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Background: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Purpose: 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. [ABSTRACT FROM AUTHOR]

Background: To evaluate the clinical significance of tumor response to induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients and further to develop a nomogram for predicting survival prognosis. Methods: A total of 498 patients with stage III‐IVA NPC applying IC and concurrent chemotherapy were reviewed (training cohort, n = 376; validation cohort, n = 122). Results: Tumor response was an independent predictor for clinical outcomes. The nomogram included age, N stage, pretreatment Epstein–Barr virus DNA, lymphocyte‐to‐monocyte ratio, and tumor response achieved an ideal C‐index of 0.703 (95% CI 0.655–0.751) in the validation cohort for predicting overall survival (OS), which outperformed than that of the TNM system alone (C‐index, 0.670, 95% CI: 0.622–0.718). In addition, the nomogram could successfully classified patients into different risk groups. Conclusions: We established and validated a precise and convenient nomogram based on tumor response for predicting the OS of LANPC patients. [ABSTRACT FROM AUTHOR]

Background: The prognostic significance of wait time between definite diagnosis and initial radical radiotherapy is not well established in patients with locoregionally advanced nasopharyngeal carcinoma (LA‐NPC) receiving both induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT). Methods: From 2010 to 2018, 648 patients with LA‐NPC treated with IC followed by CCRT were included. Results: A total of 172 pairs of patients with LA‐NPC were selected by propensity score matching (PSM). Compared to patients with an acceptable wait time (≤75 days), patients with a prolonged wait time (>75 days) had a significant lower 5‐year DMFS rate (86.6% vs. 74.1%, p = 0.006). Subgroup analyses indicated that the unfavorable effects of longer waiting times were mainly seen among stage IVa patients. Conclusions: A prolonged wait time (>75 days) between definite diagnosis and initial radical radiotherapy has negative prognostic effects on patients with LA‐NPC receiving IC plus CCRT, particularly those with IVa stage. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) versus CCRT combined with adjuvant chemotherapy (AC) in patients with stage II–IVA nasopharyngeal carcinoma (NPC), we conducted a retrospective study and a meta-analysis combining the results of our studies. Patients and Methods: We used the propensity score matching (PSM) to balance variables. A total of 168 patients were chosen by one-to-two PSM, including 101 patients with IC + CCRT and 67 cases with CCRT + AC. We used the Kaplan–Meier curve to compare survival outcomes and also used Cox regression analysis to determine independent prognostic factors. For meta-analysis, we determined the related studies by searching the PubMed database. We used STATA v12 software to perform meta-analysis of the extracted data and calculate pooled hazard ratios, 95% confidence intervals of survival outcomes, and risk ratios for the toxicities. Results: In this retrospective study, there was no significant difference in 5-year overall survival (76.9% vs. 79.0%, P = 0.966), progression-free survival (71.3% vs. 68.5%, P = 0.332), distant metastasis-free survival (80.5% vs. 74.2%, P = 0.140), and locoregional relapse-free survival (91.5% vs. 91.8%, P = 0.894) among patients with NPC with IC + CCRT versus CCRT + AC after PSM. For meta-analysis, six articles (including our study) reporting 1,052 cases of IC + CCRT and 883 cases of CCRT + AC were included in the meta-analysis. There was no difference of OS (pooled HR = 0.90, 95% CI: 0.63–1.29, P = 0.561), PFS (pooled HR = 1.07, 95% CI: 0.87–1.33, P = 0.633), DMFS (pooled HR= 0.98, 95% CI: 0.76-1.25, P =0.861), and LRRFS (pooled HR = 1.06, 95% CI: 0.76–1.48, P = 0.724). Conclusion: The efficacy of IC + CCRT and CCRT + AC was comparable in patients with stage II–IVA NPC. In terms of compliance and acute adverse reactions, IC + CCRT may be a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

Objective: The 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. Methods: Between 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. Results: When 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. Conclusion: The 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. [ABSTRACT FROM AUTHOR]

Purpose: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To establish and validate an effective nomogram to predict clinical outcomes for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Materials and Methods: The clinicopathological parameters and follow-up information of 402 locoregionally advanced NPC patients (training cohort, n = 302; validation cohort, n = 100) were retrospectively enrolled. The nomogram was built with the important prognostic variables identified by Cox regression analysis. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. The predictive power and clinical utility of the nomogram were assessed using the Harrell concordance index (C-index), calibration curve, and decision curve analysis. We compared the eighth staging system model with the nomogram to analyze whether the model could improve the accuracy of prognosis Results: Epstein–Barr virus (EBV) DNA load, the gross tumor volume (GTVnx), and cervical lymph node tumor volume (GTVnd) after induction chemotherapy were the independent predictors of OS and PFS. The calibration curves indicated superb agreement between the nomogram-predicted probabilities and observed actual probabilities of survival. The C-index and area under the receiver operator characteristic curve (AUC) of the nomogram integrating these significant factors and N stage, and TNM stage were higher than those of the eighth TNM system alone. In addition, the decision curve analyses demonstrated the clinical value and higher overall net benefit of the nomogram. High-risk groups identified by the nomogram had significantly poorer OS and PFS than the low-risk group (p < 0.05). Conclusions: The multidimensional nomogram incorporating TNM stage, EBV DNA load, and tumor volume after induction chemotherapy led to a more precise prognostic prediction and could be helpful for stratifying risk and guiding treatment decisions in locoregionally advanced NPC patients who have undergone induction chemotherapy and concurrent chemoradiation. [ABSTRACT FROM AUTHOR]

• Vandetanib enhanced PDT-mediated cytotoxicity through the impairment of NHEJ repair of DNA double strand breaks. • Vandetanib inhibits PDT-induced EGFR-mediated DNA-PKcs activation. • Vandetanib + PDT modulates tumour microenvironment through vasculature shutdown, coupled with inhibition of EGFR signalling. • MAPK-ERK1/2 pathway is a potential target to overcome the eventual tumour regrowth post-vandetanib + PDT treatment in HNSCC. Epidermal growth factor receptor (EGFR) overexpression is characteristic in head and neck cancers and is associated with tumour regrowth following photodynamic therapy (PDT). We investigated vandetanib, which selectively blocks EGFR and vascular endothelial growth factor receptor-2 (VEGFR-2), to enhance the efficacy of PDT. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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 < 0.001). The 1‐, 2‐, and 3‐year OS in RT group was 52%, 35%, and 11%, while that in HR group was 55%, 42%, and 25%, respectively, in type II PVTT (P = 0.612). In type III PVTT, the 1‐, 2‐, and 3‐year OS in RT group was 16%, 3%, and 0%, respectively, while that in HR group was 11%, 0%, and 0%, respectively (P = 0.041). Multivariate analysis revealed that tumor size ≥10 cm, Child‐Pugh class B, and type III PVTT are independent predictors of poor prognosis in HCC with PVTT. Conclusion: 3D‐CRT appears to be an effective treatment for patients with HCC involving type II/III PVTT. [ABSTRACT FROM AUTHOR]

Objective The tumor, node, and metastasis staging system of nasopharyngeal carcinoma (NPC) has limitations in predicting prognosis. The aim of this study was to explore the prognostic value of tumor diameter for patients with NPC who were treated with intensity-modulated radiotherapy. Study Design Case series with chart review. Setting Affiliated Cancer Hospital of Guangxi Medical University. Subjects and Methods The cases of 137 NPC patients treated with intensity-modulated radiotherapy were retrospectively reviewed. Tumor diameter was measured on pretreatment magnetic resonance images. Receiver operating characteristic curve was used to find the optimal cutoff value of tumor diameter and to examine the predictive ability of tumor diameter combined with T classification. Results The mean tumor diameter increased with the advancing of T classification. The 5-year cumulative survival rates for patients with a tumor diameter <43 mm vs ≥43 mm were 88.4% vs 61.8% ( P < .001), respectively. In multivariate analysis, tumor diameter was an independent prognostic factor for 5-year cumulative survival. For patients with T3 + T4, the 5-year cumulative survival rate was higher in the group with a tumor diameter <43 mm vs ≥43 mm (86.2% vs 60.2%, P = .022). The area under the receiver operating characteristic curve was 70.3% for tumor diameter combined with T classification, superior to T classification (area under the curve = 66.2%). Conclusion Tumor diameter may be related to the extent of tumor invasion and can provide important information on prognosis. The incorporation of 43 mm as a cutoff value of tumor diameter may help to refine the predictive power of the current staging system for NPC. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare the 2008 Chinese and the 7th edition of the American Joint Committee on Cancer (AJCC) staging systems for nasopharyngeal carcinoma and to provide proposals for updating T and N staging systems of the present staging system. Methods: Between January 2007 and December 2012, a cohort of 752 patients with biopsy-proven, newly diagnosed, non-metastatic nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy were retrospectively analysed. Prognoses were compared by T stage, N stage, and clinical stage according to the two staging systems for overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS). Results: In terms of both the T and N staging systems, the two current staging systems were comparable in predicting OS. The T classification of the 2008 Chinese staging system was better in predicting LRFS, while the N classification of the 7th edition AJCC staging system was superior in predicting DMFS. In the modern era of intensity-modulated radiotherapy, the staging system should be updated by down-staging the current stage T2 to T1, and it might be rational to merge subcategories N1 and N2. Conclusions: The two current staging systems each had advantages in predicting prognosis. It seems reasonable to downstage T2 to T1 and to merge N1 and N2. [ABSTRACT FROM AUTHOR]

Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) and CCRT alone were the optional treatment regimens for T3-4N1M0 nasopharyngeal carcinoma (NPC) patients. Therefore, we established a nomogram to predict clinical prognosis and guide individualized IC in T3-4N1M0 NPC. Overall, 699 T3-4N1M0 NPC patients treated with CCRT with or without IC between January 2010 and December 2018 were examined. Overall survival (OS) was the main endpoint. A nomogram was developed that included prognostic variables selected by multivariable analysis. The risk score, which was calculated according to the nomogram, was used for risk stratification. The survival difference of patients undergoing CCRT with or without IC was then compared in risk-stratified subgroups. The nomogram yielded C-indexes of 0.708 (95% confidence interval [CI]: 0.682-0.734) in the training cohort and 0.670 (95% CI: 0.625-0.715) in the validation cohort. Calibration curves for 1-, 3- and 5-year OS suggested a good association between the nomogram predicted and observed probabilities. High-risk patients stratified by nomogram benefited from IC (IC + CCRT vs CCRT: 5-year OS: 77.8% vs 58.8%; P = 0.040; 5-year disease-free survival: 75.0% vs 58.2%; P = 0.017), whereas in the low-risk group, the application of IC was associated with worse locoregional recurrence-free survival and distant metastasis-free survival. This nomogram can serve as a reliable model for prognostic prediction and can be used to guide individualized treatment of T3-4N1M0 NPC. High-risk patients are candidates for IC before CCRT, while the use of IC for low-risk patients should be considered carefully. [ABSTRACT FROM AUTHOR]

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). 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. 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. Here, we highlighted significant heterogeneity between two publicly available radiomics pipelines that could affect the downstream association with prognostic clinical factors in NPC 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. [ABSTRACT FROM AUTHOR]

The present study aimed to define high-risk patients who may benefit from additional adjuvant chemotherapy (AC) after concurrent chemotherapy in combination with intensity-modulated radiotherapy among patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). A cohort of 511 NPC patients who received concomitant chemoradiotherapy (CCRT) with or without AC between January 2007 and December 2012 were retrospectively analysed. One hundred seventy-seven patients received CCRT alone, whereas 334 received CCRT + AC. The survival analysis showed that ages >45 years old, T3-T4 stages, N2-N3 disease and serum albumin levels ≤42 g/L were significant independent prognostic factors for overall survival (OS). Using these four risk factors, a prognostic model for OS was created as follows: (1) low-risk group: 0-1 risk factors; and (2) high-risk group: 2-4 risk factors. In the CCRT alone and CCRT + AC groups, significant differences in survival were found between the high- and low-risk groups. Patients in the high-risk group exhibited improved OS due to the addition of AC to CCRT, but no survival benefits were found in the low-risk group. In conclusion, high-risk patients may benefit from the addition of AC to CCRT regarding OS. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2020 Guan, Liu, Li, Pan, Liang, Cheng and Zhu.)

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 <0.001), which was higher than any single dosimetric parameter. Our results indicated that the nomogram provided a more accurate prediction of grade 2-3 xerostomia 1 year after treatment.

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., (Creative Commons Attribution License)

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.

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., Competing Interests: CONFLICTS OF INTEREST The authors confirm no conflicts of interest in this work.

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., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

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., Competing Interests: CONFLICTS OF INTEREST The authors disclose no potential conflicts of interest.

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.

Radioresistance is a significant obstacle in the treatment of endemic nasopharyngeal carcinoma (NPC). The present study aimed to identify proteins associated with radioresistance in NPC in vitro and in vivo . Proteomics analyses were conducted to screen for differentially-expressed proteins (DEPs) in parental CNE-2 cells and CNE-2R cells. Using proteomics approaches, 16 DEPs were identified. Of these DEPs, nucleophosmin (NPM1), annexin A3 and nm23-H1, were verified using western blot analyses. The tumorigenicity was investigated using mouse xenograft tumorigenicity assays, and tumor growth curves were generated. The protein expression of NPM1, annexin A3 and nm23-H1 was examined by immunohistochemically staining tumor tissues. NPM1 and annexin A3 protein levels were downregulated in the CNE-2R cells, whereas nm23-H1 expression was upregulated. In vivo tests showed that compared with the CNE-2 tumors, CNE-2R tumor growth was significantly retarded (P<0.05). CNE-2 tumor progression was inhibited by irradiation, but CNE-2R tumor progression was not, indicating that the CNE-2R cells were also radioresistant in vivo . NPM1 and annexin A3 expression was significantly lower in non-irradiated (NIR)-CNE-2R tumors compared with NIR-CNE-2 tumors (P<0.01). However, Nm23-H1 protein levels were significantly higher (P<0.05). Overall, the present study established comparable radioresistant and radiosensitive tumor models of human NPC, and identified candidate biomarkers that may correlate with radioresistance. The data showed that dysregulation of NPM1, annexin A3 and nm23-H1 expression correlated with the cellular and tumor radioresponse. These proteins are involved in the regulation of intracellular functions, including stress responses, cell proliferation and DNA repair. However, further clinical evaluations are required.

Background: Whether concurrent chemotherapy treatment is superior to radiotherapy alone as an adjuvant regimen for postoperative cervical carcinoma with risk factors remains controversial., Materials and Methods: 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., Results: 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)., Conclusions: Concurrent chemoradiotherapy improves survival in postoperative cervical cancer cases with high risk factors but not in those with intermediate risk factors.

In this study, we evaluate the efficacy of short-course radiotherapy (SCRT) versus long-course radiotherapy (LCRT) in the treatment of metastatic spinal cord compression (MSCC).PubMed, EMBASE, and Web of Science were searched up to April 2015. Relevant data were extracted based on inclusion and exclusion criteria. Methodological quality of randomized controlled trial (RCT) was evaluated using modified Jadad scale; non-RCT was evaluated using Newcastle-Ottawa Scale. Meta-analysis was performed using RevMan 5.3 software.Fourteen studies with 2239 patients were included. Results of meta-analysis showed that there were no significant differences between SCRT and long-course radiotherapy LCRT in 6-month overall survival rate (risk ratio [RR] = 0.97, 95% confidence interval [CI] 0.88, 1.07, P = 0.55), 1-year overall survival rate (RR = 0.94, 95% CI 0.85, 1.04, P = 0.22), motor function improvement (RR = 0.96, 95% CI 0.81, 1.13, P = 0.63), no change on motor function (RR = 0.98, 95% CI (0.88, 1.09), P = 0.74], and deterioration on motor function (RR = 0.96, 95% CI 0.71, 1.31, P = 0.78). Compared with SCRT, LCRT significantly increased 6-month local control rate (RR = 0.87, 95% CI 0.80, 0.95, P = 0.002), 1-year local control rate (RR = 0.83, 95% CI 0.71, 0.97, P = 0.02), and 2-year local control rate (RR = 0.83, 95% CI 0.79, 0.87, P < 0.00001).Both LCRT and SCRT provided similar survival rates and functional outcome, but LCRT showed better local control rates than SCRT. However, considering low cost and good patient's compliance, SCRT may be a better choice.

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.

Incidence rates of nasopharyngeal carcinoma are high in Indonesia, Singapore and South-Eastern China. Chemoradiotherapy has been the standard regimen for locally advanced nasopharyngeal carcinoma according to guidelines from the National Comprehensive Cancer Network. Recently, advances in the management of nasopharyngeal carcinoma have transferred into better treatment outcomes. Most phase III clinical trials support the addition of concurrent chemotherapy to radiotherapy for the initial treatment of these patients. Studies evaluating effects and toxicity of concurrent chemotherapy with different regimens have been reported. However, the status of adding adjuvant chemotherapy or induction chemotherapy remains controversial. Recent studies have shown that adjuvant chemotherapy with two or three cycles may improve survival for nasopharyngeal carcinoma with stage N2-3 disease or with persistently detectable plasma EBV DNA after radiotherapy. This review examines the pertinent issues and latest studies concerning the management of loco-regionally advanced NPC, regarding concurrent chemotherapy, adjuvant chemotherapy, and induction chemotherapy in decades.

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.

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.

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.

Purpose: The main objective of the present study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy followed by adjuvant chemotherapy compared with concurrent chemoradiotherapy alone in the treatment of 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. Randomized controlled trials (RCTs) that compared concurrent chemoradiotherapy followed by adjuvant chemotherapy with concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma were included. Meta-analysis was 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: Five studies were included. Risk ratios of 1.02 (95%CI 0.89-1.15), 0.93 (95%CI 0.72-1.21), 1.07 (95%CI 0.87-1.32), 0.95 (95%CI 0.80-1.13) were observed for 3 years overall survival, 5 years failure-free survival, 5 years loco- regional failure-free survival and 5 years distant metastasis failure-free survival. There were no treatment-related deaths in both groups of five studies. Hematologic and gastrointestinal toxicity were the most significant for patients during adjuvant chemotherapy. The level of evidence was low., Conclusion: Compared with concurrent chemoradiotherapy alone, concurrent chemotherapy followed by adjuvant chemotherapy did not improve prognosis. More toxicity was found during adjuvant chemotherapy.