Search

In the original publication [...]

Abstract 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.

Heavy metal cadmium (Cd) at high concentrations severely disturbs plant growth and development. The E3 ubiquitin ligase involved in protein degradation is critical for plant tolerance to abiotic stress, but the role of E3 ubiquitin ligases in Cd tolerance is largely unknown in tomato. Here, we characterized an E3 ubiquitin ligase gene Sl1, which was highly expressed in roots under Cd stress in our previous study. The subcellular localization of Sl1 revealed that it was located in plasma membranes. In vitro ubiquitination assays confirmed that Sl1 had E3 ubiquitin ligase activity. Knockout of the Sl1 gene by CRISPR/Cas9 genome editing technology reduced while its overexpression increased Cd tolerance as reflected by the changes in the actual quantum efficiency of PSII photochemistry (ΦPSII) and hydrogen peroxide (H2O2) accumulation. Cd-induced increased activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) were compromised in sl1 mutants but were enhanced in Sl1 overexpressing lines. Furthermore, the content of Cd in both shoots and roots increased in sl1 mutants while reduced in Sl1 overexpressing plants. Gene expression assays revealed that Sl1 regulated the transcript levels of heavy metal transport-related genes to inhibit Cd accumulation. These findings demonstrate that Sl1 plays a critical role in regulating Cd tolerance by relieving oxidative stress and resisting heavy metal transportation in tomato. The study provides a new understanding of the mechanism of plant tolerance to heavy metal stress.

Abstract 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

Abstract 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 4000 vs. ≤ 4000 copies/mL were 83.5% vs. 93.9% (P 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis (both P

Abstract 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.

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.

Abstract 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

Abstract 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.

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.

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.

The relationship between risk of glioma and alcohol consumption has been widely studied, but results have been conflicting. We therefore conducted a meta-analysis of observational studies to systematically assess the relationship between alcohol drinking and risk of glioma. Two electronic databases (PubMed and EMBASE) were searched from inception to 8 August 2013 to identify pertinent studies that linked alcohol drinking with glioma risk. We used a random-effects model to calculate the overall relative risk (RR) with corresponding 95% confidence intervals (CIs). Fifteen case-control and four cohort studies were identified for this analysis. The combined RR for total alcohol drinkers versus non-drinkers was 0.96 (95% CI: 0.89–1.04). In the subgroup analysis by geographic area, a significant association was observed in North American studies (RR = 0.78, 95% CI: 0.65–0.93), but not in European or Asian/Australian studies. In the subgroup analysis by study design, a borderline significant association emerged in population-based case-control studies (RR = 0.82, 95% CI: 0.68–0.99), but not in hospital-based case-control studies (RR = 1.00, 95% CI: 0.99–1.01) or cohort group (RR = 1.03, 95% CI: 0.88–1.20). Our results show no material association between alcohol consumption and risk of glioma existed. Further prospective evidences are needed to confirm this association.

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 (Solanum lycopersicum) 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.

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.

Background and objectivesStudies of the association between excess body weight and risk of meningioma have produced inconsistent results. Therefore, a meta-analysis of published studies was performed to better assess the association between meningioma and excess body weight.MethodsA literature search was conducted in the PubMed and EMBASE databases without any limitations. The reference lists of identified articles were also screened for additional studies. The summary relative risks (RRs) and 95% confidence intervals (CI) were calculated using fixed- or random-effects models.ResultsA total of 6 studies provided risk estimates for overweight or obesity. Overall, the combined RRs were 1.12 (95% CI = 0.98-1.28) for overweight and 1.45 (95% CI = 1.26-1.67) for obesity. After stratification by gender, no significant association was observed for obese men (RR = 1.30, 95% CI = 0.64-2.62), while significant association was detected for obese women (RR = 1.46, 95% CI = 1.26-1.69). No substantial differences emerged across strata of study design and geographic areas.ConclusionThe results of this meta-analysis suggest that obesity but not overweight is associated with an increased risk of meningioma. Due to the limited number of studies, further research is needed to confirm the association.

BACKGROUND: Intracavitary brachytherapy (ICBT) is usually applied as boost radiotherapy for superficial residual of nasopharyngeal carcinoma (NPC) after primary extern-beam radiptherapy (ERT). Here, we evaluated the outcome of endoscope-guided interstitial intensity-modulated brachytherapy (IMBT) boost radiation for deep-seated residual NPC. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred and thirteen patients with residual NPC who were salvaged with brachytherapy boost radiation during 2005-2009 were analyzed retrospectively. Among these patients, 171 patients had superficial residual NPC (≤1 cm below the nasopharyngeal epithelium) were treated with ICBT boost radiation, and interstitial IMBT boost radiation was delivered to 42 patients with deep-seated residual NPC (>1 cm below the nasopharyngeal epithelium). We found that IMBT boost subgroup had a higher ratio of T2b (81.0% VS 34.5%, P

Background and objectivePrevious investigations of glioma risk in women have focused on oral contraceptive (OC), hormone replacement therapy (HRT), and reproductive factors. However, the results of published studies were inconclusive and inconsistent. Thus, a meta-analysis based on published case-control studies was performed to assess the role of exogenous and endogenous hormones factors in glioma risk.MethodsThe PubMed and EMBASE databases were searched without any restrictions on language or publication year. Reference lists from retrieved articles were also reviewed. We included case-control studies reporting relative risks (RRs) with corresponding 95% confidence intervals (CIs) (or data to calculate them) between oral contraceptive (OC) and hormone replacement therapy (HRT) use, reproductive factors and glioma. Random-effects models were used to calculate the summary risk estimates.ResultsFinally, 11 eligible studies with 4860 cases and 14,740 controls were identified. A lower risk of glioma was observed among women who were ever users of exogenous hormones (OC RR = 0.707, 95% CI = 0.604-0.828; HRT: RR = 0.683, 95% CI = 0.577-0.808) compared with never users. An increased glioma risk was associated with older age at menarche (RR = 1.401, 95% CI = 1.052-1.865). No association was observed for menopause status, parous status, age at menopause, or age at first birth and glioma risk.ConclusionThe results of our study support the hypothesis female sex hormones play a role in the development of glioma in women. Additional studies are warranted to validate the conclusion from this meta-analysis and clarity the underlying mechanisms.

Background and objectiveA number of studies have focused on the association between oral contraceptive (OC), hormonal replacement therapy (HRT) and reproductive factors and meningioma risk, but the results were inconsistent. Thus, a meta-analysis was performed to obtain more precise estimates of risk.MethodsWe conducted a literature search using PubMed and EMBASE databases to July 2013, without any limitations. Random effects models were used to summarize results.ResultsTwelve case-control and six cohort studies were included in this meta-analysis. We found that an increased risk of meningioma was associated with HRT use(RR = 1.19, 95% CI = 1.01-1.40), postmenopausal women(RR = 1.32, 95% CI = 1.07-1.64) and parity(RR = 1.18, 95% CI = 1.00-1.40).No significant associations were observed for OC use (RR = 0.93, 95% CI = 0.83-1.03), age at menarche(RR = 1.06, 95% CI = 0.92-1.21), age at menopause(RR = 1.03, 95% CI = 0.81-1.30), or age at first birth(RR = 0.94, 95% CI = 0.80-1.10).ConclusionIn conclusion, the results of our study support the hypothesis that longer exposure to effect of female sex hormones may increase the risk of meningioma in women, yet additional studies are warranted to confirm our findings and identify the underlying biological mechanisms.

BACKGROUND:To compare volumetric modulated arc therapy (VMAT) with conventional step and shoot intensity modulated radiation therapy (s-IMRT) in nasopharyngeal carcinoma (NPC) patients, and identify which T category patient gains the maximum benefit from VMAT. METHODS:Fifty-two patients that randomly selected from 205 patients received VMAT at a single center were retrospectively replanned with s-IMRT. For a fair comparison, the planning target volume (PTV) coverage of the 2 plans was normalized to the same level. A standard planning constraint set was used; the constraints for the organs at risk (OARs) were individually adapted. The calculated doses to the PTV and OARs were compared for s-IMRT and VMAT plans generated using the Monaco treatment planning system. RESULTS:VMAT and s-IMRT plans had similar PTV coverage and OAR sparing within all T categories. However, in stratified analysis, VMAT plans lead to better or similar sparing of the OARs in early T category patients; and lead to poorer sparing of the OARs in advanced T category patients (P

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To improve corrosion-resistance of shallow-buried concrete urban utility tunnels (UUTs), basalt fiber reinforced polymer (BFRP) bars are applied to reinforce UUTs. As the UUT must have excellent survival capability under accidental explosions, a shallow-buried BFRP bars reinforced UUT (BBRU) was designed and constructed. Repetitive blast experiments were carried out on this BBRU. Dynamic responses, damage evolutions and failure styles of the BBRU under repetitive explosions were revealed. The tunnel roof is the most vulnerable component and longitudinal cracks develop along the tunnel. When the scaled distance is larger than 1.10 m/kg1/3, no cracks are observed in the experiments. When the BBRU is severely damaged, there are five cracks forming and developing along the roof. The roof is simplified as a clamped-supported one-way slab, proved by the observation that the maximum strain of the transverse bar is much larger than that of the longitudinal bar. Dynamic responses of the roof slab are predicted by dynamic Euler beam theory, which can consistently predict the roof displacement under large-scaled-distance explosion. Compared with the UUT reinforced with steel bars, the BBRU has advantages in blast resistance with smaller deflections and more evenly-distributed cracks when the scaled distance is smaller than 1.260 m/kg1/3 and the steel bars enter plastic state. Longer elastic defamation of the BFRP bars endows the UUT more excellent blast resistance under small-scaled-distance explosions.

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. [ABSTRACT FROM AUTHOR]

Background: To identify the radiation volume effect and significant dosimetric parameters for temporal lobe injury (TLI) and determine the radiation dose tolerance of the temporal lobe (TL) in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT).Methods: Twenty NPC patients with magnetic resonance imaging (MRI)-diagnosed unilateral TLI were reviewed. Dose-volume data was retrospectively analyzed.Results: Paired samples t-tests showed all dosimetric parameters significantly correlated with TLI, except the TL volume (TLV) and V₇₅ (the TLV that received ≥75 Gy, P = 0.73 and 0.22, respectively). Receiver operating characteristic (ROC) curves showed V₁₀ and V₂₀ (P = 0.552 and 0.11, respectively) were the only non-significant predictors from V₁₀ to V₇₀ for TLI. D(0.5cc) (dose to 0.5 ml of the TLV) was an independent predictor for TLI (P < 0.001) in multivariate analysis; the area under the ROC curve for D(0.5cc) was 0.843 (P < 0.001), and the cutoff point 69 Gy was deemed as the radiation dose limit. The distribution of high dose 'hot spot' regions and the location of TLI were consistent.Conclusions: A D0.5cc of 69 Gy may be the dose tolerance of the TL. The risk of TLI was highly dependent on high dose 'hot spots' in the TL; physicians should be cautious of such 'hot spots' in the TL during IMRT treatment plan optimization, review and approval. [ABSTRACT FROM AUTHOR]

Background: This prospective study was conducted to evaluate inter- and intra-fraction errors in nasopharyngeal carcinoma (NPC) patients undergoing volumetric modulated arc therapy (VMAT) using cone-beam computed tomography (CBCT) and to thus obtain planning target volume (PTV) margins to effectively guide treatment in the future. Methods: Fifteen NPC patients scheduled to undergo VMAT were prospectively enrolled in the study. For each patient, three CBCT scans were obtained; one after daily conventional positioning, one after online correction with 2 mm tolerance and one after 1 week of VMAT delivery. The scans were registered to the planning CT to determine the inter- and intra-fraction errors. Patient positioning errors were analyzed for time trends over the course of radiotherapy. PTV margins were calculated from the systematic (∑) and random (σ) errors. Results: The average absolute values of the pre-correction, post-correction and intra-fraction errors (in order) were 1.1, 0.6 and 0.4 mm in the medial-lateral (ML) direction, 1.2, 0.7 and 0.5 mm in the superior-inferior (SI) direction and 1.1, 0.7 and 0.5 mm in the anterior-posterior (AP) direction. The corresponding ∑ were 1.0-1.4 mm, 0.4-0.5 mm and 0.2-0.4 mm, while the corresponding s were 0.7-0.8 mm, 0.6-0.7 mm and 0.5-0.6 mm. With time, gradual increases in both the inter- and intra-fraction three-dimensional displacements were observed (P = 0.019 and P = 0.044, respectively). The total PTV margins accounting for pre-correction and intra-fraction errors were 3.4-4.1 mm and those accounting for post-correction and intra-fraction errors were 1.7-2.2 mm. Conclusions: CBCT is an effective modality to evaluate and improve the accuracy of VMAT in NPC patients. Inter- and intra-fraction three-dimensional displacements increased as a function of time during the course of radiotherapy. In our institution, we recommend a PTV margin of 5 mm for NPC patients undergoing VMAT without CBCT and 3 mm for those treated with rigorous daily CBCT scans. [ABSTRACT FROM AUTHOR]

Skin dose is one of the key issues for clinical dosimetry in radiation therapy. Currently planning computer systems are unable to accurately predict dose in the buildup region, leaving ambiguity as to the dose levels actually received by the patient’s skin during radiotherapy. This is one of the prime reasons why in vivo measurements are necessary to estimate the dose in the buildup region. A newly developed metal-oxide-semiconductor-field-effect-transistor (MOSFET) detector designed specifically for dose measurements in rapidly changing dose gradients was introduced for accurate in vivo skin dosimetry. The feasibility of this detector for skin dose measurements was verified in comparison with plane parallel ionization chamber and radiochromic films. The accuracy of a commercial treatment planning system (TPS) in skin dose calculations for intensity-modulated radiation therapy treatment of nasopharyngeal carcinoma was evaluated using MOSFET detectors in an anthropomorphic phantom as well as on the patients. Results show that this newly developed MOSFET detector can provide a minimal but highly reproducible intrinsic buildup of 7 mg cm-2 corresponding to the requirements of personal surface dose equivalent Hp (0.07). The reproducibility of the MOSFET response, in high sensitivity mode, is found to be better than 2% at the phantom surface for the doses normally delivered to the patients. The MOSFET detector agrees well with the Attix chamber and the EBT Gafchromic® film in terms of surface and buildup region dose measurements, even for oblique incident beams. While the dose difference between MOSFET measurements and TPS calculations is within measurement uncertainty for the depths equal to or greater than 0.5 cm, an overestimation of up to 8.5% was found for the surface dose calculations in the anthropomorphic phantom study. In vivo skin dose measurements reveal that the dose difference between the MOSFET results and the TPS calculations was on average -7.2%, ranging from -4.3% to -9.2%. The newly designed MOSFET detector encapsulated into a thin water protective film has a minimal reproducible intrinsic buildup recommended for skin dosimetry. This feature makes it very suitable for routine IMRT QA and accurate in vivo skin dosimetry. [ABSTRACT FROM AUTHOR]

The feasibility of a recently designed metal–oxide–semiconductor field effect transistor (MOSFET) dosimetry system for dose verification of high dose rate (HDR) brachytherapy treatment planning was investigated. MOSFET detectors were calibrated with a 0.6 cm3 NE-2571 Farmer-type ionization chamber in water. Key characteristics of the MOSFET detectors, such as the energy dependence, that will affect phantom measurements with HDR 192Ir sources were measured. The MOSFET detector was then applied to verify the dosimetric accuracy of HDR brachytherapy treatments in a custom-made water phantom. Three MOSFET detectors were calibrated independently, with the calibration factors ranging from 0.187 to 0.215 cGy/mV. A distance dependent energy response was observed, significant within 2 cm from the source. The new MOSFET detector has a good reproducibility (<3%), small angular effect (<2%), and good dose linearity (R2=1). It was observed that the MOSFET detectors had a linear response to dose until the threshold voltage reached approximately 24 V for 192Ir source measurements. Further comparison of phantom measurements using MOSFET detectors with dose calculations by a commercial treatment planning system for computed tomography-based brachytherapy treatment plans showed that the mean relative deviation was 2.2±0.2% for dose points 1 cm away from the source and 2.0±0.1% for dose points located 2 cm away. The percentage deviations between the measured doses and the planned doses were below 5% for all the measurements. The MOSFET detector, with its advantages of small physical size and ease of use, is a reliable tool for quality assurance of HDR brachytherapy. The phantom verification method described here is universal and can be applied to other HDR brachytherapy treatments. [ABSTRACT FROM AUTHOR]