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1.
Cancer Commun (Lond) ; 40(1): 32-42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32112522

RESUMO

BACKGROUND: Capecitabine was previously used as a second-line or salvage therapy for metastatic nasopharyngeal carcinoma (NPC) and has shown satisfactory curative effect as maintenance therapy in other metastatic cancers. This study aimed to explore the role of capecitabine as maintenance therapy in de novo metastatic NPC patients with different plasma Epstein-Barr virus (EBV) DNA levels before treatment. METHODS: We selected de novo metastatic NPC patients treated with locoregional radiotherapy (LRRT) for this retrospective study. The propensity score matching (PSM) was applied to balance potential confounders between patients who underwent capecitabine maintenance therapy and those who did not with a ratio of 1:3. Overall survival (OS) was the primary endpoint. The association between capecitabine maintenance therapy and survival was assessed using the log-rank test and a Cox proportional hazard model. RESULTS: Among all patients eligible for this study, 64 received capecitabine maintenance therapy after LRRT. After PSM, 192 patients were identified in the non-maintenance group. In the matched cohort, patients treated with capecitabine achieved a higher 3-year OS rate compared with patients in the non-maintenance group (68.5% vs. 61.8%, P = 0.037). Multivariate analysis demonstrated that capecitabine maintenance therapy was an independent prognostic factor. In subgroup analysis, 3-year OS rate was comparable between the maintenance and non-maintenance groups in patients with high pretreatment EBV DNA levels (˃30,000 copies/mL) (54.8% vs. 45.8%, P = 0.835), whereas patients with low pretreatment EBV DNA levels (≤30,000 copies/mL) could benefit from capecitabine maintenance therapy in OS (90.0% vs. 68.1%, P = 0.003). CONCLUSION: Capecitabine maintenance therapy may be superior to non-maintenance therapy in prolonging OS for de novo metastatic NPC patients with pretreatment EBV DNA ≤ 30,000 copies/mL.

2.
Aging (Albany NY) ; 122020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221045

RESUMO

PURPOSE: This study aimed to elucidate the optimal cumulative cisplatin dose (CCD) for concurrent chemoradiotherapy (CCRT) according to the post-induction chemotherapy (IC) plasma Epstein-Barr virus (EBV) DNA level. RESULTS: EBV DNA was detected and undetected in 179 and 370 patients, respectively. Of the entire cohort, 73/549 (13.3%) patients received a total CCD ≥ 160 mg/m2 and 476/549 (86.7%) patients, <160 mg/m2. CCD enhancement was not associated with a survival benefit in patients with undetected EBV DNA after IC. However, among patients with post-IC detectable EBV DNA, higher 3-year PFS and locoregional relapse-free survival (LRFS) rates were observed in those who received a CCD ≥ 160 mg/m2. Multivariate analysis also showed CCD was an independent prognostic factor for PFS and LRFS in patients with post-IC detectable EBV DNA. CONCLUSIONS: CCD enhancement was not associated with a survival benefit in patients with undetected EBV DNA after IC. However, among patients with post-IC detectable EBV DNA, those receiving ≥160 mg/m2 CCD showed significantly improved 3-year PFS and LRFS. METHODS: NPC patients (549) treated with IC and CCRT were included. Prognosis was assessed using a multivariate Cox proportional hazards model. Furthermore, grade 1-4 toxicities were compared between different CCD groups.

3.
BMC Cancer ; 20(1): 89, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013967

RESUMO

BACKGROUND: We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC. METHODS: The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA < 1500 copies) and high-risk group (pre-EBV DNA ≥ 1500 copies). Progression free survival (PFS), overall survival (OS), locoregional relapse free survival (LRFS), distant metastasis free survival (DMFS) and grade 3-4 toxicities were compared among different IC regimens. The survival rates were compared using log-rank test and a Cox proportional hazards model was used to perform multivariate analyses. RESULTS: A multivariate analysis revealed TPF to be more effective than TP. Among stage III patients, no significant difference in clinical outcome between the different IC regimens was showed, while TPF was associated with significantly better survival conditions in the stage IV patients. A further subgroup analysis revealed that only patients with pre-EBV DNA ≥ 1500 copies could benefit from the application of TPF among stage IV NPC. In terms of acute toxicities, PF was associated with fewer grade 3/4 acute toxicities. CONCLUSIONS: In low-risk NPC patients, PF-based IC showed similar efficacy as TPF and TP but was associated with fewer grade 3/4 acute toxicities. In high-risk patients, however, the TPF regimen was superior to PF and TP, although grade 3/4 toxicities were more common with the TPF regimen.

4.
Cancer Med ; 9(5): 1661-1670, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31925942

RESUMO

OBJECTIVE: We aimed to establish and validate two nomograms that predict progression-free survival (PFS) and overall survival (OS) in patients with stage II-IVa nasopharyngeal carcinoma (NPC) while evaluating the benefit of concurrent chemotherapy. PATIENTS AND METHODS: We randomly divided 3412 patients newly diagnosed with stage II-IVa NPC between 2008 and 2013 into training and validation 'A' cohorts (n = 1706 each). Another set of patients diagnosed between 2014 and 2016 served as validation cohort 'B' (n = 1503). A Cox multivariate model using the backward stepwise approach was applied to develop the nomograms, which were assessed for accuracy (Harrel C index) and calibration. RESULTS: The 3- and 5-year PFS rates in the training cohort were 86.8% (95% confidence interval [CI] 85.0%-88.6%) and 82.3% (95% CI 80.1%-84.5%), respectively. For the PFS nomogram, 5 variables were selected based on a backward procedure in the multivariate Cox model (gender, T stage, N stage, Epstein-Barr virus DNA, and treatment method). The same variables plus patient age and diabetes mellitus were used for the OS nomogram. The Harrell C indices of the training, validation A, and validation B cohorts were 0.711, 0.700, and 0.703, respectively, for PFS, and 0.775, 0.743, and 0.727, respectively, for OS. Both nomograms performed well in terms of calibration in the training and validation cohorts. CONCLUSIONS: Our nomograms are reliable prognostic predictors of PFS and OS in patients with stage II-IVa NPC. These nomograms could robustly estimate an individual's benefit from concurrent chemotherapy, which assists in treatment decision-making.

5.
Oral Oncol ; 100: 104490, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790913

RESUMO

BACKGROUND AND PURPOSE: Our previous phase III randomized trial demonstrated that the addition of concurrent chemotherapy to radiotherapy (RT) could improve survival in stage II nasopharyngeal carcinoma (NPC). Based on the study, we sought to develop a nomogram for predicting the 5-year and 10-year survival of patients with stage II NPC and estimating the benefit of concurrent chemoradiotherapy (CCRT) for individual patients. MATERIALS AND METHODS: Data of 199 enrolled patients from the original trial was analyzed to build a nomogram. Overall survival (OS) was the primary endpoint. The discrimination and calibration capacities were evaluated using Harrell Concordance Index (C-index) and calibration curves, respectively. Internal validation of the nomogram was performed by a separate cohort of 306 patients from the same cancer center. RESULT: In training cohort, patients in CCRT group achieved higher 5-year and 10-year OS compared with patients in RT group. Three independent prognostic factors, which were age, N stage and treatment method from multivariable analysis were extracted to enter the nomogram. T stage was also included due to its importance in clinical decisions. The Harrell C-index of the nomogram in training and validation cohort was 0.748 and 0.653 respectively. The calibration curves showed an acceptable agreement between prediction and observed probability. CONCLUSION: We developed and validated a nomogram to predict the 5-year and 10-year OS in stage II NPC patients. The nomogram could serve as a pragmatic tool in clinical decisions to estimate the individual risk of stage II patients and identify those who could benefit from chemotherapy.

6.
Cancer Lett ; 468: 27-40, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31604115

RESUMO

Patients with recurrent nasopharyngeal carcinoma (NPC) have more co-existing distant metastasis than those of no-recurrence and are more likely to suffer distant metastasis after re-irradiation than patients with newly diagnosed NPC. However, the relationship between radioresistance and distant metastasis and the mechanisms involved in radioresistance-associated metastasis are still unclear. In this study, we proved that C-C motif chemokine ligand 2 (CCL2) expression was significantly elevated in HONE1-IR cells and recurrent NPC tumour. Inhibition of CCL2 enhanced sensitivity to radiotherapy in NPC cells. Moreover, autocrine CCL2 promoted NPC cell adaptive radioresistance, metastasis and epithelial-mesenchymal transition. Additionally, p53 activated CCL2 transcription. High CCL2 expression was highly associated with poorer locoregional recurrence free survival, progression free survival and overall survival in patients with newly diagnosed NPC. Notably, high CCL2 expression was an independent prognostic factor for distant metastasis free survival in recurrent NPC patients. Our results provide insights into the autocrine signalling mechanisms of CCL2 and suggest that inhibition of autocrine CCL2 may be a candidate treatment strategy for management of radioresistant NPC.

7.
J Cancer ; 10(23): 5614-5621, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737097

RESUMO

Objectives: To evaluate the prognostic significance of Adult Comorbidity Evaluation-27 (ACE-27) for elderly patients (age ≥70 years) with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with Intensity-Modulated Radiotherapy (IMRT), with or without chemotherapy. Methods: 206 elderly patients with locoregionally advanced NPC treated from December 2006 to December 2016 were involved into analysis as the training cohort. Besides, a separate cohort of 72 patients from the same cancer center collected between January 2003 and October 2006 served as the validation cohort. By using propensity score matching (PSM), we created a balanced cohort by matching patients who received chemoradiotherapy with patients who received IMRT alone. Treatment toxicities were calculated between CRT and RT groups using the χ2 test. The primary endpoint was cancer-specific survival (CSS). Multivariate analysis was performed to assess the relative risk for each factor by using a Cox's proportional hazards regression model. Results: The median follow-up was 39.0 months (range = 3-137 months). In the PSM cohort, patients in the CRT group achieved comparable survival compared with patients in the RT group. The 3-year CSS rate was 64.3% and 65.2%, respectively (P =0.764). In multivariate analysis, the addition of chemotherapy to IMRT was not an independent prognostic factor for CSS, whereas a high ACE-27 score was an independent risk factor. In subgroup analysis with ACE-27 score ≥ 2, the 3-year CSS rate was worse in patients from the CRT group (63.5% vs. 46.3%, P = 0.041). Conclusions: CRT is comparable to IMRT alone for elderly patients with locoregionally advanced NPC. The ACE-27 tool may help to identify high-risk subgroup for poor disease outcome and tailor individualized treatment.

8.
Drug Des Devel Ther ; 13: 3207-3216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686783

RESUMO

Objective: We aimed to investigate the efficacy and safety of cetuximab (CTX) or nimotuzumab (NTZ) on the addition of palliative chemotherapy (PCT) in patients with de novo metastatic nasopharyngeal carcinoma (NPC). Materials and methods: From 2007 to 2016, 451 eligible patients with de novo metastatic NPC were enrolled in the study. With propensity score matching technique, we created a well-balanced cohort by matching patients who received CTX/NTZ plus PCT (62 patients) with those receiving PCT alone (248 patients) in a ratio of 1:4. The primary endpoint was overall survival (OS). All potential prognostic factors were involved in the multivariate analysis with the Cox regression hazards model. Kaplan-Meier curves were used to compare the survival status, and log-rank test to measure the significance. Results: The median follow-up time was 27.7 months (range, 1-126 months). No significant difference in survival was observed between the CTX/NTZ plus PCT group and PCT group. (3-year OS: 63.0% vs 58.1%; P=0.485). The administration of CTX/NTZ was not found to be an independent prognostic factor in multivariate analysis. With regard to toxicity, the development of a G3-4 skin reaction and mucositis was more common in patients receiving CTX plus PCT. Interaction effects analysis did not show any significant interaction effects on OS between the treatment regimen and prognostic factors (P>0.05). Conclusion: The efficacy of CTX/NTZ and PCT is comparable to single PCT treatment in terms of survival outcomes among de novo metastatic NPC patients. Moreover, the application of CTX exacerbated skin reactions and mucositis.

9.
BMC Cancer ; 19(1): 908, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511059

RESUMO

BACKGROUND: This study aimed to evaluate the prognostic value of maximal standard uptake values (SUVmax) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) comparing with Epstein-Barr virus (EBV) DNA levels in de novo metastatic nasopharyngeal carcinoma (NPC) patients. METHODS: From December 2006 to December 2016, 253 de novo metastatic NPC patients assessed by PET/ computed tomography were involved in current study. SUVmax-T, SUVmax-N, and SUVmax-M referred to the SUVmax at the primary tumor, cervical lymph nodes, and metastatic lesions respectively. Overall survival (OS) was the primary endpoint. RESULT: Patients who died during the follow-up had significantly higher SUVmax-N, SUVmax-M, and EBV DNA level than those in the patients who were alive. SUVmax-N and SUVmax-M were positively correlated with EBV DNA level. The cut-off values of SUVmax-T, SUVmax-N, SUVmax-M, and EBV DNA were 17.0, 12.7, and 6.9, and 13,800 copies/mL respectively, which were determined by receiver operating characteristic (ROC) curve analysis. Patients with elevated SUVmax-N, SUVmax-M, and EBV DNA levels had a lower 3-year OS rate. In multivariate analysis, the independent prognostic factors of OS included EBV DNA, metastatic site, and locoregional radiotherapy application, while SUVmax was not an independent prognostic factor. CONCLUSION: In de novo metastatic NPC patients, higher SUVmax-N and SUVmax-M were associated with worse prognosis. However, the predictive ability of SUVmax-N and SUVmax-M was poorer than that of EBV DNA.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Fluordesoxiglucose F18 , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/etiologia , Tomografia por Emissão de Pósitrons , Adulto , Idoso , DNA Viral , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/etiologia , Neoplasias Nasofaríngeas/mortalidade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Curva ROC
10.
Cancer Med ; 8(16): 6841-6852, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31513364

RESUMO

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.

11.
Cancer Manag Res ; 11: 6253-6263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31372033

RESUMO

Objective: This study aimed to establish a nomogram to predict the risk of post-radiation necrosis in nasopharyngeal carcinoma (NPC) patients. Background: This study was performed to identify influencing factors for developing post-radiation necrosis, and to establish an effective nomogram model to predict individual risks in NPC patients. Methods: 7144 NPC patients receiving radical radiotherapy from 2007 to 2012 were involved in the study, and 207 of them developed nasopharyngeal necrosis (NPN). The clinical characteristics and baseline laboratory results were collected and analyzed. Independent predictive factors were selected using the Cox proportional model and incorporated into the nomogram. The receiver operating characteristic curve and the calibration curve were used to verify discrimination and calibration. Results: The experience of re-irradiation contributed most to the occurrence of NPN (HR, 15.56, 95% CI 10.84-22.35, p<0.001). Clinical factors including age, pathology type, history of diabetes, and original T stage were independent predictors of NPN. Factors reflecting patients' baseline nutritional and inflammatory status such as hemoglobin, albumin, and C-reactive protein were also significantly associated with the development of NPN. With all independent predictive factors incorporated, a nomogram was generated, and it showed excellent discrimination and calibration. Conclusion: This study was the first large-scale cohort study focusing on the development of NPN and established a nomogram to predict its occurrence based on the clinical and laboratory indicators. The nomogram demonstrated good discriminative capacity and satisfactory agreement, which would offer valuable clues for clinicians to distinguish the high-risk NPN population and maintain close surveillance.

12.
Oral Oncol ; 97: 31-36, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421468

RESUMO

OBJECTIVE: We aimed to investigate whether zoledronic acid (ZA) can prevent skeletal-related events (SREs) and offer survival benefits for nasopharyngeal carcinoma (NPC) patients with bone-only metastasis at diagnosis. MATERIALS AND METHODS: A total of 228 newly diagnosed NPC cases with bone-only metastasis were eligible for this retrospective study. Using the propensity score method (PSM) method, a well-balanced cohort was created for further analysis. Overall survival (OS) was the primary endpoint. The difference in survival was evaluated using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were derived from a Cox regression model. Cumulative incidence competing risk analyses using Fine and Gray's method was used to test the cumulative incidence of SREs between the different treatment groups. RESULT: In the PSM cohorts, patients in the platinum-based palliative chemotherapy (PCT) + ZA group and PCT alone group achieved similar 3-year OS (57.3% vs. 46.4%; log rank P = 0.188). Multivariate analysis indicated that ZA administration was not an independent prognostic factor (HR, 0.783; 95% CI, 0.267-2.300; P = 0.657). There was no significant difference in acute treatment toxicity between the 2 treatment groups, although the cumulative incidence of bone-related events (SREs) was significantly lower in the PCT + ZA group (Fine-Gray P = 0.026). CONCLUSION: ZA combined with PCT could not improve OS in NPC patients with bone-only metastasis at diagnosis. However, the incidence of SREs could be effectively prevented via ZA application.

13.
Eur J Cancer ; 119: 87-96, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31425966

RESUMO

BACKGROUND: Initial 3-year results from our clinical trial in locoregionally advanced nasopharyngeal carcinoma (NPC) patients showed that induction chemotherapy (IC) with cisplatin and fluorouracil resulted in improved disease-free survival (DFS) with a marginally significant effect on distant metastasis-free survival (DMFS), but the effect of IC on locoregional relapse-free survival and overall survival (OS) did not differ significantly. Here, we present 5-year follow-up results. PATIENTS AND METHODS: Our trial was a randomised, open-label phase III trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. The IC followed by CCRT group received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 d1-5) every 3 weeks for two cycles before CCRT. Both groups were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The primary end-points were DFS and DMFS. We did efficacy analyses in the 476 randomised patients (intention-to-treat population). RESULTS: After a median follow-up of 82.6 months, the 5-year DFS rate was 73.4% (95% confidence interval [CI] 67.7-79.1) in the IC followed by CCRT group and 63.1% (95% CI 56.8-69.4) in the CCRT alone group (p = 0.007). The 5-year DMFS rate was also significantly higher in the IC followed by CCRT group (82.8%, 95% CI 77.9-87.7) than in the CCRT alone group (73.1%, 95% CI 67.2-79.0, p = 0.014). Our updated analysis revealed an OS benefit of IC: the 5-year OS rate was 80.8% in the IC followed by CCRT group versus 76.8% in the CCRT alone group (p = 0.040). The proportion of patients with eye damage was significantly higher in the CCRT alone group than the IC followed by CCRT group (16.4% [39/238] versus 9.7% [23/238], p = 0.029). CONCLUSION: IC followed by CCRT provides long-term DFS, DMFS and OS benefits compared with CCRT alone in locoregionally advanced NPC and, therefore, can be recommended for these patients.

14.
Int J Radiat Oncol Biol Phys ; 105(3): 581-590, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31319091

RESUMO

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.


Assuntos
Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Estudos de Coortes , DNA Viral/sangue , Feminino , Humanos , Imagem por Ressonância Magnética/mortalidade , Imagem por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Papillomaviridae/genética , Prognóstico , Intervalo Livre de Progressão , Radioterapia/métodos , Radioterapia/mortalidade , Radioterapia/tendências , Radioterapia de Intensidade Modulada/mortalidade , Radioterapia de Intensidade Modulada/tendências , Taxa de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X/tendências , Falha de Tratamento , Adulto Jovem
15.
Br J Radiol ; 92(1102): 20190209, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31265322

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignancy with unique clinical biological profiles such as associated Epstein-Barr virus infection and high radiosensitivity. Radiotherapy has long been recognized as the mainstay for the treatment of NPC. However, the further efficacy brought by radical radiotherapy has reached the bottleneck in advanced patients, who are prone to develop recurrence and distant metastasis after treatment. The application of photon therapy makes it possible for radiation dose escalation in refractory cases and may provide second chance for recurrent patients with less unrecoverable tissue damage. The concept of adaptive radiotherapy is put forward in consideration of target volume shrinkage during treatment. The replanning procedure offers better protection for the organ at risk. However, the best timing and candidates for adaptive radiotherapy is still under debate. The current tendency of artificial intelligence in NPC mainly focuses on image recognition, auto-segmentation and dose prediction. Although artificial intelligence is still in developmental stage, the future of it is promising.To further improve the efficacy of NPC, multimodality treatment is encouraged. In-depth studies on genetic and epigenetic variations help to explain the great heterogeneity among patients, and could further be applied to precise screening and prediction, personalized radiotherapy and the evolution of targeted drugs. Given the clinical benefit of immunotherapy in other cancers, the application of immunotherapy, especially immune checkpoint inhibitor, in NPC is also of great potential. Results from ongoing clinical trials combining immunotherapy with radiotherapy in NPC are expected.


Assuntos
Inteligência Artificial , Previsões , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Inteligência Artificial/tendências , Humanos , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Órgãos em Risco/efeitos da radiação , Medicina de Precisão/métodos , Terapia com Prótons/métodos , Lesões por Radiação/prevenção & controle , Radioterapia/métodos , Radioterapia de Intensidade Modulada/métodos
16.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1789-1792, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31342703

RESUMO

In order to scientifically prevent and control Dendrobium catenatum southern blight disease,the main factors related to this disease occurrence,the pathogen( Sclerotium delphinii),environmental factors( temperature and humidity) and D. catenatum germplasms,were investigated. The results showed that reaching 25-30 ℃ temperature and over 95% humidity simultaneously should be the main conditions for the occurrence and prevalence of D. catenatum southern blight disease. Moreover,the S. delphinii-infected plants and their contaminated substrates were the disease spreading sources. Therefore,removing the infected plants,dealing with the contaminated substrates,keeping air ventilation,and reducing air humidity are the effective ways to prevent and control the occurrence and prevalence of D. catenatum southern blight disease. The research also indicated that D. catenatum has different resistances to the southern blight disease depending on germplasm. The present study lays important foundations for the breeding of D. catenatum diseaseresistant varieties and the further analysis of the infection and resistance mechanisms underlying southern blight disease.


Assuntos
Basidiomycota/patogenicidade , Dendrobium/microbiologia , Doenças das Plantas/microbiologia , Umidade , Temperatura Ambiente
17.
Oral Oncol ; 94: 73-79, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31178215

RESUMO

BACKGROUND AND PURPOSE: No nomogram has been established for de novo metastatic NPC patients previously. Thus, we retrospectively involved 502 de novo NPC patients to develop a practical clinical tool by combining prognostic biomarkers to estimate individual risk. METHODS: The nomogram was based on a primary cohort involving 353 patients from 2007 to 2013; all independent prognostic factors were integrated for inclusion in the model. The predictive accuracy of the model was evaluated by concordance index (C-index). A calibration curve was used to compare predicted and observed survival. We confirmed the results using a validation cohort study on 149 patients enrolled from 2014 to 2016. RESULTS: Five independent prognostic factors derived from multivariable analysis were entered into the nomogram. The C-index of the nomogram was 0.724. The calibration curves for probability of 3- and 5-year overall survival (OS) showed satisfactory agreement between predicted survival and actual observed survival. The Kaplan-Meier survival curves showed a significant difference in survival among different risk groups according to the total score. All results were confirmed in the validation cohort. CONCLUSION: We established a convenient nomogram that provides individual prediction of OS for patients with de novo metastatic NPC.

18.
Cancer Med ; 8(9): 4214-4225, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31210417

RESUMO

OBJECT: To ascertain the treatment effect of concurrent chemotherapy (CCT) in stage II-III nasopharyngeal carcinoma (NPC) patients with different Epstein-Barr virus (EBV) DNA level in intensity-modulated radiotherapy (IMRT) era. METHODS: A total of 2742 patients diagnosed with stage II-III NPC were involved in this study. Patients received IMRT with/without CCT. Overall survival (OS) was the primary endpoint. Receiver operating characteristics curve was used to determine the cut-off value of pre-DNA based on OS. After propensity score matching, the role of CCT was explored in patients with different EBV DNA level. RESULTS: In our cohort, the cut-off value of pre EBV DNA was 1460 copies/mL (area under curve [AUC], 0.695-0.769; sensitivity, 0.766; specificity, 0.599). Patients with high EBV DNA level showed poor survival in OS, progression free survival (PFS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). In patients with EBV DNA level >1460 copies/mL, the concurrent chemoradiotherapy (CCRT) group achieved higher 3-year OS compared with IMRT groups. However, the CCRT and IMRT groups showed comparable OS in patients with EBV DNA ≤1460 copies/mL. In multivariate analyses, CCT was a protective factor for OS, PFS, and LRFS in high-risk patients (EBV DNA level >1460 copies/mL), while not an independent prognostic factor among the low-risk patients (EBV DNA level ≤1460 copies/mL). CONCLUSION: Pre-EBV DNA could be a useful tool to guide individualized treatment for stage II-III NPC patients. Additional CCT to IMRT improved the survival for patients with high pre-EBV DNA, while those with low pre-EBV DNA could not.

19.
J Natl Compr Canc Netw ; 17(6): 703-710, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31200353

RESUMO

BACKGROUND: The goal of this study was to explore the value of adding neoadjuvant chemotherapy (NACT) or adjuvant chemotherapy (ACT) to concurrent chemoradiotherapy (CCRT) in patients with nasopharyngeal carcinoma (NPC) with different risks of treatment failure. PATIENTS AND METHODS: A total of 2,263 eligible patients with stage III-IVb NPC treated with CCRT ± NACT or ACT were included in this retrospective study. Distant metastasis-free survival (DMFS), overall survival, and progression-free survival were calculated using the Kaplan-Meier method and differences were compared using the log-rank test. RESULTS: Patients in the low-risk group (stage N0-1 disease and Epstein-Barr virus [EBV] DNA <4,000 copies/mL) who received NACT followed by CCRT achieved significantly better 5-year DMFS than those treated with CCRT alone (96.2% vs 91.3%; P= .008). Multivariate analyses also demonstrated that additional NACT was the only independent prognostic factor for DMFS (hazard ratio, 0.42; 95% CI, 0.22-0.80; P=.009). In both the intermediate-risk group (stage N0-1 disease and EBV DNA ≥4,000 copies/mL and stage N2-3 disease and EBV DNA <4,000 copies/mL) and the high-risk group (stage N2-3 disease and EBV DNA ≥4,000 copies/mL), comparison of NACT or ACT + CCRT versus CCRT alone indicated no significantly better survival for all end points. CONCLUSIONS: The addition of NACT to CCRT could reduce distant failure in patients with low risk of treatment failure.

20.
Radiother Oncol ; 137: 83-94, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31078941

RESUMO

BACKGROUND AND PURPOSE: Nasopharyngeal carcinoma (NPC) patients can be separated into two risk subgroups according to tumor responses to induction chemotherapy (IC). We aimed to elucidate the optimal cumulative cisplatin dose (CCD) of concurrent chemoradiotherapy (CCRT) for different NPC patient subgroups. PARTICIPANTS AND METHODS: A total of 990 patients with incident NPC diagnosed between 2008 and 2017 treated with IC plus CCRT were included in our observational study. The clinicopathological features of patients with different tumor responses were compared using the Chi-square test or Fisher's exact test. Prognosis was assessed using a multivariate Cox proportional hazards model. In addition, acute and late toxicities were compared between different CCD groups. RESULTS: After IC, 761/990 (76.9%) patients had a complete tumor response (CR)/partial response (PR) and 229 (23.1%) had stable disease (SD)/disease progression (PD). An unsatisfactory tumor response (SD/PD) after IC correlated with poor clinical outcome (3-year PFS 61.4% vs. 83.2%, P < 0.001 and 3-year LRFS 80.9% vs. 94.5%, P < 0.001). Patients who achieved CR/PR after IC received a CCD >200 mg/m2 and showed higher 3-year PFS and DMFS rates than those receiving a CCD <100 mg/m2 (PFS: 85.4% vs. 77.9%, P = 0.045; DMFS: 89.4% vs. 77.9%, P = 0.015). Multivariate analysis also showed that CCD was an independent prognostic factor for PFS and DMFS in CR/PR subgroup. Moreover, the medium dose group showed similar efficacy as high dose group but was associated with fewer grade 1-4 acute toxicities. However, application of different CCD didn't result in significantly different survival outcomes in SD/PD subgroup. CONCLUSIONS: Tumor response to IC was an independent prognostic factor for patients with NPC. For the patients who achieved CR/PR after IC, patients receiving high CCD showed significantly improved 3-year PFS and DMFS compared with patients receiving low CCD. Balancing toxicity and efficacy, 200 mg/m2 seemed to be the optimal dose in the CR/PR groups. However, enhancement of CCD did not provide survival benefit for patients who achieved SD/PD after IC, and treatment options for these patients require further consideration.

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