Objective:Radiomics pipelines have been developed to extract novel information from radiological images, which may help in phenotypic profiling of tumours that would correlate to prognosis. Here, we compared two publicly available pipelines for radiomics analyses on head and neck CT and MRI in nasopharynx cancer (NPC).Methods and materials:100 biopsy-proven NPC cases stratified by T- and N-categories were enrolled in this study. Two radiomics pipeline, Moddicom (v. 0.51) and Pyradiomics (v. 2.1.2) were used to extract radiomics features of CT and MRI. Segmentation of primary gross tumour volume was performed using Velocity v. 4.0 by consensus agreement between three radiation oncologists. Intraclass correlation between common features of the two pipelines was analysed by Spearman’s rank correlation. Unsupervised hierarchical clustering was used to determine association between radiomics features and clinical parameters.Results:We observed a high proportion of correlated features in the CT data set, but not for MRI; 76.1% (51 of 67 common between Moddicom and Pyradiomics) of CT features and 28.6% (20 of 70 common) of MRI features were significantly correlated. Of these, 100% were shape-related for both CT and MRI, 100 and 23.5% were first-order-related, 61.9 and 19.0% were texture-related, respectively. This interpipeline heterogeneity affected the downstream clustering with known prognostic clinical parameters of cTN-status and GTVp. Nonetheless, shape features were the most reproducible predictors of clinical parameters among the different radiomics modules.Conclusion:Here, we highlighted significant heterogeneity between two publicly available radiomics pipelines that could affect the downstream association with prognostic clinical factors in NPCAdvances in knowledge:The present study emphasized the broader importance of selecting stable radiomics features for disease phenotyping, and it is necessary prior to any investigation of multicentre imaging datasets to validate the stability of CT-related radiomics features for clinical prognostication.

ObjectiveThis study aimed to explore whether concurrent chemoradiotherapy (CCRT) with or without Adjuvant Chemotherapy (AC) could improved the survival in stage II nasopharyngeal carcinoma (NPC).MethodsPatients with stage II NPC treated with CCRT (n=80) or CCRT+AC (n=40) or IMRT alone (n=42) between January 2007 and September 2014 were retrospectively analyzed. The three patient groups were matched based on prognostic factors. All patients were treated with IMRT. The endpoints were overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRRFS), and failure-free survival (FFS). The treatment-related acute toxicity reactions between the three groups were compared also.ResultsThe three groups indicated similar outcomes: survival of the CCRT group, CCRT+AC group and RT alone group were (93.9%, 95.0%, 95.2%, P=0.937) for OS, (96.8%, 94.9%, 93.0%, P=0.756) for LRRFS, (91.1%, 97.5%, 100%, P=0.185) for DMFS and (84.9%, 92.5%, 93.0%, P=0.597) for FFS. Both the univariate and multivariate analysis indicated that older age predicted lower LRRFS and FFS. The CCRT and CCRT+AC groups showed more acute toxicity reactions, especially in bone marrow suppression, Liver dysfunction, gastrointestinal reactions (nausea/vomiting) and weight loss.ConclusionCCRT with/without AC could not improve the survival conditions of patients with stage II NPC, but remarkably increased treatment-associated acute toxic reactions when compared with IMRT alone.

It was previously reported that poly-(adenosine diphosphate-ribose) polymerase-1 (PARP-1) regulated ionizing radiation (IR)-induced autophagy in CNE-2 human nasopharyngeal carcinoma cells. The present study aimed to investigate whether PARP-1-mediated IR-induced autophagy occurred via activation of the liver kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in CNE-2 cells. In addition, the effect of PARP-1 and AMPK inhibition on the radiation sensitization of CNE-2 cells was investigated. CNE-2 cells were treated with 10 Gy IR in the presence or absence of the AMPK activator 5-amino-1-β-D-ribofuranosyl-1H-imidazole-4-carboxamide (AICAR). In addition, IR-treated CNE-2 cells were transfected with lentivirus-delivered small-hairpin RNA or treated with the AMPK inhibitor Compound C. Western blot analysis was used to assess the protein expression of PARP-1, phosphorylated (p)-AMPK, microtubule-associated protein 1 light chain 3 (LC3)-II and p-P70S6K. Cell viability and clone formation assays were performed to determine the effect of PARP-1 silencing and AMPK inhibition on the radiation sensitization of CNE-2 cells. The results showed that IR promoted PARP-1, p-AMPK and LC3-II protein expression as well as decreased p-P70S6K expression compared with that of the untreated cells. In addition, AICAR increased the expression of p-AMPK and LC3-II as well as decreased p-P70S6K expression compared with that of the IR-only group; however, AICAR did not increase PARP-1 expression. Furthermore, PARP-1 gene silencing decreased the expression of PARP-1, p-AMPK and LC3-II as well as increased p-P70S6K expression. Compound C decreased p-AMPK and LC3-II expression as well as increased p-P70S6K expression; however, Compound C did not increase PARP-1 expression. Western blot analysis detected limited expression of p-LKB1 in all treatment groups. Cell viability and clone formation assays revealed that PARP-1 or AMPK inhibition reduced the proliferation of CNE-2 cells following IR. In conclusion, the present study demonstrated that PARP-1 promoted autophagy via the AMPK/mTOR pathway; in addition, PARP-1 or AMPK inhibition contributed to the radiation sensitization of CNE-2 cells following IR. However, it remains to be elucidated whether PARP-1 is an upstream mediator of the LKB1 pathway in CNE-2 cells following IR.

Although radiotherapy is generally effective in the treatment of major nasopharyngeal carcinoma (NPC), this treatment still makes approximately 20% of patients radioresistant. Therefore, the identification of blood or biopsy biomarkers that can predict the treatment response to radioresistance and that can diagnosis early stages of NPC would be highly useful to improve this situation. Proteomics is widely used in NPC for searching biomarkers and comparing differentially expressed proteins. In this review, an overview of proteomics with different samples related to NPC and common proteomics methods was made. In conclusion, identical proteins are sorted as follows: Keratin is ranked the highest followed by such proteins as annexin, heat shock protein, 14-3-3σ, nm-23 protein, cathepsin, heterogeneous nuclear ribonucleoproteins, enolase, triosephosphate isomerase, stathmin, prohibitin, and vimentin. This ranking indicates that these proteins may be NPC-related proteins and have potential value for further studies.

◥Purpose: Bevacizumab is considered a promising therapy for brain necrosis after radiotherapy, while some patients fail to derive benefit or even worsen. Hence, we developed and validated a radiomics model for predicting the response to bevacizumab in patients with brain necrosis after radiotherapy.Experimental Design: A total of 149 patients (with 194 brain lesions; 101, 51, and 42 in the training, internal, and external validation sets, respectively) receiving bevacizumab were enrolled. In total, 1,301 radiomic features were extracted from the pretreatment MRI images of each lesion. In the training set, a radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm. Multivariable logistic regression analysis was then used to develop a radiomics model incorporated in the radiomics signature and independent clinical predictors. The performance of the model was assessed by its discrimination, calibration, and clinical usefulness with internal and external validation.Results: The radiomics signature consisted of 18 selected features and showed good discrimination performance. The model, which integrates the radiomics signature, the interval between radiotherapy and diagnosis of brain necrosis, and the interval between diagnosis of brain necrosis and treatment with bevacizumab, showed favorable calibration and discrimination in the training set (AUC 0.916). These findings were confirmed in the validation sets (AUC 0.912 and 0.827, respectively). Decision curve analysis confirmed the clinical utility of the model.Conclusions: The presented radiomics model, available as an online calculator, can serve as a user-friendly tool for individualized prediction of the response to bevacizumab in patients with brain necrosis after radiotherapy.

Purpose The prognosis of inflammation-related indicators like lactate dehydrogenase/albumin ratio (LAR) and the platelet/lymphocyte ratio (PLR) in nasopharyngeal carcinoma (NPC) is not yet clear. Our objective is to establish and verify the nomogram using LAR and PLR ratio for the first time to explore the prognostic value in NPC. Patients and Methods This was a retrospective collection of 1661 patients with non-metastatic NPC admitted to our hospital from 2010 to 2017. The final variables of overall survival (OS) and progression-free survival (PFS) were selected by Cox regression analysis to establish nomograms, and the methods to verify the prediction precision and discriminative ability of the nomograms were concordance index (C index), the receiver operating characteristic (ROC) curve and calibration curve. The risk stratification was carried out through the nomograms and compared with the current staging system by the Kaplan–Meier methods. Results Multivariate Cox analysis resulted that age, plasma Epstein–Barr Virus (EBV) DNA, T stage, N stage, white blood cells (WBC), PLR and LAR were independent prognostic risk factors for OS and PFS, and sex is an independent prognostic risk factor for OS. The C-indexes of OS nomogram were 0.722 (95% CI: 0.706–0.738) and 0.747 (95% CI: 0.717–0.777) in the training cohort and validation cohort, which were statistically higher than the current 8th AJCC staging system (0.646 and 0.688). The C-indexes of PFS nomogram were 0.696 (95% CI: 0.680–0.713) and 0.690 (95% CI: 0.660–0.720), which were also statistically higher than the current 8th AJCC staging system (0.632 and 0.666). Otherwise, ROC curves and the calibration curve for probability also confirmed satisfied consistency with actual observations. Conclusion LAR is a novel useful independent factor in NPC. The proposed nomogram LAR and PLR resulted in more accurate prognostic prediction than current staging system for NPC patients.

BackgroundPreviously, we found that c-jun was highly expressed in radiation-resistant human nasopharyngeal carcinoma cells (CNE-2R) compared with human nasopharyngeal carcinoma cells (CNE-2).Materials and methodsIn this study, we first used the scratch assays and transwell assays to detect the migration and invasion of CNE-2R and CNE-2 cells and tested the epithelial mesenchymal transformation (EMT)-related proteins E-cadherin and N-cadherin by Western blot analysis. Subsequently, c-jun was knocked down to establish the effect of c-jun on EMT, migration, and invasion of CNE-2R cells both in vitro and in vivo.ResultsA high EMT level, CNE-2R cells were more capable of migration and invasion than CNE-2 cells. Moreover, silencing of c-jun has upregulated the expression of E-cadherin and downregulated N-cadherin in CNE-2R cells, and subsequently the migration and invasion capacity of the cells was decreased. Consistent with in vitro results, in vivo studies indicated that the c-jun silencing reduced pulmonary migration of CNE-2R cells. Immunohistochemistry of lung metastatic tumor tissue showed that E-cadherin was upregulated, and N-cadherin was downregulated.ConclusionThese findings suggest that silencing of c-jun in CNE-2R cells reduces cells migration, invasion, and EMT both in vitro and in vivo.

Compared with the control group, induction chemotherapy followed by concurrent chemoradiotherapy was well tolerated but could not significantly improve prognosis in terms of overall survival, loco-regional failure-free survival or distant metastasis failure-free survival.