C Allele of the PPARδ+294T>C Polymorphism Confers a Higher Risk of Hypercholesterolemia, but not Obesity and Insulin Resistance: A Systematic Review and Meta-Analysis.

The relationships of the PPARα Leu162Val and PPARδ+294 T>C polymorphisms with metabolic indexes have been reported to be inconsistent and even contradictory. The meta-analysis was conducted to clarify the relationships between the two variants and the indexes of obesity, insulin resistance, and blood lipids. PubMed, Google Scholar, Embase, and Cochrane Library were searched for eligible studies. Standardized mean difference with 95% confidence interval was calculated to estimate the differences in the metabolic indexes between the genotypes of the Leu162Val and+294 T>C polymorphisms. Heterogeneity among studies was assessed by Cochran's x2-based Q-statistic test. Publication bias was identified by using Begg's test. Forty-one studies (44 585 subjects) and 33 studies (23 018 subjects) were identified in the analyses for the Leu162Val and+294 T>C polymorphisms, respectively. C allele carriers of the+294 T>C polymorphism had significantly higher levels of total cholesterol and low-density lipoprotein cholesterol than TT homozygotes in the whole population. Notably, C allele carriers of the+294 T>C polymorphism had significantly higher levels of triglycerides and total cholesterol in East Asians, but lower levels of triglycerides in West Asians than TT homozygotes. Regarding the Leu162Val polymorphism, it was found that Val allele carriers had significantly higher levels of blood glucose than Leu/Leu homozygotes only in European Caucasians. The meta-analysis demonstrates that C allele of the+294 T>C polymorphism in PPARδ gene confers a higher risk of hypercholesterolemia, which may partly explain the relationship between this variant and coronary artery disease.

RhesusBase PopGateway: Genome-Wide Population Genetics Atlas in Rhesus Macaque.

Although population genetics studies have significantly accelerated the evolutionary and functional interrogations of genes and regulations, limited polymorphism data are available for rhesus macaque, the model animal closely related to human. Here, we report the first genome-wide effort to identify and visualize the population genetics profile in rhesus macaque. On the basis of the whole-genome sequencing of 31 independent macaque animals, we profiled a comprehensive polymorphism map with 46,146,548 sites. The allele frequency for each polymorphism site, the haplotype structure, as well as multiple population genetics parameters were then calculated on a genome-wide scale. We further developed a specific interface, the RhesusBase PopGateway, to facilitate the visualization of these annotations, and highlighted the applications of this highly integrative platform in clarifying the selection signatures of genes and regulations in the context of the primate evolution. Overall, the updated RhesusBase provides a comprehensive monkey population genetics framework for in-depth evolutionary studies of human biology.

Pretreatment Serum Lactate Dehydrogenase Level as an Independent Prognostic Factor of Nasopharyngeal Carcinoma in the Intensity-Modulated Radiation Therapy Era.

BACKGROUND The aims of this study were to analyze the prognostic value of baseline lactate dehydrogenase (LDH) among nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT), and to evaluate the potential application of LDH in monitoring treatment efficacy dynamically. MATERIAL AND METHODS From June 2005 to December 2010, 1188 patients with non-metastatic NPC who underwent IMRT with or without chemotherapy were reviewed. Univariate and multivariate analyses were performed to evaluate the predictive value of baseline LDH. Wilcoxon signed-rank test was used to analyze the difference between baseline and post-radiotherapy LDH, and to compare post-radiotherapy LDH with the LDH in cases of distant failure. RESULTS Patients with elevated LDH had significant inferior survival rates, in terms of overall survival (70.0% vs. 83.2%, p=0.010), disease-specific survival (71.1% vs. 85.7%, p=0.002), and distant metastasis-free survival (71.1% vs. 83.4%, p=0.009), but not correlated with locoregional relapse-free survival (p=0.275) or progression-free survival (p=0.104). Subgroup analysis demonstrated that this predictive effect was more significant with advanced stage. Sixty-five post-radiotherapy LDH levels were available from the 90 patients with high LDH at initial diagnosis, and these levels fell in 65 patients, with 62 cases (95.4%) falling within the normal range. Of the 208 patients who experienced distant metastasis, 87 had an available LDH level at that time. Among them, 69 cases (79.3%) had an increased level compared with the post-radiotherapy LDH level. CONCLUSIONS Pretreatment LDH is a simple, cost-effective biomarker that could predict survival rates and might be used in individualized treatment. It is also a potential biomarker that might reflect tumor burden and be used to monitor therapy efficacy.

Early response to chemoradiotherapy for nasopharyngeal carcinoma treatment: Value of dynamic contrast-enhanced 3.0 T MRI.

PURPOSE: To prospectively evaluate the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) value for predicting early nasopharyngeal carcinoma (NPC) chemoradiotherapy (CRT) response. MATERIALS AND METHODS: Forty-two patients with advanced NPC were recruited and received three DCE-MRI exams before treatment (Pre-Tx), as well as 3 days (Day 3-Tx) and 40 days (Day 40-Tx) after chemotherapy initiation (two neoadjuvant chemotherapy cycles, NAC). We used DCE-Tool to measure primary tumor kinetic parameters (K(trans) , Kep , ve , and vp ) using the extended Tofts model. Kinetic parameters and corresponding changes were compared between responders and nonresponders after NAC or CRT treatment using Student's t or Mann-Whitney U tests. RESULTS: Response to two NAC cycles correlated with short-term local control (P = 0.01). Compared to the nonresponder group, the responder group presented with significantly larger ΔK(trans) (0-3) , ΔKep(0-3) , and Δvp(0-3) values after NAC (P < 0.05). The complete response group after CRT exhibited significantly lower K(trans) (Day 40-Tx) and larger ΔK(trans) (0-3) values than the residual group (P = 0.05). High sensitivity (range: 74.1%-90%) and moderate-to-high specificity (range: 50%-84.3%) distinguished nonresponders from responders grouping after NAC or CRT, with diagnostic efficiency ranging from 69.3%-88%. CONCLUSION: Our study showed kinetic parameter changes earlier after chemotherapy were potential markers for NPC patients receiving CRT therapy following NAC.

Advantages of intensity modulated radiotherapy in recurrent T1-2 nasopharyngeal carcinoma: a retrospective study.

BACKGROUND: Recurrent T1-2 Nasopharyngeal Carcinoma (rT1-2) may be salvaged by 3D - CRT (3D-Conformal Radiotherapy), IMRT (Intensity Modulated Radiotherapy), Brachytherapy (BT), BT with external radiotherapy. The purpose of this study is to address the efficacy and toxicity profile of aforementioned four modalities for rT1-2 NPC. METHODS: 168 patients, median age 48 years (range 16-75 years) proven rT1-2 NPC were diagnosed and treated with four different irradiation modalities (3D-CRT, IMRT, BT, BT with external radiotherapy). Median time to recurrence was 30 months (range 1-180 months). The median follow-up time was 28 months (range, 4-135 months). RESULTS: 161 patients completed a median dose of 6445 cGy (ranging 30 to 87 Gy). Seven patients prematurely terminated their treatment due to acute side-effects and received 30-49 Gy. The 1- and 3-year local regional recurrent free survival (LRRFS), distant free survival (DFS), and overall survival (OS) rates were 82.03% vs. 82.03% vs. 82.58%, 51.33% vs. 51.33% vs. 53.41, respectively. Gender and recurrence T-classification were the two significant adverse prognostic factors for LRRFS, DFS, and OS rates. Grade 3 or 4 toxicities were tolerable. CONCLUSION: 3D-CRT, IMRT, BT, BT with external radiotherapy are feasible and efficacious for rT1-2 NPC. In toxicity 3D-CRT/IMRT group is lower than BT group. IMRT is superior for rT1-2 NPC.

Dynamic contrast-enhanced MRI of nasopharyngeal carcinoma: a preliminary study of the correlations between quantitative parameters and clinical stage.

PURPOSE: To evaluate the relationship between quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinical stage of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-one newly diagnosed NPC patients received MRI examination on Philips Achieva 3.0 Tesla TX MR system. We used DCE-Tool (Philips Healthcare, Best, The Netherlands) to investigate parameters from primary tumors. Tumor/node/metastasis and corresponding clinical stages were determined based on 2009 UICC 7th edition. The correlations between quantitative parameters and clinical stage were correlated using Pearson correlation analysis. RESULTS: Mean K(trans) , Kep , ve , and vp for primary tumors were 0.500 ± 0.188/min, 0.744 ± 0.273/min, 0.986 ± 0.595, and 0.052 ± 0.071, respectively. Both K(trans) and Kep of tumors showed moderate negative correlation with clinical stage, T stage and N stage (P < 0.05), while ve showed moderate positive correlation with them (P < 0.05). vp revealed a moderate negative correlation with T stage (r = -0.369; P < 0.004). Kep and ve have significant differences between many early and advanced stages patients. CONCLUSION: DCE-MRI is feasible to assess vascular permeability of NPC patients. Our results first revealed that the quantitative parameters were significantly related to clinical stage of NPC. Thus, DCE-MRI may be valuable to add noninvasive prognostic indicators in evaluating NPC.

HER2-targeted therapies for HER2-positive early-stage breast cancer: present and future.

Breast cancer (BC) has the second highest incidence among cancers and is the leading cause of death among women worldwide. The human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20%-30% of BC patients. The development of HER2-targeted drugs, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), has improved the operation rate and pathological remission rate and reduced the risk of postoperative recurrence for HER2-positive early-stage BC (HER2+ EBC) patients. This review systematically summarizes the mechanisms, resistance, therapeutic modalities and safety of HER2-targeted drugs and helps us further understand these drugs and their use in clinical practice for patients with HER2+ EBC.

Early assessment of induction chemotherapy response of nasopharyngeal carcinoma by pretreatment diffusion-weighted magnetic resonance imaging.

OBJECTIVES: This study aimed to evaluate the feasibility of pretreatment diffusion-weighted imaging in predicting response after induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC). METHODS: Fifty-four patients with stage III and IV NPC underwent MRI examination at baseline, after 2 cycles of chemotherapy, and at the end of chemoradiotherapy. Apparent diffusion coefficient (ADC) values were compared between effective and ineffective subjects after IC. RESULTS: Mean ADC in effective groups was significantly (P < 0.05) higher than that in the ineffective group. Average and minimum ADCs demonstrated higher sensitivity than maximum ADC for predicting IC response, with 68.4%, 71.1%, and 50.0%, respectively, at an equivalent 68.7% specificity. We observed negative correlations between pretreatment ADC and tumor regression after chemotherapy (γ = - 0.425, P = 0.001) and after chemoradiotherapy (γ = - 0.418, P = 0.003). CONCLUSIONS: Pretreatment ADC was a valuable biomarker for predicting IC response of NPC. Noninvasive diffusion-weighted imaging provides additional indicator in guiding optical therapeutic options for patients with NPC.

Minor alleles of FTO rs9939609 and rs17817449 polymorphisms confer a higher risk of type 2 diabetes mellitus and dyslipidemia, but not coronary artery disease in a Chinese Han population.

Background: Relationships of the polymorphisms in fat mass and obesity-associated gene (FTO) and peroxisome proliferator-activated receptor delta gene (PPARD) with metabolic-related diseases remain to be clarified. Methods: One thousand three hundred and eighty-one subjects were enrolled. Metabolic-related diseases including obesity, dyslipidemia, hyperhomocysteinemia, hyperuricemia, hypertension, type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) were defined based on diagnostic criteria. FTO rs9939609 and rs17817449, and PPARD rs2016520 and rs2267668 polymorphisms were genotyped by using polymerase chain reaction-restricted fragment length polymorphism method. Results: Patients with T2DM or dyslipidemia had a higher frequency of AA, AT or AA + AT genotypes as well as A allele of FTO rs9939609 polymorphism than those free of T2DM or dyslipidemia (P ≤ 0.04 for all). Patients with T2DM or dyslipidemia had a higher frequency of GG, GT or GG + GT genotypes as well as G allele of FTO rs17817449 polymorphism than those free of T2DM or dyslipidemia (P ≤ 0.03 for all). Multivariate logistic regression analyses showed that FTO rs9939609 and rs17817449 polymorphisms were independently associated with T2DM as well as dyslipidemia after adjustment for age, sex, smoking and other metabolic diseases. FTO rs9939609 and rs17817449 polymorphisms were not associated with obesity, hyperhomocysteinemia, hyperuricemia, hypertension and CAD. Obese or T2DM carriers of the AA or AT genotype of the FTO rs9939609 polymorphism had a higher prevalence of dyslipidemia compared to non-obese or non-T2DM carriers of the AA or AT genotype (P = 0.03 for both). Among the carriers of GG or GT genotype of the FTO rs17817449 polymorphism, the prevalence of dyslipidemia in obese patients was higher than that in non-obese subjects (P < 0.01). PPARD rs2016520 and rs2267668 polymorphisms were not correlated with any of the metabolic-related diseases in the study population. Conclusion: Minor alleles of FTO rs9939609 and rs17817449 polymorphisms confer a higher risk of T2DM and dyslipidemia, and the risk is further increased among obese individuals. PPARD rs2016520 and rs2267668 polymorphisms are not associated with metabolic-related diseases.

Prioritizing sufficient dose to gross tumor volume over normal tissue sparing in intensity-modulated radiotherapy treatment of T4 nasopharyngeal carcinoma.

BACKGROUND: In intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), priority is often given minimize dose to the critical organs at risk (OARs) to avoid potential morbid sequelae. However, in T4 NPC, dosimetric inadequacy enforced by dose constraints on OARs may significantly impact tumor control. METHODS: This was a single-institute cohort that patients diagnosed between July 2005 and December 2010 with T4 NPC treated with IMRT. All patients were re-classification according to the 7th-AJCC stage. RESULTS: Overall, the average doses such as Dmax , D1% , D2% and D1cc for various Central nervous system (CNS) OARs including brainstem, optic nerve, chiasm, temporal lobes and spinal cord were found to exceed published guidelines as RTOG0225. However, no clinical toxicities were seen during the follow-up period except for 13% patients with temporal lobe necrosis. CONCLUSION: Our retrospective review showed that its feasible to maximize gross tumor volume dose coverage while exceeding most CNS OAR constraint standards, with ideal local control and no obvious increase of craniocerebral toxicity.

Long Noncoding RNA HOXA11-AS Modulates the Resistance of Nasopharyngeal Carcinoma Cells to Cisplatin via miR-454-3p/c-Met.

To elucidate the mechanism of action of HOXA11-AS in modulating the cisplatin resistance of nasopharyngeal carcinoma (NPC) cells. HOXA11-AS and miR-454-3p expression in NPC tissue and cisplatin-resistant NPC cells were measured via quantitative reverse transcriptase polymerase chain reaction. NPC parental cells (C666-1 and HNE1) and cisplatin-resistant cells (C666-1/DDP and HNE1/DDP) were transfected and divided into different groups, after which the MTT method was used to determine the inhibitory concentration 50 (IC50) of cells treated with different concentrations of cisplatin. Additionally, a clone formation assay, flow cytometry and Western blotting were used to detect DDP-induced changes. Thereafter, xenograft mouse models were constructed to verify the in vitro results. Obviously elevated HOXA11-AS and reduced miR-454-3p were found in NPC tissue and cisplatin-resistant NPC cells. Compared to the control cells, cells in the si-HOXA11-AS group showed sharp decreases in cell viability and IC50, and these results were reversed in the miR-454-3p inhibitor group. Furthermore, HOXA11-AS targeted miR-454-3p, which further targeted c-Met. In comparison with cells in the control group, HNE1/DDP and C666-1/DDP cells in the si-HOXA11-AS group demonstrated fewer colonies, with an increase in the apoptotic rate, while the expression levels of c-Met, p-Akt/Akt and p-mTOR/mTOR decreased. Moreover, the si-HOXA11-AS-induced enhancement in sensitivity to cisplatin was abolished by miR-454-3p inhibitor transfection. The in vivo experiment showed that DDP in combination with si-HOXA11-AS treatment could inhibit the growth of xenograft tumors. Silencing HOXA11-AS can inhibit the c-Met/AKT/mTOR pathway by specifically upregulating miR-454-3p, thus promoting cell apoptosis and enhancing the sensitivity of cisplatin-resistant NPC cells to cisplatin.

Depicting distant metastatic risk by refined subgroups derived from the 8th edition nasopharyngeal carcinoma TNM.

BACKGROUND: Tumor-nodal-metastasis (TNM) is the most important survival predictor in nasopharyngeal carcinoma (NPC). Distant metastasis (DM) is the predominant failure pattern of NPC in the intensity-modulated radiotherapy (IMRT) era. The DM risk appears to be different for T-N subsets within the same clinical stage. Appropriately depicting DM risk has emerged as an important issue in tailoring individualized treatment and underpins the reason for this study. METHODS: A total of 1616 non-metastatic (M0) NPC patients treated with IMRT were included. All were re-staged according to the 8th edition AJCC/UICC TNM (TNM-8). DM-free survival (DMFS) was calculated and compared among T-N subsets within each stage and DM risk groups were derived by Recursive-partitioning analysis (RPA) based on ordinal T and N categories. RESULTS: Significant heterogeneity in DM risk was evident among T-N subsets within cTNM-8 stages II-IV. The RPA algorithm classified patients into four DM risk groups: RPA-I (T1N0-1 and T2-3N0), RPA-II (T2-3N1), RPA-III (T4N0-1 and T1-3N2) and RPA-IV (T4N2 and T1-4N3), with 5-year DMFS of 93.4% (95% CI: 91.3-96.1), 84.3% (80.8-87.8), 78.9% (75.4-82.4) and 63.6% (56.3-70.9), respectively (p < 0.001). Compared to cTNM-8 stage grouping, RPA grouping had a lower Akaike information criterion (AIC) and higher Harrell's concordance index (c-index) for DMFS. CONCLUSIONS: Significant heterogeneity in DM risk exists among T-N subsets within cTNM-8 stages. The RPA groups demonstrated improved intra-group hazard consistency compared to cTNM-8 stage groups. While further validation is warranted, these RPA prognostic groupings provide a strong anatomic foundation to augment DM prediction for optimal targeting in future clinical trials.

Prognostic Evaluation of Nasopharyngeal Carcinoma with Bone-Only Metastasis after Therapy.

PURPOSE: To evaluate the prognosis of nasopharyngeal carcinoma (NPC) patients who developed bone-only metastasis after primary treatment and the stratification of these patients into different risk groups based on independent prognostic factors. MATERIALS AND METHODS: Eighty NPC patients who developed bone-only metastasis after definitive radiotherapy from October 2005 to December 2010 were enrolled. All these patients received palliative treatment for bone metastasis, including chemotherapy and/or radiotherapy. Clinical features, treatment modality, and laboratory parameters were examined with univariate and multivariate analyses. RESULTS: The median follow-up time was 15.5 months (range, 2-67 months) for the whole cohort. The median overall metastatic survival (OMS) time and the 2-year estimate OMS rate were 26.5 months and 52%, respectively. Multivariate analysis indicated that patients with short metastases-free interval, multiple bone metastases sites, high serum lactic dehydrogenase levels, and treated with radiotherapy or chemotherapy alone had significantly worse outcomes. Patients were stratified into three different risk groups based on the number of adverse factors present. The OMS curves of the three groups were all significantly different (p<0.001). CONCLUSION: Severl prognostic factors were found to be associated with worse outcomes. According to the number of adverse factors present, bone-only metastasis patients can be stratified into three risk groups with significantly different prognoses. Such grouping may help in improving the design of clinical trials and in guiding individualized treatment for NPC patients with bone-only metastasis.

Impact of intensity-modulated radiotherapy on nasopharyngeal carcinoma: Validation of the 7th edition AJCC staging system.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the 7th edition UICC/AJCC staging system for nasopharyngeal carcinoma (NPC) patients who were treated with intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS: The clinical data of 1241 NPC patients with initial magnetic resonance imaging (MRI) scans were studied retrospectively. All MRIs were independently reevaluated and restaged according to the 7th edition by two radiologists specializing in head and neck cancers. Analysis of prognostic factors in local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were performed. RESULTS: The proportion of patients in Stage I, II, III, IVA and IVB were 4.8%, 26.2%, 45.4%, 18.4%, and 5.2%, respectively. The differences of LRFS between T1 and T2, and between T2 and T3 were not significant (P=0.055 and 0.605, respectively). Hazard ratios (HRs) for DSS and OS between T2 and T3 or between T3 and T4 differed significantly, but not between T1 and T2. The differences of DMFS between N0 and N1, between N1 and N2 were significant. However no significant difference was found in DMFS between N2 and N3a, or between N2 and N3b. For patients with T1-T3 disease, although skull base infiltration did not impact local failure, it was an independent prognostic factor for both distant failure and cancer death. CONCLUSION: When treated with IMRT, the difference in the LRFS, DSS, and OS between T1 and T2 patients diminished, indicating that it is rational to merge T2 into T1. The prognostic value of the N classification of the current staging system had not changed much compared to the 6th edition.

[Recombinant adenovirus p53 agent injection combined with radiotherapy in treatment of nasopharyngeal carcinoma: a phase II clinical trial].

OBJECTIVE: To evaluate the efficacy and toxicity of recombinant adenovirus p53 agent (SBN-1) combined with radiotherapy in treatment of nasopharyngeal carcinoma. METHODS: Twenty-nine cases with nasopharyngeal carcinoma were randomly divided into two groups: gene therapy + radiotherapy group (GTRT group, n = 16, SBN-1 was injected intratumorally once a week for 8 weeks, and radiotherapy with the dosage of 60-70 Gy was given 3 days after the first injection of SBN-1) and radiotherapy group (RT group, n = 213, the same regimen of radiotherapy was given only). CT and MRI were conducted 4, 8, and 12 weeks after to evaluate the size of tumor. Then the patients were followed-up every month. Toxicity was evaluated by physical examination, KPS scoring, blood, urine, and feces routines, serum BUN, creatine, AST, ALT, LDH, and AKP, electrocardiography, and X-ray. RESULTS: The tumors of the patients group were reduced by 70.9 +/- 18.1% and 49.4 +/- 22.8% in the GTRT group and the RT group respectively (P < 0.001) 4 weeks after treatment; and were reduced by 94.9 +/- 10.2% and 80.4 +/- 17.0% in the GTRT group and RT group respectively (P < 0.001) 8 weeks after treatment. The rates of complete regression of tumor 12 weeks after the treatment were 75% and 15% in the GTRT group and RT group respectively (P < 0.005). 3 cases presented mild, self-limited fever and no other side effects were noted. CONCLUSION: Local injection of SBN-1 combined with radiotherapy to treat nasopharyngeal carcinoma is safe and significantly more effective than single radiotherapy.

Diffusion-weighted magnetic resonance imaging for early response assessment of chemoradiotherapy in patients with nasopharyngeal carcinoma.

PURPOSE: To prospectively evaluate the feasibility of diffusion-weighted magnetic resonance imaging (DWI) for monitoring early treatment response to chemoradiotherapy (CRT) of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Thirty-one patients with stage III and IV NPC were enrolled in this study from February 2012 to November 2012．T2-weighted and DWI sequences with diffusion factor of 0 and 800mm²/s were performed using a 3.0 T Philips Achieva TX scanner at baseline and 3 days, 20 days (after the first cycle of chemotherapy), 50 days (6 days after radiotherapy initiation) after neoadjuvant chemotherapy (NAC) initiation. The diameter of each primary lesion and target metastatic lymph node before and after the first cycle of NAC was measured and classified into stable disease (SD), partial response (PR) or completed response (CR) based on RECIST 1.1. The apparent diffusion coefficient (ADC) values and changes compared to baseline at each time point were compared between responders (CR and PR) and non-responders (SD). The rates of residual at the end of CRT were compared between these two groups. RESULTS: A significant increase in ADC was observed at each stage of therapy (P=.001) in lesions of primary and metastatic. The ADC values (ADC), ADC changes (ΔADC) and percentage ADC changes (Δ%ADC) of day 20 in responders were significantly higher than in non-responders for both primary lesions (p=.005, p=.006, p=.008, respectively) and metastatic lymph nodes (p=.002, p=.002, p=.003). Non-responders showed a higher rate of residual for both primary lesions (p=.008) and metastatic lymph nodes (p=.024) than responders. CONCLUSIONS: DW MR imaging allows for detecting early treatment response of NPC. Patients with high ADC values and large ADC increase early after NAC initiation tended to respond better to CRT. Thus, accessing the curative effect of NAC in advanced NPC provides the opportunity to adjust following CRT regimen.

Prognostic significance of expression of cyclooxygenase-2, vascular endothelial growth factor, and epidermal growth factor receptor in nasopharyngeal carcinoma.

BACKGROUND: The association between expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and the long-term outcomes in treated nasopharyngeal carcinoma (NPC) was studied. METHODS: Expression of COX-2, VEGF, and EGFR by immunohistochemical (IHC) staining was assessed in 128 patients with NPC. Overall survival (OS), disease-free survival (DFS), locoregional control, and distant metastasis-free survival rates were compared for different expression levels of each marker. Multivariate analysis was by the Cox regression model. RESULTS: Median follow-up after radiation therapy ± chemotherapy was 116 months. Univariate and multivariate analyses demonstrated that COX-2, VEGF, EGFR, and clinical stage were all independent predictors for OS, DFS, locoregional control, and distant metastasis-free survival rates. CONCLUSIONS: High expression of COX-2, VEGF, and EGFR were independent adverse prognostic factors for long-term outcomes in nonmetastatic NPC independent of clinical stage.

[Clinical analysis of 60 cases with radiative nasopharyngeal necrosis in nasopharyngeal carcinoma].

OBJECTIVE: To study the clinical characteristics, diagnosis, treatment and prognostic factors of patients with postradiation nasopharyngeal necrosis (PRNN) in nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with PRNN were studied retrospectively, 50 males and 10 females, age ranging from 30 - 70 years of (median 51.5 years). All patients were treated with endoscopic debridement and systemic or local anti-inflammatory treatment. Kruskal-Wallis H test was used to assess the interval time between irradiation completion and necrosis onset and related factors of treatment outcome. Multivariate Cox proportional hazards regression survival analysis was performed to analyze risk factors. RESULTS: The latent period between the last irradiation and the onset of the symptom ranged from 1 to 156 months, with a median of 5 months. The median interval time was 7.0 months in 1 course group and 4.5 months in ≥2 courses group (χ2=5.527, P=0.031), and 7.5 months in T2 group and 5.0 months in ≥T3 group (χ2=4.330, P=0.037), respectively. Forty-one patients of them had nasopharyngeal infection, and the difference in curative effect between infection group and non-infection group was significantly (χ2=14.775, P<0.001). Symptoms were alleviated in all patients after endoscopic debridement and systemic or local anti-inflammatory treatment. Follow-up for all patients ranged from 2 to 46 months (median 12.5 months). Seven patients with internal carotid artery exposure died of sudden nasopharyngeal massive bleeding and fifteen patients died of tumor or systemic exhaustion; five cases were lost, and the rest were all in survival. Inter carotid artery erosion was an independent prognostic risk factor according to multivariate Cox proportional hazards regression survival analysis (P<0.05). CONCLUSIONS: Endoscopic debridement is effective in treating irradiation-related nasopharyngeal necrosis. The occurrence of nasopharyngeal necrosis is related to infection, irradiation dose and course, and T stage. Internal carotid artery erosion is a severe situation and also an independent prognostic factor for the patients. The most common causes of death were nasopharyngeal bleeding and systemic exhaustion.

Baseline plasma proteomic analysis to identify biomarkers that predict radiation-induced lung toxicity in patients receiving radiation for non-small cell lung cancer.

PURPOSE: To identify new plasma proteomic markers before radiotherapy start to predict later grade ≥2 radiation-induced lung toxicity (RILT2). METHODS: Fifty-seven patients with non-small cell lung cancer received radiotherapy (RT) were eligible. Forty-eight patients with minimum follow-up of 1 year, nine with RILT2 with tumor stage matched to 39 without RILT2, were enrolled for this analysis. Platelet-poor plasma was obtained within 2 weeks before radiotherapy. The plasma proteomes were compared using a multiplexed quantitative proteomics approach involving ExacTag labeling, reverse-phase high-performance liquid chromatography, and nano liquid chromatography electrospray ionization tandem mass spectrometry. Z scores and Bonferroni-adjusted p values for the two-sample mean comparison were used to identify the differential protein expression between patients with and without RILT2. RESULTS: More than 200 proteins were identified and quantified. After excluding proteins that were not detected in at least 40% of the 48 patient samples, C4b-binding protein alpha chain and vitronectin had significantly higher (p < 0.001 and p = 0.02) expression levels in patients with RILT2 compared with patients without RILT2. These two proteins were validated by Western blot. Ingenuity pathway analysis revealed that they both play important roles in the inflammatory response and are associated with the known pathways of radiation-induced lung damage. CONCLUSIONS: This proteomic approach demonstrates new plasma protein biomarkers before treatment for future studies on RILT2 prediction.

Comparative survival in patients with postresection recurrent versus newly diagnosed non-small-cell lung cancer treated with radiotherapy.

PURPOSE: To compare the survival of postresection recurrent vs. newly diagnosed non-small-cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. METHODS AND MATERIALS: The study population consisted of 661 consecutive patients with NSCLC registered in the radiation oncology databases at two medical centers in the United States between 1992 and 2004. Of the 661 patients, 54 had postresection recurrent NSCLC and 607 had newly diagnosed NSCLC. Kaplan-Meier and Cox regression models were used for the survival analyses. RESULTS: The distribution of relevant clinical factors between these two groups was similar. The median survival time and 5-year overall survival rates were 19.8 months (95% confidence interval [CI], 13.9-25.7) and 14.8% (95% confidence interval, 5.4-24.2%) vs. 12.2 months (95% CI, 10.8-13.6) and 11.0% (95% CI, 8.5-13.5%) for recurrent vs. newly diagnosed patients, respectively (p = .037). For Stage I-III patients, no significant difference was observed in the 5-year overall survival (p = .297) or progression-free survival (p = .935) between recurrent and newly diagnosed patients. For the 46 patients with Stage I-III recurrent disease, multivariate analysis showed that chemotherapy was a significant prognostic factor for 5-year progression-free survival (hazard ratio, 0.45; 95% CI, 0.224-0.914; p = .027). CONCLUSION: Our institutional data have shown that patients with postresection recurrent NSCLC achieved survival comparable to that of newly diagnosed NSCLC patients when they were both treated with radiotherapy or chemoradiotherapy. These findings suggest that patients with postresection recurrent NSCLC should be treated as aggressively as those with newly diagnosed disease.