risk of distant metastasis.

Objective To provide a complete toxicity profile, toxicity spectrum, and a safety ranking of immune checkpoint inhibitor (ICI) drugs for treatment of cancer. Design Systematic review and network meta-analysis. Data sources Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched to include relevant studies published in English between January 2007 and February 2018. Review methods Only head-to-head phase II and III randomised controlled trials comparing any two or three of the following treatments or different doses of the same ICI drug were included: nivolumab, pembrolizumab, ipilimumab, tremelimumab, atezolizumab, conventional therapy (chemotherapy, targeted therapy, and their combinations), two ICI drugs, or one ICI drug with conventional therapy. Eligible studies must have reported site, organ, or system level data on treatment related adverse events. High quality, single arm trials and placebo controlled trials on ICI drugs were selected to establish a validation group. Results 36 head-to-head phase II and III randomised trials (n=15 370) were included. The general safety of ICI drugs ranked from high to low for all adverse events was as follows: atezolizumab (probability 76%, pooled incidence 66.4%), nivolumab (56%, 71.8%), pembrolizumab (55%, 75.1%), ipilimumab (55%, 86.8%), and tremelimumab (54%, not applicable). The general safety of ICI drugs ranked from high to low for severe or life threatening adverse events was as follows: atezolizumab (49%, 15.1%), nivolumab (46%, 14.1%), pembrolizumab (72%, 19.8%), ipilimumab (51%, 28.6%), and tremelimumab (28%, not applicable). Compared with conventional therapy, treatment-related adverse events for ICI drugs occurred mainly in the skin, endocrine, hepatic, and pulmonary systems. Taking one ICI drug was generally safer than taking two ICI drugs or one ICI drug with conventional therapy. Among the five ICI drugs, atezolizumab had the highest risk of hypothyroidism, nausea, and vomiting. The predominant treatment-related adverse events for pembrolizumab were arthralgia, pneumonitis, and hepatic toxicities. The main treatment-related adverse events for ipilimumab were skin, gastrointestinal, and renal toxicities. Nivolumab had a narrow and mild toxicity spectrum, mainly causing endocrine toxicities. Integrated evidence from the pooled incidences, subgroup, and sensitivity analyses implied that nivolumab is the best option in terms of safety, especially for the treatment of lung cancer. Conclusions Compared with other ICI drugs used to treat cancer, atezolizumab had the best safety profile in general, and nivolumab had the best safety profile in lung cancer when taking an integrated approach. The safety ranking of treatments based on ICI drugs is modulated by specific treatment-related adverse events. Systematic review registration PROSPERO CRD42017082553.

Background Promising efficacy and manageable toxicity of docetaxel-based concurrent chemoradiotherapy (CCRT) were reported in head and neck cancer. In addition, the effect of CCRT in combination with cisplatin and/or 5-fluorouracil on both locoregionally advanced and metastatic/recurrent nasopharyngeal carcinoma (NPC) was verified. However, CCRT with docetaxel for locoregionally advanced NPC are not well studied. This study aimed to compare effectiveness and toxicities of CCRT with weekly docetaxel versus tri-weekly cisplatin for locoregionally advanced NPC. Methods Clinical data of patients with locoregionally advanced NPC newly diagnosed between January 2010 and December 2014 receiving CCRT with either weekly docetaxel (15 mg/m2) or tri-weekly cisplatin (80–100 mg/m2) were reviewed. Propensity score matching at a 1:1 ratio was performed to balance baseline characteristics. Adverse events and survival were compared between the two groups. Results A total of 962 patients were included as the whole cohort, and 448 patients were matched and were regarded as the matched cohort. The median follow-up duration was 48 months for the whole cohort. The 3-year nodal recurrence-free survival rate was significantly increased for patients treated with docetaxel in both the whole (hazard ratio [HR] = 0.37, 95% confidence interval [CI] 0.19–0.72, P = 0.030) and matched cohorts (HR = 0.33, 95% CI 0.14–0.79, P = 0.023). However, no significant differences were observed in overall survival, local recurrence-free survival, and distant metastasis-free survival between the two groups in both cohorts. Significantly higher rates of grade 3 radiodermatitis (6.7% vs. 1.8%, P = 0.001), mucositis (74.5% vs. 37.9%, P

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is revolutionizing the management of brain metastases (BMs). This study was to explore the value of upfront cranial radiotherapy (RT) in EGFR-mutated non-small cell lung cancer (NSCLC) with BMs compared with EGFR-TKIs alone.Methods: We searched all topic-related comparative articles in public databases (MEDLINE, EMBASE, Cochrane Library, and Web of Science) and conference proceedings. Outcomes of interest were intracranial objective response rate (ORR), overall survival (OS), and intracranial progression-free survival (PFS). Statistical analyses were calculated using Review Manager 5.3 software.Results: Thirteen comparative studies that included a total of 1,456 patients were eligible. Upfront brain RT had significantly higher OS (HR = 0.78, 95% CI = 0.65–0.93, P = 0.005) than EGFR-TKI alone. Upfront RT plus TKI had superior OS (HR = 0.71, 95% CI = 0.58–0.86, P = 0.0005) and intracranial PFS (HR = 0.69, 95% CI = 0.49–0.99, P = 0.04). The pooled data favored upfront whole brain RT (WBRT) plus TKI in terms of intracranial PFS (HR = 0.64, 95% CI = 0.48–0.85, P = 0.002) and OS (HR = 0.75, 95% CI = 0.57–1, P = 0.05). Upfront stereotactic radiosurgery (SRS) was associated with better OS (HR = 0.37, 95% CI = 0.26–0.54, P < 0.00001). Similar results were observed when analysis was restricted to the use of erlotinib or geftinib.Conclusions: The upfront use of brain RT seemed critical, especially for SRS. Upfront administration of upfront WBRT plus EGFR-TKI had better survival outcomes and seemed superior to EGFR-TKI alone.

The prognosis of patients who have Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without EBV-related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV-related NPC by incorporating the measurement of plasma EBV DNA.In total, 979 patients with NPC who received intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT.The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression-free survival and overall survival in univariate analysis (all P.001) and multivariate analysis (all P.05). Recursive partitioning analysis of the primary cohort to incorporate EBV DNA generated the following proposed stage groupings: stage RI (T1N0), RIIA (T2-T3N0 or T1-T3N1, EBV DNA ≤2000 copies/mL), stage RIIB (T2-T3N0 or T1-T3N1, EBV DNA2000 copies/mL; T1-T3N2, EBV DNA ≤2000 copies/mL), stage RIII (T1-T3N2, EBV DNA2000 copies/mL; T4N0-N2), and stage RIVA (any T and N3). In the validation cohort, the 5-year progression-free survival rate was 100%, 87.9%, 76.7%, 68.7%, and 50.4% for proposed stage RI, RIIA, RIIB, RIII, and RIV NPC, respectively (P.001). Compared with the eighth edition TNM stage groupings, the proposed stage groupings incorporating EBV DNA provided better hazard consistency, hazard discrimination, outcome prediction, and sample size balance.The proposed stage groupings have better prognostic performance than the eighth edition of the TNM staging system. EBV DNA titers should be included in the TNM staging system to assess patients who have EBV-related NPC.

Cell-based therapy is a promising strategy to alleviate neuropathic pain caused by spinal cord injury (SCI). We transplanted olfactory ensheathing cells (OECs) into SCI rats with neuropathic pain and quantitatively detected the sensory nerve function. The expression levels of P2X4 receptor (P2X4R), 200kD neurofilament heavy polypeptide (NF200), and glial fiber acidic protein (GFAP) were measured by immunofluorescence and Western blot analyses. Results showed that NF200 expression significantly increased, GFAP expression decreased, and sensory nerve function improved. In addition, OEC transplantation inhibited the overexpression of P2X4R, which plays an important role in neuropathic pain. Thus, OEC is a candidate target for the treatment of sensory functional loss and P2X4R-mediated neuropathic pain caused by SCI.

Background The value of Epstein–Barr virus (EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma (NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment follow-up in the patients with NPC who have undergone intensity-modulated radiotherapy. Methods The medical records of 385 NPC patients treated with intensity-modulated radiotherapy between November 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within 3 months after treatment, and then every 3–12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed. Results Of the 385 patients, 267 (69.4%) had detectable pretreatment plasma EBV DNA (> 0 copy/mL) and 93 (24.2%) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months (range 9.3–73.8 months). Detectable EBV DNA during posttreatment follow-up was found in 14.4% (17/118) and 28.5% (76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8% (40/313) of patients who remained disease-free, 56.4% (22/39) of patients with locoregional recurrence alone, and 93.9% (31/33) of patients with distant metastasis as the first recurrence event (P