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The optimal number of cycles of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) is unclear. We aimed to combine the tumor response during IC and tumor stage to individualize the number of IC cycles.Totally, 498 LANPC patients who received IC plus CCRT between 2014 and 2018 were reviewed. Tumor response during IC was used to stratify patients with different risks. All patients were classified into those who received two cycles of IC and those who were treated with three cycles. Propensity score matching methods were performed to compare the treatment efficiency.After two cycles of IC, 340/498 (68.3%) cases showed complete tumor response (CR)/partial response (PR) and 158 (31.7%) achieved stable disease (SD)/disease progression (PD). Unfavorable responders (SD/PD) exhibited poor survival outcomes. The three-cycle IC regimen was correlated with better OS and PFS than the two-cycle regimen for N2-3 patients in the CR/PR group. However, the use of different IC cycle strategies achieved similar survival outcomes for SD/PD or N0-1 patients. The incidences of acute toxicities were higher in the IC = 3 group.Tumor response during IC could be a powerful predictor of LANPC and could be used to guide the individualized number of IC cycles. A three-cycle IC regimen seemed to be preferable for N2-3 patients who received CR/PR during IC. However, an additional cycle of IC could not benefit N0-1 or SD/PD patients, and the optimal treatment strategies for these patients require further consideration.

Background The optimal cumulative cisplatin dose (CCD) during radiation therapy for locoregionally advanced nasopharyngeal carcinoma (LA‐NPC) patients receiving induction chemotherapy (IC) plus CCRT remains controversial. This study aimed to explore the treatment efficiency of CCD for high‐and low‐risk patients with LA‐NPC. Methods Data from 472 LA‐NPC patients diagnosed from 2014 to 2018 and treated with IC plus CCRT were reviewed. After propensity score matching, the therapeutic effects of a CCD > 200 and CCD ≤ 200 mg/m2 were evaluated comparatively. Five factors selected by multivariate analysis were incorporated to develop a nomogram. Subgroup analysis was conducted to explore the role of different CCDs in nomogram‐defined high‐ and low‐risk groups. Additionally, acute toxicities were evaluated comparatively between the high‐ and low‐CCD groups. Results After matching, there was no difference between different CCD groups for all patients in terms of 3‐year overall survival (OS), distant metastasis‐free survival (DMFS), locoregional recurrence‐free survival (LRRFS), or progression‐free survival (PFS). A nomogram was built by integrating pretreatment EBV DNA, clinical stage, and post‐IC EBV DNA, post‐IC primary gross tumor and lymph node volumes obtained a C‐index of 0.674. The high‐risk group determined by the nomogram had poorer 3‐year PFS, OS, DMFS, and LRRFS than the low‐risk group. A total of CCD > 200 mg/m2 increased the survival rates of 3‐year PFS and DMFS (PFS: 72.5% vs. 54.4%, p = 0.012; DMFS: 81.9% vs. 61.5%, p = 0.014) in the high‐risk group but not in the low‐risk group. Moreover, the high CCD increased treatment‐related acute toxicities. Conclusions A high CCD was associated with better 3‐year PFS and DMFS rates than a low dose for high‐risk patients but could not produce a survival benefit for low‐risk patients.

Ru-Rong Peng,1 Zhong-Guo Liang,1 Kai-Hua Chen,1 Ling Li,1 Song Qu,1 Xiao-Dong Zhu1,2 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Oncology, Affiliated Wu-Ming Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Xiao-Dong ZhuDepartment of Radiation Oncology, Guangxi Medical University Cancer Hospital, 71 He-di Road, Nanning, 530021, People’s Republic of ChinaTel +86 15778028340Email zhuxdonggxmu@126.comPurpose: 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.Keywords: intensity-modulated radiotherapy, nasopharyngeal carcinoma, lactate dehydrogenase to albumin ratio, platelet-to-lymphocyte ratio, tumor–node–metastasis staging system

Yu-Ting Jiang,1 Kai-Hua Chen,1 Zhong-Guo Liang,1 Jie Yang,1 Song Qu,1,2 Ling Li,1,2 Xiao-Dong Zhu1– 3 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Guangxi, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High‐Incidence‐ Tumor, Guangxi Medical University, Ministry of Education, Guangxi, People’s Republic of China; 3Department of Oncology, Affiliated Wuming Hospital of Guangxi Medical University, Guangxi, People’s Republic of ChinaCorrespondence: Xiao-Dong Zhu, Tel/Fax +86-771-5331466, Email zhuxiaodong@gxmu.edu.cnPurpose: We aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in advanced N-stage nasopharyngeal carcinoma (NPC).Patients and Methods: A total of 624 NPC patients with N2-3 stage received CCRT with or without IC were retrospectively reviewed. We constructed a nomogram for predicting overall survival (OS) based on the result of the multivariate analysis in the training cohort (n = 468) and then tested it on the validation cohort (n = 156). Harrell’s concordance indices (C-index) and time-independent receiver operating characteristic (tdROC) analysis were applied to evaluate the discriminatory ability of the nomogram and compare it with TNM staging. IC plus CCRT was compared with CCRT in the whole cohort and two risk groups based on the nomogram with balanced baseline characteristics. In addition, acute toxicities were compared between different treatment groups.Results: The nomogram showed good prognostic accuracy with a C-index of 0.716 (95% CI 0.669– 0.763) in the validation cohort. The 5-year OS of low and high-risk groups stratified by the nomogram were significantly different. IC+CCRT was significantly associated with superior OS as compared with CCRT (75.4 vs 52.6%, p = 0.009) in the high-risk group. However, no significant difference between IC plus CCRT and CCRT was observed (p = 0.843) in the low-risk group. IC plus CCRT was associated with more grade 1– 4 acute toxicities.Conclusion: Our study can help clinicians select NPC patients with advanced N stage who benefit from IC.Keywords: nasopharyngeal carcinoma, advanced N-stage, induction chemotherapy, survival, nomogram

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 Improved antitumor responses have been observed in patients after combination radiation therapy (RT) and immune checkpoint blockade (ICB). Whether these clinical responses are linked to the host systemic immune system has not been elucidated. Methods and Materials In this single-institution prospective observational study, peripheral blood was longitudinally collected from 10 patients with metastatic disease who had responded to anti-PD-1/anti-PD-L1 ICB and received RT (8-50 Gy in 1-5 fractions) upon disease progression at the following timepoints: baseline (pre-RT), 1 to 2 weeks post-RT, and post-ICB (cycle 1) on reintroduction post-RT. To thoroughly characterize the interaction between combined RT-ICB and the host immune system, we performed high-dimensional, mass cytometry–based immunophenotyping of circulating lymphocytes using a 40-marker panel addressing lineage, differentiation, activation, trafficking, cytotoxicity, and costimulatory and inhibitory functions. Phenotypic expression of circulating lymphocytes was compared across patients and time points and correlated with post-RT tumor responses. Results Foremost, we demonstrated excellent posttreatment clinical responses, including 4 local responses with >50% reduction in radiated tumor size, 1 out-of-field response, and 4 patients who resumed ICB for >1 year. Baseline and post-RT immune states were highly heterogeneous among patients. Despite this interindividual heterogeneity in baseline immune states, we observed a systemic immune reaction to RT-ICB common across patients, histology, and radiation sites; a subset of pre-existing Ki-67+ CD8+ T cells were increased post-RT and further expanded upon reintroduction of ICB post-RT (2.3-fold increase, P = .02). Importantly, RT did not alter the phenotypic profile of these Ki-67+ CD8+ T cells, which was characterized by a distinct activated and differentiated effector phenotype. Conclusions Collectively, these findings point toward a sustained reinvigoration of host antitumor immunity after RT-ICB and suggest an expansion in activated Ki-67+ CD8+ T cells as a possible demonstration of this synergy, thereby providing new insights that may support the development of optimal sequencing strategies.

Background The aim of this study was to develop a prognostic nomogram for early stage extranodal natural killer/T-cell lymphoma, nasal type (ENKL) treated with high-dose radiotherapy (RT). Patients and Methods A total of 81 patients at 2 cancer centers with stage I to IIE ENKL who received chemotherapy (CT) and high-dose RT were retrospectively analyzed. The development of the nomogram was on the basis of the Cox proportional hazards model. We implemented the concordance index (C-index) and performed a calibration curve to determine its predictive and discriminatory capacity and compared our nomogram with the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI). Results The nomogram included 4 important variables and used a multivariate analysis: lactate dehydrogenase, primary tumor invasion, tumor response, and CT regimen. The 5-year OS rate and progression-free survival were 64.7% and 57.5%, respectively for the entire group. The C-index of the nomogram for overall survival (OS) prediction was 0.87, and it was superior to the predictive power of the IPI and KPI. The calibration curve showed that the nomogram accurately predicted the 5-year OS. Conclusion The proposed nomogram could provide an individualized risk estimate of the OS for early stage ENKL treated with CT and high-dose RT.

Purpose To construct a prognostic index (PI) for overall survival (OS) to stratify nasopharyngeal carcinoma (NPC) into high-risk and low-risk groups. We also applied the model to investigate the role of the addition of adjuvant chemotherapy (AC) to concurrent chemoradiotherapy (CCRT) regimens for the treatment of NPC. Methods A prognostic model was established based on a retrospective study of 362 patients from January 2008 to June 2011. The discriminative and calibration abilities of the model were evaluated by Harrell's concordance index (C-index), and calibration curves. Bootstrapping was used to perform for internal validation. External validation was conducted using 324 patients diagnosed with NPC from July 2011 to December 2012 at the same institution. Survival analyses were performed between CCRT-AC and CCRT alone groups for the high-risk and low-risk groups. Results The primary PI comprised covariates that were associated with OS in the training cohort, including T stage, N stage, age, and plasma alkaline phosphatase (ALP). Internal and external validation showed that the discrimination of the PI for OS was significantly better than that of the 8th edition AJCC staging system. Discretization by using a fixed PI score cut-off of 407.96 determined from the training data set yielded high- and low-risk subgroups with distinct OS outcomes in the validation cohort. Adjuvant chemotherapy improved OS in high-risk patients (HR 0.620, 95% CI 0.408 to 0.941; P = 0.023) but increased the risk of distant metastasis (HR, 4.222, 95% CI, 0.959 to 18.585; P = 0.038) in low-risk patients. Conclusion The proposed prognostic model achieved good prediction and calibration of OS for patients with NPC. The addition of adjuvant chemotherapy might be a double-edged sword, bringing survival benefit to high-risk patients but greater risk of distant metastasis to low-risk patients.

Background and aim Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Southern China, Southeast Asia. Radiotherapy is the main treatment for NPC. Still, about 20% of patients with NPC have a recurrence. No effective serum biomarkers are available for recurrent nasopharyngeal carcinoma (rNPC) to date. This study aimed to explore whether amyloid beta (A4) precursor protein (APP) might serve as a valuable diagnostic and prognostic biomarker for patients with rNPC. Methods In a previous study, a tandem mass tag-based proteomic test was performed, which screened 59 differentially expressed proteins (DEPs) between nonrecurrent nasopharyngeal carcinoma (nrNPC) and rNPC. In this study, a protein-protein interaction was conducted to screen the key proteins among the 59 DEPs. APP was validated and evaluated by enzyme-linked immunosorbent assay in 70 serum samples [recurrence (n = 35) and no-recurrence (n = 35)]. Also, the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of APP. Results The area under the ROC curve was 0.666 (95% CI: 0.514-0.818, P = 0.044). The best cutoff point of the relative expression levels for APP was 1.23 (concentration = 16.95 ng/mL), at which the sensitivity was 55.2% and the specificity was 90.9%. Conclusion The findings indicated that APP might be a valuable diagnostic and prognostic biomarker for patients with rNPC.

ObjectiveThe present study aimed to evaluate the role of integrating the pretreatment neutrophil-to-lymphocyte ratio (NLR) into the eighth edition of the AJCC staging system for nasopharynx cancer in an endemic region.MethodsBetween May 2007 and December 2012, a total of 713 cases with NPC were retrospectively analyzed. The separation ability in terms of overall survival (OS), local failure-free survival (LFFS), distant metastasis-free survival (DMFS), and failure-free survival (FFS) was evaluated. The discriminatory ability was assessed using Harrell’s concordance index (c-index). Recursive partitioning analysis (RPA) was conducted and incorporated with pretreatment NLR.ResultsWhen integrated with NLR, the separate and discriminatory abilities for N classifications were improved in terms of OS and DMFS, but not for T categories. By using Recursive partitioning analysis, five subgroups were generated. Compared with the overall stage, the integration of NLR could not enhance the separate and discriminatory abilities. However, patients in the RPA 4 group gained significant benefits in terms of OS (HR 0.390 (95%CI 0.212-0.716), P = 0.002) and FFS (HR 0.548 (95%CI 0.314-0.958), P = 0.032) from the additional adjuvant chemotherapy after concurrent chemoradiotherapy.ConclusionThe integration of NLR into the 8th edition of the AJCC staging system could enhance the separation and discriminatory abilities for N classifications, but not for T categories. In addition, patients in the RPA 4 group could benefit from the addition of adjuvant chemotherapy to concurrent chemoradiotherapy.

Chang Yan,1 De-Song Shen,1 Xiao-Bo Chen,2 Dan-Ke SU,3 Zhong-Guo Liang,1 Kai-Hua Chen,1 Ling Li,1 Xia Liang,1 Hai Liao,3 Xiao-Dong Zhu1,4 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2School of First Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 4Affiliated Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530100, People’s Republic of ChinaCorrespondence: Xiao-Dong ZhuDepartment of Radiation Oncology, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning City, Guangxi, 530021, People’s Republic of ChinaTel +86 771 533 1466Email zhuxdonggxmu@126.comHai LiaoDepartment of Radiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of ChinaTel +86 771 533 4950Email 42442427@qq.comPurpose: We aimed to construct of a nomogram to predict progression-free survival (PFS) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) with risk stratification using computed tomography (CT) radiomics features and clinical factors.Patients and Methods: A total of 311 patients diagnosed with LA-NPC (stage III–IVa) at our hospital between 2010 and 2014 were included. The region of interest (ROI) of the primary nasopharyngeal mass was manually outlined. Independent sample t-test and LASSO-logistic regression were used for selecting the most predictive radiomics features of PFS, and to generate a radiomics signature. A nomogram was built with clinical factors and radiomics features, and the risk stratification model was tested accordingly.Results: In total, 20 radiomics features most associated with prognosis were selected. The radiomics nomogram, which integrated the radiomics signature and significant clinical factors, showed excellent performance in predicting PFS, with C-index of 0.873 (95% CI: 0.803∼ 0.943), which was better than that of the clinical nomogram (C-index, 0.729, 95% CI: 0.620∼ 0.838) as well as of the TNM staging system (C-index, 0.689, 95% CI: 0.592– 0.787) in validation cohort. The calibration curves and the decision curve analysis (DCA) plot obtained suggested satisfying accuracy and clinical utility of the model. The risk stratification tool was able to predict differences in prognosis of patients in different risk categories (p< 0.001).Conclusion: CT-based radiomics features, an in particular, radiomics nomograms, have the potential to become an accurate and reliable tool for assisting with prognosis prediction of LA-NPC.Keywords: computed tomography, locoregionally advanced nasopharyngeal carcinoma, radiomics, nomogram

Background Epidermal growth factor receptor (EGFR) overexpression is characteristic in head and neck cancers and is associated with tumour regrowth following photodynamic therapy (PDT). Purpose We investigated vandetanib, which selectively blocks EGFR and vascular endothelial growth factor receptor-2 (VEGFR-2), to enhance the efficacy of PDT. Methods We assessed the in vitro therapeutic efficacy of: 1) vandetanib; 2) PDT with the photosensitizer Chlorin e6 (Fotolon®); and 3) combined PDT + vadetanib treatment in CAL-27 oral squamous cell carcinoma (OSCC) cell line by cell viability, γH2AX foci immunostaining, cell cycle arrest and western blot. We also performed in vivo tumour regression study and immunohistochemical staining of formalin-fixed paraffin-embedded (FFPE) regressed and regrown tumour tissues. Results First, we observed significantly higher cytotoxicity and residual DNA damage in vandetanib + PDT-treated CAL-27 OSCC cells than tumour cells treated with PDT alone. This is due to impaired DNA DSB repair caused by downregulation of EGFR-mediated DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activation. Next, combined vandetanib and PDT resulted in significant tumour growth delay in vivo that is linked to reduction of PDT-induced EGFR phosphorylation and cellular proliferation, along with loss of tumour vasculature. In particular, we observed significant revascularisation of the microenvironment that is associated with upregulated ERK1/2 phosphorylation in regrown tumours post-vandetanib + PDT, thereby corroborating the importance of microenvironmental modification for the observed drug-PDT synergistic interaction. Conclusion Taken together, our data suggests that vandetanib enhances the efficacy of PDT through both direct and indirect effects on the cellular DNA repair machinery and tumour microenvironment, respectively.

Fang Su*, Kaihua Chen*, Zhongguo Liang, Song Qu, Ling Li, Long Chen, Yunli Yang, Chunhua Wu, Xia Liang, Xiaodong ZhuDepartment of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workObjective: Even in early-stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult tumor location. To compare the safety and efficacy of different fractions on the survival of patients with tumors smaller than 10 cm in size, hepatocellular carcinoma (HCC) patients ineligible for curative therapies were treated with three-dimensional conformal radiotherapy (3DCRT).Methods: A total of 198 HCC patients who had tumors smaller than 10 cm and were not eligible for surgical resection or local ablation therapy received 3DCRT. Participants were separated into two groups. The treatment for Group A (n=111) was a median total dose of 53Gy with a fraction of 2.5–4.9Gy given three times a week, while treatment for Group B (n=87) was a median total dose of 52Gy with a fraction of 5.0–7.0 Gy given three times a week. Propensity score matching (PSM) was conducted, and after the PSM, 81 pairs of patients arose. The Kaplan–Meier method was adopted to analyze overall survival; multivariate analysis was applied to identify the prognostic factors of survival.Results: The median follow-up time was 19.7months (ranging from 1 to 186months). The median survival for Group A patients versus Group B patients was 14.4 versus 24.8months (P=0.003), respectively. The overall survival rates at 1, 3, and 5years were 57.7%, 30.6%, and 18.9% for Group A patients and 73.6%, 43.7%, and 33.3% for Group B patients, respectively (P=0.009). In addition, the results in the PSM model appeared to be similar between the two groups. After PSM, the association between four independent prognostic factors and worse overall survival was discovered as follows: tumor size (>5 cm), Child–Pugh class B, portal vein tumor thrombosis, and fraction of 2.5−4.9Gy/fx. The two groups also shared similar toxicities.Conclusions: Higher fraction dose radiotherapy delivered by 3DCRT was effective, as it offered a survival benefit without aggravating the toxicities in patients with small- to medium-sized HCC tumors who were ineligible for curative therapies.Keywords: three-dimensional conformal radiotherapy, higher fraction dose, hepatocellular carcinoma, curative therapy, survival

Purpose: To investigate N-staging Assessment of pretreatment Shear wave elastrography (SWE) in small cervical lymph nodes (0. 5 cm ≤ maximum diameter < 1 cm, intact capsule, no central necrosis, sCLNs) in nasopharyngeal carcinoma (NPC) patients.Methods: Pathological biopsy proven 28 NPC patients with sCLNs shown in pretreatment magnetic resonance (MR) images and 40 target lymph nodes were enrolled. All target lymph nodes were divided into metastasis and benign lymph node groups according to pathology. SWE was used to exam the real time SWE imaging of each target lymph nodes before conducting ultrasonography guided fine needle biopsy. The minimum (Emin), maximum (Emax), and mean (Emean) elasticity indices (kPa) of target lymph nodes were recorded. The SWE examination was repeated three times for the same target lymph node and each elasticity indices for statistic was determined by average of three measurements. SPSS 21.0 statistics software is used for statistical analysis. The receiver operating characteristic (ROC) curve was performed to obtain the cutoff value of elasticity indices of metastatic sCLNs. Statistical significance was assumed when the P < 0.05.Results: Nine lymph nodes were metastatic and 31 were benign. The Emin, Emax, and Emean of benign group were 8.15 ± 6.12, 25.05 ± 12.37, and 16.05 ± 8.29 kPa, respectively; Emin, Emax, and Emean of metastasis group were 11.5 ± 6.17, 41.38 ± 17.87, and 23.48 ± 6.50 kPa, respectively. The difference of the Emax and Emean between metastasis and benign group were statistically significant (P = 0.003 and 0.018). The area under the ROC curve of Emin, Emax, and Emean of metastasis lymph node were 0.685 (P = 0.095), 0.785 (P = 0.010), and 0.765 (P = 0.017), respectively. Emax of 27 kPa and Emean of 17 kPa were taken as the cutoff value of diagnosis for metastasis sCLNs: the sensitivity, specificity, and accuracy were 77.8 and 100%, 71.0 and 61.3%, 75.0 and 70.0%, respectively.Conclusions: Pretreatment SWE has high accuracy in evaluating the sCLNs in NPC patients and is helpful for accurate N-staging and survival prognosis. It can be used as a clinical supplementary examination.

Serum microRNAs (miRNAs) have been reported as novel biomarkers for various diseases. But circulating biomarkers for predicting the radiosensitivity of nasopharyngeal carcinoma (NPC) have not been used in clinical practice. To screen out of differently expressed serum miRNAs from NPC patients with different radiosensitivity may be helpful for its individual therapy. NPC patients with different radiosensitivity were enrolled according to the inclusion and exclusion criteria. RNA was isolated from serum of these NPC patients before treatment. We investigated the differential miRNA expression profiles using microarray test (GSE139164), and the candidate miRNAs were validated by reverse transcription-quantitative real time polymerase chain reaction (RT-qPCR) experiments. Receiver operating characteristic (ROC) analysis has been applied to estimate the diagnostic value. In this study, 37 serum-specific miRNAs were screened out from 12 NPC patients with different radiosensitivity by microarray test. Furthermore, RT-qPCR analysis confirmed that hsa-miR-1281 and hsa-miR-6732-3p were significantly downregulated in the serum of radioresistant NPC patients (P

Zhong-Guo Liang,* Guo-Xiang Lin,* Bin-Bin Yu,* Fang Su, Ling Li, Song Qu, Xiao-Dong Zhu Department of Radiation Oncology, The Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China *These authors contributed equally to this work Purpose: The present study aimed to study the role of autophagy in the radiosensitivity of the radioresistant human nasopharyngeal carcinoma cell line CNE-2R.Methods: Before being irradiated, CNE-2R cells were treated with the autophagy inhibitor chloroquine diphosphate (CDP) or the autophagy inducer rapamycin (RAPA). Microtubule-associated protein light chain 3 (LC3-II) and p62 were assessed using Western blotting analysis 48 hours after CNE-2R cells were irradiated. The percentage of apoptotic cells was assessed via flow cytometry. CNE-2R cell viability was evaluated using the Cell Counting Kit-8 (CCK8). The radiosensitivity of cells was assessed via clone formation analysis.Results: The level of autophagy in CNE-2R cells improved as the radiation dose increased, reaching the maximum at a dose of 10 Gy. Autophagy was most significantly inhibited by 60 µmol/L CDP in CNE-2R cells, but was obviously enhanced by 100 nmol/L RAPA. Compared with the irradiation (IR) alone group, in the IR + CDP group, autophagy was significantly inhibited, viability was low, the rate of radiation-induced apoptosis was increased, and radiosensitivity was upregulated. In contrast, cells of the IR + RAPA group exhibited greater autophagy, higher viability, a lower rate of radiation-induced apoptosis, and downregulated radiosensitivity.Conclusion: The autophagy level is negatively correlated with radiosensitivity for the radioresistant human nasopharyngeal carcinoma cell line CNE-2R. Keywords: nasopharyngeal carcinoma, autophagy, radiosensitivity

Objective This study aimed to evaluate the safety and efficacy of three‐dimensional conformal radiotherapy (3D‐CRT) and hepatic resection for patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT). Methods We retrospectively analyzed 323 HCC patients involving PVTT. Among them, 134 patients underwent 3D‐CRT, while 189 controls treated with hepatic resection (HR). Survival rate and prognostic analysis were performed using Kaplan‐Meier method and Cox regression analyses. Results The 1‐, 2‐, and 3‐year overall survival (OS) of RT group and HR group was 54% vs 62%, 33% vs 47%, and 18% vs 43%, respectively (P = 0.003). In the subgroup of PVTT type analysis, the 1‐, 2‐, and 3‐year OS in RT group was 65%, 39%, and 19%, respectively, while that in HR group was 83%, 53%, and 42%, respectively, in type I PVTT (P

Background Previously, 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 methods In 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. Results A 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. Conclusion These findings suggest that silencing of c-jun in CNE-2R cells reduces cells migration, invasion, and EMT both in vitro and in vivo.

Background We undertook a meta-analysis to evaluate the clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for the detection of distant metastases in patients with non-small cell lung cancer (NSCLC) at initial staging. Materials and methods All topic-related studies were comprehensively searched in the MEDLINE and Embase databases. We obtained the summary estimates and constructed the summary receiver operating characteristic curve for 18F-FDG PET/CT using the bivariate regression model. Results Across 10 studies (1333 patients), the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for 18F-FDG PET/CT were 0.81 (95% confidence interval [CI] = 0.63-0.92), 0.96 (95% CI = 0.94-0.98), 22.9 (95% CI = 13.3-39.5), and 0.20 (95% CI = 0.09-0.42), respectively. Overall weighted area under the curve was 0.97 (95% CI = 0.96-0.98). Conclusion 18F-FDG PET/CT has a good diagnostic performance for distant metastasis staging in patients with NSCLC at initial staging.

BACKGROUND The purpose of this study was to determine whether cofilin-2 could serve as a protein marker for predicting radiotherapy response and as a potential therapeutic target in nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS Cofilin-2 protein levels in serum and tissue samples from patients with NPC were assessed by sandwich ELISA and IHC. In vitro, cofilin-2 levels in CNE-2R cells were significantly higher than those of CNE-2 cells. Meanwhile, CNE-2R cells were silenced for cofilin-2 to obtain a stable cofilin-2-RNAi-LV3 cell line. Then, cell proliferation, radiosensitivity, invasion and migration abilities, cell cycle, and apoptosis were evaluated by Cell Counting Kit 8 assay (CCK-8), flow cytometry (FCM), clone formation assay, and in vitro. RESULTS The secreted levels of the cofilin-2 protein in radioresistant NPC patients were significantly higher than those of radiosensitive cases. After cofilin-2 knockdown in nasopharyngeal carcinoma CNE-2R cells, proliferation was decreased, while apoptosis and radiosensitivity were enhanced; cell cycle distribution was altered, and the transplanted tumors in nude mice grew significantly less. CONCLUSIONS Overall, our findings suggest that cofilin-2 acts as a marker for predicting radiotherapy response and is a potential therapeutic target in nasopharyngeal carcinoma.

We compared treatment outcomes in patients with stage II nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT). Stage II (2010 UICC/AJCC staging system) NPC patients treated with IMRT (n = 178) or 2D-CRT (n = 73) between January 2007 and December 2014 were retrospectively analyzed. Patients were matched using the propensity score-matching method. The primary endpoint was overall survival (OS). Secondary endpoints were local relapse-free survival (LRFS), regional relapse-free survival (RRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS). Acute and late toxicity reactions to IMRT and 2D-CRT were also compared. In an unmatched cohort of 251 patients, no significant survival differences were found between those receiving IMRT and those receiving 2D-CRT (5-year OS, 95.67% vs 94.44%, P = 0.0556; LRFS, 97.34% vs 98.59%, P = 0.6656; RRFS, 99.26% vs 100%, P = 0.6785; DMFS, 96.5% vs 98.63%, P = 0.7910; DFS, 92.2% vs 97.24%, P = 0.8719). In the propensity-matched cohort of 146 patients, 5-year OS (97.06% vs 94.44%, P = 0.1325), LRFS (96.75% vs 98.59%, P = 0.8869), RRFS (100% vs 100%, P = 1.0000), DMFS (98.63% vs 98.63%, P = 0.4225), and DFS (95.37% vs 97.24%, P = 0.5634) were similar between patients treated with IMRT or 2D-CRT. However, IMRT correlated with fewer acute and late toxicity reactions. Thus although IMRT provides no survival advantage, it has a lower incidence of toxicity than 2D-CRT in stage II NPC patients.

The present study aimed to identify whether CD166 can be used as a biomarker for predicting the response of nasopharyngeal carcinoma (NPC) to radiotherapy. The serum concentration of CD166 in patients with NPC were detected by enzyme-linked immunosorbent assay. The secreted level of CD166 with radioresistant NPC was significantly higher than that with radiosensitive NPC. In vitro, the CD166 positive rate in the CNE2 cell membrane was significantly lower than that in the CNE2R cell membrane. The magnetic-activated cell sorting technology was used to obtain CNE-2R-CD166(+) and CNE-2R-CD166(−) cell lines. Then radiosensitivity, cell proliferation, and apoptosis were assessed using colony formation assay, cell counting kit 8 assay (CCK-8), and flow cytometry, respectively. The radiation sensitivity ratio was 1.28, indicating that the CNE2R-CD166(−) cells had a stronger radiation sensitivity. The result of CCK-8 assay indicated that the survival fraction of CNE2R-CD166(+) cells was significantly higher than that of CNE2R-CD166(−) cells. The apoptotic rate of CNE2R-CD166(+) cells was significantly lower than that of CNE2R-CD166(−) cells. Our data demonstrate that the secreted protein CD166 may be can used as a biomarker for predicting the response of NPC to radiotherapy.

// Qiulu Zhong 1 , Xiaodong Zhu 1 , Ling Li 1 , Song Qu 1 , Zhongguo Liang 1 , Fanyan Zeng 1 and Xinbin Pan 1 1 Department of Radiation Oncology, The Affiliated Cancer Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China Correspondence to: Xiaodong Zhu, email: // Keywords : nasopharyngeal carcinoma; intensity-modulated radiotherapy; concurrent chemoradiotherapy; concurrent chemoradiotherapy plus adjuvant chemotherapy Received : August 15, 2016 Accepted : December 07, 2016 Published : January 23, 2017 Abstract Purpose: To evaluate the efficacy of IMRT combined with concurrent chemotherapy followed by adjuvant chemotherapy compared with IMRT combined with concurrent chemotherapy alone in patients with nasopharyngeal carcinoma. Methods: From January 2007 to December 2014, we collected 797 staged II-IVb [UICC = Union for International Cancer Control criteria (7th edition)] NPC patients for analysis. After 1:1 matching ,we selected 261 cases as the CCRT group, another 261 patients as the CCRT+AC group. Using Kaplan-Meier to calculate the overall survival (OS), locoregional failure-free survival(LFFS), distant metastasis failure-free survival(DMFS). The log-rank test and Cox-proportional hazards model to evaluate the prognostic factors. Results: After matching, there were 261 patients in each group. In CCRT+AC group, The 1-,2- and 3- year os rates were a little higher than in CCRT group(99.6% vs 97.9%,97.4% vs 96.2%,93.8% vs 86.9%, P = 0.150). There were no significant difference in 1-,2-,3- year OS, LFFS, DMFS between the two groups. In subgroup analysis, a little higher OS rate in CCRT+AC group for staged III, IV and T4(III:100% vs 100%, 97.6% vs 95.8%, 94.0% vs 84.0%; IV: 99.1% vs 95.4%, 96.3% vs 95.4%, 90.5% vs 79.4%, P = 0.047;T4:99.1% vs 95.2%, 97.1% vs 95.2%, 90.9% vs 78.2%, P = 0.055). No significant difference were observed in OS, LFFS,DMFS between the groups. Conclusion: IMRT combined with concurrent chemotherapy followed by adjuvant chemotherapy might improved 1-,2-,3- year of OS. Whether or not add adjuvant chemotherapy it had similar LFFS rate and DMFS rate in patients with nasopharyngeal carcinoma. Locally advanced NPC patients (III, IV and T4)might benefit from the adjuvant chemotherapy.

Purpose To construct a prognostic index (PI) for overall survival (OS) to stratify nasopharyngeal carcinoma (NPC) into high-risk and low-risk groups. We also applied the model to investigate the role of the addition of adjuvant chemotherapy (AC) to concurrent chemoradiotherapy (CCRT) regimens for the treatment of NPC. Methods A prognostic model was established based on a retrospective study of 362 patients from January 2008 to June 2011. The discriminative and calibration abilities of the model were evaluated by Harrell’s concordance index (C-index), and calibration curves. Bootstrapping was used to perform for internal validation. External validation was conducted using 324 patients diagnosed with NPC from July 2011 to December 2012 at the same institution. Survival analyses were performed between CCRT-AC and CCRT alone groups for the high-risk and low-risk groups. Results The primary PI comprised covariates that were associated with OS in the training cohort, including T stage, N stage, age, and plasma alkaline phosphatase (ALP). Internal and external validation showed that the discrimination of the PI for OS was significantly better than that of the 8th edition AJCC staging system. Discretization by using a fixed PI score cut-off of 407.96 determined from the training data set yielded high- and low-risk subgroups with distinct OS outcomes in the validation cohort. Adjuvant chemotherapy improved OS in high-risk patients (HR 0.620, 95% CI 0.408 to 0.941; P = 0.023) but increased the risk of distant metastasis (HR, 4.222, 95% CI, 0.959 to 18.585; P = 0.038) in low-risk patients. Conclusion The proposed prognostic model achieved good prediction and calibration of OS for patients with NPC. The addition of adjuvant chemotherapy might be a double-edged sword, bringing survival benefit to high-risk patients but greater risk of distant metastasis to low-risk patients.

Xerostomia is a common radiation-induced late complication after radiotherapy. Identifying predictive factors for xerostomia will lead to better treatments and improve the quality of life. This study was conducted to establish an effective predictive nomogram for xerostomia by assessing stage I-IVb (AJCC 7th edition) NPC patients between September 2015 and March 2016. Xerostomia was evaluated via the RTOG/EORTC system. The primary endpoint was grade 2-3 xerostomia 1 year after treatment. The predictive factors for xerostomia were analysed using logistic regression analysis. A nomogram was constructed based on combining the predictors and clinical variables. In total, 102 patients with grade 0-1 xerostomia and 93 patients with grade 2-3 xerostomia were included. The independent predictive factors for xerostomia were V25, V30, V35, and V45 of the ipsilateral parotid gland and mean dose of the contralateral parotid gland. The calibration plot for the probability of xerostomia showed good agreement between prediction by the nomogram and actual observation. The concordance index of the nomogram for predicting xerostomia was 0.796 (95% CI: 0.735-0.857, P

Background: Lactate dehydrogenase (LDH) is a known prognostic biomarker for the endemic variant of nasopharyngeal carcinoma (NPC). Here, we investigate whether serial changes in LDH level between chemotherapy (CT) cycles are associated with tumour response to CT. Methods: Patients with biopsy-proven, recurrent or treatment-naïve metastatic NPC (mNPC) were recruited. All patients had received at least two cycles of platinum-based doublet or triplet CT, with serial assessment of LDH prior to every cycle of chemotherapy (CT1–6). Patients harbouring conditions that affect LDH levels (IU/L) were excluded. Tumour response was assessed after every two cycles of CT by RECIST v1.1. Results: A total of 158 patients were analysed, including 77 with recurrent and 81 with treatment-naïve mNPC. High pre-CT LDH was associated with an inferior overall survival [hazard ratio 1.93 for ⩾240 versus CTn: LDHCTn–1) were associated with tumour response [partial response versus progressive disease: median value across CT1–6 = 168–190 versus 222–398 (absolute); 0.738–0.988 versus 1.039–1.406 (ratio)], albeit LDH ratio had a tighter variance between patients. Finally, we showed that an LDH ratio cut-off of 1.0 at CT1, CT3 and CT5 was predictive of progressive disease at CT2, CT4, CT6 [area under the curve of 0.73 (0.65–0.80)]. Conclusion: Herein, we characterised the longitudinal variation of LDH in response to CT in mNPC. Our findings suggest the potential utility of interval LDH ratio to predict subsequent tumour response to CT.

Background: It is unclear whether Cetuximab (CTX) or Nimotuzumab (NTZ) concurrent with radiotherapy delivers equivalent or improved results with fewer toxicities over standard cisplatin (CDDP) concurrent with radiotherapy in locally advanced nasopharyngeal carcinoma (NPC). Methods: The strategy involved searching the PubMed, Embase, Cochrane Library, China National Knowledge Internet Web, Wanfang and Chinese Biomedical databases. Controlled clinical trials that compared concurrent CTX/NTZ with radiotherapy versus CDDP with radiotherapy in local-regionally advanced NPC were included. Results: In all, 1,239 patients in six clinical trials were included in the analysis. The hazard ratios (HRs) between the CTX/NTZ and CDDP groups were 1.01 (95% confidence interval (CI) 0.63-1.64), 1.06 (95% CI 0.50-2.25), 1.04 (95% CI 0.61-1.76), and 1.05 (95% CI 0.73-1.50) for overall survival, local-regional failure-free survival, distant metastasis failure-free survival, and disease-free survival, respectively. Significant differences were found in the incidences of grade 3-4 anaemia [Risk ratio (RR) 0.11 95% CI 0.02-0.58], grade 3-4 neutropenia (RR 0.23 95% CI 0.12- 0.44), grade 3-4 thrombocytopenia (RR 0.31 95% CI 0.12- 0.79), and grade 3-4 vomiting (RR 0.04 95% CI 0.00-0.29) in favour of the CTX/NTZ group. However, the patients in the CTX/NTZ group experienced a higher incidence of grade 3-4 skin rash (RR 6.45 95% CI 3.84-10.84). Conclusions: Regarding the efficacy and side effects, the combination of CTX / NTZ and radiotherapy may be an alterative treatment regimen of standard CDDP concurrent with radiotherapy in local-regionally advanced NPC, especially in patients who cannot tolerate or who refuse chemotherapy.

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.

Nasopharyngeal carcinoma is an endemic disease within specific regions in the world. Radiotherapy is the main treatment. In recent decades, intensity-modulated radiation therapy has undergone a rapid evolution. Compared with two-dimensional radiotherapy and/or three-dimensional conformal radiotherapy, evidence has shown it may improve quality of life and prognosis for patients with nasopharyngeal carcinoma. In addition, helical tomotherapy is an emerging technology of intensity-modulated radiation therapy. Its superiority in dosimetric and clinical outcomes has been demonstrated when compared to traditional intensity-modulated radiation therapy. However, many challenges need to be overcome for intensity-modulated radiation therapy of nasopharyngeal carcinoma in the future. Issues such as the status of concurrent chemotherapy, updating of target delineation, the role of replanning during IMRT, the causes of the main local failure pattern require settlement. The present study reviews traditional intensity-modulated radiation therapy, helical tomotherapy, and new challenges in the management of nasopharyngeal carcinoma.

Radioresistance is a major cause leads to treatment failure in nasopharyngeal carcinoma (NPC). In our previous study, we identified that QSOX1 is a differentially expressed protein in NPC cell lines with variable radiosensitivities. The present study aimed to investigate the biological behavior of QSOX1 in nasopharyngeal carcinoma (NPC) and its effect on radiosensitivity. The levels of QSOX1 detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in radioresistant NPC patient sera and tissue samples were markedly lower than those in radiosensitive samples. Small hairpin RNAs (shRNAs) were employed to knock down endogenous QSOX1 expression in CNE-2 cells, and then, radiosensitivity, apoptosis, migration and invasion were assessed using colony formation, Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays, respectively. Tumor growth and radioresistance were also evaluated using a xenograft model in nude mice. The shRNA-mediated knockdown of QSOX1 significantly increased cell survival under irradiation (IR) and weakened radiosensitivity, which was likely due to a reduction in the cell apoptosis rate after IR. Moreover, QSOX1 silencing led to the suppression of cellular migration and invasion. Similar results were obtained with the xenograft mouse model. Thus, targeting QSOX1 will provide a new avenue for increasing the sensitivity of NPC to radiotherapy.

Xueling Chen,1 Xiaodong Zhu,1–3 Zhongguo Liang,1 Ling Li,1–3 Song Qu,1–3 Kaihua Chen,1 Xinbin Pan1 1Department of Radiation Oncology, Affiliated Tumor Hospital, Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, 2Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, 3Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China Purpose: Whether neoadjuvant chemotherapy (NCT) followed by concurrent chemoradiotherapy (CCRT) could improve survival in nasopharyngeal carcinoma (NPC) remains controversial especially in the era of intensity-modulated radiation therapy (IMRT), and we explored the role of NCT for NPC patients.Patients and methods: A retrospective review was conducted of 255 NPC patients treated with NCT+CCRT (n=67) or CCRT alone (n=188) based on IMRT between December 2006 and December 2012. To control the imbalance, a 1:2 match was performed using propensity score matching (PSM) method based on patient’s heterogeneity and regimens of concurrent ­chemotherapy (CCT). The long-term treatment outcomes and toxicity between NCT group (n=67) and concurrent chemoradiotherapy (CRT) group (n=134) after PSM were compared.Results: The 5-year overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant failure-free survival (DFFS) were 78.8%, 69.1%, 90.0%, 90.0%, 100% and 78.3% for NCT group, while 79.5%, 75.7%, 92.7%, 94.2%, 96.1% and 82.7% for CRT group (P=0.305, 0.448, 0.790, 0.512, 0.104 and 0.671). It indicated that the treatment method (NCT+CCRT vs CCRT) was not the independent prognostic factor for the survival in NPC patients, and only patients who had completed at least two cycles of CCT got better OS, RFS and DFFS (P=0.009, 0.016 and 0.043), whether to receive NCT or not. No difference in the incidences of any acute and most late toxicity between the two groups was shown.Conclusion: Our study did not show the exact advantage of NCT followed by CCRT compared with CCRT alone or higher incidences of toxicity in NCT group. It suggests that NCT might not be necessary if two or more cycles of CCT are finished well in the era of IMRT, and when NCT is finished well, less than two cycles of CCT with IMRT could be enough. However, in the era of IMRT, the role of NCT still needs to be further explored. Keywords: propensity score matching, PSM, nasopharyngeal carcinoma, concurrent chemotherapy, IMRT

// Xiaoqian Chen 1 , Xianfeng Long 1 , Zhongguo Liang 1 , Hao Lei 2 , Ling Li 1 , Song Qu 1 and Xiaodong Zhu 1 1 Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning 530021, China 2 Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430079, China Correspondence to: Xiaodong Zhu, email: zhuxdonggxmu@126.com Keywords: nasopharyngeal carcinoma, serum albumin, serum ferritin, distant metastasis, intensity-modulated radiotherapy Received: January 21, 2017 Accepted: March 29, 2017 Published: April 25, 2017 ABSTRACT Purpose: To evaluate the potential risk factors for distant metastasis of nasopharyngeal carcinoma in Chinese patients following standard intensity-modulated radiotherapy and chemotherapy. Methods: The potential risk factors for distant metastasis in 622 patients with newly-diagnosed primary nasopharyngeal carcinoma following standard radiotherapy and chemotherapy were evaluated retrospectively by stratification, univariate and multivariate analyses. The 5-year overall survival, distant metastasis-free survival, local recurrence-free survival and progression-free survival rates were determined. Results: Univariate and multivariate analyses indicated that N2-3 stage, serum ferritin > 300 μg/L and serum albumin < 42 g/L were independent risk factors for distant metastasis of nasopharyngeal carcinoma ( P < 0.001, P = 0.013, P = 0.002, respectively). A risk prediction model was developed as follows: 1) low-risk group: 0-1 risk factor; and 2) high-risk group: 2-3 risk factors. Compared with low-risk group, the high-risk group had significantly lower 5-year distant metastasis-free survival (76.4% vs. 89.6%, P < 0.001), overall survival (76% vs. 85.9%, P < 0.001), local recurrence-free survival (88% vs. 92.4%, P = 0.029) and progression-free survival rates (68.2% vs. 83.7%, P < 0.001). In the high-risk group, patients with three risk factors had the lowest distant metastasis-free survival rate ( P = 0.036). Conclusions: Combination of higher N stage, serum ferritin and lower serum albumin levels may be valuable for predicting distant metastasis of nasopharyngeal carcinoma patients following standard intensity-modulated radiotherapy and chemotherapy.

The aim of the present analysis was to compare the efficacy and safety profile of S-1-based chemotherapy (SBCT) versus capecitabine-based chemotherapy (CBCT) for advanced gastric cancer (AGC) and advanced colorectal cancer (ACRC). A meta-analysis was performed, which included eligible randomized controlled trials (RCTs) that were identified using RevMan 5.1.0 software. A total of 1,064 patients from 11 RCTs, comprising of 527 patients in the SBCT group and 537 patients in the CBCT group, were included in the analysis. For AGC, the meta-analysis of overall survival (OS) [hazard ratio (HR), 0.98; 95% confidence interval (CI), 0.85-1.12], time to progression (HR, 0.95; 95% CI, 0.80-1.12) and overall response rate (ORR) [odds ratio (OR), 1.06; 95% CI, 0.72-1.55] of patients in the SBCT group indicated no statistical significance when compared with those in the CBCT group. Furthermore, for ACRC, a pooled analysis demonstrated no significant difference between the SBCT and CBCT groups (OS: HR, 0.82; 95% CI, 0.61-1.10; progression-free survival: HR, 0.79; 95% CI=0.60-1.04; ORR: OR, 1.27; 95% CI, 0.91-1.78). The statistically significant differences identified in the overall meta-analysis indicated a low incidence of grade 3-4 hand-foot-syndrome (OR, 0.15; 95% CI, 0.06-0.36) in the SBCT group; however no statistically significant difference was observed in the incidence of grade 3-4 anemia, thrombocytopenia, leucopenia, neutropenia, diarrhea, stomatitis or nausea/vomiting. The SBCT treatment exhibited similar efficacy and an approximately equivalent safety profile compared with the CBCT treatment and was an alternative to CBCT for patients with AGC or ACRC; however, further investigation is required to provide confirmation.

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 NPC Advances 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.

Purpose: To evaluate the efficacy and toxicity of induction chemotherapy followed by concurrent chemoradiotherapy (the treatment group) versus concurrent chemoradiotherapy with or without adjuvant chemotherapy (the control group) for locoregionally advanced nasopharyngeal carcinoma. Methods: The search strategy included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet Web, Chinese Biomedical Database and Wanfang Database. We also searched reference lists of articles and the volumes of abstracts of scientific meetings. All randomized controlled trials were included for a meta-analysis performed with RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to rate the level of evidence. Results: Eleven studies were included. Risk ratios of 0.99 (95%CI 0.72-1.36), 0.37 (95%CI 0.20-0.69), 1.08 (95%CI 0.84-1.38), 0.98 (95%CI 0.75-1.27) were observed for 3 years overall survival, 3 years progression-free survival, 2 years loco-regional failure-free survival and 2 years distant metastasis failure-free survival. There were no treatment-related deaths in either group in the 11 studies. Risk ratios of 1.90 (95%CI 1.24-2.92), 2.67 (95%CI 0.64-11.1), 1.04 (95%CI 0.79-1.37), 0.98 (95%CI 0.27-3.52) were found for grade 3-4 leukopenia, grade 3-4 thrombocytopenia, grade 3-4 mucous membrane, and grade 3-4 hepatic hematologic and gastrointestinal toxicity, the most significant toxicities for patients. Conclusion: 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.

Whether concurrent chemotherapy treatment is superior to radiotherapy alone as an adjuvant regimen for postoperative cervical carcinoma with risk factors remains controversial.A literature search strategy was used to examine Pubmed, Embase, the Cochrane Library, the China National Knowledge Internet Web, the Chinese Biomedical Database and the Wanfang Database. Article reference lists and scientific meeting abstracts were also screened. Controlled trials comparing concurrent chemoradiotherapy versus radiotherapy alone in postoperative cervical cancer were included. The methodological quality of non-randomized controlled trials was evaluated using the Newcastle-Ottawa Scale. Randomized controlled studies were evaluated with the Cochrane handbook. A meta-analysis was performed with RevMan 5.3.A total of 1,073 patients from 11 clinical trials were analysed, with 582 patients in the concurrent chemoradiotherapy group and 491 patients in the radiotherapy group. Hazard ratios (HR) of 0.47 (95% CI 0.31-0.72) and 0.50 (95% CI 0.35-0.72) were observed for overall survival and progression-free survival, indicating a benefit from the additional use of concurrent chemotherapy. Subgroup analyses demonstrated that cervical cancer with high risk factors significantly benefitted from concurrent chemotherapy when examining overall survival (HR 0.44, 95% CI 0.28-0.67) and progression-free survival (HR 0.48, 95% CI 0.33-0.70), but patients with intermediate risk factors showed no benefit from concurrent chemotherapy in overall survival (HR 1.72, 95% CI 0.28-10.41) and progression-free survival (HR 1.09, 95% CI 0.19-6.14). No significant differences were observed for grade 3-4 anaemia (risk ratio (RR) 3.87, 95% CI 0.69-21.84), grade 3-4 thrombocytopenia (RR 3.04, 95% CI 0.88- 10.58), grade 3-4 vomiting or nausea (RR 1.71, 95% CI 0.27-10.96), or grade 3-4 diarrhoea (RR 1.40, 95% CI 0.69-2.83). Significant differences were observed for grade 3-4 neutropenia in favour of the radiotherapy group (RR 7.23, 95% CI 3.94-13.26).Concurrent chemoradiotherapy improves survival in postoperative cervical cancer cases with high risk factors but not in those with intermediate risk factors.

To date, there are no serum biomarkers available for the prediction of recurrent nasopharyngeal carcinoma (rNPC). The diagnosis of rNPC mostly depends on imaging and biopsy of diseased tissue; however, both of these methods work mostly if the target tumor is at an advanced stage. Therefore, the identificaqtion of recurrent biomarkers is urgently required. In the present study, we used tandem mass tag (TMT) labeling and high performance liquid chromatography (HPLC) fractionation followed by liquid chromatography-tandem mass spectrometry (LC‑MS/MS) to identify differentially expressed proteins. Serum was collected from 40 patients with NPC [recurrence (n=20) and no recurrence (n=20)]. Compared to non‑recurrent NPC (nrNPC), we found 59 proteins to be significantly dysregulated in rNPC; most of these have been previously reported to play a role in carcinogenesis. The dysregulation of calmodulin (CALM) was confirmed in 74 new patients [recurrence (n=32) and no recurrence (n=42)] by ELISA. Moreover, we performed a preliminary pathway analysis which revealed that oxidative phosphorylation was altered in the patients with rNPC compared to those with nrNPC. Taken together, these data identify a potential diagnostic biomarker for rNPC and elucidate the potential molecular mechanisms that are dysregulated and contribute to the pathogenesis of rNPC.

// Kai-Hua Chen 1 , Xiao-Dong Zhu 1,2,3 , Ling Li 1,2,3 , Song Qu 1,2,3 , Zhen-Qiang Liang 1 , Xia Liang 1 , Xin-Bin Pan 1 , Zhong-Guo Liang 1 and Yan-Ming Jiang 1 1 Department of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China 2 Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China 3 Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University, Nanning, Guangxi, China Correspondence to: Xiao-Dong Zhu, email: // Keywords : nasopharyngeal neoplasm, stage II, concurrent chemoradiotherapy, adjuvant chemotherapy, intensity-modulated radiotherapy, prognosis Received : May 11, 2016 Accepted : August 11, 2016 Published : September 12, 2016 Abstract Objective: This study aimed to explore whether concurrent chemoradiotherapy (CCRT) with or without Adjuvant Chemotherapy (AC) could improved the survival in stage II nasopharyngeal carcinoma (NPC). Methods: Patients 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. Results: The 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. Conclusion: CCRT 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.