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1.
Otolaryngol Head Neck Surg ; 166(3): 490-497, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34182810

RESUMO

OBJECTIVE: Salvage endoscopic nasopharyngectomy (ENPG) is a reasonable choice for resectable recurrent nasopharyngeal carcinoma (rNPC). However, in past decades, complete removal of the tumor was not feasible when the recurrent lesion was adjacent to the internal carotid artery (ICA). The present article introduces innovative strategies to ensure sufficient surgical margins while avoiding accidental injury to the ICA. STUDY DESIGN: Retrospective study. SETTING: Tertiary care center. METHODS: We retrospectively reviewed rT2-3 rNPC patients with tumor lesions adjacent to the ICA (<5 mm) who underwent ENPG at the Sun Yat-sen University Cancer Center between January 2015 and June 2020. Thirty-seven patients were selected for this study. Seventeen patients underwent ENPG using direct dissection, 10 patients underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, and 10 patients underwent ICA embolization followed by ENPG. RESULTS: With a median follow-up duration of 31 months (range, 5 to 53 months), the 2-year overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival rates of salvage ENPG for rNPC adjacent to the ICA were 88.7%, 72.0%, 72.0%, and 97.3%, respectively. The incidences of grade 1-2 and grade 3-5 postoperative complications were 16.2% and 13.5%, respectively. Two patients experienced ICA rupture during direct dissection but were out of danger after vascular embolization therapy. One patient had a positive margin. Two patients had severe nasopharyngeal wound infections with mucosal flap necrosis. CONCLUSION: ENPG combined with ICA pretreatment allows the feasible and effective resection of rNPC lesions adjacent to the ICA.


Assuntos
Artéria Carótida Interna , Neoplasias Nasofaríngeas , Artéria Carótida Interna/patologia , Artéria Carótida Interna/cirurgia , Doença Crônica , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
2.
Oral Oncol ; 121: 105494, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34425533

RESUMO

BACKGROUND: Our previous trial confirmed that induction chemotherapy (IC) improved long-term survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). In this study, we investigated the impact of IC on long-term quality of life (QoL) in this cohort. METHODS: Our trial was a randomised, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. All participants completed two self-administered questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (H&N35). As per protocol, the questionnaires had to be completed before knowledge of treatment allocation by the patient (baseline). Patients were then approached to enroll at the time of the present study period. RESULTS: Ultimately, QoL data from 228 patients were included in the analysis. Most scales were both statistically and clinically decreased in both groups between baseline and the latest follow-up. The IC followed by CCRT group had significantly better outcome in role functioning, cognitive functioning, social functioning, fatigue, pain, and constipation in QLQ-C30 scales at the last follow-up. Similarly, in H&N35 scales, a significantly better result was observed in pain, sexuality, sticky saliva, pain killers use, nutritional supplements, and weight loss, but a poorer result in senses problems, for those treated by IC followed by CCRT. CONCLUSION: IC followed by CCRT seemed to have better long-term QoL outcomes compared with CCRT alone in patients with locoregionally advanced NPC.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Humanos , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Dor
3.
J Cancer ; 12(14): 4424-4432, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093843

RESUMO

Introduction: Biopsy is essential for some patients with suspected distant metastasis, so we aim to figure out whether biopsy of distant metastasis is associated with impaired survival in NPC. Methods: A total of 743 synchronous metastatic NPC patients from 2004 to 2016 were analyzed from the population-based Surveillance, Epidemiology, and End Results program. Propensity score matching was used to control confounders and create a well-balanced cohort. Five-year survival rate estimates and Kaplan-Meier survival curves were calculated. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival. Results: Of 743 eligible patients, 194 (26.11%) underwent biopsy of distant metastasis. After control for demographic and clinicopathologic characteristics, patients with biopsy of distant metastasis achieved comparable 5-year overall survival (OS) (20.3% vs 24.7%; P = 0.41) and 5-year cancer specific survival (CSS) (31.0% vs 33.6%; P = 0.35) with patients without biopsies. Multivariate analysis further confirmed that biopsy of distant metastasis was not associated with impaired OS (HR = 1.03, 95% CI = 0.84-1.25; P = 0.80) or CSS (HR = 1.07, 95% CI = 0.86-1.34; P = 0.54). Conclusions: Biopsy of distant metastasis was not associated with impaired survival outcomes for synchronous metastatic NPC patients. Biopsy of distant metastasis could be another diagnosed choice for patients with suspected distant metastasis.

4.
Theranostics ; 11(13): 6427-6444, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995666

RESUMO

Background: Reportedly, nasopharyngeal carcinoma (NPC) patients with MHC I Class aberration are prone to poor survival outcomes, which indicates that the deficiency of tumor neoantigens might represent a mechanism of immune surveillance escape in NPC. Methods: To clearly delineate the landscape of neoantigens in NPC, we performed DNA and RNA sequencing on paired primary tumor, regional lymph node metastasis and distant metastasis samples from 26 patients. Neoantigens were predicted using pVACseq pipeline. Subtype prediction model was built using random forest algorithm. Results: Portraying the landscape of neoantigens in NPC for the first time, we found that the neoantigen load of NPC was above average compared to that of other cancers in The Cancer Genome Atlas program. While the quantity and quality of neoantigens were similar among primary tumor, regional lymph node metastasis and distant metastasis samples, neoantigen depletion was more severe in metastatic sites than in primary tumors. Upon tracking the clonality change of neoantigens, we found that neoantigen reduction occurred during metastasis. Building a subtype prediction model based on reported data, we observed that subtype I lacked T cells and suffered from severe neoantigen depletion, subtype II highly expressed immune checkpoint molecules and suffered from the least neoantigen depletion, and subtype III was heterogenous. Conclusions: These results indicate that neoantigens are conducive to the guidance of clinical treatment, and personalized therapeutic vaccines for NPC deserve deeper basic and clinical investigations to make them feasible in the future.


Assuntos
Antígenos de Neoplasias/imunologia , Carcinoma Nasofaríngeo/secundário , Neoplasias Nasofaríngeas/imunologia , Adulto , Antígenos de Neoplasias/genética , DNA de Neoplasias/genética , DNA Viral/análise , DNA Viral/genética , Feminino , Antígenos HLA/genética , Antígenos HLA/imunologia , Herpesvirus Humano 4/genética , Humanos , Mutação INDEL , Inibidores de Checkpoint Imunológico/uso terapêutico , Estimativa de Kaplan-Meier , Metástase Linfática/imunologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/virologia , Polimorfismo de Nucleotídeo Único , Intervalo Livre de Progressão , RNA Neoplásico/genética , Receptores de Antígenos de Linfócitos T/imunologia , Evasão Tumoral , Microambiente Tumoral/imunologia , Infecções Tumorais por Vírus/virologia
5.
Oral Oncol ; 115: 105200, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33610003

RESUMO

INTRODUCTION: The current metastatic category (M) of nasopharyngeal carcinoma (NPC) is a "catch-all" category, we previously successfully established a M1 subdivision system based on prognostic metastatic characteristics in epidemic areas. We aimed to figure out metastatic characteristics associated with survival outcomes of NPC in non-epidemic areas. METHODS: A total of 428 newly diagnosed de novo metastatic NPC patients from 2010 to 2016 were analyzed from the population-based Surveillance, Epidemiology, and End Results program. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival. RESULTS: The most frequently involved metastatic locations were the bones (53.04%), the lungs (36.68%), the livers (29.21%) and the distant lymph nodes (24.07%). Univariate analysis indicated that bone involvement (HR = 1.39, 95% CI = 1.09-1.77), liver involvement (HR = 1.44, 95% CI = 1.12-1.85) and multiple metastatic locations (HR = 1.32, 95% CI = 1.04-1.67) were negative prognostic factors of overall survival (OS) for patients with synchronous metastasis. We established a new M1 subdivision system based on metastatic characteristics: M1a, without bone and liver involvement; M1b, single bone or liver involvement; M1c, multiple metastatic locations including bone and/or liver. Multivariate analysis confirmed that our new subcategories were associated with significantly different OS (M1b vs M1a: HR = 1.54, 95% CI = 1.11-2.16; M1c vs M1a: HR = 2.03, 95% CI = 1.47-2.78). CONCLUSIONS: Synchronous metastatic NPC patients with multiple metastatic locations involved bone and/or liver were prone to suffer from dismal OS and might need more attentions for selection of treatment modality.


Assuntos
Carcinoma Nasofaríngeo/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Projetos Piloto , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
6.
Head Neck ; 43(1): 98-107, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32985734

RESUMO

BACKGROUND: Surgical access for retropharyngeal lymph node (RPLN) dissection is difficult. We aimed to examine the efficacy of transcervical endoscopic RPLN dissection (TSE-RPLND) for recurrent RPLN in nasopharyngeal carcinoma (NPC). METHODS: From April 2013 to February 2019, a total of 31 patients with NPC diagnosed with RPLN recurrence underwent TSE-RPLND. The clinical characteristics, complications, and survival outcomes were retrospectively analyzed. RESULTS: The mean duration of surgery, quantity of bleeding and postoperative hospitalization stay were 347.9 minutes, 107.7 mL, and 8.7 days, respectively. After a median follow-up of 31.0 months, the 2-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival rates were 63.9%, 95.2%, 59.9%, and 83.3%, respectively. The long-term incidences of swallowing problems, permanent nutrient tube, tongue atrophy, and shoulder problems were 6 (19.4%), 3 (9.7%), 3 (9.7%), and 3 (9.7%), respectively. CONCLUSIONS: TSE-RPLND is an effective method to treat RPLN recurrence in NPC, but nerve injury-related complications should not be ignored.


Assuntos
Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Dissecação , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/cirurgia , Estudos Retrospectivos
7.
Laryngoscope ; 131(6): E1895-E1902, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33378575

RESUMO

OBJECTIVES: Nasopharyngeal carcinoma (NPC) patients with retropharyngeal lymph node (RPLN) recurrence typically undergo reirradiation and experience severe radiotoxicity. Salvage open surgery is challenging because gaining access to the retropharyngeal space is complex and risky. Thus, only several centers can perform this procedure, and complications are common. We applied transoral robotic surgery RPLN dissection (TORS-RPLND) to NPC patients with RPLN recurrence to address the problem with open surgery. MATERIALS AND METHODS: From March 2017 to October 2020, 10 NPC patients with RPLN recurrence underwent TORS-RPLND using the da Vinci Si/Xi Surgical System. We applied the balloon occlusion test to protect the internal carotid artery, induction chemotherapy to shrink large tumors preoperatively, and ultrasound positioning to effectively locate unrecognizable RPLNs during surgery. Clinical characteristics, complications, and survival outcome data were retrospectively collected. RESULTS: Of 10 patients, 8 underwent en bloc resection via TORS-RPLND, and the remaining 2 patients were converted to open surgery because we failed to identify the RPLN during TORS. After introducing intraoperative ultrasound positioning, no such failure occurred. The mean operative time and intraoperative blood loss were 297 ± 120 min and 40 ± 43 ml, respectively. All surgical margins were negative. TORS-related complications were mild, and the most severe one was grade 3 dysphagia in one patient who underwent conversion to open surgery (10%). With a median follow-up of 19 months, only 1 (10%) patient developed cervical recurrence. CONCLUSIONS: TORS-RPLND is feasible, safe, and effective in the treatment of NPC patients with RPLN recurrence, especially with the help of intraoperative ultrasound positioning. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1895-E1902, 2021.


Assuntos
Excisão de Linfonodo/métodos , Carcinoma Nasofaríngeo/cirurgia , Recidiva Local de Neoplasia/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Ultrassonografia de Intervenção
8.
JAMA Oncol ; 6(9): 1345-1352, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32701129

RESUMO

Importance: The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear. Objective: To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC. Design, Setting, and Participants: Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months. Interventions: The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2 over 120 hours and 100 mg/m2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy. Main Outcomes and Measures: The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety. Results: Overall, 126 patients were enrolled (105 men [83.3%] and 21 women [16.7%]; median [IQR] age, 46 [39-52] years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio [HR], 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group. Conclusions and Relevance: In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC. Trial Registration: ClinicalTrials.gov Identifier: NCT02111460.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Radioterapia de Intensidade Modulada , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Metástase Neoplásica , Intervalo Livre de Progressão
9.
Head Neck ; 42(4): 807-812, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31976616

RESUMO

BACKGROUND: Endoscopic surgery was widely applied as radical treatment for early cancer. We aimed to demonstrate the details of endoscopic nasopharyngectomy (ENPG) for nasopharyngeal carcinoma (NPC). METHODS: Before operation, we first defined the gross tumor volume (GTV) and surgical tumor volume (STV) for resection. STV was defined as gross tumor volume plus an additional 0.5-1.0 cm peripheral mucosa margin and a 2-3 mm basal margin on the surface skull base. The surgeon was required to follow this planned STV to remove the tumor. RESULTS: En bloc resection was achieved in the endoscopic operation, and multiple margin biopsies were proved pathologically negative. Comparison between preoperative and postoperative magnetic resonance imaging revealed that actual STV (aSTV) had contained the STV completely. Mostly, no death, recurrence, or distant metastasis was observed in this case during the 3-year follow-up. CONCLUSIONS: Techniques of ENPG for treating newly diagnosed localized stage I NPC patients were feasible.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Faringectomia , Taxa de Sobrevida
10.
Zhen Ci Yan Jiu ; 44(12): 916-21, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31867913

RESUMO

OBJECTIVE: To compare the differences in clinical effects on hyperlipidemia of turbid phlegm obstruction pattern/syndrome treated with the different Jin's three-needle therapies so as to provide a new approach and theoretic evidence for the clinical optimal scheme of acupuncture on hyperlipidemia. METHODS: A total of 90 patients were randomly divided into education group, electroacupuncture group and catgut embedding group (30 cases in each). The routine health education was given to the education group. On the base of the treatment as the education group, electroacupuncture was applied to the electroacupuncture group for 30 min each time, twice a week; and the catgut embedding was applied to the catgut embedding group at the same acupoints as the electroacupuncture group, once a week. The treatment was given consecutively for 8 weeks in each group. Before and after treatment, the obesity indices [weight, waistline, body mass index (BMI)], blood lipid indices[serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)] and insulin resistance indices [fasting blood glucose(FBG), fasting plasma insulin(FINS), homeostasis model assessment-estimated insulin resistance (HOMA-IR)] were observed in the three groups before and after treatment. RESULTS: After treatment, in the electroacupuncture group and the catgut embedding group, the results of the obesity indices, e.g. weight, waistline and BMI, the levels of blood lipid, e.g.TC, TG, LDL-C and the insulin resistance indices, e.g. FINS and HOMA-IR were all obviously decreased compared with those before treatment (P<0.05, P<0.01), and the level of HDL-C apparently increased than that before treatment (P<0.01). In the catgut embedding group, FBG was obviously decreased after treatment as compared with that before treatment (P<0.01). After treatment, the improvements in LDL-C and HDL-C in the catgut embedding group were superior to those in the electroacupuncture group (P<0.05). Regarding the obesity indices and insulin resistance indices, the differences were not statistically significant in comparison between the catgut embedding group and the electroacupuncture group (all P>0.05). The total effective rate was 90.0% in the catgut embedding group (27/30) and it was 83.3% (25/30) in the electroacupuncture group, either of them was better than 60.0% (18/30) in the education group , indicating the statistical significance (P<0.01, P<0.05). CONCLUSION: On the base of health education, either the catgut embedding therapy or electroacupuncture of Jin's three-needle treatment achieves the positive regulation on the abnormal lipid metabolism and insulin resistance. The hypoglycemic effect and the impro-ving effect in LDL-C and HDL-C of the catgut embedding therapy are superior to electroacupuncture.


Assuntos
Eletroacupuntura , Hiperlipidemias , Pontos de Acupuntura , Categute , Humanos , Hiperlipidemias/terapia
11.
Cancer Commun (Lond) ; 39(1): 75, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730020

RESUMO

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy (IMRT) as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma (NPC), but the radiation-related complications and relatively high medical costs remain a consequential burden for the patients. Endoscopic nasopharyngectomy (ENPG) was successfully applied in recurrent NPC with radiation free and relatively low medical costs. In this study, we examined whether ENPG could be an effective treatment for localized stage I NPC. METHODS: Ten newly diagnosed localized stage I NPC patients voluntarily received ENPG alone from June 2007 to September 2017 in Sun Yat-sen University Cancer Center. Simultaneously, the data of 329 stage I NPC patients treated with IMRT were collected and used as a reference cohort. The survival outcomes, quality of life (QOL), and medical costs between two groups were compared. RESULTS: After a median follow-up of 59.0 months (95% CI 53.4-64.6), no death, locoregional recurrence, or distant metastasis was observed in the 10 patients treated with ENPG. The 5-year overall survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival among the ENPG-treated patients was similar to that among the IMRT-treated patients (100% vs. 99.1%, 100% vs. 97.7%, 100% vs. 99.0%, 100% vs. 97.4%, respectively, P > 0.05). In addition, compared with IMRT, ENPG was associated with decreased total medical costs ($ 4090.42 ± 1502.65 vs. $ 12620.88 ± 4242.65, P < 0.001) and improved QOL scores including dry mouth (3.3 ± 10.5 vs. 34.4 ± 25.8, P < 0.001) and sticky saliva (3.3 ± 10.5 vs. 32.6 ± 23.3, P < 0.001). CONCLUSIONS: ENPG alone was associated with promising long-term survival outcomes, low medical costs, and satisfactory QOL and might therefore be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refused radiotherapy. However, the application of ENPG should be prudent, and prospective clinical trials were needed to further verify the results.


Assuntos
Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/cirurgia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/economia , Carcinoma Nasofaríngeo/economia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/economia , Neoplasias Nasofaríngeas/patologia , Qualidade de Vida , Radioterapia de Intensidade Modulada/economia , Adulto Jovem
12.
Cancer Res ; 79(23): 5930-5943, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484669

RESUMO

The genetic events occurring in recurrent nasopharyngeal carcinoma (rNPC) are poorly understood. Here, we performed whole-genome and whole-exome sequencing in 55 patients with rNPC and 44 primarily diagnosed NPC (pNPC), with 7 patients having paired rNPC and pNPC samples. Previously published pNPC exome data were integrated for analysis. rNPC and pNPC tissues had similar mutational burdens, however, the number of clonal mutations was increased in rNPC samples. TP53 and three NF-κB pathway components (TRAF3, CYLD, and NFKBIA) were significantly mutated in both pNPC and rNPC. Notably, mutations in TRAF3, CYLD, and NFKBIA were all clonal in rNPC, however, 55.6% to 57.9% of them were clonal in pNPC. In general, the number of clonal mutations in NF-κB pathway-associated genes was significantly higher in rNPC than in pNPC. The NF-κB mutational clonality was selected and/or enriched during NPC recurrence. The amount of NF-κB translocated to the nucleus in samples with clonal NF-κB mutants was significantly higher than that in samples with subclonal NF-κB mutants. Moreover, the nuclear abundance of NF-κB protein was significantly greater in pNPC samples with locoregional relapse than in those without relapse. Furthermore, high nuclear NF-κB levels were an independent negative prognostic marker for locoregional relapse-free survival in pNPC. Finally, inhibition of NF-κB enhanced both radiosensitivity and chemosensitivity in vitro and in vivo. In conclusion, NF-κB pathway activation by clonal mutations plays an important role in promoting the recurrence of NPC. Moreover, nuclear accumulation of NF-κB is a prominent biomarker for predicting locoregional relapse-free survival. SIGNIFICANCE: This study uncovers genetic events that promote the progression and recurrence of nasopharyngeal carcinoma and has potential prognostic and therapeutic implications.See related commentary by Sehgal and Barbie, p. 5915.


Assuntos
Carcinoma , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Mutação , NF-kappa B/genética , Recidiva Local de Neoplasia
13.
Eur J Cancer ; 119: 87-96, 2019 09.
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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adulto , Idoso , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Quimioterapia de Indução/métodos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Cancer Commun (Lond) ; 38(1): 74, 2018 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-30577735

RESUMO

BACKGROUND: Postradiation nasopharyngeal necrosis (PRNN) is a severe complication after radiotherapy in patients with nasopharyngeal carcinoma (NPC), which can severely affect the quality of life and threaten the patient's life. Only 13.4%-28.6% of patients can be cured by traditional repeated endoscopic debridement. Here, we introduced an innovative curative-intent endoscopic surgery for PRNN patients and evaluated its clinical efficacy. METHODS: Clinical data of 72 PRNN patients who underwent radical endoscopic necrectomy, followed by reconstruction using a posterior pedicle nasal septum and floor mucoperiosteum flap were analyzed to determine the efficacy of this surgery. The endpoints were complete re-epithelialization of the nasopharyngeal defect, relief of headache, and overall survival (OS). RESULTS: All surgeries were successfully performed without any severe postoperative complications or death. The median value of numeric rating scales of pain decreased from 8 before surgery to 0 after surgery (P < 0.001). Fifty-one patients (70.8%) achieved complete re-epithelialization of the nasopharyngeal defect. The number of cycles of radiotherapy (odds ratio [OR], 7.254; 95% confidence interval [CI] 1.035-50.821; P = 0.046), postoperative pathological result (OR, 34.087; 95% CI 3.168-366.746; P = 0.004), and survival status of flap (OR, 261.179; 95% CI 17.176-3971.599; P < 0.001) were independent risk factors of re-epithelialization of the nasopharyngeal defects. Postoperative pathological result (hazard ratio [HR], 5.018; 95% CI 1.970-12.782; P = 0.001) was an independent prognostic factor for OS. The 2-year OS rate of the entire cohort was 77.9%. CONCLUSION: Curative-intent endoscopic necrectomy followed by construction using the posterior pedicle nasal septum and floor mucoperiosteum flap is a novel, safe, and effective treatment of PRNN in patients with NPC.


Assuntos
Endoscopia/métodos , Carcinoma Nasofaríngeo/cirurgia , Qualidade de Vida/psicologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Huan Jing Ke Xue ; 37(2): 475-81, 2016 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-27363133

RESUMO

Based on the monitored atmospheric water vapor stable isotopes and observed meteorological elements at Changsha during the period from November 12, 2014 to April 13, 2015, the variations of water vapor stable isotopes and the relationships between isotope ratios and temperature, absolute humidity, precipitation amount were analyzed in this paper. The results indicated that: (1) Seasonal variations of delta18O and 82H in atmospheric water vapor at Changsha were remarkable, with high values in winter. delta18O and delta2H in atmospheric water vapor were positively correlated with absolute humidity in winter. There were some fluctuations of the delta18O and delta2H in atmospheric water vapor, especially when the precipitation events occurred. Precipitation events had a significant effect on the variations of delta18O and delta2H in atmospheric water vapor, and low values were often accompanied with precipitation events; (2) Diurnal Variations of delta18O and delta2H in atmospheric water vapor had a close correlation with the atmospheric water vapor content, whereas the absolute humidity was mainly controlled by the strength of the local evapotranspiration and atmospheric turbulence. The "precipitation amount effect" was observed during the process of a single precipitation event; (3) Values of delta18O and delta2H in atmospheric water vapor were always lower than those of precipitation in Changsha, but he variation trends were completely consistent, the average difference values were 8.6% per hundred and 66.82% per hundred, respectively; (4) The meteoric vapor line (MVL) in cold months was delta2H =7.18 delta18O + 10.58, the slope and intercept of MVL were always lower than those of MWL, and the slope and intercept of MVL in spring were significantly higher than those of winter.


Assuntos
Monitoramento Ambiental , Umidade , Hidrogênio/análise , Isótopos de Oxigênio/análise , Estações do Ano , China , Chuva , Temperatura
16.
Langmuir ; 29(17): 5199-206, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23557099

RESUMO

We report an investigation of an electrochemically switched heterocyclization reaction on hydroquinone-terminated self-assembled monolayers (SAMs). This reaction involves an electrochemically modulated hydroquinone/benzoquinone transformation step in the SAMs and a subsequent heterocyclization step taking place between the electrochemically generated benzoquinone moieties in SAMs and l-cysteine in solution. The reaction process was monitored by XPS and electrochemical surface-enhanced Raman spectroscopy (EC-SERS). The surface reaction proceeds as a two-step reaction to give a benzothiazine product, which is in contrast to the much more complicated multiple step reactions in solution. This result suggests that the tight molecular packing in the SAMs does not hinder the intramolecular heterocylization reaction, but prevents the intermolecular coupling reaction from happening. This work provides insights to the control and detection of biomolecule related multistep reactions occurring at solid-liquid interface.


Assuntos
Benzoquinonas/química , Cisteína/química , Técnicas Eletroquímicas , Ouro/química , Hidroquinonas/síntese química , Ciclização , Hidroquinonas/química , Estrutura Molecular , Propriedades de Superfície
17.
Chemistry ; 19(19): 5948-54, 2013 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-23508669

RESUMO

The preparation of chemically modified graphene (CMG) generally involves the reduction of graphite oxide (GO) by using various reducing reagents. Herein, we report a free-radical-promoted synthesis of CMG, which does not require any conventional reductant. We demonstrated that the phenyl free radical can efficiently promote the conversion of GO into CMG under mild conditions and produces phenyl-functionalized CMG. This pseudo-"reduction" process is attributed to a free-radical-mediated elimination of the surface-attached oxygen-containing functionalities. This work illustrates a new strategy for preparing CMG that is alternative to the conventional means of chemical reduction. Furthermore, the phenyl-functionalized graphene shows an excellent performance as an electrode material for lithium-battery applications.

18.
J Nanosci Nanotechnol ; 12(1): 508-12, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22524011

RESUMO

Thin films of graphene oxide, graphene and copper (II) phthalocyanine dye have been successfully fabricated by electrostatic layer-by-layer (LbL) assembly approach. We present the first variable angle spectroscopic ellipsometry (VASE) investigation on these graphene-dye hybrid thin films. The thickness evaluation suggested that our LbL assembly process produces highly uniform and reproducible thin films. We demonstrate that the refractive indices of the graphene-dye thin films undergo dramatic variation in the range close to the absorption of the dyes. This investigation provides new insight to the optical properties of graphene containing thin films and shall help to establish an appropriate optical model for graphene-based hybrid materials.


Assuntos
Cristalização/métodos , Grafite/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Óxidos/química , Análise Espectral/métodos , Teste de Materiais/métodos , Conformação Molecular , Tamanho da Partícula , Propriedades de Superfície
19.
Chem Commun (Camb) ; 47(20): 5747-9, 2011 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-21503310

RESUMO

Graphene sheets modified by phenylacetylene moieties provide a facile platform for attaching various photoactive functional molecules via"click" chemistry. The produced photoactive graphene materials are well-dispersed in various solvents and show dramatically improved photo-current responses.

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