Publications by authors named "Li-Xia Lu"

51 Publications

A nomogram for predicting survival of head and neck mucosal melanoma.

Cancer Cell Int 2021 Apr 17;21(1):224. Epub 2021 Apr 17.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.

Objectives: We aimed to understand the clinical characteristics and better predict the prognosis of patients with mucosal melanoma of the head and neck (MMHN) using a nomogram.

Methods: Three hundred patients with nometastatic MMHN were included. Multivariable Cox regression was performed to analyze independent prognostic factors for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS), and these factors were used to develop a nomogram. Concordance indexes (C-indexes), calibration plots, and receiver operating characteristic (ROC) analysis were performed to test the predictive performance of the nomogram in both the primary (n = 300) and validation cohorts (n = 182).

Results: The primary tumor site, T stage and N stage were independent risk factors for survival and were included in the nomogram to predict the 3- and 5-year OS, DFS, DMFS, and LRRFS in the primary cohort. The C-indexes (both > 0.700), well-fit calibration plots, and area under the ROC curve (both > 0.700) indicated the high diagnostic accuracy of the nomogram, in both the primary and validation cohorts. The patients were divided into three groups (high-risk, intermediate-risk, and low-risk groups) according to their nomogram scores. The survival curves of OS, DFS, DMFS, and LRRFS were well separated by the risk groups in both cohorts (all P < 0.001).

Conclusions: The nomogram can stratify MMHN patients into clinically meaningful taxonomies to provide individualized treatment.
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http://dx.doi.org/10.1186/s12935-021-01927-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052848PMC
April 2021

Endoscopic surgery compared with intensity-modulated radiotherapy in resectable locally recurrent nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial.

Lancet Oncol 2021 03 15;22(3):381-390. Epub 2021 Feb 15.

Department of Otolaryngology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou Key Laboratory of Otorhinolaryngology, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China; Department of Otolaryngology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: The role of surgery compared with reirradiation in the primary treatment of patients with resectable, locally recurrent nasopharyngeal carcinoma (NPC) who have previously received radiotherapy is a matter of debate. In this trial, we compared the efficacy and safety outcomes of salvage endoscopic surgery versus intensity-modulated radiotherapy (IMRT) in patients with resectable locally recurrent NPC.

Methods: This multicentre, open-label, randomised, controlled, phase 3 trial was done in three hospitals in southern China. We included patients aged 18-70 years with a Karnofsky Performance Status score of at least 70 who were histopathologically diagnosed with undifferentiated or differentiated, non-keratinising, locally recurrent NPC with tumours confined to the nasopharyngeal cavity, the post-naris or nasal septum, the superficial parapharyngeal space, or the base wall of the sphenoid sinus. Eligible patients were randomly assigned (1:1) to receive either endoscopic nasopharyngectomy (ENPG group) or IMRT (IMRT group). Randomisation was done manually using a computer-generated random number code and patients were stratified by treatment centre. Treatment group assignment was not masked. The primary endpoint was overall survival, compared between the groups at 3 years. Efficacy analyses were done by intention to treat. Safety analysis was done in patients who received treatment according to the treatment they actually received. This trial was prospectively registered at the Chinese Clinical Trial Registry, ChiCTR-TRC-11001573, and is currently in follow-up.

Findings: Between Sept 30, 2011, and Jan 16, 2017, 200 eligible patients were randomly assigned to receive either ENPG (n=100) or IMRT (n=100). At a median follow-up of 56·0 months (IQR 42·0-69·0), 74 patients had died (29 [29%] of 100 patients in the ENPG group and 45 [45%] of 100 patients in the IMRT group). The 3-year overall survival was 85·8% (95% CI 78·9-92·7) in the ENPG group and 68·0% (58·6-77·4) in the IMRT group (hazard ratio 0·47, 95% CI 0·29-0·76; p=0·0015). The most common grade 3 or worse radiation-related late adverse event was pharyngeal mucositis (in five [5%] of 99 patients who underwent ENPG and 26 [26%] of 101 patients who underwent IMRT). Five [5%] of the 99 patients who underwent ENPG and 20 [20%] of the 101 patients who underwent IMRT died due to late toxic effects specific to radiotherapy; attribution to previous radiotherapy or trial radiotherapy is unclear due to the long-term nature of radiation-related toxicity.

Interpretation: Endoscopic surgery significantly improved overall survival compared with IMRT in patients with resectable locally recurrent NPC. These results suggest that ENPG could be considered as the standard treatment option for this patient population, although long-term follow-up is needed to further determine the efficacy and toxicity of this strategy.

Funding: Sun Yat-sen University Clinical Research 5010 Program.
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http://dx.doi.org/10.1016/S1470-2045(20)30673-2DOI Listing
March 2021

Toxicological responses, bioaccumulation, and metabolic fate of triclosan in Chlamydomonas reinhardtii.

Environ Sci Pollut Res Int 2020 Apr 20;27(10):11246-11259. Epub 2020 Jan 20.

College of Food Science and Light Industry, Nanjing Tech University, Puzhu South Street No. 30, Nanjing, 211816, China.

Triclosan (TCS) is a broad-spectrum antimicrobial agent that is broadly used in personal care products. It has been shown to cause the contamination of a variety of aquatic environments. Since algae has been the primary producers of aquatic ecosystems, understanding the toxicological mechanisms and the metabolic fate of TCS is vital for assessing its risk in an aquatic environment. In our study, 0.5-4 mg L TCS treatments for 72 h in a culture of Chlamydomonas reinhardtii (C. reinhardtii) showed progressive inhibition of cell growth and reduced the chlorophyll content. The EC value of C. reinhardtii after 72 h was 1.637 mg L, which showed its higher level of resistance to TCS in comparison with other algal species. The exposure to TCS led to oxidative injuries of algae in relation to the increment of malonaldehyde content, cell membrane permeability, and HO levels. Furthermore, the oxidative stress from TCS stimulated a series of antioxidant enzyme activities and their gene expressions. Simultaneously, the accumulated TCS in C. reinhardtii arouses the detoxification/degradation-related enzymes and related gene transcriptions. In the medium, approximately 82% of TCS was removed by C. reinhardtii. Importantly, eight TCS metabolites were identified by ultra-performance liquid chromatography-high-resolution mass spectrometry and their relative abundances were measured in a time-course experiment. Six of these metabolites are reported here for the first time. The metabolic pathways of triclosan via C. reinhardtii including reductive dechlorination, hydroxylation, sulfhydrylation, and binding with thiol/cysteine/GSH/glycosyl were manifested to broaden our understanding of the environmental fate of TCS. Graphical Abstract.
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http://dx.doi.org/10.1007/s11356-020-07704-9DOI Listing
April 2020

Detection of methylation status of Epstein-Barr virus DNA C promoter in the diagnosis of nasopharyngeal carcinoma.

Cancer Sci 2020 Feb 5;111(2):592-600. Epub 2020 Feb 5.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.

The detection of Epstein-Barr virus (EBV) DNA load in nasopharyngeal (NP) brushing samples for diagnosis of nasopharyngeal carcinoma (NPC) has attracted great attention. Further improvements that eliminate the need for clinical settings will greatly extend its application. A total of 250 participants were recruited to obtain NP brushing samples. Brush sampling both with and without the guide of endoscopy was conducted in 38 NPC patients. EBV DNA load, EBV RNA transcript and EBV DNA C promoter methylation status were, respectively, evaluated. Typical latency II transcripts were observed in brushing samples from NPC patients but not controls. Unlike in tissues, multiple lytic gene transcripts were observed not only in NPC patients but also in controls. Apart from EBV RNA transcript, samples from NPC patients also showed higher levels of EBV DNA load and C promoter methylation degree than their controls. Qualitative analysis further showed that EBV DNA C promoter was methylated in all NPC patients but in only 18.4% of the control group. Combined analysis of EBV DNA methylated degree and EBV DNA load increased the sensitivity to 100% in the detection of NPC. Using qualitative methylated type as the criteria, up to 89.5% of samples collected via blind brushing showed consistent results with samples collected via endoscopy-guided brushing from NPC patients. Detection of the methylation status of EBV DNA C promoter in NP brushing samples shows great potential in diagnosing NPC and may provide an appealing alternative for the non-invasive detection and screening of NPC without the need for clinical settings.
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http://dx.doi.org/10.1111/cas.14281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004524PMC
February 2020

Development and external validation of a nomogram for predicting the overall survival of patients with stage II nasopharyngeal carcinoma after curative treatment.

Cancer Manag Res 2019 10;11:4403-4412. Epub 2019 May 10.

Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, People's Republic of China.

To facilitate decision-making support for individual patients, development and external validation of a nomogram was undertaken to reveal prognostic factors and predict the value of concurrent chemoradiotherapy (CCRT) compared with radiotherapy (RT) for stage-II nasopharyngeal carcinoma (NPC) patients. Clinical data of 419 and 309 patients with American Joint Committee on Cancer (2017) stage-II NPC in two institutions in China were collected retrospectively. Overall survival (OS) and progression-free survival were compared using Kaplan-Meier estimates. Cox regression analysis was used to identify the prognostic factors for building the nomogram. Predictive accuracy and discriminative ability were measured using the Concordance Index. Finally, there were 24 and 20 deaths in the development and validation group, respectively. Patients with stage T2N1, N1 stage, involvement of retropharyngeal and unilateral cervical lymph nodes, and who had RT alone had worse OS (=0.019, 0.035, 0.003 and 0.010, respectively; log-rank test) than patients with stage T1N1 and T2N0, N0 stage, involvement of retropharyngeal or unilateral cervical lymph nodes, and CCRT, respectively. After multivariate analysis of the training set, age, neutrophil-to-lymphocyte ratio, therapy type, and pretreatment plasma concentration of Epstein-Barr virus DNA were independent prognostic factors of OS. A nomogram was established externally by involving all the factors stated above. The Concordance Index for the established nomogram to predict the OS of the training set was 0.793 (95% CI 0.689-0.897), and 0.803 (95% CI 0.696-0.910) in the validation set. These data suggest that the nomogram was validated externally, could predict long-term outcome accurately, and enable accurate stratification of risk groups for stage-II NPC. Our model facilitated individualized care of NPC patients.
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http://dx.doi.org/10.2147/CMAR.S202151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519021PMC
May 2019

Locoregional Control and Mild Late Toxicity After Reducing Target Volumes and Radiation Doses in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma Treated With Induction Chemotherapy (IC) Followed by Concurrent Chemoradiotherapy: 10-Year Results of a Phase 2 Study.

Int J Radiat Oncol Biol Phys 2019 07 5;104(4):836-844. Epub 2019 Apr 5.

Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan University, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China. Electronic address:

Purpose: To evaluate the long-term locoregional control, failure patterns, and late toxicity after reducing the target volume and radiation dose in patients with locoregionally advanced nasopharyngeal carcinoma patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT).

Methods And Materials: Previously untreated patients with locoregionally advanced nasopharyngeal carcinoma were recruited into this prospective study. All patients received 2 cycles of IC followed by CCRT. The gross tumor volumes of the nasopharynx (GTVnx) and the neck lymph nodes (GTVnd) were delineated according to the post-IC tumor extension and received full therapeutic doses (68 Gy and 62-66 Gy, respectively). The primary tumor shrinkage after IC was included in the high-risk clinical target volume (CTV1) with a reduced dose of 60 Gy. The locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. The location and extent of locoregional recurrences were transferred to pretreatment planning computed tomography for dosimetry analysis.

Results: There were 112 patients enrolled in this study. The average mean dose of post-GTVnx, post-GTVnd (left), post-GTVnd (right), post-CTV1, and post-low-risk clinical target volume (CTV2) was 75.24, 68.97, 69.16, 70.49, and 63.37 Gy, respectively. With a median follow-up of 125.95 months, the 10-year LRRFS, DMFS and OS were 89.0%, 83.3%, and 75.9%, respectively. There were 8 local recurrences and 6 regional recurrences in 12 patients. All 8 of the local recurrences were in-field; among the 6 regional recurrences, 4 were in-field, 1 was marginal, and 1 was out-field. The most common late toxicities were grade 1 to 2 subcutaneous fibrosis, hearing loss, and xerostomia. No grade 4 late toxicities were observed.

Conclusions: Reduction of the target volumes according to the post-IC tumor extension and radiation dose to the post-IC tumor shrinkage could yield excellent long-term locoregional control with limited marginal and out-field recurrences and mild late toxicities.
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http://dx.doi.org/10.1016/j.ijrobp.2019.03.043DOI Listing
July 2019

Efficacy and safety of primary surgery with postoperative radiotherapy in head and neck mucosal melanoma: a single-arm Phase II study.

Cancer Manag Res 2018 14;10:6985-6996. Epub 2018 Dec 14.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, People's Republic of China,

Background: There still remains no well-established treatment strategy for head and neck mucosal melanoma (HNMM). We aim to evaluate the effectiveness and safety of primary surgery with postoperative radiotherapy for this disease.

Patients And Methods: A single-arm, Phase II clinical trial was conducted at Sun Yat-Sen University Cancer Center. Patients with nonmetastatic, histologically proven HNMM were prospectively enrolled. Patients received primary surgery followed by intensity-modulated radiotherapy with an equivalent dose at 2 Gy per fraction of 65-70 Gy to CTV1 (high-risk regions including tumor bed) and 50-55 Gy to CTV2 (low-risk regions). Additional use of adjuvant chemotherapy (AC) depended on consultation from a multidisciplinary team. This trial is registered with ClinicalTrials.gov, number NCT03138642.

Results: A total of 33 patients were enrolled and analyzed between July 2010 and November 2016. There were 18 (54.5%) patients with T3 disease and 15 (45.5%) patients with T4a disease. The median age at diagnosis was 58 years (range 27-83 years), and 61% of the cohort were males. The overall median follow-up duration was 25.3 months (range 5.3-67.1 months). The 3-year overall survival (OS), local relapse-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) rates were 44.4, 91.7, 78.1, and 41.7%, respectively. Patients with T4a disease showed significantly inferior OS (=0.049) and DMFS (=0.040) than those with T3 disease. Prophylactic neck radiation (PNR) was nearly associated with superior RRFS (=0.078). However, there was no significant difference in OS, LRFS, RRFS, and DMFS for patients treated with or without AC (>0.05 for all). Toxicities were generally mild to moderate.

Conclusion: Primary surgery with postoperative radiotherapy yielded excellent local control and acceptable toxicity profile for HNMM. Nevertheless, high rates of distant metastases resulted in limited survival.
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http://dx.doi.org/10.2147/CMAR.S185017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298389PMC
December 2018

Additional Cervical Lymph Node Biopsy is Not a Significant Prognostic Factor for Nasopharyngeal Carcinoma in the Intensity-Modulated Radiation Therapy Era: A Propensity Score-matched Analysis from an Epidemic Area.

J Cancer 2018 30;9(16):2844-2851. Epub 2018 Jul 30.

Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510060, Guangdong, P.R. China.

: This study aimed to evaluate the prognostic value of cervical lymph node biopsy and whether different biopsy methods would lead different outcomes in NPC in the intensity-modulated radiotherapy (IMRT) era. : 1492 patients with biopsy-proven, non-metastatic NPC, and treated by IMRT with or without chemotherapy were retrospectively reviewed. Cervical lymph node biopsy was performed in 183 (12.3%) patients: 61(4.1%) by needle puncture and 118(7.9%) by excision biopsy. Propensity-score matching was used to match patients in both arms at an equal ratio. Overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRFS), and nodal relapse-free survival (NRFS) were assessed using the Kaplan-Meier method and compared using the log-rank test. Independent prognostic factors were identified using the Cox proportional hazards model. In the original cohort of 1492 patients, patients receiving cervical lymph node biopsy had comparable survival (OS: = 0.736, DMFS: = 0.749, LRFS: = 0.538, NRFS: = 0.093,) with patients receiving isolated napharynx biopsy. The results for the propensity-match cohort of 316 patients were similar. Interestingly, compared with the control group and needle puncture biopsy group, a slightly lower nodal recurrence rate was observed in the excision biopsy group ( = 0.082 and = 0.072, respectively). Adjusting for the known prognostic factors in multivariate analysis, cervical biopsy did not cause a higher risk of death, distant metastasis, or nodal relapse. Pretreatment cervical lymph node biopsy is not associated with impaired survival in NPC, suggesting the resist of the biopsy and more aggressive treatment after the biopsy may be unnecessary.
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http://dx.doi.org/10.7150/jca.25505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096379PMC
July 2018

The Novel Prognostic Score Combining Red Blood Cell Distribution Width and Body Mass Index (COR-BMI) Has Prognostic Impact for Survival Outcomes in Nasopharyngeal Carcinoma.

J Cancer 2018 6;9(13):2295-2301. Epub 2018 Jun 6.

Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510060, PR China.

A novel inflammation-and nutrition-based scoring system based on red blood cell distribution width and body mass index (COR-BMI) has prognostic value in nasopharyngeal carcinoma (NPC). Here, we assessed the prognostic value of COR-BMI in NPC. Retrospective study of 2,318 patients with non-metastatic NPC treated at Sun Yat-sen University Cancer Center was conducted. Patients were stratified into three groups using the COR-BMI score, which is based on two objective and easily measurable parameters: red blood cell distribution width (RDW) and body mass index (BMI). Kaplan-Meier survival analyses were used to compare groups; multivariate Cox proportional models were used to calculate overall survival (OS) and disease-free survival (DFS). Four-year overall survival (OS) rates were 88.7%, 84.5%, and 71.4% for patients with COR-BMI scores of 0, 1, and 2 respectively ( = 0.006). Multivariate Cox proportional hazard analysis revealed COR-BMI was an independent predictor of OS (HR for COR-BMI 1: 1.239, 95% CI: 1.012-1.590; HR for COR-BMI 2: 2.367, 95% CI: 1.311-4.274, = 0.013), but not DFS ( = 0.482). In subgroup analysis of metastatic NPC, OS rates decreased as COR-BMI increased. In patients with a COR-BMI score of 1, radiotherapy plus chemotherapy led to better OS than radiotherapy alone. COR-BMI may serve as an indicator of poor prognosis in both NPC and metastatic NPC. Radiotherapy plus chemotherapy may benefit patients with a COR-BMI score of 1.
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http://dx.doi.org/10.7150/jca.24838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036710PMC
June 2018

Comparison of the seventh and eighth editions of the UICC/AJCC staging system for nasopharyngeal carcinoma: analysis of 1317 patients treated with intensity-modulated radiotherapy at two centers.

BMC Cancer 2018 May 29;18(1):606. Epub 2018 May 29.

Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510060, Guangdong, People's Republic of China.

Background: In the intensity-modulated radiotherapy (IMRT) era, great improvement has been made in survival of nasopharyngeal carcinoma (NPC). The 7th edition of the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system seems "outdated " as it mainly based on the study in 2D/3D era, and thus the 8th edition has made some amendments according to recent studies. We aimed to compare and evaluate these two editions of staging system for NPC in patients treated with intensity-modulated radiotherapy.

Methods: A total of 1317 patients with biopsy-proven, non-metastatic NPC treated with IMRT between 2009 and 2014 at two institutions were retrospectively assessed. All patients were assessed by magnetic resonance imaging and restaged according to the 7th and 8th editions. Prognostic factors for local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were assessed and compared using the Kaplan-Meier method and log-rank test. The Cox proportional hazards model was also used to calculate the hazard ratio (HR).

Results: In both 7th and 8th edition, insignificant difference could be observed between T2 and T3 disease, T2 and T4 disease (all P > 0.05) for LRFS, while the difference of LRFS between T3 and T4 disease was significant in the previous edition (P = 0.001) but insignificant (P = 0.279) after revision. For OS, highly similar survival curve could be seen between T2 and T3 disease in both edition (all P > 0.1). DMFS and OS were not significantly different between N3a and N1-3b categories of the 7th edition (all P > 0.05). In contrast, obvious segregation was observed between N3 and the other N categories after the revision and combination in the 8th edition (all P < 0.05). DFS and OS were not significantly different between stage IVA and IVB of the 7th edition (P = 0.057 and P = 0.365, respectively); therefore, combining these stages in the 8th edition was reasonable.

Conclusion: The overall stages and N categories of the 8th edition of the UICC/AJCC staging system provide better segregation of survival outcomes than the 7th edition. The 8th edition is also more clinically applicable as it has reduced ambiguity and revised out-of-date definitions. However, the T categories need further optimizing as the 8th edition failed to solve the problem of similar survival between adjacent T-classification, which has been exited since 7th edition.
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http://dx.doi.org/10.1186/s12885-018-4419-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975550PMC
May 2018

Cervical lymph node carcinoma metastasis from unknown primary site: a retrospective analysis of 154 patients.

Cancer Med 2018 05 2;7(5):1852-1859. Epub 2018 Apr 2.

Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Despite advances in diagnosis and treatment, the existence of cervical lymph node carcinoma of unknown primary site (CCUP) has always been an urgent problem worldwide. There is still no consensus on the optimal management for CCUP. In this retrospective review, we analyze the clinical characteristics of CCUP patients treated at our institution and examine how these characteristics and treatments were associated with survival. Clinicopathologic features, treatments, and survival outcomes of 154 CCUP patients were collected from the hospital records and analyzed. Survival was estimated by Kaplan-Meier methods and compared by the log-rank test. Cox proportional hazards regression analysis was used to assess the factors independently associated with overall survival (OS) and progression-free survival (PFS). Median follow-up period was 26.44 months (range, 0.53-146.53 months). Multivariate analysis showed N stage, pathologic type, and lymph node extranodal extension (ENE) to be independent prognostic factors for OS in CCUP patients, but not PFS. Subgroup analysis of patients who received radiotherapy showed that radiotherapy to the pharyngeal mucosa was associated with better OS (P = 0.045), but not with better PFS. Advanced N stage, nonsquamous cell carcinoma, and lymph node ENE predict poor prognosis in patients with CCUP. In addition, radiotherapy to suspicious mucosa is accompanied by better OS. These study findings should be useful to clinicians when selecting the treatment approach.
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http://dx.doi.org/10.1002/cam4.1458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943546PMC
May 2018

Apolipoprotein A-I Is a Prognosticator of Nasopharyngeal Carcinoma in the Era of Intensity-modulated Radiotherapy.

J Cancer 2018 11;9(4):702-710. Epub 2018 Jan 11.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine; Guangzhou, Guangdong 510060, China.

In the era of intensity-modulated radiotherapy (IMRT), distant metastasis remains the major cause of death from nasopharyngeal carcinoma (NPC). This study aimed to evaluate the clinical value of pretreatment serum lipid profiles in predicting clinical outcome of NPC. A total of 1927 consecutive patients who had untreated NPC and completed radical IMRT between Jan. 2010 and Dec. 2011 were retrospectively reviewed. Pretreatment serum lipid indexes including total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-I (apoAI) and apolipoprotein B were analyzed for their association with survivals, together with the clinical features (age, sex, pathological type, anemia, chemotherapy sequence and Epstein-Barr virus deoxyribonucleic acid). Hazard ratio (HR) and 95% confidence interval (CI) were calculated for each independent prognosticator. After univariate and multivariate survival analysis, low apoAI level (< 1.125 mmol/L) appeared to predict poor 5-year overall survival (OS), disease-free survival (DFS) and distant-metastasis-free survival (DMFS).The HRs were 1.549 (95% CI, 1.137-2.109), 1.293 (95% CI, 1.047-1.597) and 1.288 (95% CI, 1.022-1.623), respectively. Subgroup survival analysis showed that the apoAI maintained predicting independence for OS, DFS and DMFS in patients with locally advanced NPC, even in those treated with concurrent chemoradiotherapy. NPC patient with low serum level of pretreatment apoAI might be at risk of distant metastasis. Treatment aiming to eradicate distant metastasis might improve survival of these patients.
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http://dx.doi.org/10.7150/jca.22836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858492PMC
January 2018

Dynamic changes in plasma Epstein-Barr virus DNA load during treatment have prognostic value in nasopharyngeal carcinoma: a retrospective study.

Cancer Med 2018 04 1;7(4):1110-1117. Epub 2018 Mar 1.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat sen University Cancer Center, Guangzhou, Guangdong, China.

Circulating plasma Epstein-Barr virus DNA (EBV DNA) is related to tumor recurrence and metastasis and has potential as a dynamic, sensitive, and specific marker in nasopharyngeal carcinoma (NPC). We investigated the clinical significance of assessing plasma EBV DNA load at various time points during treatment. Patients with NPC (n = 949) for whom plasma EBV DNA load was measured by real-time quantitative polymerase chain reaction (RT-qPCR) before treatment (pre-EBV) and at midtreatment (mid-EBV), end of treatment (end-EBV), and 3 months after completing treatment (3 m-EBV) were retrospectively assessed. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal EBV DNA cutoff point for each time point. Overall survival (OS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were compared using Kaplan-Meier estimates. High pre-EBV, high mid-EBV, high end-EBV, and high 3 m-EBV were all associated with significantly poorer OS, DMFS, and PFS in the entire cohort. Detectable end-EBV and 3 m-EBV was associated with significantly poorer OS, DMFS, and PFS. Among patients with detectable end-EBV, adjuvant therapy significantly improved OS (HR 2.419; 95% CI 1.297-4.51, P = 0.03) and DMFS (HR 2.45; 95% CI 1.243-4.828, P = 0.04), but not PFS (P = 0.17). EBV DNA represents a dynamic biomarker for monitoring treatment and predicting survival in NPC. Assessing plasma EBV DNA before, during, and after chemoradiotherapy could be clinically valuable and enable selection of patients most likely to benefit from additional therapy and improve assessment of treatment response and disease surveillance. Further multicenter prospective investigations are warranted.
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http://dx.doi.org/10.1002/cam4.1381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911595PMC
April 2018

Plasma Fibrinogen Correlates with Metastasis and is Associated with Prognosis in Human Nasopharyngeal Carcinoma.

J Cancer 2017 10;8(3):403-409. Epub 2017 Feb 10.

Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, China.; State Key Laboratory of Oncology in Southern China, Guangzhou, China.; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

The purpose of this observational study was to evaluate the prognostic significance of the pre-treatment plasma fibrinogen level for survival outcomes in nasopharyngeal carcinoma (NPC). A total of 998 patients with NPC treated at a single centre in China were retrospectively enrolled, of whom 182 (18.2%) developed distant metastasis during follow-up. Survival analyses were performed by the Kaplan-Meier method and Cox regression modelling to measure 3-year overall survival (OS) and distant metastasis-free survival (DMFS). Median OS for the entire cohort was 37.8 months. Using the cut-off value of 3.345 g/L identified in receiver operating curve analysis for fibrinogen, a high pre-treatment plasma fibrinogen level were associated with older age ( = 0.034), advanced TNM stage ( = 0.004) and development of distant metastasis ( < 0.001; Chi-square test). Multivariate Cox proportional hazard analysis demonstrated the pre-treatment plasma fibrinogen level was an independent significant prognostic factor for OS and DMFS in both the entire cohort and also among patients who developed distant metastasis during follow-up. This study suggests the pre-treatment plasma fibrinogen level may serve as an independent prognostic marker to predict the survival outcomes of patients with NPC, including patients with metastatic disease.
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http://dx.doi.org/10.7150/jca.17028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332891PMC
February 2017

Epstein-Barr virus mir-bart1-5p detection via nasopharyngeal brush sampling is effective for diagnosing nasopharyngeal carcinoma.

Oncotarget 2016 Jan;7(4):4972-80

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

Epstein-Barr virus (EBV)-encoded microRNAs (miRNAs) are highly expressed in nasopharyngeal carcinoma (NPC) cases in high-risk areas, and may be involved in tumorigenesis. Using quantitative RT-PCR, we detected four EBV-encoded BamHI A rightward transcript (BART) miRNAs (mir-bart1-5p, mir-bart5, mir-bart6-5p and mir-bart17-5p) exclusively in 53 NPC biopsies as compared to 69 controls. In a larger patient group, that included 215 NPC cases and 209 controls, significantly higher levels of all four EBV miRNAs were detected in tumor cells harvested directly from the nasopharynx using a less invasive nasopharyngeal (NP) brush than in the controls (p < 0.001). One EBV miRNA, mir-bart1-5p, holds particular promise for use as a diagnostic indicator of NPC (with 93.5% sensitivity and 100% specificity), and its relative expression level was reflective of disease progression. Detection of this miRNA was effective for diagnosing early-stage NPC, even in cases that were falsely diagnosed as negative based on histopathological analysis, plasma EBV DNA load, and VCA-IgA and EA-IgA titers. EBV-encoded mir-bart1-5p detection via NP brush sampling could act as an efficient and less invasive method assisting clinical diagnosis of NPC.
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http://dx.doi.org/10.18632/oncotarget.6649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826258PMC
January 2016

Quantification of Epstein-Barr virus DNA load in nasopharyngeal brushing samples in the diagnosis of nasopharyngeal carcinoma in southern China.

Cancer Sci 2015 Sep 14;106(9):1196-201. Epub 2015 Jul 14.

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Nasopharyngeal carcinoma (NPC) is highly incident in southern China, where 40% of world's new cases arise each year. Detection of Epstein-Barr virus (EBV) DNA load in nasopharyngeal (NP) brush/swab samples has gradually been established as a method for diagnosis of NPC. However, its applicable value in NPC diagnosis has never been investigated in southern China. It is important to explore whether such a test could be applicable to our local population. A total of 245 consecutive participants undergoing NP brushing examination were recruited to obtain the NP brushing samples in this study. Quantitative PCR assays were used to obtain the EBV DNA load. Mann-Whitney, ANOVA and receiver operating characteristic tests were used to analyze its diagnostic value. NP brushing samples from NPC patients showed extremely high levels of EBV DNA load (mean = 46360 copy/ng DNA) compared to its expression from non-NPC control (mean = 28 copy/ng DNA) and high-risk control (mean = 50 copy/ng DNA) groups. It produced 96% sensitivity and 97% specificity, at the COV = 225 copy/ng DNA. Furthermore, EBV DNA load could reflect disease progress. Our data showed a better performance of EBV DNA load in NP brushing samples compared with an initial biopsy, immunoglobulin A (IgA) antibody titers to viral capsid antigen in serum and EBV DNA load in plasma. Detection of EBV DNA load in NP brushing samples could be an effective supplement for NPC diagnosis. Being minimally invasive and low cost, NP brush sampling combined with EBV DNA detection demonstrates great potential for screening high-risk populations for NPC.
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http://dx.doi.org/10.1111/cas.12718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582989PMC
September 2015

Carboxylesterase-mediated insecticide resistance: Quantitative increase induces broader metabolic resistance than qualitative change.

Pestic Biochem Physiol 2015 Jun 23;121:88-96. Epub 2014 Dec 23.

State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Carboxylesterases are mainly involved in the mediation of metabolic resistance of many insects to organophosphate (OP) insecticides. Carboxylesterases underwent two divergent evolutionary events: (1) quantitative mechanism characterized by the overproduction of carboxylesterase protein; and (2) qualitative mechanism caused by changes in enzymatic properties because of mutation from glycine/alanine to aspartate at the 151 site (G/A151D) or from tryptophan to leucine at the 271 site (W271L), following the numbering of Drosophila melanogaster AChE. Qualitative mechanism has been observed in few species. However, whether this carboxylesterase mutation mechanism is prevalent in insects remains unclear. In this study, wild-type, G/A151D and W271L mutant carboxylesterases from Culex pipiens and Aphis gossypii were subjected to germline transformation and then transferred to D. melanogaster. These germlines were ubiquitously expressed as induced by tub-Gal4. In carboxylesterase activity assay, the introduced mutant carboxylesterase did not enhance the overall carboxylesterase activity of flies. This result indicated that G/A151D or W271L mutation disrupted the original activities of the enzyme. Less than 1.5-fold OP resistance was only observed in flies expressing A. gossypii mutant carboxylesterases compared with those expressing A. gossypii wild-type carboxylesterase. However, transgenic flies universally showed low resistance to OP insecticides compared with non-transgenic flies. The flies expressing A. gossypii W271L mutant esterase exhibited 1.5-fold resistance to deltamethrin, a pyrethroid insecticide compared with non-transgenic flies. The present transgenic Drosophila system potentially showed that a quantitative increase in carboxylesterases induced broader resistance of insects to insecticides than a qualitative change.
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http://dx.doi.org/10.1016/j.pestbp.2014.12.016DOI Listing
June 2015

[Effect of human concentration nucleoside transporters 1 and multi-drug resistance protein 4 gene polymorphism on response of chronic hepatitis B to nucleoside analogues treatment].

Sichuan Da Xue Xue Bao Yi Xue Ban 2014 Nov;45(6):950-5

West China Hospital, Sichuan University, Chengdu, China

Objective: To investigate the effect of human concentration nucleoside transporters 1 (hCNT1/ SLC28A1) and multi-drug resistance protein 4 (MRP4/ABCC4) gene polymorphism on the response of chronic hepatitis B patients to nucleoside analogues treatment.

Methods: There were 136 patients of chronic hepatitis B treated with entecavir (68) or telbivudine (68). The allele and gene frequency distributing of the four loci of hCNT1/SLC28A1 and MRP4/ABCC4 as well as the polymorphisms were detected in all patients by multiplex snapshot single base extension method. Based on the treatment response, the patients were divided into primary partial response (PPR) group and complete viral response (CVR) group, hCNTI/SLC28A1 and MRP4/ABCC4 gene polymorphism between these two groups were analyzed.

Results: The rates of PPR and CVR were 56. 6%00 (77 136) and 43. 4% (59/136) respectively. There was no statistical difference in baseline HBV DNA value, hepatitis B virus genotype and HBeAg status between PPR and CVR groups (P=0.148, P= 0. 622,P=0. 071) . The distribution of allelotype rs2290272 C/T and rs11568658 G/G in PPR group were higher than those in CVR group (P=0.043. P=0.049). Haplotype of C/A/T/C and C/C/G/G in CVR group were higher than those in PPR group (P=0. 024,P=0. 005).

Conclusion: The single nucleotide polymorphisms (SNPs) of two candidate genes, including rs2290272 C/T of hCNT1/SLC28A1 and rs11568658 G/G of MRP4/ABCC4, may weak the response of chronic hepatitis B to nucleoside analogues treatment, as well as haplotype of C/A/T/C and C/C/G/G may enhance the response.
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November 2014

Lack of association between the COMT rs4680 polymorphism and ovarian cancer risk: evidence from a meta-analysis of 3,940 individuals.

Asian Pac J Cancer Prev 2014 ;15(18):7941-5

Department of Pathology, Shihezi University School of Medicine, Shihezi, China E-mail :

Catechol-O-methyltransferase (COMT) is involved in estrogen metabolism and is vital to estrogen-induced carcinogenesis, including that of ovarian cancer. Although many recent epidemiologic studies have investigated associations between the COMT rs4680 polymorphism and ovarian cancer risk, the results remain inconclusive. We therefore performed a meta-analysis to derive a more precise estimate of associations. Systematic searches of the PubMed, Embase, Web of Science, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and Chinese Biomedicine databases were undertaken to retrieve eligible studies. Odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were pooled to assess the strength of the association. In total, 8 case-control studies involving 1,293 cases and 2,647 controls were included in the meta-analysis. Overall, the results showed no evidence of significant association between the COMT rs4680 polymorphism and ovarian cancer risk in any of the assessed genetic models. Subgroup analyses by ethnicity also did not reveal any significant association in any genetic model (p>0.05). In conclusion, our findings suggest that the COMT rs4680 polymorphism may not contribute to the risk of ovarian cancer.
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http://dx.doi.org/10.7314/apjcp.2014.15.18.7941DOI Listing
June 2015

Functions of corneal endothelial cells do not change after uptake of superparamagnetic iron oxide nanoparticles.

Mol Med Rep 2013 Jun 10;7(6):1767-72. Epub 2013 Apr 10.

Department of Ophthalmology, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, P.R. China.

To avoid donor tissue shortages, ex vivo cultured human corneal endothelial cell (HCEC) transplantation is a promising therapeutic resource. Superparamagnetic iron oxide nanoparticle (SPION) cell labeling assists HCEC transplantation by attaching the posterior corneal stroma in ex vivo animal models. However, possible functional changes of the HCECs following SPION labeling remain to be determined. In this study, we used SPIONs to label cultured rabbit CECs (RCECs) in order to observe important cell functions and the levels of cell markers. The synthetic SPIONs exhibited superparamagnetism at room temperature, with saturation magnetization of 55.4 emu/g and negligible remanence or coercivity. The ζ-potential was -24.5 mV and the diameter was 101 ± 55 nm. Immunostaining demonstrated a normal density of zonula occluden-1 (ZO-1), nestin and Ki-67 at cellular junctions or in nuclei from RCECs following SPION labeling at 16 µg/ml. MTT cytotoxicity assay, homotypic adhesion assay, quantitative flow cytometric Ki-67 analysis and RCEC pump function measurement demonstrated no significant differences between the cells with or without SPION labeling (P<0.05, for all assays). Results of this study demonstrated successful labeled cultured RCECs with synthetic SPIONs. Labeled cells possessed several important characteristics required to maintain the transparency and refractive parameters of the cornea, including hexagonal cell morphology, higher cell adhesion ability and proliferative potential, cell pump function and the positive expression of several cell markers.
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http://dx.doi.org/10.3892/mmr.2013.1418DOI Listing
June 2013

Effect of combining different calcium concentration dialysate on calcium balance in peritoneal dialysis patients.

Chin Med J (Engl) 2012 Nov;125(22):4009-13

Department of Nephrology, Peking University People's Hospital, Beijing, China.

Background: Calcium and phosphorus metabolic disturbance are common in dialysis patients and associated with increased morbidity and mortality. Therefore, maintaining the balance of calcium and phosphate metabolism and suitable intact parathyroid hormone (iPTH) level has become the focus of attention. We investigated the effects of different peritoneal dialysate calcium concentrations on calcium phosphate metabolism and iPTH in continuous ambulatory peritoneal dialysis (CAPD) patients.

Methods: Forty stable CAPD patients with normal serum calcium were followed for six months of treatment with 1.25 mmol/L calcium dialysate (DCa1.25, PD4, 22 patients) or a combination of 1.75 mmol/L calcium dialysate (DCa1.75, PD2) and PD4 (18 patients) twice a day respectively. Total serum calcium (after albumin correction), serum phosphorus, iPTH, alkaline phosphatase (ALP) and blood pressure were recorded before and 1, 3 and 6 months after treatment commenced.

Results: No significant difference was found in baseline serum calcium, phosphorus between the two patient groups, but the levels of iPTH were significantly different. No significant changes were found in the dosage of calcium carbonate and active vitamin D during 6 months. In the PD4 group, serum calcium level at the 1st, 3rd, 6th months were significantly lower than the baseline (P < 0.05). There was no significant difference in serum phosphorus after 6 months treatment. iPTH was significantly higher (P < 0.001) at the 1st, 3rd, and 6th months compared with the baseline. No differences were seen in ALP and blood pressure. In the PD4+PD2 group, no significant changes in serum calcium, phosphorus, iPTH, ALP and BP during the 6-month follow-up period.

Conclusions: Treatment with 1.25 mmol/L calcium dialysate for six months can decrease serum calcium, increase iPTH, without change in serum phosphorus, ALP, and BP. The combining of PD4 and PD2 can stabilize the serum calcium and avoid fluctuations in iPTH levels.
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November 2012

Results of a phase 2 study examining the effects of omitting elective neck irradiation to nodal levels IV and Vb in patients with N(0-1) nasopharyngeal carcinoma.

Int J Radiat Oncol Biol Phys 2013 Mar 11;85(4):929-34. Epub 2012 Sep 11.

Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.

Purpose: To evaluate the patterns of nodal failure and toxicity in clinically negative necks of N0-1 nasopharyngeal carcinoma (NPC) patients who were treated with intensity modulated radiation therapy (IMRT) but did not receive elective neck irradiation (ENI) to level IV and Vb nodes.

Methods And Materials: We conducted a phase 2 prospective study in N0-1 NPC patients treated with IMRT. ENI included the retropharyngeal nodes and levels II to Va but omitted levels IV and Vb in clinically negative necks. Patterns of nodal failure, regional control (RC), and late toxicity were evaluated.

Results: Between 2001 and 2008, a total of 212 patients (128 N0 and 84 N1) were enrolled in the study. Seven patients (4 in-field and 3 out-of-field) developed nodal failure. One patient (0.5%) developed nodal failure at level Vb, but no patients developed nodal failure at level IV. The 5-year RC rates of the entire group, N0 patients and N1 patients were 95.6%, 98.2%, and 91.3%, respectively. Fifteen patients (7.1%) developed distant metastases. The 5-year distant failure-free survival (DFFS) and overall survival (OS) rates were 91.4% and 89.8%, respectively. The rates of grade 2 or greater skin dystrophy, subcutaneous fibrosis and xerostomia were 6.2%, 16.6%, and 17.9%, respectively.

Conclusions: The rate of out-of-field nodal failure when omitting ENI to levels IV and Vb in clinically negative necks of patients with N0-1 NPC was extremely low; therefore, a further phase 3 study is warranted.
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http://dx.doi.org/10.1016/j.ijrobp.2012.07.2356DOI Listing
March 2013

Long-term treatment outcome of recurrent nasopharyngeal carcinoma treated with salvage intensity modulated radiotherapy.

Eur J Cancer 2012 Dec 25;48(18):3422-8. Epub 2012 Jul 25.

State Key Laboratory of Oncology in Southern China, Guangzhou, China.

Purpose: To evaluate the long-term treatment outcome in patients with recurrent nasopharyngeal carcinoma (NPC) treated with salvage intensity modulated radiotherapy (IMRT).

Materials And Methods: One hundred and fifty one previously irradiation NPC patients with recurrent disease and re-irradiated by IMRT between 2001 and 2006 had been reviewed. The disease was re-stage I in 7, re-stage II in 21, re-stage III in 50 and re-stage IV in 73. Thirty-seven patients received concurrent chemotherapy, 39 had induction chemotherapy and 75 had radiotherapy alone.

Results: All patients completed the planned IMRT. The median volume of the recurrent gross target volume of nasopharynx (rGTVnx) was 42.2 cm(3) (range 1.5-146.3 cm(3)). The median mean re-irradiation dose to the rGTVnx was 70.4Gy (range 62.1-77.6Gy). The median follow-up time after re-irradiation was 40.0 months (range 1.9-116.9 month). The 5-year local control rate (LCR) and overall survival rate (OS) for re-stage I, II, III, IV were 80.0%, 85.0%, 80.0%, 78.7% and 71.4%, 62.9%, 35.5%, 30.2%, respectively. Multivariate analysis indicated that rT classification (hazard ratio (HR), 2.02; 95%confidence interval (CI), 1.03-3.97; P=0.04) and the volume of rGTVnx (HR, 2.05; 95%CI, 1.31-3.22; P<0.01) were independent predictors for OS. Patients (39.0%) with re-stage III or IV disease experienced Grade 3 or 4 late toxicities.

Conclusion: Re-irradiation by IMRT for recurrent NPC resulted in encouraging local control. The clinical outcome for patients with early re-stage diseases was satisfactory. Further investigations, focus on optimising radiation dose and establishing effective treatment strategies, are warranted for advanced recurrent disease in order to improve overall survival and minimise late toxicity.
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http://dx.doi.org/10.1016/j.ejca.2012.06.016DOI Listing
December 2012

Effect and Predictive Elements for 52 Weeks' Telbivudine Treatment on Naïve HBeAg positive Chronic Hepatitis B.

Hepat Mon 2011 Dec 20;11(12):980-5. Epub 2011 Dec 20.

Epidemiology Department,West China School of public Health, Sichuan University, Chengdu, China.

Background: Antiviral treatment with nucleoside analogs has been used for chronic hepatitis B (CHB). Each kind of nucleoside analog has its own characteristics and suitability for patients. Telbivudine (LdT, brand name: Sebivo, Beijing Novartis Pharma Ltd) is the newest nucleoside analog, with strong and rapid viral suppression. However, its resistance rate is relatively high during long-term application, due to low genetic barriers to resistance. So, it is necessary to increase the effect and reduce resistance with effective management, according to baseline factors and early on-treatment responses.

Objectives: To reveal possible predictive factors of the effect of telbivudine (LdT) treatment on naïve HBeAg-positive chronic hepatitis B (CHB) patients to optimize treatment.

Patients And Methods: A total 71 naïve chronic hepatitis B (CHB) patients who met the inclusion criteria were enrolled. All patients were treated with LdT 600 mg Qd for at least 52 weeks. Multiple logistic regression analyses were done to investigate the predictive values of baseline factors and responses at Week 24.

Results: The reduction in hepatitis virus B (HBV) DNA level was 6.44 ± 2.38 lg copies/mL at Week 52 compared with baseline. The complete virus response (CVR), biochemical response (BR), serological response (SR), and drug resistance (DR) were 61.99%, 77.46%, 35.21%, and 8.45% respectively. By multiple regression analysis, baseline alanine aminotransferase (ALT) levels significantly affected CVR (P = 0.024, OR = 1.008), and baseline ALT and baseline HBV DNA levels were independent compact factors of SR (P = 0.012, OR = 1.007; P = 0.001, OR = 0.423). The differences in CVR, SR, and DR in patients with ALT > 120 Iu/mL compared with patients with ALT ≤ 120 Iu/mL were statistically significant. The differences in SR in patients with HBV DNA > 107 copies/mL compared with patients with HBV DNA ≤ 107 copies/mL were statistically significant. Additionally, CVR, BR, and SR were differed significantly between patients with HBV DNA lower than 300 copies/mL at Week 24 and patients with HBV DNA higher than 300 copies/mL (P = 0.000, P = 0.0016, and P = 0.000, respectively).

Conclusions: There were more responders among naïve HBeAg-positive chronic hepatitis B patients with lower HBV DNA levels (especially lower than 107 copies/mL) and higher ALT values (especially higher than 120 Iu/mL at baseline) to LdT treatment. Adjustments for treatment strategy should be considered if HBV DNA > 300 copies/mL at Week 24 is observed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282031PMC
http://dx.doi.org/10.5812/kowsar.1735143x.4203DOI Listing
December 2011

Long-term outcomes and prognostic factors of re-irradiation for locally recurrent nasopharyngeal carcinoma using intensity-modulated radiotherapy.

Clin Oncol (R Coll Radiol) 2012 Oct 29;24(8):569-76. Epub 2011 Dec 29.

Department of Radiation Oncology, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, China.

Aims: To analyse the outcomes and to evaluate the prognostic factors involved in the re-irradiation of locally recurrent nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT).

Materials And Methods: A retrospective analysis of 239 NPC patients with local recurrence who were re-irradiated with IMRT between 2001 and 2008 was conducted. The distribution of disease re-staging was 5.4% for stage I, 18.4% for stage II, 29.7% for stage III and 46.4% for stage IV. Cisplatin-based chemotherapy was administered to 117 patients (49.0%) in addition to the IMRT.

Results: The mean D(95) and the V(95) of the gross tumour volume (GTV) were 66.78 Gy and 98.61%, respectively. The mean dose to the GTV was 70.04 Gy (61.73-77.54 Gy). The 5 year overall survival, local recurrence-free survival, distant metastasis-free survival and disease-free survival were 44.9, 85.8, 80.6 and 45.4%, respectively. In a univariate analysis, patient age, recurrent T (rT), recurrent N (rN), recurrent stage, tumour volume, mean dose and mean fractional dose of the GTV were significant prognostic factors for overall survival. In a multivariate analysis, only patient age, rN stage, recurrent stage, mean fractional dose and tumour volume remained significant for overall survival.

Conclusions: Re-irradiation using IMRT is available to improve local tumour control and to prolong patients' survival. A smaller tumour volume, higher fractional dose, younger patient ages, lower rN(0) stage and early recurrent stage are all independent prognostic factors for overall survival of recurrent NPC. It is of clinical importance to select the appropriate recurrent NPC cases for salvage re-irradiation by IMRT.
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http://dx.doi.org/10.1016/j.clon.2011.11.010DOI Listing
October 2012

[Effect of Lamivudine on chronic hepatitis B patients with chemotherapy or immunosuppressive agents therapy and research the drug resistance].

Sichuan Da Xue Xue Bao Yi Xue Ban 2011 Sep;42(5):666-71

Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To study the effect of Lamivudine on chronic hepatitis B patients with chemotherapy or immunosuppressive agents therapy, and research the drug resistance.

Methods: Thirty-one cases of chronic hepatitis B patients who needed chemotherapy or immunosuppressive agents therapy were enrolled and divided into two group, HBeAg-positive group (n = 20) and HBeAg-negative group (n = 11), then given Lamivudine for preventive treatment. Virus response, biochemical response and serum response were evaluated as effective index, and analyzed the difference between the two groups for statistical significance. Meanwhile, drug resistance rate, impact factor of resistance and security were analyzed.

Results: At the end of 48 weeks' treatment, the rate of HBV DNA under the detection limit was 41.94%, and the decline of HBV DNA compared with baseline was 2.35 lg. The normalization rate of ALT, the negative rate of HbeAg and the seroconversion rate of HBeAg/HBeAb were 92.31%, 25% and 20% respectively. HBeAg-positive group and HBeAg-negative group patients in the complete virus response, the decline of HBV DNA compared with baseline and the resistance rate had no statistics significance (P > 0.05). At the same time, virology breakthrough occurred in four patients, and resistance mutation was detected in three cases among them. The resistance rate was 9.68%. The type of genotype mutation were all rtM204I. Multi-factor regression analysis showed that the baseline factors including age, gender, HBeAg status, baseline HBV DNA level and baseline ALT had no significant compact on drug resistance. Serious adverse reactions were not found in all patients.

Conclusion: For chronic hepatitis B patients who needed chemotherapy or immunosuppressive agents treatment, Lamivudine for preventive antiviral therapy is a good option with good antiviral effect and safety. It is necessary to pay attention to the occurrence of drug resistance.
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September 2011

Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: long-term results of a phase 2 study.

Cancer 2011 May 16;117(9):1874-83. Epub 2010 Nov 16.

Department of Radiation Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou, China.

Background: The aim of this phase 2 study was to determine the long-term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy.

Methods: Eighty-one patients with pathologically diagnosed locally advanced NPC were enrolled in this study. IMRT was delivered with the SMART boost technique at prescribed doses of 68 grays (Gy)/30 fraction to the nasopharynx gross target volume. Concurrent cisplatin chemotherapy (80 mg/m(2) /d on Days 1 and 22) was administered.

Results: The mean actual physical dose delivered to the nasopharynx gross target volume was 73.8 Gy, and the mean biologically effective dose (BED) for the nasopharynx gross target volume was 84.8 Gy. With a median follow-up of 54 months, 4 (4.9%) patients experienced local recurrence. The 5-year local control rate was 94.9%. Eighteen patients died. Among them, 66.7% died of distant metastasis. The 5-year disease-free and overall survivals were 76.7% and 74.5%, respectively. The most common late toxicities among 68 patients with ≥4 years follow-up were grade 1-2 xerostomia, hearing loss, skin dystrophy, and subcutaneous fibrosis. No grade 4 late toxicities were noted.

Conclusions: IMRT with SMART to enhance BED and concurrent chemotherapy is feasible in patients with locally advanced NPC. Long-term results showed excellent local control with fewer late toxicities, although no further improvement was noted in overall survival, and the major cause of death was distant metastasis. Exploration of more effective combined chemoradiation strategies is warranted.
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http://dx.doi.org/10.1002/cncr.25754DOI Listing
May 2011

Intensity-modulated radiation therapy reduces radiation-induced trismus in patients with nasopharyngeal carcinoma: a prospective study with >5 years of follow-up.

Cancer 2011 Jul 24;117(13):2910-6. Epub 2011 Jan 24.

Department of Radiation Oncology, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Background: Intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) provides better temporomandibular joint (TMJ) sparing and, thus, may reduce the incidence of radiation-induced trismus after radiotherapy. The objectives of this study were to evaluate radiation-induced trismus in patients with NPC who had received IMRT and to assess the pretreatment factors, relevant treatment factors, and dosimetry parameters associated with trismus.

Methods: A prospective, single-arm measurement study with more than 5 years of follow-up was designed. Patients with newly diagnosed stage I through IVB NPC who received treatment with IMRT were eligible. Patients received 66 to 70 grays (Gy) to the gross tumor volume. The maximal interincisal distance (MID) was measured at baseline and 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years after they completed IMRT.

Results: The trial enrolled 211 consecutive patients from 2001 to 2004. The mean dose to the TMJ ranged from 6.18 Gy to 51.36 Gy (median dose, 29.88 Gy). Compared with baseline MID levels, normalized MID levels at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years after IMRT were 94.6% ± 9.9%, 92.5% ± 10.5%, 92% ± 10.6%, 92.2% ± 10.5%, 92.1% ± 10.2%, and 90.3% ± 11.4%, respectively (P < .001). According to a revised subjective-objective management-analytical (SOMA) scale, grade 1/2 trismus was identified in 12 of 211 patients (5.7%), and no grade 3/4 trismus was observed. There was an increasing risk of trismus after IMRT when the MID was <40.5 mm at baseline compared with an MID >40.5 mm (P = .007). No dosimetric parameter was associated with trismus.

Conclusions: IMRT was able to reduce the radiation dose to the TMJ and likely reduced the incidence and severity of radiation-induced trismus after radiotherapy.
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http://dx.doi.org/10.1002/cncr.25773DOI Listing
July 2011

[Burden and related factors among care-takers of patients with Parkinson's disease].

Zhonghua Liu Xing Bing Xue Za Zhi 2010 Jun;31(6):692-5

Department of Neurology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, China.

Objective: To assess the impact on caretaker who looked after patients with Parkinson's disease (PD) and to identify the main factors related to their burden.

Methods: 115 consecutive pairs of PD patients and their caretakers were included. Caregiver Burden Inventory (CBI) was used to assess the burden of PD on the caretakers. Patients were evaluated by neurologists using the United Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr Scale (H-Y Scale), the Activity of Daily Living Scale (ADL), the Parkinson's Disease Questionnaire (PDQ-39), the Hamilton Depression Rating Scale (HAMD), the Hamilton Anxiety Rating Scale (HAMA), the Montreal Cognitive Assessment (MoCA) and the Mini-mental State Examination (MMSE). Multiple linear stepwise regression models were fitted to ascertain the factors linked to the CBI.

Results: Based on multiple linear stepwise regression analysis, ADL (β = -0.813, t = -6.265, P = 0.000) and PDQ-39 (β = 0.285, t = 4.256, P = 0.000) of patients and the age of caretakers (β = 0.327, t = 3.107, P = 0.002) proved to be the main predictors of CBI.

Conclusion: Many factors might comprehensively affect the burden of PD on caretakers of the patients. Attention needs to be given to the early identification of factors that generating stress on caretakers in order to improve their quality of life.
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June 2010

Different clinical significance of pre- and post-treatment plasma Epstein-Barr virus DNA load in nasopharyngeal carcinoma treated with radiotherapy.

Clin Oncol (R Coll Radiol) 2011 Mar 12;23(2):128-33. Epub 2010 Oct 12.

Shanghai Lung Tumour Clinical Medical Center, Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.

Aims: To correlate the pre-treatment plasma Epstein-Barr virus (EBV) DNA with tumour burden and to explore the prognostic implications of pre- and post-treatment plasma EBV DNA load in nasopharyngeal carcinoma patients treated with radiotherapy.

Materials And Methods: Plasma EBV DNA load was measured using a real-time quantitative polymerase chain reaction assay in 69 patients with nasopharyngeal carcinoma before and after radiation treatment and correlated with tumour volume and treatment outcome. Tumour volume was calculated by multiplying the sum of the areas of gross extent of the primary tumour and regional lymph nodes shown by computed tomography images and/or magnetic resonance imaging. Prognostic models for distant metastasis and overall survival were constructed using a multivariable fractional polynomial algorithm.

Results: The pre-treatment plasma EBV DNA concentration was significantly associated with tumour volume (Spearman correlation coefficient, 0.61; P<0.001). The multivariable fractional polynomial algorithm selected post-treatment EBV DNA and administration of chemotherapy as prognostic factors for distant metastasis (P<0.001, P=0.021, respectively), as well as for overall survival (P<0.001, P=0.018, respectively).

Conclusions: Pre- and post-treatment plasma EBV DNA load have important clinical significance. Pre-treatment plasma EBV DNA concentration reflects tumour burden, whereas clearance of circulating plasma EBV DNA after treatment predicts the risk of distant metastasis and overall survival.
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http://dx.doi.org/10.1016/j.clon.2010.09.001DOI Listing
March 2011