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Purpose: To estimate the influence of prolonged radiation treatment time (RTT) on survival outcomes in nasopharyngeal carcinoma after continuous intensity-modulated radiation therapy., Methods and Materials: Retrospectively review 321 patients with NPC treated between October 2009 and December 2010 and all of them underwent simultaneous accelerated intensity-modulated radiation therapy. The fractionated dose was 2-2.47 Gy/F (median 2.27 Gy), and the total dose for nasopharyngeal region was 64-74 Gy/ 28-33 fractions. The association of prolonged RTT and treatment interruption with PFS, LRFS and DFFS were assessed by univariate analysis and multivariate analysis. Survival analyses were carried out using Kaplan-Meier methodology and the log-rank test was used to assess the difference. The Cox regression proportional hazard model was used for multivariate analyses and evaluating the prognostic parameters for PFS, LRFS and DFFS., Results: Univariate analysis revealed no significant associations between prolonged RTT and PFS, LRFS, DFFS when dichotomized using various cut-off values (all P>0.05). In multivariate analysis, RTT (range, 36-63 days) as a continuous variable, had no influence on any survival outcome as well (P>0.05). T and N classification were independent prognostic factors for PFS, LRFS and DFFS (all P<0.05, except T classification for LRFS, P = 0.057). Age was an independent prognostic factor for PFS (hazard ratio [HR], 1.033; P = 0.008) and DFFS (HR, 1.032; P = 0.043)., Conclusion: We conclude that no such association between survival outcomes and radiation treatment duration (range: 36-63 days) can be found in the present retrospective study, however, we have to remind that prolongation in treatment should be limited in clinical application and interruptions caused by any reason should be minimized as much as possible.

Introduction: Patients with metastatic nasopharyngeal carcinoma (NPC) have variable survival outcomes. We have previously shown that an elevated peripheral blood lymphocyte-to-monocyte ratio (LMR) is associated with an increased metastatic risk in patients with primary NPC. The present study aimed to investigate the prognostic value of pretreatment LMR in a large cohort of metastatic NPC patients., Methods: Clinical data of 672 patients with metastatic NPC diagnosed between January 2003 and December 2009 were analyzed. The peripheral lymphocyte and monocyte counts were retrieved, and LMR was calculated. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate COX proportional hazards analyses were performed to evaluate the association of LMR with overall survival (OS)., Results: Univariate analysis revealed that an elevated absolute lymphocyte count (≥1.390×10(9)/L) and LMR (≥2.475) as well as a decreased monocyte count (<0.665×10(9)/L) were significantly associated with prolonged OS. Multivariate Cox proportional hazard analysis showed that LMR (hazard ratio [HR]=0.50, 95% confidence interval [CI]=0.41-0.60, P<0.001), absolute lymphocyte count (HR=0.77, 95% CI=0.64-0.93, P=0.007), and monocyte count (HR=1.98, 95% CI=1.63-2.41, P<0.001) were independent prognostic factors. By stratification analyses, only LMR remained a significant predictor of prognosis., Conclusion: We identified pretreatment LMR as an independent prognostic factor for patients with metastatic NPC. Independent validation of our findings is needed.

Objectives: The aim of this study was to compare the metastatic patterns of synchronous bone metastasis (SBM) and metachronous bone metastasis (MBM) in nasopharyngeal carcinoma (NPC). Methods: This study included bone metastases in NPC patients from 2005 to 2016 in a Chinese hospital. Cohort 1 was collected from 2005 to 2010 for discovery, and Cohort 2 from 2011 to 2016 for validation. The chi‐squared test, Wilcoxon rank sum test, and Kaplan–Meier technique were used to compare site, time, and survival between cohorts 1 and 2. Prognostic factors were analyzed using univariate or multivariate Cox regression. Results: Cohort 1 had 112 individuals with SBM and 394 with MBM, and cohort 2 had 328 with SBM and 307 with MBM. The thoracic vertebra was the most frequently affected site of metastasis. Patients with SBM more often had metastasis to the cervical vertebrae compared with patients with MBM (34.5% vs. 22.3%, p < 0.05). Patients with SBM had better overall survival (42.2 months, 95% CI: 33.9–50.7) than patients with MBM (24.9 months, 95% CI: 22.2–28.7). Age at bone metastasis detection, metastasis to other organs, and more bone metastasis locations were associated with worse prognosis. The majority of MBMs occurred at 7 to 18 months after NPC diagnosis. Conclusion: Radiotherapy does not modify the metastatic patterns of NPC bone metastases. Patients with SBM tend to have metastasis to the cervical vertebra, which is close to the nasopharynx. Paying more attention to bone metastases during follow‐up in the first 2 years after an NPC diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Diffusion‐weighted imaging lesions (DWILs) are associated with unfavorable outcome in intracerebral hemorrhage (ICH). We proposed a novel predictive nomogram incorporating DWILs. Methods: A total of 738 patients with primary ICH in a tertiary hospital were prospectively enrolled as a training cohort. DWILs were defined as remote focal hyperintensities on DWI corresponding to low intensities on apparent diffusion coefficient images and remote from the focal hematoma. The outcome of interest was modified Rankin Scale scores of 4–6 at 90 days after onset. Multivariate logistic regression was used to construct a nomogram. Model performance was tested in the training cohort and externally validated with respect to discrimination, calibration, and clinical usefulness in another institute. Additionally, the nomogram was compared with the ICH score in terms of predictive ability. Results: Overall, 153 (20.73%) and 23 (15.54%) patients developed an unfavorable outcome in the training and validation cohorts, respectively. The multivariate analysis revealed that age, National Institutes of Health Stroke Scale (NIHSS) score, anemia, infratentorial location, presence of DWILs, and prior ICH were associated with unfavorable outcome. Our ANAID‐ICH nomogram was constructed according to the aforementioned variables; the area under the receiver operating characteristic curve was 0.842 and 0.831 in the training and validation sets, respectively. With regard to the 90‐day outcome, the nomogram showed a significantly higher predictive value than the ICH score in both cohorts. Conclusions: The ANAID‐ICH nomogram comprising age, NIHSS score, anemia, infratentorial location, presence of DWILs, and prior ICH may facilitate the identification of patients at higher risk for an unfavorable outcome. [ABSTRACT FROM AUTHOR]

Purpose: Radiotherapy is the most important primary treatment for patients with nasopharyngeal carcinoma. Generally, the treatment duration of radiotherapy takes six or six and half weeks with 30 to 33 fractions. The current study was conducted to evaluate the association between prognosis and the duration of radiotherapy in nasopharyngeal carcinoma patients. Methods: Patients with primary nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy and concurrent cisplatin-based chemotherapy, with or without induction chemotherapy between January, 2008 and December, 2013 at a single institution were retrospectively reviewed. Results: In total, 1292 patients were included. At a median follow-up of 71.0 months (range 2.0–126.0 months), locoregional recurrence, distant failure and death were observed in 8.8%, 12.2% and 15.6% of all patients, respectively. Estimated 5-year locoregional relapse–free survival, distant metastasis–free survival, progression-free survival and overall survival in patients with radiation ≤ 7 weeks versus patients with radiation >7 weeks were: 93.2% versus 87.0% (P < 0.001), 89.4% versus 84.4% (P = 0.016), 79.8% versus 70.6% (P < 0.001) and 87.2% versus 78.4% (P < 0.001), respectively. Conclusions: Prolonged duration of radiotherapy with a significantly higher risk of distant metastasis and death in nasopharyngeal carcinoma patients. Understanding this point, healthcare providers should make efforts to avoid prolonged duration of radiotherapy to minimize the risk of treatment failure. [ABSTRACT FROM AUTHOR]

Rovalpituzumab tesirine is a promising delta-like protein 3 (DLL3)-targeted antibody-drug conjugate for the treatment of small-cell lung cancer (SCLC). Thyroid transcription factor-1 (TTF-1) and DLL3 protein are associated with SCLC, and may be used to identify patients, who respond to the DLL3-targeted therapy. However, little is known about the expression pattern of the DLL3 protein, and the prognostic value of DLL3 and TTF-1 for SCLC. A total of 335 patients with SCLC were identified, including 11 patients with paired biopsy of primary site and lobectomy specimens, and 37 patients with paired specimens of primary and metastatic site. The DLL3 expression levels of individuals were evaluated using the anti-DLL3 antibody. No differences in DLL3 expression levels were observed in paired biopsy and lobectomy specimens (P=0.774), and paired primary and metastatic sites (P=0.472). SCLC cases with high DLL3 expression levels were more frequent in male patients (P=0.041), smokers (P=0.023) and patients with positive TTF-1 expression (P=0.006) compared with DLL3-low SCLC. DLL3-high SCLC exhibited worse overall survival compared with DLL3-low SCLC (log-rank test, P=0.007). Patients with TTF-1+ SCLC experienced a significantly worse overall survival compared with patients with TTF-1- SCLC (P<0.001). DLL3-low/TTF-1- was defined as a distinct molecular subgroup of SCLC with optimal prognosis (P<0.001). DLL3-low/TTF-1- was an independent prognostic marker for SCLC (P=0.001). In conclusion, the present study, to the best of our knowledge, provided novel evidence for SCLC intratumoral and intertumoral homogeneity with the identification of DLL3 protein levels. Therefore, it is reliable to use biopsy specimens to evaluate DLL3 expression levels for identification of patients who may benefit from DLL3-targeted therapy. In addition, DLL3 and TTF-1 are two protein markers with potential clinical value in risk stratification for patients with SCLC. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are transcripts of more than 200 nucleotides that lack the ability to encode protein. Convincing studies have indicated that lncRNAs can act as oncogenes or tumor suppressors by regulating gene expression. The novel lncRNA NR2F1-AS1 was recently found to be abnormally expressed in various malignancies, including hepatocellular carcinoma, gastric cancer, colorectal cancer, pancreatic cancer, breast cancer, lung cancer, thyroid cancer, esophageal squamous cell carcinoma, osteosarcoma, and neuroblastoma. NR2F1-AS1 can modify cell proliferation, invasion, migration, apoptosis, the cell cycle, and glycolysis through various mechanisms involving direct or indirect effects on pathways. Furthermore, NR2F1-AS1 may be a potential therapeutic target and prognostic marker in cancer, as it has been related to the clinicopathological characteristics of cancer patients. Here, we summarize and clarify recent research advances regarding the expression, function, molecular mechanisms, and clinical implications of NR2F1-AS1 in multiple malignant tumors. • NR2F1-AS1 is upregulated in most tumors, but decreased in CRC and CSCC. • NR2F1-AS1 functions as oncogene in the majority of malignancies, while acts as suppressor gene in a few tumors, such as CRC and CSCC. • NR2F1-AS1 can modify cell proliferation, invasion, migration, apoptosis, cell cycle mainly by CeRNA mechanism in tumors. • NR2F1-AS1 is maybe a potential prognostic and therapeutic target in cancer. [ABSTRACT FROM AUTHOR]

Conclusion: The prognosis and late adverse effects of radiotherapy (RT) in the patients with nasopharyngeal carcinoma (NPC) with or without dermatomyositis (DM) were similar, although the NPC patients with DM had higher Epstein-Barr virus (EBV) VCA-IgA titers and more severe acute side effects. Gender, TNM stage, and chemotherapy were independent prognostic factors of overall survival for NPC with DM. Glucocorticoid treatment did not affect the survival of NPC patients with DM. Objectives: We evaluated the clinical characteristics, prognosis, and differences in the toxicity of RT in patients with NPC with or without DM. Methods: A paired study of 172 NPC cases with DM (DM group) or without DM (control group) from Sun Yat-sen University Cancer Center was conducted. Results: The DM group had higher EBV VCA-IgA titers than the control group ( p = 0.017) and more acute adverse effects of RT ( p < 0.001). No significant differences in the overall survival or late adverse effects were found between the two groups. Gender, TNM stage, and chemotherapy were independent prognostic factors for the overall survival in the DM group. No significant differences in the overall survival were found between the patients in the DM group who were taking glucocorticoids and those who were not. [ABSTRACT FROM AUTHOR]

Recent studies provide convincing evidence that a combined immunohistochemical or fluorescence in situ hybridization (FISH) score of MYC, BCL2, BCL6 proteins and MYC translocations predicted outcome in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, by far, all these researches are based on Western populations. Therefore, we investigate the prognostic relevance of MYC-, BCL2- and BCL6-rearrangements and protein expression by immunohistochemistry and FISH from 336 de novo DLBCL, NOS treated with CHOP or R-CHOP. Breaks in MYC and BCL6, and fusion in IGH/BCL2 were detected in 9.7%, 20.0%, and 11.1% of the cases, respectively, and were not significantly associated with clinical outcomes. Protein overexpression of MYC (≥40%), BCL2 (≥70%) and BCL6 (≥50%) was encountered in 51%, 51% and 36% of the tumors, respectively. On the basis of MYC, BCL2 and BCL6 expression, double-hit scores (DHSs) and triple-hit score (THS) were assigned to all patients with DLBCL. Patients with high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS had multiple adverse prognostic factors including high LDH level, poor performance status, advanced clinical stage, high International Prognostic Index (IPI) score, and non-germinal center B-cell. In univariate analysis, high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS were associated with inferior OS and PFS in both CHOP and R-CHOP cohorts (P<0.05). The highly significant correlations with OS and PFS were maintained in multivariate models that controlled for IPI (P<0.05). DLBCLs with high DHSs and high THS share the clinical features and poor prognosis of double-hit lymphoma (P>0.05). These data together suggest that the immunohistochemical DHSs and THS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP or CHOP. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To evaluate the prognostic value of serum endostatin levels in patients with advanced-stage nasopharyngeal carcinoma (NPC). Materials and methods: Between August 2003 and March 2005, 218 patients with advanced-stage NPC were enrolled in this study, including 70 patients in the training cohort and 148 in the validation cohort. The pre-treatment serum endostatin and vascular endothelial growth factor (VEGF) levels were measured using competitive enzyme immunoassays. For the normal control, serums samples from 20 healthy individuals were also collected. Results: Serum endostatin levels in the patients with advanced-stage NPC were significantly higher than those of controls, but VEGF levels were similar in the two groups. Univariate analysis revealed significant differences between the high and low endostatin level groups regarding 5 year overall survival (63.9% versus 90.5%; P = 0.003), progression-free survival (PFS) (50.2% versus 79.3%; P = 0.003) and distant metastasis-free survival (DMFS) (59.1% versus 85.3%; P = 0.01) in the training cohort. Using the same cut-off value generated from the training cohort, there were also significant unfavourable correlations between serum endostatin levels and overall survival (P = 0.001), PFS (P = 0.001) and DMFS (P = 0.002) in the second independent validation cohort. Multivariate analysis using the entire group (n = 218) revealed that the serum endostatin level was an independent unfavourable prognostic factor for overall survival (hazard ratio 4.8; 95% confidence interval 2.48–9.23; P < 0.0001), PFS (hazard ratio 3.44; 95% confidence interval 2.06–5.74; P < 0.0001) and DMFS (hazard ratio 3.65; 95% confidence interval 1.92–6.94; P < 0.0001) in patients with advanced-stage NPC. No associations were observed between the outcomes and the serum VEGF levels in patients with advanced-stage NPC. Conclusions: High endostatin levels are associated with poor survival and this knowledge may improve the risk stratification of patients with advanced-stage NPC. [Copyright &y& Elsevier]

Objective The study is performed to explore the correlations of forkhead box O3 (FoxO3) and forkhead box O4 (FoxO4) expressions with clinicopathological features and prognosis of bladder cancer. Methods Bladder cancer tissues and adjacent normal tissues from the recruited 222 patients were collected. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry were applied to determine the expressions of FoxO3 and FoxO4. Spearman correlation analysis was conducted to examine the correlation between the expressions of FoxO3 and FoxO4. All patients were followed up and overall survival (OS) and disease-free survival (DFS) were recorded. Kaplan-Meier survival curve was drawn to determine the associations of FoxO3 and FoxO4 expressions and postoperative survival. Cox proportional hazards model was conducted to analyze the risk factors for poor prognosis of bladder cancer. Results The mRNA and expressions of FoxO3 and FoxO4 proteins in the bladder cancer tissues were lower than that in the adjacent normal tissues (both P < 0.05). The positive rates of FoxO3 and FoxO4 were lower in the patients with lymph node metastasis than that in the patients without lymph node metastasis ( P < 0.05), and significantly lower in the patients with non-muscle invasive bladder cancer (T is -T 1 ) than in those with non-muscle invasive bladder cancer (T 2 -T 3 ) in TNM staging, and remarkably lower in the patients with high grade than in those with low grade in the histological type ( P < 0.05). Furthermore, the expressions of FoxO3 and FoxO4 were positively correlated in the bladder cancer tissues ( P < 0.05). Negative expressions of FoxO3 and FoxO4 and lymph node metastasis were the risk factors for the poor prognosis of bladder cancer. Conclusions The FoxO3 and FoxO4 expressions may potentially associate with the clinicopathological features and prognosis of bladder cancer. [ABSTRACT FROM AUTHOR]

The study aims to investigate the role of long non-coding RNA (lncRNA) GAS5 in the diagnosis and prognosis of patients suffering from thyroid cancer (TC). A total of 212 patients with TC and 61 patients with benign thyroid tumor were enrolled in the study. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the lncRNA GAS5 expression in TC and benign tumor tissues. All TC patients were categorized into high-risk and low-risk groups according to the MACIS, AGES and AMES prognostic scoring system. A 5-year follow-up was conducted in order to determine the disease free survival (DFS) rates and overall survival (OS) rates. The associations between lncRNA GAS5 expression and prognosis of TC patients were analyzed by The Kaplan-Meier survival curves and the Cox regression models. There was a decrease in the lncRNA GAS5 expression in TC tissues in comparison to benign tumor tissues. Expression of lncRNA GAS5 showed significant association with tumor node metastasis (TNM) staging, lymph node metastasis and the multiple cancer foci of TC. AMES high-risk patients showed a decreased expression of lncRNA GAS5 expression than the AMES low-risk patients. The AGES and MACIS high-risk patients showed lower lncRNA GAS5 expression than low-risk patients. The survival rate of TC patients with high lncRNA GAS5 expression was higher than that of TC patients with low lncRNA GAS5 expression during the DFS and OS periods. Cox regression analysis indicated that lncRNA GAS5 expression, TNM staging, lymph node metastasis and multiple cancer foci were independent risk factors for poor prognosis in TC patients. LncRNA GAS5 may be closely related to the diagnosis and prognosis of TC. [ABSTRACT FROM AUTHOR]

Objective: Thus far, there is no final conclusion on the treatment of local recurrent nasopharyngeal carcinoma (lrNPC) patients. Herein, we developed a nomogram which combined prognostic biomarkers to predict clinical outcome and guide individual treatment.Materials and Methods: From 2006 to 2016, 303 patients with lrNPC were retrospectively reviewed. Overall survival (OS) was the primary endpoint. The nomogram was established with the significant prognostic factors (P < 0.05) selected by multivariate analysis using Cox regression model. Harrell Concordance Index (C-index), calibration curves, and decision curve analysis (DCA) were applied to evaluate this model.Results: Four independent prognostic factors (age, hypertension, relapsed T (rT) stage, and Epstein-Barr virus DNA) identified from multivariable analysis were included into the nomogram. The C-index of the nomogram was 0.687. The calibration curves for 1-, 3-, and 5-year OS rate showed satisfactory agreements between the predicted and actual values. The decision curve analysis also exhibited a preferable net benefit of this model. All patients were subdivided into three risk groups based on the nomogram. Local treatment was associated with higher OS than palliative chemotherapy alone in the low (P < 0.001) and intermediate-risk groups (P = 0.001). However, no significant difference was observed between different treatment methods in the high-risk group (P = 0.176).Conclusion: We established the nomogram for patients with lrNPC to predict OS and guide individual treatment, which showed satisfactory performance in accuracy, discrimination capability, and clinical utility. [ABSTRACT FROM AUTHOR]