Publications by authors named "Zhen-Yu Qi"

50 Publications

Individualized elective irradiation of the clinically node-negative neck in definitive radiotherapy for head and neck squamous cell carcinoma.

Cancer Commun (Lond) 2021 Apr 26;41(4):303-315. Epub 2021 Feb 26.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong, 510060, P. R. China.

Background: Oral cavity (OC), oropharyngeal (OP), hypopharyngeal (HP), and laryngeal (LA) squamous cell carcinoma (SCC) have a high incidence of regional lymph node metastasis (LNM). Elective irradiation for clinically node-negative neck is routinely administered to treat lymph nodes harboring occult metastasis. However, the optimal elective irradiation schemes are still inconclusive. In this study, we aimed to establish individualized elective irradiation schemes for the ipsilateral and contralateral node-negative neck of these four types of cancer.

Methods: From July 2005 to December 2018, 793 patients with OC-SCC, 464 with OP-SCC, 413 with HP-SCC, and 645 with LA-SCC were recruited retrospectively. Based on the actual incidence of LNM and the tumor characteristics, risk factors for contralateral LNM, as well as node level coverage schemes for elective irradiation, were determined using logistic regression analysis. Additionally, we developed a publicly available online tool to facilitate the widespread clinical use of these schemes.

Results: For the ipsilateral node-negative neck, elective irradiation at levels I-III for OC-SCC and levels II-IVa for OP-, HP- and LA-SCC are generally recommended. In addition, level VIIa should be included in patients with OP-SCC. Multivariate analyses revealed that posterior hypopharyngeal wall and post-cricoid region involvement were independently associated with level VIIa metastasis in HP-SCC (all P < 0.05). For the contralateral node-negative neck, multivariate analyses revealed that ipsilateral N2b2-N3, tumors with body midline involvement, and degree of tumor invasion were the independent factors for contralateral LNM (all P < 0.05). In patients who require contralateral neck irradiation, levels I-II are recommended for OC-SCC, and additional level III is recommended for patients with ipsilateral N3 disease. Levels II-III are recommended for OP-, HP-, and LA-SCC, and additional level IVa is recommended for patients with advanced T or ipsilateral N classifications. Furthermore, additional level VIIa is recommended only for OP-SCC with T4 and ipsilateral N3 disease.

Conclusion: Based on our findings, we suggest that individualized and computer-aided elective irradiation schemes could reduce irradiation volumes in OC-, OP- and HP-SCC patients, as compared to current guidelines, and could thus positively impact the patients' quality of life after radiotherapy.
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http://dx.doi.org/10.1002/cac2.12145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045930PMC
April 2021

The E3 ubiquitin ligase gene SlRING1 is essential for plant tolerance to cadmium stress in Solanum lycopersicum.

J Biotechnol 2020 Dec 10;324:239-247. Epub 2020 Nov 10.

Department of Horticulture/Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zhejiang University, Hangzhou, 310058, China. Electronic address:

The E3 ubiquitin ligases participate in the degradation of plant proteins and play a regulatory role in stress response. However, the role of tomato E3 ubiquitin ligase genes in plant response to heavy metal stress remains elusive. Here, we identified 17 tomato E3 ubiquitin ligase genes using blast analysis of highly expressed E3 ubiquitin ligase genes of Arabidopsis thaliana. Through organ expression analysis, three E3 ubiquitin ligase genes with higher expression levels in roots were further screened out, and they were named Sl1, SlRHE1, and SlRING1. Among these three genes, SlRING1 expression was the highest in response to cadmium (Cd) stress. Silencing SlRING1 significantly decreased chlorophyll content, Fv/Fm, photosynthetic rate, and biomass accumulation under Cd stress. The levels of HO, electrolyte leakage, and malondialdehyde significantly increased in SlRING1-silenced plants under Cd stress compared with that in non-silenced tomato plants. Cd stress-induced increases in the transcript levels of antioxidant and detoxification genes such as CAT, DHAR, MDHAR, GSH, and PCS were compromised by SlRING1 silencing. Moreover, Cd accumulation in shoots and roots significantly increased in SlRING1-silenced plants compared with non-silenced tomato plants. These findings suggest that SlRING1 plays a positive role in plant tolerance to Cd stress in tomato.
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http://dx.doi.org/10.1016/j.jbiotec.2020.11.008DOI Listing
December 2020

Clinical features and survival outcomes between ascending and descending types of nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: A big-data intelligence platform-based analysis.

Radiother Oncol 2019 08 15;137:137-144. Epub 2019 May 15.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, PR China. Electronic address:

Purpose: To compare clinical features and survival outcomes in patients with ascending type (type A) and descending type (type D) nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era.

Materials And Methods: A total of 5194 patients with type A and type D NPC treated at Sun Yat-sen University Cancer Center were randomly selected. Tumors that were mainly advanced local disease (T3-4 stage) with early stage cervical lymph node involvement (N0-1 stage) were determined as type A, while tumors with advanced lymph node disease (N2-3 stage) but early stage local invasion (T1-2 stage) were classified as type D NPC. Kaplan-Meier's analysis was used to evaluate survival rates, and log-rank test survival curves were used for comparison. In the multivariate analysis Cox proportional hazard models were developed.

Results: There was a larger proportion of type A tumors (82%) than type D tumors (18%). Compared to patients with type A tumors, those with type D tumors had increased likelihood of distant metastasis, regional recurrence, disease recurrence, and death (P < 0.001 for all), however, not for local recurrence (P < 0.001). The HR (hazard ratio) for death following recurrence of disease for type D tumors were 1.6 compared to type A tumors. Multivariate analysis revealed that elevated EBV DNA, elevated lactate dehydrogenase, alcohol consumption, and no family history of cancer attributed to the development of type D tumors. Annual hazard rate in type A patients increased, peaking at 12-18 months after initial treatment and downward thereafter. Similar trend also occurred in type D during the first 5 years following treatment. Notably, a minor peak was also observed 7-8 years post treatment.

Conclusions: In the IMRT era, recurrence patterns differed across tumor types. Type D NPC had a more aggressive clinical course and worse outcomes compared with type A NPC.
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http://dx.doi.org/10.1016/j.radonc.2019.04.025DOI Listing
August 2019

Evolution and Dosimetric Analysis of Magnetic Resonance Imaging-Detected Brain Stem Injury After Intensity Modulated Radiation Therapy in Nasopharyngeal Carcinoma.

Int J Radiat Oncol Biol Phys 2019 09 7;105(1):124-131. Epub 2019 May 7.

State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Cancer Center. Electronic address:

Purpose: To evaluate the evolution of radiation-induced brain stem injury (BSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy (IMRT) and to identify the critical dosimetric predictors of BSI.

Methods And Materials: A total of 6288 NPC patients treated with IMRT between 2009 and 2015 were retrospectively reviewed. Among these 6288 patients, 24 had radiation-induced BSI, which manifested as edematous lesions and contrast-enhanced lesions (CLs) on magnetic resonance imaging. Latency, symptoms, and evolution of BSI were assessed. Critical dosimetric predictors of BSI were identified using a penalized regression model with performance evaluated by receiver operating characteristic curve analysis.

Results: Median BSI latency was 14.5 months (range, 7.6-37.5 months), and 9 out of 24 patients (37.5%) were clinically symptomatic. Edematous lesions and CLs were both present in all patients. Necrosis was significantly more common in larger CLs (P = .007). After median follow-up of 12.5 months, 13 out of 24 patients (54.2%) had complete remission, and 5 out of 24 patients (20.8%) had partial remission. Remission was unaffected by whether or not symptomatic treatment was given. Maximum point dose (Dmax) was identified as the critical predictor of BSI (area under the receiver operating curve = 0.898), with the optimal cutoff equivalent dose in 2-Gy fractions (D) being 67.4 Gy (sensitivity = 0.833, 20 out of 24; specificity = 0.835, 5234 out of 6264). Patients with Dmax ≥67.4 Gy (D) were significantly more likely to develop BSI (odds ratio = 25.29; 95% CI, 8.63-74.14; P < .001) than those with Dmax <67.4 Gy (D).

Conclusions: In patients with NPC treated with IMRT, BSI generally tends to improve over time. Dmax = 67.4 Gy (D) appears to be the dose constraint for brain stem, potentially providing clinicians with greater choice and flexibility when balancing the tumor target coverage and brain stem protection. Further studies are needed to validate our findings.
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http://dx.doi.org/10.1016/j.ijrobp.2019.04.032DOI Listing
September 2019

Risk Assessment of Secondary Primary Malignancies in Nasopharyngeal Carcinoma: A Big-Data Intelligence Platform-Based Analysis of 6,377 Long-term Survivors from an Endemic Area Treated with Intensity-Modulated Radiation Therapy during 2003-2013.

Cancer Res Treat 2019 Jul 11;51(3):982-991. Epub 2018 Oct 11.

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

Purpose: The incidence, risk factors and survival impact of secondary primary malignancies (SPMs) among survivors of nasopharyngeal carcinoma (NPC) treated with definitive intensity-modulated radiation therapy (IMRT) with or without chemotherapy are poorly characterized.

Methods And Materials: Consecutive patients (n=6,377) from the big-data intelligence platform at Sun Yat-sen University Cancer Center, China (in a high-incidence area) with newly diagnosed non-metastatic pathologically proven non-keratinizing undifferentiated NPC treated with IMRT±chemotherapy between January 2003 and June 2013 were retrospectively analyzed. Cumulative incidence of SPMs was calculated using the Kaplan-Meier method. Cox proportional hazards model was used to identify potential risk factors for SPMs and assess whether SPMs affect overall survival.

Results: Of the 6,377 patients, 189 (3.0%) suffered SPMs (median follow-up, 62 months). One-, 2-, 3-, 4-, and 5-cumulative risks of SPMs were 0.4%, 0.9%, 1.6%, 2.2%, and 2.6%, respectively. Latency from start of IMRT to SPMs diagnosis was 37 months (range, 6 to 102 months). In patients with SPMs, 14.3% suffered SPMs within 1 year post-IMRT: 1-3 years, 38.1%; 3-5 years, 33.9%; and >5 years, 13.7%. Lung cancer was the most common SPM (50/6,377, 0.78%). Multivariate analysis demonstrated sex (male, 64% increase), age (≥50 years, 68% increase), and smoking history (41% increase) were significant risk factors for SPMs, and SPMs were associated with poorer overall survival.

Conclusion: This large cohort study confirms SPMs a dreadful complication for long-term survivors of NPC treated with IMRT. SPMs negatively impact overall survival in NPC. Close follow-up is recommended for older male survivors with a smoking history.
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http://dx.doi.org/10.4143/crt.2018.298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639237PMC
July 2019

The detrimental effects of radiotherapy interruption on local control after concurrent chemoradiotherapy for advanced T-stage nasopharyngeal carcinoma: an observational, prospective analysis.

BMC Cancer 2018 Jul 16;18(1):740. Epub 2018 Jul 16.

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

Background: Previous studies have reported radiotherapy interruption (RTI) is associated with poor local control in two-dimensional radiotherapy (2DRT) era. However, it remains unclear whether RTI still affects local control for advanced T stage (T3-4) in the intensity-modulated radiation therapy (IMRT) era. We aim to evaluate whether RTI affects local control for T3-4 NPC treated with definitive IMRT.

Methods: In this observational prospective study, 447 T3-4 NPC patients treated with IMRT plus concurrent chemotherapy were included. All patients completed the planned radiotherapy course, and RTI was defined as the actual time taken to finish the prescribed course of radiotherapy minus the planned radiotherapy time. Receiver operating characteristic (ROC) curve was used for determined the cutoff point of RTI. The effects of RTI on local control were analyzed in multivariate analysis.

Results: At 5 years, the local relapse-free survival (LRFS) and overall survival (OS) rates were 93.7 and 85.7%, respectively. The cutoff RTI for LRFS was 5.5 days by ROC curve. Compared to patients with RTI >  5 days, patients with RTI ≤ 5 days had a significantly lower rate of LRFS (97% vs. 83%; P < 0.001). In multivariate analysis, RTI was a risk factor independently associated with LRFS (HR = 9.64, 95% CI, 4.10-22.65), but not for OS (HR = 1.09, 95% CI, 0.84-1.64).

Conclusions: The current analysis demonstrates a significant correlation between prolonged RTI and local control in NPC, even when concurrent chemotherapy is used. We consider that attention to RTI seems to be warranted for patients with advanced T-stage NPC in the era of IMRT.
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http://dx.doi.org/10.1186/s12885-018-4495-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048841PMC
July 2018

Melatonin alleviates low-sulfur stress by promoting sulfur homeostasis in tomato plants.

Sci Rep 2018 07 5;8(1):10182. Epub 2018 Jul 5.

Department of Horticulture/Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zhejiang University, Yuhangtang Road 866, Hangzhou, 310058, PR China.

Despite involvement of melatonin (MT) in plant growth and stress tolerance, its role in sulfur (S) acquisition and assimilation remains unclear. Here we report that low-S conditions cause serious growth inhibition by reducing chlorophyll content, photosynthesis and biomass accumulation. S deficiency evoked oxidative stress leading to the cell structural alterations and DNA damage. In contrast, MT supplementation to the S-deprived plants resulted in a significant diminution in reactive oxygen species (ROS) accumulation, thereby mitigating S deficiency-induced damages to cellular macromolecules and ultrastructures. Moreover, MT promoted S uptake and assimilation by regulating the expression of genes encoding enzymes involved in S transport and metabolism. MT also protected cells from ROS-induced damage by regulating 2-cysteine peroxiredoxin and biosynthesis of S-compounds. These results provide strong evidence that MT can enhance plant tolerance to low-S-induced stress by improving S uptake, metabolism and redox homeostasis, and thus advocating beneficial effects of MT on increasing the sulfur utilization efficiency.
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http://dx.doi.org/10.1038/s41598-018-28561-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033901PMC
July 2018

Identification and characterization of new Muscodor endophytes from gramineous plants in Xishuangbanna, China.

Microbiologyopen 2019 04 21;8(4):e00666. Epub 2018 Jun 21.

State Key Laboratory for Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

The endophytic fungi Muscodor spp. produce volatile organic compounds (VOCs) which can inhibit and even kill pathogenic fungi, bacteria, and nematodes. Nine endophytic fungal strains, isolated from the shoots of gramineous plants including Arthraxon hispidus, Eleusine indica, Oplismenus undulatifolius, and Oryza granulata, were identified as Muscodor through phylogenetic analysis of the internal transcribed spacer. Through an SPSS K-means cluster analysis, the nine Muscodor strains were divided into four groups based on the antifungal activities of the VOCs produced by these fungi determined by a two-section confrontation test. The first group contains the strains Y-L-54, W-S-41, Y-S-35, W-T-27, and Y-L-56, which showed the strongest activity. The second and third groups contain W-S-35 and Y-L-43, which showed stronger and moderate activity, respectively. The fourth group contains W-S-38 and N-L-7, which were the weakest in inhibiting the tested pathogens. Thirty-five compounds and the relative amounts of VOCs were determined by SPME-GC-MS and comparison with the NIST14 mass spectrometry database and Agilent MassHunter qualitative and quantitative analyses. These 35 compounds were classified into two different categories: (a) the product of fatty acid degradation, and (b) the intermediate and final metabolite of the metabolic pathway with the precursor of mevalonic acid. SPSS clustering analysis showed that the chemical components of VOCs might be correlated with their bioactivity rather than their phylogenetic assignment and some of the identified compounds might be responsible for antifungal activity. In conclusion, new Muscodor endophytes were recorded in tropical gramineous plants and a number of strains showed remarkable bioactive properties. Therefore, they have important potential applications in the fields of plant disease control.
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http://dx.doi.org/10.1002/mbo3.666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460276PMC
April 2019

Delineation of Neck Clinical Target Volume Specific to Nasopharyngeal Carcinoma Based on Lymph Node Distribution and the International Consensus Guidelines.

Int J Radiat Oncol Biol Phys 2018 03 8;100(4):891-902. Epub 2017 Nov 8.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China. Electronic address:

Purpose: To establish the regional lymph node (LN) distribution probability map and draw the neck clinical target volume specific to nasopharyngeal carcinoma (NPC).

Methods And Materials: One thousand patients with pathologically proven NPC were enrolled from January 2010 to December 2011. The center point of the LNs with a minimal axial diameter of ≥4 mm was marked on a single treatment planning computed tomography scan. The neck LN levels I to X using the 2013 updated international consensus guidelines were also contoured. LN distribution probability maps and distribution curves were established. The relationships between the LN distribution and consensus guidelines were analyzed to propose modifications for clinical target volume boundaries specific to NPC.

Results: A total of 10,651 LNs from 959 patients were marked. Based on the distribution of LNs and consensus guidelines, most of the LN levels defined in the 2013 updated consensus guidelines were confirmed to be comprehensive and applicable for NPC. However, for level Vb, 13.3% of cases (11 of 83) had LNs beyond the posteromedial border. For level VIIa (retropharyngeal LN), 1.5% of cases (12 of 819) had LNs above the cranial boundary, and 5 cases had LNs that emerged in the medial group. Moreover, we confirmed that no LN had been detected in certain areas of levels Ib, II, IVa, and Vc. Accordingly, a new level VIIc was proposed to include the medial group of retropharyngeal LNs, moderately extended boundaries for levels Vb and VIIa were recommended, and reduced boundaries are possibly adaptable for levels Ib, II, IV, and Vc.

Conclusions: Most LN levels in the 2013 updated consensus guidelines are comprehensive and applicable for NPC. We have proposed a new level VIIc to include a medial group of retropharyngeal LNs, recommended moderate extended boundaries for levels Vb and VIIa, and suggested that the boundaries for levels Ib, II, IV, and Vc might be reduced.
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http://dx.doi.org/10.1016/j.ijrobp.2017.11.004DOI Listing
March 2018

Melatonin Alleviates High Temperature-Induced Pollen Abortion in Solanum lycopersicum.

Molecules 2018 Feb 11;23(2). Epub 2018 Feb 11.

Department of Horticulture/Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zhejiang University, Hangzhou 310058, China.

Melatonin is a pleiotropic signal molecule that plays critical roles in regulating plant growth and development, as well as providing physiological protections against various environmental stresses. Nonetheless, the mechanisms for melatonin-mediated pollen thermotolerance remain largely unknown. In this study, we report that irrigation treatment with melatonin (20 µM) effectively ameliorated high temperature-induced inactivation of pollen and inhibition of pollen germination in tomato () plants. Melatonin alleviated reactive oxygen species production in tomato anthers under high temperature by the up-regulation of the transcription and activities of several antioxidant enzymes. Transmission electron micrograph results showed that high temperature-induced pollen abortion is associated with a premature degeneration of the tapetum cells and the formation of defective pollen grains with degenerated nuclei at the early uninuclear microspore stage, whilst melatonin protected degradation of organelles by enhancing the expression of heat shock protein genes to refold unfolded proteins and the expression of autophagy-related genes and formation of autophagosomes to degrade denatured proteins. These findings suggest a novel function of melatonin to protect pollen activity under high temperature and support the potential effects of melatonin on reproductive development of plants.
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http://dx.doi.org/10.3390/molecules23020386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017144PMC
February 2018

Prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum Epstein-Barr virus DNA copy number in predicting distant metastasis in patients with N1 nasopharyngeal carcinoma.

Chin J Cancer 2017 12 29;36(1):98. Epub 2017 Dec 29.

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, Guangdong, 510060, P. R. China.

Background: According to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system, over 50% of patients with nasopharyngeal carcinoma (NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node (GTVnd) and pretreatment serum copy number of Epstein-Barr virus (EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.

Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic (ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.

Results: The 5-year distant metastasis-free survival (DMFS) rates for patients with GTVnd > 18.9 vs. ≤ 18.9 mL were 82.2% vs. 93.2% (P < 0.001), and for patients with EBV DNA copy number > 4000 vs. ≤ 4000 copies/mL were 83.5% vs. 93.9% (P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis (both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-, moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1, 87.4, and 73.8%, respectively (P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification (hazard ratio [HR], 4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).

Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.
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http://dx.doi.org/10.1186/s40880-017-0264-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747160PMC
December 2017

Optimal cumulative cisplatin dose in nasopharyngeal carcinoma patients receiving additional induction chemotherapy.

Cancer Sci 2018 Mar 31;109(3):751-763. Epub 2018 Jan 31.

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

To clarify the optimal cumulative cisplatin dose (CCD) in locoregionally-advanced nasopharyngel carcinoma (NPC) patients receiving induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). Using the NPC-specific database from the established big-data intelligence platform at Sun Yat-Sen University Cancer Center, 583 non-disseminated, locoregionally-advanced NPC patients receiving IC plus CCRT were enrolled. Propensity score matching (PSM) analysis was conducted to control for confounding factors. The median CCD was 160 mg/m after IC (range, 40-300 mg/m ); only 74 patients (12.7%) achieved CCD >200 mg/m . Patients receiving >200 mg/m CCD did not show significantly improved 5-year overall survival (OS) (HR = 1.19; 95% confidence intervals [CI] 0.69-2.06, P = .53) and progression-free survival (PFS) (HR = 1.03; 95% CI: 0.63-1.68, P = .92) compared with patients receiving <200 mg/m CCD. Further investigations of the potential of median CCD (160 mg/m ) to yield survival benefits revealed that there were no significant differences in survival endpoints between patients receiving CCD >160 mg/m and CCD < 160 mg/m in both the original and PSM cohorts. In addition, subgroup analysis indicated a favorable PFS, but not OS, with higher cisplatin administration in patients with pretreatment Epstein-Barr virus deoxyribonucleic acid (EBV DNA) <1000 copies/mL (HR = 0.26, 95% CI: 0.07-0.93, P = .03) and receiving <3 IC cycles (HR = 0.59, 95% CI 0.33-1.07, P = .08). Our analysis of real world data provided references for the optimal CCD in locoregionally-advanced NPC receiving additional IC. The causal relationship between 200 mg/m CCD and improved survival was not defined; 160 mg/m CCD might be enough. However, for patients with EBV DNA <1000 copy/mL and receiving <3 IC cycles, a higher dose might be necessary.
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http://dx.doi.org/10.1111/cas.13474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834779PMC
March 2018

Patient- and treatment-related risk factors associated with neck muscle spasm in nasopharyngeal carcinoma patients after intensity-modulated radiotherapy.

BMC Cancer 2017 Nov 23;17(1):788. Epub 2017 Nov 23.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.

Background: To evaluate the incidence of neck muscle spasm in nasopharyngeal carcinoma (NPC) patients that received intensity-modulated radiotherapy (IMRT), and to analyse the patient- and treatment-related risk factors associated with neck muscle spasm.

Methods: A sample of 152 IMRT-treated, biopsy-proven, nondisseminated NPC patients were retrospectively analysed. All had documented IMRT treatment plans and had returned for follow-up review at 4 years post-radiotherapy. Spasm of the sternocleidomastoid (SCM) muscle was graded from 0 to 3 (absent to severe) and this grade served as the clinical endpoint. Risk factors were identified using logistic regression analysis.

Results: Within 4 years of radiotherapy, neck muscle spasm developed in 23.68% of the patients; Grades 0, 1, 2 and 3 were respectively assigned to 83.55, 7.57, 6.58 and 2.30% of assessed SCMs. Multivariate analysis indicated that gender, N stage, V60 (percentage of SCM volume that received >60 Gy) were independent prognostic variables, and that the optimal threshold for using V60 to predict neck muscle spasm was 61.92% (sensitivity = 0.900, specificity = 0.953).

Conclusions: Gender, N stage and V60 were independent predictive factors for post-radiotherapy neck muscle spasm, and a V60 of ≤61.92% in the SCM was relatively safe.
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http://dx.doi.org/10.1186/s12885-017-3780-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701496PMC
November 2017

Proposal of a Pretreatment Nomogram for Predicting Local Recurrence after Intensity-Modulated Radiation Therapy in T4 Nasopharyngeal Carcinoma: A Retrospective Review of 415 Chinese Patients.

Cancer Res Treat 2018 Oct 15;50(4):1084-1095. Epub 2017 Nov 15.

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

Purpose: Local relapse-free survival (LRFS) differs widely among patients with T4 category nasopharyngeal carcinoma (NPC). We aimed to build a nomogram incorporating clinicopathological information to predict LRFS in T4 NPC after definitive intensity-modulated radiation therapy (IMRT).

Materials And Methods: Retrospective study of 415 Chinese patients with non-metastatic T4 NPC treated with definitive IMRT with or without chemotherapy at our cancer center between October 2009 and September 2013. The nomogram for LRFS at 3 and 5 years was generated based on multivariate Cox proportional hazards regression, and validated using bootstrap resampling, assessing discriminative performance using the concordance index (C-index) and determining calibration ability via calibration curves.

Results: Five-year LRFS was 88.8%. We identified and incorporated four independent prognostic factors for LRFS: ethmoid sinus invasion, primary gross tumor volume, age, and pretreatment body mass index. The C-index of the nomogram for local recurrence was 0.732 (95% confidence interval, 0.726 to 0.738), indicating excellent predictive accuracy. The calibration curve revealed excellent agreement between nomogram-predicted and observed LRFS probabilities. Risk subgroups based on total point score cutoff values enabled effective discrimination of LRFS.

Conclusion: This pretreatment nomogram enables clinicians to accurately predict LRFS in T4 NPC after definitive IMRT, and could help to facilitate personalized patient counselling and treatment strategies.
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http://dx.doi.org/10.4143/crt.2017.359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192920PMC
October 2018

Combined prognostic value of pretreatment anemia and cervical node necrosis in patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: A large-scale retrospective study.

Cancer Med 2017 Dec 16;6(12):2822-2831. Epub 2017 Oct 16.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China.

This study investigated the combined prognostic value of pretreatment anemia and cervical node necrosis (CNN) in patients with nasopharyngeal carcinoma (NPC). Retrospective review of 1302 patients with newly diagnosed nonmetastatic NPC treated with intensity-modulated radiotherapy (IMRT) ± chemotherapy. Patients were classified into four groups according to anemia and CNN status. Survival was compared using the log-rank test. Independent prognostic factors were identified using the Cox proportional hazards model. The primary end-point was overall survival (OS); secondary end-points were disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS). Pretreatment anemia was an independent, adverse prognostic factor for DMFS; pretreatment CNN was an independent adverse prognostic factor for all end-points. Five-year survival for non-anemia and non-CNN, anemia, CNN, and anemia and CNN groups were: OS (93.1%, 87.2%, 82.9%, 76.3%, P < 0.001), DFS (87.0%, 84.0%, 73.9%, 64.6%, P < 0.001), DMFS (94.1%, 92.1%, 82.4%, 72.5%, P < 0.001), and LRRFS (92.8%, 92.4%, 88.7%, 84.0%, P = 0.012). The non-anemia and non-CNN group had best survival outcomes; anemia and CNN group, the poorest. Multivariate analysis demonstrated combined anemia and CNN was an independent prognostic factor for OS, DFS, DMFS, and LRRFS (P < 0.05). The combination of anemia and CNN is an independent adverse prognostic factor in patients with NPC treated using IMRT ± chemotherapy. Assessment of pretreatment anemia and CNN improved risk stratification, especially for patients with anemia and CNN who have poorest prognosis. This study may aid the design of individualized treatment plans to improve treatment outcomes.
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http://dx.doi.org/10.1002/cam4.1233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727247PMC
December 2017

Responses of Plant Proteins to Heavy Metal Stress-A Review.

Front Plant Sci 2017 5;8:1492. Epub 2017 Sep 5.

Agricultural Experiment Station, Zhejiang UniversityHangzhou, China.

Plants respond to environmental pollutants such as heavy metal(s) by triggering the expression of genes that encode proteins involved in stress response. Toxic metal ions profoundly affect the cellular protein homeostasis by interfering with the folding process and aggregation of nascent or non-native proteins leading to decreased cell viability. However, plants possess a range of ubiquitous cellular surveillance systems that enable them to efficiently detoxify heavy metals toward enhanced tolerance to metal stress. As proteins constitute the major workhorses of living cells, the chelation of metal ions in cytosol with phytochelatins and metallothioneins followed by compartmentalization of metals in the vacuoles as well as the repair of stress-damaged proteins or removal and degradation of proteins that fail to achieve their native conformations are critical for plant tolerance to heavy metal stress. In this review, we provide a broad overview of recent advances in cellular protein research with regards to heavy metal tolerance in plants. We also discuss how plants maintain functional and healthy proteomes for survival under such capricious surroundings.
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http://dx.doi.org/10.3389/fpls.2017.01492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591867PMC
September 2017

Pretreatment Nomograms for Local and Regional Recurrence after Radical Radiation Therapy for Primary Nasopharyngeal Carcinoma.

J Cancer 2017 3;8(13):2595-2603. Epub 2017 Aug 3.

State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou 510060, People's Republic of China.

The aim of this study was to build nomograms to predict local recurrence (LR) and regional recurrence (RR) in patients with nasopharyngeal carcinoma (NPC) underwent intensity-modulated radiation therapy (IMRT). : A total of 1811 patients with non-metastatic NPC treated with IMRT (with or without chemotherapy) between October 2009 and February 2012 at our center were involved for building the nomograms. Nomograms for LR-free rate and RR-free rate at 3- and 5- year were generated as visualizations of Cox proportional hazards regression models, and validated using bootstrap resampling, estimating discrimination and calibration. With a median follow up of 49.50 months, the 3- and 5- year LR-free rate were 95.43% and 94.30% respectively; the 3- and 5- year RR-free rate were 95.94% and 95.41% respectively. The final predictive model for LR included age, the neutrophil/leukocyte ratio (NWR), pathological type, primary gross tumor volume, maxillary sinus invasion, ethmoidal sinus invasion and lacerated foramen invasion; the model for RR involved NWR, plasma Epstein-Barr virus (EBV) DNA copy number, cervical lymph node volume and N category. The models showed fairly good discriminatory ability with concordance indices (c-indices) of 0.76 and 0.74 for predicting LR and RR, respectively, as well as good calibration. The proposed stratification of risk groups based on the nomograms allowed significant distinction between Kaplan-Meier curves for LR and RR. The proposed nomograms resulted in more-accurate prognostic prediction for LR and RR with a high concordance, hence to inform patients with high risk of recurrence on more aggressive therapy. The prognostic nomograms could better stratify patients into different risk groups.
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http://dx.doi.org/10.7150/jca.20255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595089PMC
August 2017

Induction Chemotherapy Has No Prognostic Value in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma and Chronic Hepatitis B Infection in the IMRT Era.

Transl Oncol 2017 Oct 29;10(5):800-805. Epub 2017 Aug 29.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, People's Republic of China. Electronic address:

Background: The effectiveness of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) over CCRT alone in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and chronic hepatitis B infection in the intensity-modulated radiotherapy (IMRT) era is unknown.

Patients And Methods: A total of 249 patients with stage T1-2 N2-3 or T3-4 N1-3 NPC and chronic hepatitis B infection treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) was employed to balance covariates; 140 patients were propensity-matched (1:1 basis). Survival outcomes in the IC+CCRT and CCRT groups were compared using the Kaplan-Meier method, log-rank test and Cox proportional hazards model.

Results: No significant survival differences were observed between IC+CCRT and CCRT (5-year overall survival, 88.3% vs. 82.2%; P=.484; disease-free survival, 73.9% vs. 75.2%; P=.643; distant metastasis-free survival, 84.1% vs. 85.1%; P=.781; and locoregional failure-free survival, 87.9% vs. 85.1%; P=.834). After adjusting for known prognostic factors in multivariate analysis, IC was not an independent prognostic factor for any outcome (all P>.05); subgroup analysis based on T category (T1-2/T3-4), N category (N0-1/N2-3), and overall stage (III/IV) confirmed these results. The incidence of hepatic function damage in the IC+CCRT and CCRT groups was not significantly different.

Conclusion: IC+CCRT leads to comparable survival outcomes and hepatic function damage compared to CCRT alone in patients with locoregionally advanced NPC with chronic hepatitis B infection in the IMRT era. Further investigations are warranted.
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http://dx.doi.org/10.1016/j.tranon.2017.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576973PMC
October 2017

Prognostic value of serum Epstein-Barr virus antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment Epstein-Barr virus DNA.

Cancer Sci 2017 Aug 13;108(8):1640-1647. Epub 2017 Jul 13.

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, China.

Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum IgA antibodies against early antigen (EA-IgA) and viral capsid antigen (VCA-IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA-IgA and VCA-IgA in patients with NPC is less clear. We hypothesize that serum EA-IgA and VCA-IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non-metastatic NPC and undetectable pEBV DNA were included. Serum EA-IgA and VCA-IgA were determined by ELISA. After analysis, serum EA-IgA and VCA-IgA loads correlated positively with T, N, and overall stage (all P < 0.05). Serum EA-IgA was not associated with survival outcome in univariable analyses. But patients with serum VCA-IgA >1:120 had significantly inferior 5-year progression-free survival (80.4% vs 89.6%, P = 0.025), distant metastasis-free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse-free survival (88.4% vs 95.6%, P = 0.023; log-rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA-IgA became insignificant. Further analyses revealed that serum VCA-IgA was not an independent prognostic factor in early N (N0-1) or advanced N (N2-3) stage NPC. In summary, although both EA-IgA and VCA-IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA.
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http://dx.doi.org/10.1111/cas.13296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543490PMC
August 2017

Is pretreatment Epstein-Barr virus DNA still associated with 6-year survival outcomes in locoregionally advanced nasopharyngeal carcinoma?

J Cancer 2017 12;8(6):976-982. Epub 2017 Mar 12.

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

The objective of this study was to confirm the association between pretreatment Epstein-Barr virus (EBV) DNA (pre-DNA) load and survival outcomes after long-term follow-up in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Between November 2009 and February 2012, a total of 1036 patients with LA-NPC were enrolled. There were 762 patients in stage III and 274 in stage IVA-B. All patients were treated with radical radiotherapy with or without chemotherapy, and pre-DNA concentrations were quantified by a polymerase chain reaction assay. Patient outcomes were evaluated. The 5-year overall survival (OS), distant metastasis-free surviva (DMFS), locoregional relapse-free survival (LRFS), and progression-free survival (PFS) rates were 84.7%, 87.0%, 90.2%, and 77.1%, respectively. By using previously defined pre-DNA cutoff value (1500 copies/ml pretreatment), pre-DNA was an independent prognostic predictor for OS, DMFS, and PFS using log-rank test. Multivariate Cox analysis also confirmed these results. Subgroup analysis indicated that the 5-year OS, DMFS, and PFS rates in patients staged IVA-B with pre-DNA < 1500 copies/ml were similar to those patients staged III with pre-DNA ≥ 1500 copies/ml, whereas patients staged IVA-B patients with pre-DNA ≥ 1500 copies/ml predicted worse outcome. In this expanded study, the prognostic significance of pre-DNA was confirmed using predefined cutoff value in an independent patient group, and pre-DNA was identified as an independent prognostic marker for the risk stratification in LA-NPC.
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http://dx.doi.org/10.7150/jca.18124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436249PMC
March 2017

Influence of Cervical Node Necrosis of Different Grades on the Prognosis of Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiotherapy.

J Cancer 2017 12;8(6):959-966. Epub 2017 Mar 12.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, People's Republic of China.

To analyze the prognostic value of cervical node necrosis (CNN) observed on pretreatment magnetic resonance imaging (MRI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). The medical records of 1423 NPC patients with cervical node metastasis who underwent IMRT were retrospectively reviewed. Lymph nodes in the axial plane of pretreatment MRI were classified as follows: grade 0 CNN, no hypodense zones; grade 1 CNN, ≤33% areas showing hypodense zones; and grade 2, >33% areas showing hypodense zones. CNN was detectable in 470/1423 (33%) patients. Of these 470 patients, 213 (15%) and 257 (18%) exhibited grade 1 and grade 2 CNN. The grade 0 and grade 1 CNN groups showed significant differences with regard to distant metastasis-free survival (DMFS), but not overall survival (OS), regional relapse-free survival (RRFS), local relapse-free survival (LRFS), and disease-free survival (DFS). Significant differences were observed among the grade 0 and grade 2 CNN groups with regard to OS, RRFS, LRFS, DMFS, and DFS. Moreover, OS, LRFS, RRFS, and DFS were significantly different between the grade 1 and grade 2 CNN groups, whereas DMFS showed no significant differences. Univariate and multivariate analyses revealed CNN on MRI as a significant negative prognostic factor for OS, LRFS, RRFS, DMFS, and DFS in NPC patients. NPC patients with CNN of different grades show various prognosis and failure patterns after IMRT. CNN on MRI can be adopted as a predictive factor for formulating individualized treatment plans for NPC patients.
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http://dx.doi.org/10.7150/jca.17998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436247PMC
March 2017

Prognostic value of cervical nodal tumor volume in nasopharyngeal carcinoma: Analysis of 1230 patients with positive cervical nodal metastasis.

PLoS One 2017 10;12(5):e0176995. Epub 2017 May 10.

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

Purpose: To investigate the variability and prognostic value of nodal tumor volume (NTV) in nasopharyngeal carcinoma (NPC).

Methods And Materials: Data on 1230 patients with newly diagnosed stage T1-4N1-3M0 NPC treated with definitive radiation therapy with or without chemotherapy at a single cancer center were reviewed. NTV was determined from dose volume histogram (DVH) data. X-tile analysis was applied to identify the optimal cut-off points for the NTV with respect to regional recurrence-free survival (RRFS). Correlations between the TNM classification system, NTV and RRFS were assessed using a Cox regression model. Cross-validation based on receiver operating characteristic (ROC) curve analysis was applied to compare the prognostic predictive validity of NTV and N categories.

Results: Within a median follow-up of 49.9 (range, 1.27-76.40) months, 61/1230 (5%) patients developed regional recurrence and 154 (12.5%) developed distant metastasis. NTV values of 7.2 cc and 35.7 cc were identified as the optimal cut-off points. Patients with larger NTV had poorer prognosis. Compared with the N category, NTV was better at determining RRFS for patients with NPC. Hazard ratios increased with NTV, ranging from 1.86 (95% confidence interval [95% CI], 0.92-3.78) for NTV between 7.2 cc to 35.7 cc, and 3.67 (95% CI, 1.58-8.50) for NTV > 35.7 cc. With both NTV and N category in the same Cox regression model, only NTV remained statistically significant in the RRFS of NPC. The validation results with ROC curves also revealed that, NTV was superior to N category for predicting RRFS with significantly larger area under the ROC curve.

Conclusions: NTV offers important prognostic value for treatment outcomes in NPC, especially regional control. Volumetric analysis of nodal involvement may assist selection of patients with poor prognosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176995PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425204PMC
September 2017

HsfA1a upregulates melatonin biosynthesis to confer cadmium tolerance in tomato plants.

J Pineal Res 2017 Mar 10;62(2). Epub 2017 Feb 10.

Department of Horticulture/Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zhejiang University, Hangzhou, China.

Melatonin regulates broad aspects of plant responses to various biotic and abiotic stresses, but the upstream regulation of melatonin biosynthesis by these stresses remains largely unknown. Herein, we demonstrate that transcription factor heat-shock factor A1a (HsfA1a) conferred cadmium (Cd) tolerance to tomato plants, in part through its positive role in inducing melatonin biosynthesis under Cd stress. Analysis of leaf phenotype, chlorophyll content, and photosynthetic efficiency revealed that silencing of the HsfA1a gene decreased Cd tolerance, whereas its overexpression enhanced plant tolerance to Cd. HsfA1a-silenced plants exhibited reduced melatonin levels, and HsfA1a overexpression stimulated melatonin accumulation and the expression of the melatonin biosynthetic gene caffeic acid O-methyltransferase 1 (COMT1) under Cd stress. Both an in vitro electrophoretic mobility shift assay and in vivo chromatin immunoprecipitation coupled with qPCR analysis revealed that HsfA1a binds to the COMT1 gene promoter. Meanwhile, Cd stress induced the expression of heat-shock proteins (HSPs), which was compromised in HsfA1a-silenced plants and more robustly induced in HsfA1a-overexpressing plants under Cd stress. COMT1 silencing reduced HsfA1a-induced Cd tolerance and melatonin accumulation in HsfA1a-overexpressing plants. Additionally, the HsfA1a-induced expression of HSPs was partially compromised in COMT1-silenced wild-type or HsfA1a-overexpressing plants under Cd stress. These results demonstrate that HsfA1a confers Cd tolerance by activating transcription of the COMT1 gene and inducing accumulation of melatonin that partially upregulates expression of HSPs.
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http://dx.doi.org/10.1111/jpi.12387DOI Listing
March 2017

Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy.

Chin J Cancer 2016 12 28;35(1):103. Epub 2016 Dec 28.

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

Background: The prognostic values of staging parameters require continual re-assessment amid changes in diagnostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non-metastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era.

Methods: We reviewed the data from 749 patients with newly diagnosed, biopsy-proven, non-metastatic NPC in our cancer center (South China, an NPC endemic area) between January 2003 and December 2007. All patients underwent magnetic resonance imaging (MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insignificant explanatory variables.

Results: The 5-year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5-year survival rates were as follows: local relapse-free survival, 94.6%; nodal relapse-free survival, 97.0%; distant metastasis-free survival, 82.6%; disease-free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only significant prognostic factor for local failure (P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho's location of the cervical lymph nodes were significant prognostic factors for both distant failure and disease failure (all P < 0.05). Intracranial extension had significant prognostic value for distant failure (P = 0.040).

Conclusions: The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the significant prognostic parameters for local control have also been altered substantially.
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http://dx.doi.org/10.1186/s40880-016-0167-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192583PMC
December 2016

The Evolution of and Risk Factors for Neck Muscle Atrophy and Weakness in Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy: A Retrospective Study in an Endemic Area.

Medicine (Baltimore) 2015 Aug;94(31):e1294

From the Department of Radiation Oncology (L-LZ, Y-PM, G-QZ, L-LT, Z-YQ, LL, J-JY, JM, YS), State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University; and Department of Medical Statistics and Epidemiology (A-HL), School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.

The aim of this study was to investigate the evolution of sternocleidomastoid muscle (SCM) atrophy in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT), and the relationship between SCM atrophy and neck weakness.Data were retrospectively analyzed from 223 biopsy-proven NPC patients with no distant metastasis who underwent IMRT with or without chemotherapy. The volume of SCM was measured on pretreatment magnetic resonance imaging (MRI), and MRIs were conducted 1, 2, and 3 years after the completion of IMRT. Change in SCM volume was calculated and classified using the late effects of normal tissues-subjective, objective, management, and analytic system. The grade of neck muscle weakness, classified by the Common Terminology Criteria for Adverse Events V 3.0, was measured 3 years after the completion of IMRT.The average SCM atrophy ratio was -10.97%, -18.65%, and -22.25% at 1, 2, and 3 years postirradiation, respectively. Multivariate analysis indicated N stage and the length of time after IMRT were independent prognostic variables. There were significant associations between the degree of SCM atrophy and neck weakness.Radical IMRT can cause significant SCM atrophy in NPC patients. A more advanced N stage was associated with more severe SCM atrophy, but no difference was observed between N2 and N3. SCM atrophy progresses over time during the 3 years following IMRT. Grade of SCM atrophy is significantly associated with neck weakness.
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http://dx.doi.org/10.1097/MD.0000000000001294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616570PMC
August 2015

The role of Gliadel wafers in the treatment of newly diagnosed GBM: a meta-analysis.

Drug Des Devel Ther 2015 29;9:3341-8. Epub 2015 Jun 29.

Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China.

Background: Standard treatment for high-grade glioma (HGG) includes surgery followed by radiotherapy and/or chemotherapy. Insertion of carmustine wafers into the resection cavity as a treatment for malignant glioma is currently a controversial topic among neurosurgeons. Our meta-analysis focused on whether carmustine wafer treatment could significantly benefit the survival of patients with newly diagnosed glioblastoma multiforme (GBM).

Method: We searched the PubMed and Web of Science databases without any restrictions on language using the keywords "Gliadel wafers", "carmustine wafers", "BCNU wafers", or "interstitial chemotherapy" in newly diagnosed GBM for the period from January 1990 to March 2015. Randomized controlled trials (RCTs) and cohort studies/clinical trials that compared treatments designed with and without carmustine wafers and which reported overall survival or hazard ratio (HR) or survival curves were included in this study. Moreover, the statistical analysis was conducted by the STATA 12.0 software.

Results: Six studies including two RCTs and four cohort studies, enrolling a total of 513 patients (223 with and 290 without carmustine wafers), matched the selection criteria. Carmustine wafers showed a strong advantage when pooling all the included studies (HR = 0.63, 95% confidence interval (CI) = 0.49-0.81; P = 0.019). However, the two RCTs did not show a statistical increase in survival in the group with carmustine wafer compared to the group without it (HR = 0.51, 95% CI = 0.18-1.41; P = 0.426), while the cohort studies demonstrated a significant survival increase (HR = 0.59, 95% CI = 0.44-0.79; P < 0.0001).

Conclusion: Carmustine-impregnated wafers play a significant role in improving survival when used for patients with newly diagnosed GBM. More studies should be designed for newly diagnosed GBM in the future.
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http://dx.doi.org/10.2147/DDDT.S85943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492653PMC
April 2016

Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

PLoS One 2015 6;10(7):e0129679. Epub 2015 Jul 6.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.

Background: To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC).

Material And Methods: 205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.

Results: The median follow-up period was 37.3 months (range, 6.3-45.1 months). The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05). The most common acute and late side effects were grade 2-3 mucositis (78%) and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT), respectively.

Conclusions: VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129679PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492500PMC
March 2016

Dosimetric benefit to organs at risk following margin reductions in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy.

Chin J Cancer 2015 May 20;34(5):189-97. Epub 2015 May 20.

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

Introduction: It is important to decrease the radiation exposure of normal tissue in intensity-modulated radiation therapy (IMRT). Minimizing planning target volume (PTV) margins with more precise target localization techniques can achieve this goal. This study aimed to quantify the extent to which organs at risk (OARs) are spared when using reduced margins in the treatment of nasopharyngeal carcinoma (NPC).

Methods: Two IMRT plans were regenerated for 40 patients with NPC based on two PTV margins, which were reduced or unchanged following cone beam computed tomography online correction. The reduced-margin plan was optimized based on maximal dose reduction to OARs without compromising target coverage. Dosimetric comparisons were evaluated in terms of target coverage and OAR sparing.

Results: Improvements in target coverage occurred with margin reduction, and significant improvements in dosimetric parameters were observed for all OARs (P < 0.05) except for the right optic nerve, chiasm, and lens. Doses to OARs decreased at a rate of 1.5% to 7.7%. Sparing of the left parotid and right parotid, where the mean dose (Dmean) decreased at a rate of 7.1% and 7.7%, respectively, was greater than the sparing of other OARs.

Conclusions: Significant improvements in OAR sparing were observed with margin reduction, in addition to improvement in target coverage. The parotids benefited most from the online imaging-guided approach.
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http://dx.doi.org/10.1186/s40880-015-0016-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593376PMC
May 2015

Multi-subject atlas-based auto-segmentation reduces interobserver variation and improves dosimetric parameter consistency for organs at risk in nasopharyngeal carcinoma: A multi-institution clinical study.

Radiother Oncol 2015 Jun 26;115(3):407-11. Epub 2015 May 26.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address:

Background And Purpose: To assess whether consensus guideline-based atlas-based auto-segmentation (ABAS) reduces interobserver variation and improves dosimetric parameter consistency for organs at risk (OARs) in nasopharyngeal carcinoma (NPC).

Materials And Methods: Eight radiation oncologists from 8 institutes contoured 20 OARs on planning CT images of 16 patients via manual contouring and manually-edited ABAS contouring. Interobserver variation [volume coefficient of variation (CV), Dice similarity coefficient (DSC), three-dimensional isocenter difference (3D-ICD)] and dosimetric parameters were compared between the two methods of contouring for each OAR.

Results: Interobserver variation was significant for all OARs in manual contouring, resulting in significant dosimetric parameter variation (P<0.05). Edited ABAS significantly improved multiple metrics and reduced dosimetric parameter variation for most OARs; brainstem, spinal cord, cochleae, temporomandibular joint (TMJ), larynx and pharyngeal constrictor muscle (PCM) obtained most benefit (range of mean DSC, volume CV and main ICD values was 0.36-0.83, 12.1-84.3%, 2.2-5.0mm for manual contouring and 0.42-0.86, 7.2-70.6%, 1.2-3.5mm for edited ABAS contouring, respectively; range of dose CV reduction: 1.0-3.0%).

Conclusion: Substantial objective interobserver differences occur during manual contouring, resulting in significant dosimetric parameter variation. Edited ABAS reduced interobserver variation and improved dosimetric parameter consistency, particularly for brainstem, spinal cord, cochleae, TMJ, larynx and PCM.
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http://dx.doi.org/10.1016/j.radonc.2015.05.012DOI Listing
June 2015

Association between three eNOS polymorphisms and intracranial aneurysms risk: a meta-analysis.

Medicine (Baltimore) 2015 Jan;94(4):e452

From the Department of Neurosurgery (CY, ZQ, WX, ZW), The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu; and Department of Neurosurgery (CS), The Second Clinical Medical College of North Sichuan Medical College, Nanchong, Sichuan, China.

Endothelial nitric oxide synthase (eNOS) is the catalyst of endothelial nitric oxide (NO) synthesis. Polymorphisms in the eNOS gene may influence the risk of intracranial aneurysm (IA), but the results of existing researches are still inconsistent. Thus, we performed the present meta-analysis to derive a more precise estimation between eNOS polymorphisms (T786C, G894T, 27-bp-variable number of tandem repeat [VNTR]) and IA risk. Case-control studies evaluating the association between the eNOS polymorphisms and IA risk were searched in PubMed, Ovid & Embase, Web of Science, and Chinese Wanfang datasets with the last search up to July 15, 2014. The pooled odds ratios (ORs) for the association between eNOS polymorphisms and IA and their corresponding 95% confidence intervals (CIs) were estimated using the random or fixed-effects model. Finally, 10 studies for T786C polymorphism (1819 cases and 1893 controls), 9 studies for G894T polymorphism (1393 cases and 1508 controls), and 7 studies for 27-bp-VNTR polymorphism (1281 cases and 1406 controls) were included in the meta-analyses. In the overall analysis, no evidence of association between eNOS polymorphisms and susceptibility of IA was found. When subgrouped by race descent, significantly increased risk was detected among Asians for T786C polymorphism (heterozygous comparison of codominant model: OR = 1.294, 95% CI = 1.025-1.634; dominant model: OR = 1.277, 95% CI = 1.019-1.600), but not in Caucasians or the other 2 polymorphisms. Our meta-analysis suggested that T786C polymorphism was associated with increased risk of IA among Asians, whereas G894T and 27-bp-VNTR polymorphisms might have no influence on the susceptibility of IA.
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http://dx.doi.org/10.1097/MD.0000000000000452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602985PMC
January 2015