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This study aims to propose a novel treatment planning methodology for multi-isocenter volumetric modulated arc therapy (VMAT) craniospinal irradiation (CSI) using the special feasibility dose–volume histogram (FDVH)-guided auto-planning (AP) technique. Three different multi-isocenter VMAT -CSI plans were created, including manually based plans (MUPs), conventional AP plans (CAPs) and FDVH-guided AP plans (FAPs). The CAPs and FAPs were specially designed by combining multi-isocenter VMAT and AP techniques in the Pinnacle treatment planning system. Specially, the personalized optimization parameters for FAPs were generated using the FDVH function implemented in PlanIQ software, which provides the ideal organs at risk (OARs) sparing for the specific anatomical geometry based on the valuable assumption of the dose fall-off. Compared to MUPs, CAPs and FAPs significantly reduced the dose for most of the OARs. FAPs achieved the best homogeneity index (0.092 ± 0.013) and conformity index (0.980 ± 0.011), while CAPs were slightly inferior to the FAPs but superior to the MUPs. As opposed to MUPs, FAPs delivered a lower dose to OARs, whereas the difference between FAPs and CAPs was not statistically significant except for the optic chiasm and inner ear_L. The two AP approaches had similar MUs, which were significantly lower than the MUPs. The planning time of FAPs (145.00 ± 10.25 min) was slightly lower than that of CAPs (149.83 ± 14.37 min) and was substantially lower than that of MUPs (157.92 ± 16.11 min) with P

Nasopharyngeal carcinoma (NPC) is a malignant tumor that is endemic in Southeast Asia, North Africa, and southern China. There is an urgent need for effective early diagnosis and treatment of this disease since NPC is currently often detected at advanced stages.To reveal the underlying metabolic mechanisms and discover potential diagnostic biomarkers of NPC, we employed ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and UHPLC-Q-Exactive Orbitrap MS respectively to analyze 54 serum samples and 54 urine samples from 27 patients with NPC and 27 healthy control individuals.A total of 1230 metabolites were determined in serum samples, and 181 of the 1230 metabolites were significantly changed in NPC patients. The 181 metabolites were enriched in sixteen pathways including biosynthesis of unsaturated fatty acids, cholesterol metabolism and ferroptosis. A total of 2509 metabolites were detected in the urine samples. Among them, 179 metabolites were significantly altered in NPC patients, and these metabolites were enriched in eight pathways including TCA cycle and caffeine metabolism. Seven metabolites including creatinine and paraxanthine were found to be significantly changed in both NPC serum and urine samples. Based on them, further biomarker analysis revealed that the panel of three serum metabolites including octanoylcarnitine, creatinine and decanoyl-l-carnitine displayed a perfect diagnostic performance (AUC = 0.973) to distinguish NPC patients from controls, while the other 3-metabolite biomarker panel consisted of stachydrine, decanoyl-l-carnitine and paraxanthine had an AUC = 0.809 to distinguish NPC and control in urine samples.Altogether, this work highlighted key metabolites and metabolic pathways disturbed in NPC and presented potential biomarkers for effective diagnosis of this disease.

An in-house hybrid deformable image registration (DIR) method, which combines free-form deformation (FFD) and the viscous fluid registration method, is proposed. Its results on the planning computed tomography (CT) and the day 1 treatment cone-beam CT (CBCT) image from 68 head and neck cancer patients are compared with the results of NiftyReg, which uses B-spline FFD alone. Several similarity metrics, the target registration error (TRE) of annotated points, as well as the Dice similarity coefficient (DSC) and Hausdorff distance (HD) of the propagated organs at risk are employed to analyze their registration accuracy. According to quantitative analysis on mutual information, normalized cross-correlation, and the absolute pixel value differences, the results of the proposed DIR are more similar to the CBCT images than the NiftyReg results. Smaller TRE of the annotated points is observed in the proposed method, and the overall mean TRE for the proposed method and NiftyReg was 2.34 and 2.98 mm, respectively (p 0.001). The mean DSC in the larynx, spinal cord, oral cavity, mandible, and parotid given by the proposed method ranged from 0.78 to 0.91, significantly higher than the NiftyReg results (ranging from 0.77 to 0.90), and the HD was significantly lower compared to NiftyReg. Furthermore, the proposed method did not suffer from unrealistic deformations as the NiftyReg did in the visual evaluation. Meanwhile, the execution time of the proposed method was much higher than NiftyReg (96.98 ± 11.88 s vs. 4.60 ± 0.49 s). In conclusion, the in-house hybrid method gave better accuracy and more stable performance than NiftyReg.

This study aimed to construct a signature of N

ImportanceInduction or adjuvant chemotherapy with concurrent chemoradiotherapy (CCRT) are first-line treatment options for treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Adjuvant platinum regimens are, however, poorly tolerated, highlighting the unmet need for an efficacious, tolerable adjuvant regimen.ObjectiveTo investigate the efficacy and safety of adjuvant capecitabine with CCRT for the treatment of patients with LA-NPC.Design, Setting, and ParticipantsThis open-label randomized clinical trial recruited patients from March 31, 2014, to July 27, 2018, at 3 institutions in China, with at least 3 years of follow-up. The data collection cutoff date was February 9, 2022. Eligibility included stage III-IVb nasopharyngeal carcinoma and at least 1 of the following: T3-4N2 or T1-4N3; plasma Epstein-Barr virus DNA titer higher than 20 000 copies/mL; primary gross tumor volume larger than 30.0 cm3; fluorodeoxyglucose F 18 positron emission tomography/computed tomography maximum standard uptake value of the primary gross tumor volume larger than 10.0; or multiple nodal metastases and any larger than 4.0 cm.InterventionsPatients were randomly assigned 1:1 to receive either capecitabine (1000 mg/m2 twice daily for 14 days every 3 weeks for 8 cycles) or observation following CCRT (100 mg/m2 cisplatin every 3 weeks for 2 to 3 cycles, depending on duration of radiotherapy).Main Outcomes and MeasuresFailure-free survival in the intention-to-treat cohort was assessed using Kaplan-Meier survival curves compared with the log-rank test. Unstratified Cox proportional hazards regression models were used to estimate hazard ratios, with corresponding 95% CIs based on the Wald test.ResultsThere were 180 patients enrolled (median [IQR] age, 47 [40-55] years; 143 [79.4%] men). Among 90 patients in the capecitabine group, 76 (84.4%) had at least 2 high-risk factors; among 90 patients in the control group, 80 (88.9%) had at least 2 high-risk factors. All patients completed CCRT, except 1 patient in the capecitabine group who received 1 cycle of cisplatin. Of the 90 patients in the capecitabine group, 85 (94.4%) received capecitabine, with 71 (78.9%) completing 8 cycles. With a median (IQR) follow-up of 58.0 (49.5-80.1) months, 18 events were recorded in the capecitabine group vs 31 events in the control group. Failure-free survival was improved with adjuvant capecitabine (3 years, 83.3% vs 72.2%; 5 years, 78.5% vs 65.9%; hazard ratio, 0.53 [95% CI, 0.30-0.94]; P = .03). The incidence of grade 3 treatment-related adverse events (TRAEs) was higher in the capecitabine group than in the control group (54 of 90 patients [60.0%] vs 46 of 90 patients [51.1%]). Treatment-related adverse events included xerostomia (17 [18.9%] vs 9 [10.0%] patients), mucositis (21 [23.3%] vs 15 [16.7%] patients), and anorexia (8 [8.9%] vs 4 [4.4%] patients). The incidence of grade 3 delayed treatment-related adverse events was comparable in both groups (9 of 83 [10.8%] vs 7 of 81 [8.6%] patients).Conclusions and RelevanceIn this randomized clinical trial, adjuvant capecitabine at the full dose following CCRT was well tolerated and improved failure-free survival among patients with LA-NPC and high-risk factors. Further investigations assessing optimal dose and duration are warranted.Trial RegistrationClinicalTrials.gov Identifier: NCT02143388

Highlights • Locoregional radiotherapy can prolong OS for patients with de novo metastatic nasopharyngeal carcinoma. • Nasopharyngeal carcinoma patients with oligometastic disease can benefit from locoregional radiotherapy rather than polymetastatic disease., Background To evaluate the value of locoregional radiotherapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (dmNPC) and identify predictive factors for additional LRRT after palliative chemotherapy (PCT). Methods Overall survival (OS) was the primary endpoint. Patients who underwent PCT and LRRT were categorized as the PCT+LRRT group; patients who only received palliative chemotherapy were categorized as the PCT group. Oligometastatic diseases (OMD) was defined as ≤5 metastatic lesions and ≤2 metastatic organs. Results A total of 168 patients were included for this study. The median OS of patients in the PCT+LRRT group was significantly higher than those in the PCT group (57 months vs. 22 months, P

Background The SEC61 translocon gamma subunit (SEC61G) is a component of the SEC61 complex, which import protein into the endoplasmic reticulum. However, the correlation between SEC61G and disease prognosis in head and neck squamous cell carcinoma (HNSCC) remains unclear. Methods SEC61G expression was analyzed using publicly available datasets. The association between SEC61G and disease prognosis was evaluated. SEC61G methylation and copy number variation were investigated and gene set enrichment analysis and gene ontology analyses identified SEC61G‐associated functions. We also investigated the correlation between SEC61G and immune cell infiltration. Finally, immunohistochemistry was used to detect SEC61G expression in oropharyngeal carcinoma. Results SEC61G was overexpressed in pan‐cancers, including HNSCC, and negatively correlated with overall survival (OS) (p, SEC61G expression in oropharyngeal cancer tissues was higher than in normal adjacent tissues. Kaplan–Meier survival analyses showed that patients with high SEC61G expression had a lower overall survival and progression‐free survival than did patients with low SEC61G expression.

Background:Several studies have shown that the hyaluronan-mediated motility receptor (HMMR) is overexpressed in various cancers and could be a potential prognostic factor. However, further research is still required to determine the prognostic value and potential function of HMMR in head and neck squamous cell carcinoma (HNSCC).Materials and Methods:Transcriptomic expression data were collected from the Cancer Genome Atlas database (TCGA) and Gene Expression Omnibus and the differences in HMMR expression between normal and tumor tissues were analyzed. The correlation between the methylation level of HMMR and its mRNA expression was analyzed via cBioPortal. Additionally, the data obtained from TCGA was analyzed with MethSurv to determine the prognostic value of the HMMR methylation levels in HNSCC. Gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to explore the potential biological functions of HMMR.Results:HMMR was highly expressed in HNSCC tumor tissue compared to normal tissue (p< 0.001). Multivariate analysis (MAV) showed that high HMMR mRNA expression was an independent prognostic factor of overall survival (OS) in TCGA (HR = 1.628, 95% CI: 1.169–2.266,p= 0.004) and GSE41613 data (HR = 2.238,p= 0.013). The methylation level of HMMR negatively correlated with the HMMR expression (R= −0.12,p< 0.001), and patients with low HMMR methylation had worse OS than patients with high methylation (p< 0.001). GSEA found that HMMR expression was associated with the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses, whereas ssGSEA showed thatHMMRexpression positively correlated with the infiltration level of Th2 cells. MAV confirmed that high HMMR protein expression was an inferior independent factor for OS (HR = 2.288,p= 0.045) and progression-free survival (HR = 2.247,p= 0.038) in 70 HNSCC.Conclusions:This study demonstrated that the upregulation of HMMR mRNA and protein in HNSCC is a biomarker for poor prognosis. The biological functions of HMMR are potentially related to the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses. These findings help to elucidate the role of HMMR in carcinogenesis and lay a foundation for further study.

BACKGROUND The objective of this study was to evaluate the effect of a probiotic combination on the severity of oral mucositis (OM), which is a common, unpreventable complication induced by radiochemotherapy in patients with nasopharyngeal carcinoma who undergo concurrent radiochemotherapy (CCRT). METHODS Eligible patients (n = 99) with locally advanced nasopharyngeal carcinoma who were undergoing CCRT were randomly assigned (2:1) to receive a probiotic combination or placebo during radiochemotherapy, and the incidence of severe OM (grade 3 or higher) was the primary endpoint. RESULTS Patients taking the probiotic combination showed a significant reduction in the severity of OM. The incidences of grade 0, 1, 2, and 3 OM in the placebo group and the probiotic combination group were 0% and 12.07%, 0% and 55.17%, 54.29% and 17.24%, and 45.71% and 15.52%, respectively. Furthermore, CCRT greatly lowered the number of immune cells, whereas the probiotic combination markedly lowered the reduction rates of CD4+ T cells (76.59% vs 52.85%; P

// Jing Wang 1, 2, * , Chengxian Guo 3, * , Xiaochang Gong 1 , Fan Ao 1 , Yuling Huang 1 , Lihua Huang 4 , Yiqiang Tang 1 , Chunling Jiang 1 , Xiaoxue Xie 5 , Qing Dong 1, 6 , Min Huang 1 and Jingao Li 1 1 Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang 330029, China 2 Department of Intensive Care Unit, Jiangxi Cancer Hospital, Nanchang 330029, China 3 Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha 410013, China 4 Center for Medical Experiments, Third Xiangya Hospital, Central South University, Changsha 410013, China 5 Department of Radiation and Oncology, Hunan Provincial Tumor Hospital and Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, China 6 Department of Graduate Study, Medical School of Nanchang University, Nanchang 330006, China * These authors have contributed equally to this work Correspondence to: Jingao Li, email: lijingao@hotmail.com Keywords: base excision repair (BER) genes, single nucleotide polymorphism (SNP), nasopharyngeal carcinoma (NPC), acute radiation toxicity, short-term efficacy Received: April 07, 2017 Accepted: July 19, 2017 Published: August 10, 2017 ABSTRACT Purpose: To explore whether polymorphisms in base excision repair (BER) pathway genes are predictors of (chemo)radiotherapy outcome in patients with nasopharyngeal carcinoma (NPC). Methods: We genotyped five potentially functional single nucleotide polymorphisms (SNPs) of three genes in the BER pathway in 174 NPC patients who were treated with (chemo)radiotherapy. Sequenom MassArray was used for SNPs analysis. The efficacy at the end of radiotherapy and at 3 months after radiotherapy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Acute radiation toxicity was scored using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) acute radiation morbidity scoring criteria. Logistic regression was employed to assess the multivariate analyses. Results: We found that the wide genotype GG of X-ray repair cross-complementing 1 ( XRCC1 ) rs25489 (GG vs GA: OR=3.833, 95%CI=1.512-9.714, P =0.005; GG vs GA+AA: OR=3.610, 95%CI=1.496-8.713, P =0.004) and the wide genotype CC of 8-oxoguanine DNA glycosylase ( OGG1 ) rs1052133 (CC vs GG: OR=0.263, 95%CI=0.073-0.951, P =0.042; CC vs CG+GG: OR=0.454, 95%CI=0.195-1.053, P =0.066) were positively and negatively associated with primary tumor efficacy at the end of radiotherapy, respectively. By contrast, no association was found between BER gene polymorphisms and the treatment outcomes at 3 months post-treatment or the treatment-related acute toxicities. Conclusions: The SNPs of the BER genes may act as biomarkers for the curative effect of (chemo)radiotherapy. Further study with long-time follow-up and large population is needed for accurate assessment.

// Chengxian Guo 1, * , Yuling Huang 2, * , Jingjing Yu 1, * , Lijuan Liu 3 , Xiaochang Gong 2 , Min Huang 2 , Chunling Jiang 2 , Yulu Liao 2 , Lihua Huang 4 , Guoping Yang 1 , Jingao Li 2 1 Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China 2 Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi 330029, China 3 Department of Pharmacy, Jiangxi Cancer Hospital, Nanchang, Jiangxi 330029, China 4 Center for Medical Experiments, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China * These authors have contributed equally to this work Correspondence to: Jingao Li, email: lijingao@hotmail.com Keywords: nasopharyngeal carcinoma (NPC), cell cycle, NF-κB pathway, single nucleotide polymorphism (SNP), clinical responses Received: December 05, 2016 Accepted: February 06, 2017 Published: March 02, 2017 ABSTRACT Radiotherapy is one of the primary choices for the treatment of nasopharyngeal carcinoma (NPC) and may result in severe radiotoxicities on normal tissues. Single nucleotide polymorphisms (SNPs) in genes of cell cycle and NF-κB pathways have been linked with the prognoses of various cancers. The aim of this study was to explore whether SNPs of genes involved in cell cycle and NF-κB pathways are associated with responses to radiotherapy in NPC patients. We selected 3 SNPs in cell cycle pathway and 5 SNPs in NF-κB pathway and genotyped them in 154 NPC patients treated with radiotherapy. Multivariate logistic regression was used to determine the association of these 8 SNPs with the responses to radiotherapy. We observed that cyclin-dependent kinase inhibitor gene CDKN2A rs3088440 was significantly related with a poorer treatment efficacy on the primary tumor and cervical lymph node after radiotherapy, and also with a decreased risk of grade 3–4 acute radiation-induced myelosuppression. In some subgroups, cyclin D1 gene CCND1 rs9344 and inhibitor of κB kinase gene IKBKB rs12676482 were related with the grade 3–4 acute radiation-induced myelosuppression, and CCND1 rs9344 was also associated with grade 3–4 acute radiation-induced oral mucositis. The current results reveal that SNPs in genes of cell cycle pathwayand NF-κB pathway have the potential to predict the clinical responses to radiotherapy for NPC patients.

6005 Background: We conducted a multicenter, randomized controlled phase III clinical trial (NCT02143388) to investigate the efficacy and toxicity of adjuvant capecitabine (AC) in addition to concurrent cisplatin and radiotherapy (CCRT) compared to CCRT alone in high-risk locoregionally advanced nasopharyngeal carcinoma (LANPC) patients. Methods: Eligibility criteria included AJCC/UICC 7th ed TNM stage III-IVb and one of the following features: T3-4N2 or T1-4N3 or pre-treatment plasma EBV DNA concentration of >20,000 copy/ml or gross primary tumor volume (GTVnx) of >30 cm3 or a maximum standard uptake value (SUVmax) of >10.0 by 18FDG PET-CT within the primary tumor or multiple neck node metastases, with any larger than 4 cm. All patients were randomly assigned in a 1:1 ratio to receive CCRT (3-weekly cisplatin at 100 mg/m2 for 2-3 cycles) followed by AC (1000 mg/m2 bi-daily for 14 days every 21-day cycle for 8 cycles), or CCRT alone. The prescribed radiation doses were 68-72 Gy/30-32 fractions to the PTVnx, 60-68 Gy/30-32 fractions to PTVnd, 60-64Gy/30-32 fractions to PTVhigh-risk, 54-58Gy/30-32 fractions to PTVlow-risk. Primary end point was failure-free survival (FFS). Results: Between Mar 2014 to Jul 2018, 180 patients were recruited (90 patients in CCRT+AC arm and 90 in CCRT alone arm). All patients completed RT and ≥2 cycles of concurrent cisplatin in both treatment arms (cumulative dose intensities for cisplatin were 200 mg/m2 in both arms). 85 (94.4%) patients went on to receive AC, with 71 (78.9%) patients completing 8 cycles; 19 (22.4%) patients had dose reduction of AC. With a median follow-up of 44.8 mo, the 3-y FFS was significantly superior in the CCRT+AC arm than the CCRT arm for the intention-to-treat cohort (87.7% vs 73.3%; HR: 0.52 [95% CI: 0.29-0.77], P = 0.037). 3-year overall, distant metastasis-free and locoregional relapse-free survival were 92.6% vs 88.9% (HR [95% CI]: 0.66 [0.28-1.59]), 88.8% vs. 81.1% (HR: 0.67 [0.33-1.33]) and 91.5% vs 80.0% (HR: 0.50 [0.25-1.00]), respectively. Incidences of G3-4 acute toxicities were 57.8% (52 of 90) in CCRT+AC arm and 51.1% (46 of 90) in CCRT alone arm, with a higher incidence of hand foot syndrome (3.5% vs 0%), xerostomia (11.1% vs 3.3%), mucositis (23.3% vs 16.7%), and anemia (5.6% vs 2.2%) in the CCRT+AC arm. G3-4 late toxicities occurred in 13.3% (12 of 90) and 9.0% (8 of 89), respectively. Conclusions: The addition of capecitabine to CCRT conferred a superior disease control than CCRT alone in high-risk LANPC. Survivals in ITT and PP set. Clinical trial information: NCT02143388. [Table: see text]

In this study, we investigated the influence of elevated RAS expression on the growth of meningioma in vivo and in vitro. The IOMM-LEE cells, representing a cell line derived from malignant meningioma, were divided into blank control group (cells without any drug treatment), negative control group (cells treated with an equal volume of normal saline to replace drug), and farnesyl thiosalicylic acid (FTS)-treated group (cells treated with FTS). Methyl-thiazole-tetrazolium bromide (MTT) assay and flow cytometer (with cells after FTS (75 μmol/L) treatment for 48 h) were utilized to determine the proliferation and apoptosis, respectively, of IOMM-LEE cells after RAS inhibition. Western blot analysis was used for semi-quantitative analysis of p-ERK and p-AKT levels. Animal model of human meningioma was established with sub-renal capsule transplantation, and mice were divided into two groups: experimental group (50 mg/kg group, 75 mg/kg group, and 100 mg/kg, hypodermic injection with FTS) and control group. Proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry (IHC). Western blot analysis was used for detecting ERK and AKT signal pathway. The proliferation of IOMM-LEE cells decreased dramatically and apoptosis rate increased significantly in FTS-treated group compared to blank control group and negative control group (all P