RESUMEN
BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.
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Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Humanos , Carcinoma Nasofaríngeo/genética , Estudios Retrospectivos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/genética , Pronóstico , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Imagen por Resonancia Magnética/métodosRESUMEN
OBJECTIVES: To evaluate whether MRI-based T stage (TMRI), [18F]FDG PET/CT-based N (NPET/CT), and M stage (MPET/CT) are superior in NPC patients' prognostic stratification based on long-term survival evidences, and whether TNM staging method involving TMRI + NPET/CT + MPET/CT could improve NPC patients' prognostic stratification. METHODS: From April 2007 to December 2013, 1013 consecutive untreated NPC patients with complete imaging data were enrolled. All patients' initial stages were repeated based on (1) the NCCN guideline recommended "TMRI + NMRI + MPET/CT" ("MMP") staging method; (2) the traditional "TMRI + NMRI + Mconventional work-up (CWU)" ("MMC") staging method; (3) the single-step "TPET/CT + NPET/CT + MPET/CT" ("PPP") staging method; or (4) the "TMRI + NPET/CT + MPET/CT" ("MPP") staging method recommended in present research. Survival curve, ROC curve, and net reclassification improvement (NRI) analysis were used to evaluate the prognosis predicting ability of different staging methods. RESULTS: [18F]FDG PET/CT performed worse on T stage (NRI = - 0.174, p < 0.001) but better on N (NRI = 0.135, p = 0.004) and M stage (NRI = 0.126, p = 0.001). The patients whose N stage upgraded by [18F]FDG PET/CT had worse survival (p = 0.011). The "TMRI + NPET/CT + MPET/CT" ("MPP") method performed better on survival prediction when compared with "MMP" (NRI = 0.079, p = 0.007), "MMC" (NRI = 0.190, p < 0.001), or "PPP" method (NRI = 0.107, p < 0.001). The "TMRI + NPET/CT + MPET/CT" ("MPP") method could reclassify patients' TNM stage to a more appropriate stage. The improvement is significant in patients with more than 2.5-years follow-up according to the time-dependent NRI values. CONCLUSIONS: The MRI is superior to [18F]FDG PET/CT in T stage, and [18F]FDG PET/CT is superior to CWU in N/M stage. The "TMRI + NPET/CT + MPET/CT" ("MPP") staging method could significantly improve NPC patients' long-term prognostic stratification. CLINICAL RELEVANCE STATEMENT: The present research provided long-term follow-up evidence for benefits of MRI and [18F]FDG PET/CT in TNM staging for nasopharyngeal carcinoma, and proposes a new imaging procedure for TNM staging incorporating MRI-based T stage and [18F]FDG PET/CT-based N and M stage, which significantly improves long-term prognostic stratification for patients with NPC. KEY POINTS: ⢠The long-term follow-up evidence of a large-scale cohort was provided to evaluate the advantages of MRI, [18F]FDG PET/CT, and CWU in the TNM staging of nasopharyngeal carcinoma. ⢠A new imaging procedure for TNM stage of nasopharyngeal carcinoma was proposed.
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Neoplasias Nasofaríngeas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/patología , Pronóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Radiofármacos , Tomografía de Emisión de Positrones/métodos , Estadificación de Neoplasias , Imagen por Resonancia Magnética , Neoplasias Nasofaríngeas/patologíaRESUMEN
PURPOSE: This study aimed to establish an effective nomogram to predict primary distant metastasis (DM) in patients with nasopharyngeal carcinoma (NPC) to guide the application of PET/CT. METHODS: In total, 3591 patients with pathologically confirmed NPC were consecutively enrolled. The nomogram was constructed based on 1922 patients treated between 2007 and 2014. Multivariate logistical regression was applied to identify the independent risk factors of DM. The predictive value of the nomogram was evaluated using the concordance index (C-index), calibration curve, probability density functions (PDFs), and clinical utility curve (CUC). The results were validated in 1669 patients enrolled from 2015 to 2016. Net reclassification improvement (NRI) was applied to compare performances of the nomogram with other clinical factors. The best cut-off value of the nomogram chosen for clinical application was analyzed. RESULTS: A total of 355 patients showed primary DM among 3591 patients, yielding an incidence rate of 9.9%. Sex, N stage, EBV DNA level, lactate dehydrogenase level, and hemoglobin level were independent predictive factors for primary DM. C-indices in the training and validation cohort were 0.796 (95% CI, 0.76-0.83) and 0.779 (95% CI, 0.74-0.81), respectively. The NRI indices demonstrated that this model had better predictive performance than plasma EBV DNA level and N stage. We advocate for a threshold probability of 3.5% for guiding the application of PET/CT depending on the clinical utility analyses. CONCLUSION: This nomogram is a useful tool to predict primary DM of NPC and guide the clinical application of PET/CT individually at the initial staging.
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Neoplasias Nasofaríngeas , Nomogramas , Fluorodesoxiglucosa F18 , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico por imagen , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , PronósticoRESUMEN
OBJECTIVES: The value of using PET/CT for staging of stage I-II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. METHODS: A total of 1003 patients with pathologically confirmed NPC of stages I-II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. RESULTS: Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3-82.1] vs. 91.1% [84.8-97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8-100.0] vs. 76.4% [67.6-85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. CONCLUSIONS: This study showed PET/CT is of little value for staging of stage I-II NPC patients at initial imaging. KEY POINTS: ⢠PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. ⢠No association existed between pre-treatment PET/CT use and improved survival in stage I-II NPC patients.
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Neoplasias Nasofaríngeas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios de Casos y Controles , Fluorodesoxiglucosa F18 , Humanos , Ganglios Linfáticos/patología , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/patología , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Radiofármacos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma is limited because of their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in locally recurrent nasopharyngeal carcinoma. METHODS: This multicenter, retrospective study included 921 patients with locally recurrent nasopharyngeal carcinoma. A machine learning signature and nomogram based on pretreatment magnetic resonance imaging features were developed for predicting overall survival in a training cohort and validated in 2 independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA-sequencing analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving concordance indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables statistically improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with statistically distinct overall survival rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-sequencing analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: A magnetic resonance imaging-based radiomic signature predicted overall survival more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for locally recurrent nasopharyngeal carcinoma patients.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Nomogramas , Radiómica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aprendizaje Automático , Imagen por Resonancia Magnética , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/patología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVES: About 17.7-34.0 % of patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) responded well to anti-PD-1 monotherapy. We sought to establish a nomogram to estimate the progression-free survival (PFS) of RM-NPC patients receiving subsequent-line anti-PD-1 monotherapy. MATERIALS AND METHODS: This cohort study investigated consecutive RM-NPC patients undergoing anti-PD-1 monotherapy. A nomogram was developed in the training cohort (n = 161), using a Cox multivariate model with backward stepwise inclusion, and was validated in the validation cohort (n = 69). Its predictive accuracy was assessed using a concordance index (C-index) and calibration curve. The primary endpoint was PFS. Secondary endpoints included the objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: Liver metastasis, albumin, lactate dehydrogenase, monocyte-to-lymphocyte ratio, and plasma Epstein-Barr virus DNA were used to develop a nomogram that could separate patients into favourable- and unfavourable-prognosis groups. The C-index in the training and validation cohort were 0.70 and 0.68, respectively, which was confirmed by calibration curves. Median PFS (mPFS) was lower for the unfavourable-prognosis than for the favourable-prognosis group (1.80 vs 4.93; hazard ratio 2.49 [95 % confidence interval: 1.78-3.49]; p < 0.001), across all subgroups. OS exhibited the same pattern. The ORR and DCR were markedly lower in the unfavourable-prognosis than in the favourable-prognosis group. All results were confirmed in the validation cohort. CONCLUSION: Our model is a reliable prognostic indicator of PFS in RM-NPC patients undergoing anti-PD-1 monotherapy, allowing robust estimation of the immunotherapy benefit an individual might derive.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Pronóstico , Carcinoma Nasofaríngeo/patología , Estudios de Cohortes , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Herpesvirus Humano 4 , Neoplasias Nasofaríngeas/patologíaRESUMEN
Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6-80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0-51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients.
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Inhibidores de Puntos de Control Inmunológico , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Platino (Metal) , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the effects of occupational exposure to formaldehyde on the micronuclei frequencies in peripheral blood lymphocytes of workers. METHODS: Two hundred thirty six plywood workers were divided into 3 exposure groups (low, middle and high) according to internal exposure biomarker (formaldehyde human serum albumin conjugate, FA-HSA), which was detected by ELISA. The concentrations of formaldehyde (FA) in air of two workshops were measure using the high performance liquid chromatography. Cytokinesis-block micronucleus (CBMN) test was used to detect the micronuclei frequencies of peripheral blood lymphocyte in 236 workers. RESULTS: The average concentrations of FA in the low and high exposure workshops were 0.58 +/- 0.20 and 1.48 +/- 0.61 mg/m3, respectively, there was significant difference (P < 0.01). The average concentrations of serum FA-HAS of workers in two workshops were 69.22 +/- 15.37 and 136.29 +/- 89.49 pg/ml, respectively, there was significant difference (P < 0.01). The results of CBMN test showed that the micronucleus frequencies in low, middle and high exposure groups were 1.94 +/- 1.72, 2.10 +/- 1.92 and 2.10 +/- 1.70 per thousand, respectively, there were no significant differences between groups. However, the micronucleus frequencies in accumulative low, middle and high exposure groups were 1.36 +/- 1.36, 2.31 +/- 1.81 and 2.49 +/- 1.92 per thousand, respectively, there were significant differences between different accumulative exposure groups (P < 0.01). The results of correlation analysis indicated that there was a positive correlation between accumulative exposure levels and micronucleus frequencies (r(s) = 0.321, P < 0.01). The accumulative exposure doses may be a risk factor for high micronucleus frequencies in workers exposed to FA (P(trend) = 0.002). CONCLUSION: FA-HSA levels can serve as an internal exposure biomarker for assessing the exposure level of workers exposed to FA. Accumulative formaldehyde exposure resulted in an increase of micronuclei frequencies of peripheral blood lymphocyte in plywood workers.
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Linfocitos/citología , Exposición Profesional/análisis , Hipersensibilidad Respiratoria/sangre , Adulto , Pueblo Asiatico , Biomarcadores/sangre , Formaldehído/efectos adversos , Formaldehído/sangre , Humanos , Linfocitos/efectos de los fármacos , Pruebas de MicronúcleosRESUMEN
OBJECTIVE: To explore the characteristics of particulate matter pollution in coke oven plant, so as to provide scientific data for establishing occupational exposure limits for coke oven emissions. METHODS: Concentrations of CO, SO2, BSM, BTEX (concentrations of benzene, toluene and xylene were determined in this study), PM10, PM2.5, 16 selected PAHs in PM10 and PM2.5 were determined in the work environment of a coke oven plant in Wuhan. The work environment was divided into the adjunct area, the bottom of, the side of and the top of coke oven. RESULTS: The concentrations of CO, SO2, BSM, BETX, PM10, PM2.5, PAHs in PM10 and PM2.5 were significantly related to working environmental categories, respectively, and were increasing as the adjunct area < bottom < side < top (P (trend) < 0.05). PM10 was statistically significantly correlated with CO, SO2, benzene, BTEX and BSM (0.705, 0.823, 0.664, 0.624 and 0.734, respectively). PM2.5 was statistically significantly correlated with CO, SO2, benzene, BTEX and BSM (0.635, 0.916, 0. 680, 0.553 and 0.726, respectively). BSM was statistically significantly correlated with benzene (0.689). The ratios of PM2.5 to PM10 between different work environments were not significantly different in one-way ANOVA (P > 0.05). The distribution of aromatic rings and the concentrations of total benzo[a] pyrene equivalents in PM10 and PM2.5 were not statistically different between work environments. CONCLUSION: The concentrations of particulate matter was related with other contents of coke oven emissions in coke work environment, and the contents and types of PAHs in PM10 and PM2.5 were similar.
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Contaminantes Ocupacionales del Aire/análisis , Benceno/análisis , Coque , Material Particulado/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Benzo(a)pireno/análisis , Exposición Profesional/análisis , Tolueno/análisis , Lugar de Trabajo , Xilenos/análisisRESUMEN
OBJECTIVE: To explore the effects of smoking on urinary 10 metabolites of polycyclic aromatic hydrocarbons (PAHs) in the coke oven workers. METHODS: Occupational health examination was performed on 1401 coke oven workers in one coking plant, their urine were collected respectively. The concentrations of the ten monohydroxy polycyclic aromatic hydrocarbons in urine were detected by gas chromatography/mass spectrometry. The 1401 workers were divided into four groups, namely control, adjunct workplaces, bottom and side, top group according to their workplaces and the different concentrations of PAHs in the environment. The concentrations of the ten monohydroxy polycyclic aromatic hydrocarbons between smokers and nonsmokers in each workplace group were compared using analysis of covariance, respectively. RESULTS: The levels of concentrations of the sixteen polycyclic aromatic hydrocarbons we detected at control were significantly higher than those at other areas (P < 0.05). Comparing the ten monohydroxy polycyclic aromatic hydrocarbons levels between smokers and nonsmokers, the levels of 1-hydroxynaphthalene and 2-hydroxynaphthalene among smokers were higher than nonsmokers with statistically significance in control, adjunct workplaces, bottom and side and top groups (P < 0.05). However, the levels of 1-hydroxypyrene had no statistically significant differences between the four areas. CONCLUSION: Urinary 1-hydroxynaphthalene and 2-hydroxynaphthalene may be used as biomarkers for the impact of smoking on monohydroxy polycyclic aromatic hydrocarbons in the coke oven workers.
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Contaminantes Ocupacionales del Aire/orina , Coque , Exposición Profesional/análisis , Hidrocarburos Policíclicos Aromáticos/orina , Fumar/orina , Biomarcadores/orina , Humanos , Masculino , Naftoles/orina , Pirenos/orinaRESUMEN
BACKGROUND: Salvage radiotherapy (RT) is a potentially curative approach for advanced locally recurrent nasopharyngeal carcinoma (NPC), but it is associated with severe toxicities. We aimed to develop a model to predict which patients would benefit from salvage RT. METHODS: A total of 809 patients who were diagnosed with advanced locally recurrent NPC and treated with salvage RT or palliative chemotherapy (CT) at a high-volume cancer center were included. Patients were randomly split into a training and validation set and matched using inverse probability of treatment weighting. The primary outcome was overall survival (OS). Candidate variables associated with heterogeneous treatment effects were identified with interaction terms in Cox model and incorporated into Salvage Radiotherapy Outcome Score (SARTOS). RESULTS: The final model included five interaction terms indicating that female sex, presence of prior RT-induced grade ≥ 3 late toxicities and suboptimal performance status were associated with less benefit from salvage RT. SARTOS from the model significantly predicted treatment effects of salvage RT in matched training (Pinteration < 0.001) and validation cohorts (Pinteration = 0.027). Of patients in high SARTOS subgroup, salvage RT significantly improved survival versus palliative CT in matched training (3-year OS 67.3% vs. 42.0%, HR 0.51, 95% CI 0.32-0.82, P = 0.005) and validation cohorts (3-year OS 71.8% vs. 22.8%, HR 0.40, 95% CI 0.17-0.97, P = 0.042); in low SARTOS subgroup, salvage RT failed to induce survival benefit. CONCLUSIONS: We found that the SARTOS model could identify a subgroup of patients who benefit from salvage RT versus palliative CT, which helps personalize treatment recommendations for patients with recurrent NPC.
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Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Femenino , Humanos , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Recurrencia Local de Neoplasia/patología , Radioterapia de Intensidad Modulada/efectos adversos , Terapia RecuperativaRESUMEN
PURPOSE: Curative radiotherapy for nasopharyngeal carcinoma (NPC) can lead to acquired nasal cavity stenosis and atresia (ANCSA). As the first study to investigate risk factors of ANCSA in a large cohort of NPC patients, this article aims to develop and validate a multivariate normal tissue complication probability (NTCP) model to predict the development of ANCSA and to establish a nomogram for clinical use. METHODS AND MATERIALS: The retrospective cohort was comprised of 548 NPC patients treated with radical radiotherapy. The cohort was randomly divided into training and validation groups. Least absolute shrinkage and selection operator regression was performed for variable selection from the clinical and dosimetric characteristics in the training group. A multivariate NTCP model and a nomogram were established for the prediction of ANCSA development. Discrimination and calibration were tested using receiver operating characteristic (ROC) curves and calibration tests, respectively, for both groups. RESULTS: ANCSA was observed in 132 (24.1%) of 548 patients with NPC who underwent radical radiotherapy. The median time to ANCSA detection after treatment was 2.8 months (range, 0.0-57.7 months). Five potential predictors, including choanal invasion, low white blood cell count, high C-reactive protein level, high serum amyloid A level, and high V70Gy of the nasal cavity, were selected to develop the NTCP model based on 365 patients in the training group. The model had a fairly good discriminative power according to the ROC analysis in both the training (area under ROC curve = 0.79, 95%CI: 0.73-0.84) and validation (0.73, 0.64-0.82) groups. The calibration power was tested using the calibration test in the training (E-max = 0.069, E-avg = 0.015, p = 0.977) and validation (E-max = 0.057, E-avg = 0.032, p = 0.747) groups. CONCLUSIONS: We developed and successfully validated an NTCP model for early prediction of ANCSA in patients with NPC after radical radiotherapy. This could help clinicians assess the risk of ANCSA before the initiation of follow-ups and ensure appropriate and timely management of this complication.
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Cavidad Nasal , Neoplasias Nasofaríngeas , Constricción Patológica , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Nomogramas , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: Previous studies demonstrated that the radiation therapy, image technology, and the application of chemotherapy have developed in the last 2 decades. This study explored the survival trends and treatment failure patterns of patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with radiation therapy. Furthermore, we evaluated the survival benefit brought by the development of radiation therapy, image technology, and chemotherapy based on a large cohort from 1990 to 2012. METHODS AND MATERIALS: Data from 20,305 patients with nonmetastatic NPC treated between 1990 and 2012 were analyzed. Patients were divided into 4 calendar periods (1990-1996, 1997-2002, 2003-2007, and 2008-2012). Overall survival (OS) was the primary endpoint. RESULTS: Magnetic resonance imaging has replaced computed tomography as the most important imaging technique since 2003. Conventional 2-dimensional radiation therapy, which was the main radiation therapy technique in our institution before 2008, was replaced by intensity modulated radiation therapy later. An increasing number of patients have undergone chemotherapy since 2003. The 5-year OS across the 4 calendar periods increased at each TNM stage with progression-free survival (PFS) and locoregional relapse-free survival (LRFS) showing a similar trend, whereas distant metastasis-free survival showed small differences. Multivariate analyses showed that the application of intensity modulated radiation therapy and magnetic resonance imaging were independent protective factors in OS, PFS, LRFS, and distant metastasis-free survival. Chemotherapy benefited patients in OS, PFS, and LRFS. The main pattern of treatment failure shifted from recurrence to distant metastasis. CONCLUSIONS: The development of radiation therapy, image technology, and chemotherapy increased survival rates among patients with NPC because of excellent locoregional control. Distant failure has become the greatest challenge for NPC treatment.
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Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Estudios de Cohortes , ADN Viral/sangre , Femenino , Humanos , Imagen por Resonancia Magnética/mortalidad , Imagen por Resonancia Magnética/tendencias , Masculino , Persona de Mediana Edad , Análisis Multivariante , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Papillomaviridae/genética , Pronóstico , Supervivencia sin Progresión , Radioterapia/métodos , Radioterapia/mortalidad , Radioterapia/tendencias , Radioterapia de Intensidad Modulada/mortalidad , Radioterapia de Intensidad Modulada/tendencias , Tasa de Supervivencia , Factores de Tiempo , Tomografía Computarizada por Rayos X/tendencias , Insuficiencia del Tratamiento , Adulto JovenAsunto(s)
Isocianatos/toxicidad , Efectos Tardíos de la Exposición Prenatal , Testículo/metabolismo , Animales , Femenino , Masculino , Malondialdehído/metabolismo , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Embarazo , Superóxido Dismutasa/metabolismo , Testículo/efectos de los fármacosRESUMEN
The mobilization of soil particles changes the porosity of saturated zone during air sparging. Soil porosity is shown to be correlated with soil electrical resistivity. This study performs porosity-resistivity tests to establish the relationship between porosity and resistivity of quartz sand. Experiments, involving a large sandbox to simulate the saturated zone, are then performed to compare the resistivity of compacted sand before air injection with that after air injection. The relevant data enable the mobilization of quartz sand particles to be quantified. Results of the experiments indicate the mobilization of sand particles and an increase in porosity directly proportional to the rate at which air is injected. Besides, a layer of fine-grained particles covered the compacted sand at the upper boundary of sandbox after each air injection experiment. This is direct evidence that finer particles were transported upward during air sparging. Two methods were applied to verify the results of this study. The first verification method indicated that changes in porosity increased directly proportional to the air injection rate, which is consistent with shear theory. The other validation method indicated that the mass of sand in the tank did not change after air sparging, which indicates that the resistivity-porosity method is unbiased.