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Background Compared to conventional intensity-modulated photon radiation therapy (IMRT), intensity-modulated proton radiation therapy (IMPT) has potential to reduce irradiation-induced late toxicities while maintaining excellent tumor control in patients with nasopharyngeal carcinoma (NPC). However, the relevant cost-effectiveness remains controversial. Methods A Markov decision tree analysis was performed under the assumption that IMPT offered normal tissue complication probability reduction (NTCP reduction) in long-term dysphagia, xerostomia, and hearing loss, compared to IMRT. Base-case evaluation was performed on T2N2M0 NPC of median age (43 years old). A Chinese societal willingness-to-pay threshold (33558 US dollars [$])/quality-adjusted life-year [QALY]) was adopted. Results For patients at median age and having NTCP reduction of 10%, 20%, 30%, 40%, 50%, and 60%, their incremental cost-effectiveness ratios were $102684.0/QALY, $43161.2/QALY, $24134.7/QALY, $13991.6/QALY, $8259.8/QALY, and $4436.1/QALY, respectively; IMPT should provide an NTCP reduction of ≥24% to be considered cost-effective. Conclusions IMPT has potential to be cost-effective for average Chinese NPC patients and should be validated clinically.

Background Microvascular decompression (MVD) has become accepted as an effective therapeutic option for hemifacial spasm (HFS); however, the curative rate of MVD for HFS varies widely (50–98%) in different medical centers. This study could contribute to the improvement of the MVD procedure. Methods We retrospectively analyzed 32 patients in whom initial MVD failed in other hospitals and who underwent a second MVD at our center. The clinical characteristics, operative findings, outcome of the second MVD, and complications were recorded. Results There were 18 women and 14 men (56.3 and 43.7%, respectively). The left-to-right ratio was 19:13. The mean age of the patients was 59.8 years. We found an undiscovered conflict site located in zone 4 in 10 patients and in the root entry zone in 8 patients. The initial MVD failed in nine patients because of ignorance of the arterioles that originate from the anterior inferior cerebellar artery. There were no special findings in four patients. No Teflon felts were found in the whole surgical field in one patient. Conclusion Omission of the offending vessel is the most common cause of an unsuccessful MVD. Intraoperative abnormal muscle response associated with the Z-L response is a good measure to correctly identify the involved arterioles.

Background Whether hepatitis B virus (HBV) infection poses risk to patients with nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era remains unclear. Methods 953 patients with non-metastatic, newly diagnosed NPC who received detection of serologic hepatitis B surface antigen (HBsAg) and treated with IMRT were retrospectively reviewed. 171 patients had HBV infection (HBsAg seropositive). Propensity score matching method (PSM) and stabilized inverse probability of treatment weighting (IPTW) were used to address confounding. The survival rates were evaluated by Kaplan-Meier analysis and the survival curves were compared by Log-rank test. Prognostic factors were explored by multivariate analysis. Results No significant survival differences were observed between HBsAg-negative group and HBsAg-positive group [5-year overall survival (OS), 87.7% vs. 83.9%, P=0.181; locoregional recurrence-free survival (LRFS), 83.5% vs. 78.3%, P=0.109; distant metastasis-free survival (DMFS), 80.2% vs. 77.9%, P=0.446; progression-free survival (PFS), 77.4% vs. 71.4%, P=0.153], consistent with the results of PSM and IPTW analysis. Further analyses revealed that HBV infection was an independent prognostic factor for poor OS [multivariate analysis; hazard ratio (HR), 3.74; 95% confidence interval (CI), 1.45–9.68; P=0.006], LRFS (HR, 2.86; 95% CI, 1.37–5.95); P=0.005] in patients with stage N1, DMFS (HR, 2.65; 95% CI, 1.15–6.09; P=0.022) and PFS (HR, 2.63; 95% CI, 1.34–5.14; P=0.005). Among HBsAg-positive patients, liver protection improved OS (90.3% vs. 77.2%; P=0.022). Conclusions HBV infection is an independent risk factor for patients with stage N1 NPC in the IMRT era. Hepatic protection may benefit the survival of HBsAg-positive patients.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.

Purpose Incidental exposure of heart to ionizing irradiation is associated with an increased risk of ischemic heart disease (IHD) in breast cancer patients after radiotherapy. Intensity-modulated proton radiation therapy (IMPT) offers a promise in limiting the mean heart dose (MHD) in breast irradiation to a negligible level. However, the uncertainty in cost-effectiveness hinders its use. This cost-effectiveness analysis aims to identify patients in appropriate risk groups as targets for IMPT. Methods A Markov decision model was designed to evaluate the cost-effectiveness of IMPT versus intensity-modulated photon-radiation therapy (IMRT) in reducing the irradiation-related IHD risk. Baseline evaluation was performed on 50-year-old women patient without preexisting cardiac risk factor (CRF). Stratified for preexisting cardiac risk and photon MHD, cost-effective scenarios under different proton cost and willingness-to-pay (WTP) were identified for 40-, 50- and 60-year-old patients. Results With baseline set-ups, incremental effectiveness (IE) ranged from 0.025 quality-adjusted life-year (QALY) to 0.135 QALY when photon MHD varied from 3 to 16 Gy; IE increased from 0.043 QALY to 0.964 QALY when preexisting cardiac risk increased from the baseline level to its 10 times. IMPT was not cost-effective to patients without preexisting CRF. At the WTP of China, once proton cost reduced to $20,000, IMPT would be cost-effective to ≤ 50-year-old women patients having preexisting cardiac risk of general-population level. Conclusion Patient’s preexisting cardiac risk level should be a main consideration for the clinical decision of using protons; protons may become cost-effective to general-level patients if a substantial decrease in proton cost occurs in the future.

Ependymoma (EPN) is the third most common brain tumor in children and frequently recurs. Here, we report an integrated longitudinal analysis of epigenetic, genetic and tumorigenic changes in 30 patient-matched repeated relapses obtained from 10 pediatric patients to understand the mechanism of recurrences. Genome-wide DNA methylation analysis revealed stable molecular subtypes and convergent epigenetic reprogramming during serial relapses of the 5 RELA and 5 PFA EPNs that paralleled with elevated patient-derived orthotopic xenograft (PDOX) (13/27) formation in the late relapses. Differentially methylated CpGs (DMCs) preexisted in the primary tumors and persisted in the relapses (driver DMCs) were detected, ranging from 51 hypo-methylated in RELA to 148 hyper-methylated DMCs in PFA tumors; while newly acquired DMCs sustained in all the relapses but was absent in the primary tumors (booster DMCs) ranged from 38- 323 hyper-methylated DMCs in RELA and PFA EPNs, respectively. Integrated analysis of these DMC associated DNA methylation regions (DMRs) and RNAseq in both patient and PDOX tumors identified a small fraction of the differentially expressed genes (4.6±4.4% in RELA and 4.5±1.1% in PFA) as regulated by driver DMRs (e.g., up-regulated CACNA1H, SLC12A7, RARA in RELA and HSPB8, GMPR, ITGB4 in PFA) and booster DMRs (including the sole upregulated PLEKHG1 in RELA and NOTCH, EPHA2, SUFU, FOXJ1 in PFA tumors). Most these genes were novel to EPN relapses. Seven DMCs in RELA and 22 in PFA tumors were also identified as potential relapse predictors. Finally, integrating DNA methylation with histone modification identified LSD1 as a relapse driver gene. Combined treatment of a novel inhibitor SYC-836 with radiation significantly prolonged survival times in two PDOX models of recurrent PFA. This high-resolution epigenetic and genetic roadmap of EPN relapse and our 13 new PDOX models should significantly facilitate biological and preclinical studies of pediatric EPN recurrences.

Purpose: To identify the association between ABO blood type and the survivals in nasopharyngeal carcinoma patients. Patients and methods: We retrospectively analyzed 2439 consecutive non-metastasis nasopharyngeal carcinoma patients between January 2001 and December 2004 at the Sun Yat-sen University Cancer Center. Survival outcomes were compared using Kaplan-Meier method. Univariate and multivariate analysis was performed by Cox regression model. Chi-square test was performed to compare categorical variables. Results: In the whole patients, compared with non-O blood type (A, B, and AB) patients, O blood type patients had significantly lower 5-year distant metastasis-free survival (DMFS) (adjusted hazard ratio (aHR)= 1.268, 95% CI 1.010-1.592, P=0.041). Moreover, we observed in female patients, O blood type patients had significantly lower 5-year overall survival (OS), disease-specific survival (DSS) and DMFS than those with non-O blood type (aHR=1.495, 95% CI 1.032-2.165, P=0.034 for OS; aHR=1.566, 95% CI 1.054-2.328, P=0.026 for DSS; aHR=1.779, 95% CI 1.056-2.998, P=0.030 for DMFS). In male patients, there was no significant difference observed between O blood type patients and non-O blood type patients in any survival endpoints. Conclusion: O blood type was associated with an unfavorable DMFS in female patients with nasopharyngeal carcinoma in epidemic area, which might contribute to unfavorable OS and DSS in female patients, even contribute to a lower DMFS in the whole patients. It might be beneficial to predict metastasis so as to guide the treatment in female patients with nasopharyngeal carcinoma in epidemic area.

To investigate radiation-induced changes of computed tomography (CT) textures in parotid glands (PG) to predict acute xerostomia during radiotherapy (RT) for head and neck cancer (HNC).Daily or fraction kilovoltage CTs acquired using diagnostic CT scanners (eg, in-room CTs) during intensity-modulated RT for 59 HNC patients at 3 institutions were analyzed. The PG contours were generated on selected daily/fraction CTs. A series of histogram-based texture features, including the mean CT number (MCTN) in Hounsfield units, volume, standard deviation, skewness, kurtosis, and entropy for PGs were calculated for each fraction. Correlations between the changes of the texture features, radiation dose, and observed acute xerostomia were analyzed. A classifier model and the incurred CT-based xerostomia score (CTXS) were introduced to predict xerostomia based on combined changes of MCTN and volume of PGs. The t test and Spearman and Pearson correlation tests were used in the analyses.Substantial changes in various CT texture features of PGs were observed during RT delivery. The changes of PG MCTN or volume are not strongly correlated with the observed xerostomia grades if they are considered separately. The CTXS showed a significant correlation to the observed xerostomia grades (r = 0.71, P .00001). The CTXS-based classifier can predict the xerostomia severity with a success rate ranging from 79% to 98%. The xerostomia severity at the end of treatment can be predicted based on the CTXS determined at the fifth week with a precision and sensitivity of 100%.Significant changes in the CT histogram features of the parotid glands were observed during RT of HNC. A practical method of using the changes of MCTN and volume of PGs is proposed to predict radiation-induced acute xerostomia, which may be used to help design adaptive treatment.

Purpose To investigate the impact of field number and beam angle on ERE during IMRT planning with 1.5 T MR-Linac for lung stereotactic body radiotherapy (SBRT). Material and methods IMRT plans for three representative lung cases who treated with 1.5 T MR-Linac were generated using TPS Monaco 5.40.01. In each case, five types of plans were generated: (1) the “original plan” generated using 5-fields and beam angles manually optimized in ipsilateral tumor side, with no transverse magnetic field (TMF); (2) the plans generated by reoptimizing and recalculating the original plan, with a 1.5 T TMF; (3) the plans generated with 5-fields, with beam angles manually optimized in anterior-posterior (AP) direction; (4) the plans generated with equidistant 5-fields; and (5) the plans generated with equidistant 9-fields. These plans were compared using a variety of dose-volume-parameters (DVPs). Results The DVPs under TMF showed the presence of 1.5 T TMF can slightly change for all lung cases studied. When the plans generated with beam angles manually optimized in anterior-posterior direction, results showed that the plans improved conformity and homogeneity for PTV and reduced the dose to tissue surface. Furthermore, the results showed that the equidistant/non-equidistant comparison of the previous target anatomy result in a more favourable dose distribution for the equidistant beam setting. At last, the results showed the dose distributions for PTV with 9 and 5 equidistant beams were not significantly different. Conclusion The plan quality can be significantly changed by the presence of a 1.5 T TMF for lung SBRT with MR-Linac. The selection of optimal fields number and beam angle can substantially reduce or even eliminate these changes, without deteriorating overall plan quality.

Background: Proton beam therapy (PBT) is a new-emerging cancer treatment in China. The treatment costs are high and not yet covered by Chinese public medical insurance. The advanced form of PBT, intensity-modulated proton radiation therapy (IMPT), has been confirmed to reduce normal tissue complication probability (NTCP) compared with conventional intensity-modulated photon-radiation therapy (IMRT) in patients with oropharyngeal cancer (OPC). This study evaluated the cost-effectiveness of IMPT versus IMRT for OPC patients in China, aiming at guiding proper use of PBT. Methods: On the basis of published data, a 7-state Markov model was designed for cost-effectiveness analysis, and an evaluation of average level was performed on a base case of 56-year-old under the hypothesis that IMPT could make a 25% NTCP-reduction concerning to long-term symptomatic dysphagia and xerostomia. Model robustness was examined using probabilistic sensitivity analysis, cohort analysis and tornado diagram. One-way sensitivity analyses were performed to identify cost-effective scenarios. IMPT was considered as cost-effective if the incremental cost-effectiveness ratio (ICER) was below the societal willingness-to-pay (WTP) threshold (3 times the gross domestic product per capita / quality-adjusted life year (QALY)).Results: Compared with IMRT, IMPT could provide an extra 0.724 QALYs at an additional cost of 34,926.6 US dollars ($), and made an ICER of $48,229.8/ QALY for the base case. At current WTP level of China ($30,828/QALY), cost-effective scenarios of IMPT existed in the following independent conditions: ≥ 57.3% NTCP-reduction (IMPT compared with IMRT) in dysphagia and xerostomia; patient age ≤ 38-year-old; or the cost of IMPT ≤ $37,398.1. The estimated cost-effective population that benefit from using PBT to treat OPC increased remarkably in the past 10 years with the economic growth, and reached to 559.7 million (about 40.0% of the China’s total population) in the year 2020. Conclusions: Currently, using PBT to treat OPC could be cost-effective in considerable proportion of China’s population. Considering the economic growth, the gradual increment of medical insurance coverage, as well as the proton treatment cost reduction along with more proton facility opening in the near future, it is estimated that PBT would benefit more Chinese OPC patients with respect to cost-effectiveness.

We have previously shown that sphingosine kinase 2 (SPK2) interacts with Bcl-2 via its BH3 domain, activating autophagy by inducing the dissociation of Beclin-1/Bcl-2 complexes, and that a TAT-SPK2 peptide containing the BH3 domain of SPK2 protects neurons against ischemic injury. The goals of the present study were to establish the functional significance of these findings, by testing whether TAT-SPK2 was effective in a mouse model of ischemic stroke, and to explore potential underlying mechanisms. Mice were administered with TAT-SPK2 by intraperitoneal injection before or after transient middle cerebral artery occlusion (tMCAO). Infarct volume, neurological deficit and brain water content were assessed 24 h after reperfusion. Mitophagy inhibitor Mdivi-1 and BNIP3 siRNAs were used to examine the involvement of BNIP3-dependent mitophagy in the neuroprotection of TAT-SPK2. Mitophagy was quantified by immunoblotting, immunofluorescence and electron microscopy. The interaction between TAT-SPK2 and Bcl-2, Bcl-2 and BNIP3 was detected by co-immunoprecipitation. In the tMCAO model, pre-treatment with TAT-SPK2 significantly reduced infarct volume, improved neurological function and decreased brain edema. Neuroprotection by TAT-SPK2 was still seen when the peptide was administered 3 h after reperfusion. TAT-SPK2 also significantly improved functional recovery and reduced long-term brain atrophy of the ischemic hemisphere 30 days after administration. Our studies further showed that TAT-SPK2 directly binds to Bcl-2 and disrupts Bcl-2/Beclin-1 or Bcl-2/BNIP3 complexes to induce mitophagy. These results suggest that TAT-SPK2 protects neurons against ischemia reperfusion injury by activating BNIP3-mediated mitophagy. Agents exploiting this molecular mechanism are potential candidates for the treatment of ischemic stroke.

Background Proton beam therapy (PBT) is a new-emerging cancer treatment in China but its treatment costs are high and not yet covered by Chinese public medical insurance. The advanced form of PBT, intensity-modulated proton radiation therapy (IMPT), has been confirmed to reduce normal tissue complication probability (NTCP) as compared to conventional intensity-modulated photon-radiation therapy (IMRT) in patients with oropharyngeal cancer (OPC). Herein, we evaluated the cost-effectiveness and applicability of IMPT versus IMRT for OPC patients in China, aiming at guiding the proper use of PBT. Methods A 7-state Markov model was designed for analysis. Base-case evaluation was performed on a 56-year-old (median age of OPC in China) patient under the assumption that IMPT could provide a 25% NTCP-reduction in long-term symptomatic dysphagia and xerostomia. Model robustness was examined using probabilistic sensitivity analysis, cohort analysis, and tornado diagram. One-way sensitivity analyses were conducted to identify the cost-effective scenarios. IMPT was considered as cost-effective if the incremental cost-effectiveness ratio (ICER) was below the societal willingness-to-pay (WTP) threshold. Results Compared with IMRT, IMPT provided an extra 0.205 quality-adjusted life-year (QALY) at an additional cost of 34,926.6 US dollars ($), and had an ICER of $170,082.4/ QALY for the base case. At the current WTP of China ($33,558 / QALY) and a current IMPT treatment costs of $50,000, IMPT should provide a minimum NTCP-reduction of 47.5, 50.8, 55.6, 63.3 and 77.2% to be considered cost-effective for patient age levels of 10, 20, 30, 40 and 50-year-old, respectively. For patients at the median age level, reducing the current IMPT costs ($50,000) to a $30,000 level would make the minimum NTCP-reduction threshold for “cost-effective” decrease from 91.4 to 44.6%, at the current WTP of China (from 69.0 to 33.5%, at a WTP of $50,000 / QALY; and from 39.7 to 19.1%, at a WTP of $100,000 / QALY). Conclusions Cost-effective scenarios of PBT exist in Chinese OPC patients at the current WTP of China. Considering a potential upcoming increase in PBT use in China, such cost-effective scenarios may further expand if a decrease of proton treatment costs occurs or an increase of WTP level.

Background Cost-effectiveness is a pivotal consideration for clinical decision making of high-tech cancer treatment in developing countries. Intensity-modulated proton radiation therapy (IMPT, the advanced form of proton beam therapy) has been found to improve the prognosis of the patients with paranasal sinus and nasal cavity cancers compared with intensity-modulated photon-radiation therapy (IMRT). However, the cost-effectiveness of IMPT has not yet been fully evaluated. This study aimed at evaluating the cost-effectiveness of IMPT versus IMRT for treatment decision making of paranasal sinus and nasal cavity cancers in Chinese settings. Methods A 3-state Markov model was designed for cost-effectiveness analysis. A base case evaluation was performed on a patient of 47-year-old (median age of patients with paranasal sinus and nasal cavity cancers in China). Model robustness was examined by probabilistic sensitivity analysis, Markov cohort analysis and Tornado diagram. Cost-effective scenarios of IMPT were further identified by one-way sensitivity analyses and stratified analyses were performed for different age levels. The outcome measure of the model was the incremental cost-effectiveness ratio (ICER). A strategy was defined as cost-effective if the ICER was below the societal willingness-to-pay (WTP) threshold of China (30,828 US dollars ($) / quality-adjusted life year (QALY)). Results IMPT was identified as being cost-effective for the base case at the WTP of China, providing an extra 1.65 QALYs at an additional cost of $38,928.7 compared with IMRT, and had an ICER of $23,611.2 / QALY. Of note, cost-effective scenarios of IMPT only existed in the following independent conditions: probability of IMPT eradicating cancer ≥0.867; probability of IMRT eradicating cancer ≤0.764; or cost of IMPT ≤ $52,163.9. Stratified analyses for different age levels demonstrated that IMPT was more cost-effective in younger patients than older patients, and was cost-effective only in patients ≤56-year-old. Conclusions Despite initially regarded as bearing high treatment cost, IMPT could still be cost-effective for patients with paranasal sinus and nasal cavity cancers in China. The tumor control superiority of IMPT over IMRT and the patient’s age should be the principal considerations for clinical decision of prescribing this new irradiation technique.

Purpose This study aimed to explore the functions and mechanisms of C-C motif chemokine receptor 6 (CCR6), a gene associated with progression and metastasis of colorectal cancer (CRC), in radiosensitivity of rectal cancer (RC). Materials and Methods RNA sequencing and immunohistochemical analysis on CCR6 expression were performed in pretreatment tissues of RC patients exhibiting different therapeutic effects of radiotherapy. Colonogenic survival assay was conducted in different CRC cell lines to assess their radiosensitivity. And the impact of CCR6 expression on radiosensitivity was validated through RNA interference. The DNA damage repair (DDR) abilities of cell lines with different CCR6 expression were evaluated through immunofluorescence-based γH2AX quantification. Results The CCR6 mRNA level was higher in patients without pathologic complete remission (pCR) than in those with pCR (fold changed, 2.11; p=0.004). High-level expression of CCR6 protein was more common in the bad responders than in the good responders (76.3% vs. 37.5%, p < 0.001). The CRC cell lines with higher CCR6 expression (LoVo and sw480) appeared to be more radioresistant, compared with the sw620 cell line which had lower CCR6 expression. CCR6 knockdown made the LoVo cells more sensitive to ionizing radiation (sensitization enhancement ratio, 1.738; p < 0.001), and decreased their DDR efficiency. Conclusion CCR6 might affect the RC radiosensitivity through DDR process. These findings supported CCR6 as a predicting biomarker of radiosensitivity and a potential target of radiosensitization for RC patients.

Background To investigate the incidence of radiation esophagitis (RE) and tumor local control using esophagus sparing technique in locally advanced non-small cell lung cancer (LANSCLC) treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) and concurrent chemotherapy. Methods Eighty-seven patients with stage IIIA/B NSCLC who received definitive SIB-IMRT and concurrent chemotherapy had been divided into two groups: 1.with esophagus sparing technique; 2.without esophagus sparing technique. Chi-square test was performed to compare sex, clinical stage, histology, concurrent chemotherapy, RE and nutrition status between two groups. T-test was used to compare the dosimetric parameters. Overall survival (OS) and loco-regional failure free survival (LRFS) were calculated by the Kaplan–Meier method and compared by a log-rank test. Results There were 44 patients in the esophagus sparing group and 43 in the non-sparing group. The incidence of severe RE (Grade 3) was significantly lower in patients with esophagus sparing technique (p = 0.002). Patients in esophagus sparing group had better nutrition status (p = 0.045). With a median follow-up of 18 months (range 1–51 months), the 1-year, 2-year and 3-year OS of all the patients was 86.6, 65.4 and 43.7%. The 1-year, 2-year LRFS was 78.4, 65.9%. OS time (p = 0.301) and LRFS (p = 0.871) was comparable between two groups. Conclusions Esophagus-sparing technique is an effective and essential method to limit RE in LANSCLC treated by SIB-IMRT and concurrent chemotherapy without compromising local control.

The sodium pump Na+/K+ ATPase a1 subunit(NKA a1), an attractive cancer-related biomarker and therapeutic target, is closely related to the development and progression of several cancers including breast cancer. Currently, a NKA a1 inhibitor, UNBS1450, has already evidenced its great therapeutic potential in personalized cancer treatment. The ability of non-invasive imaging of NKA a1 expression would be useful for selecting cancer patients who may benefit from this drug. Here, we identified an S3 peptide that is specifically homed to breast cancer by phage display. All data of in vitro and in vivo experiments suggested the excellent targeting character of the S3 peptide. As the binding activity of the S3 phage was positively correlated to the level of NKA α1 expression in various breast cancer cells, NKA α1 was validated as the primary target of the S3 peptide. Based on immunohistochemistry staining result of 107 breast cancer patients, NKA α1 was verified to be a novel tracking marker and a prognostic predictor for breast cancer. Importantly, we proposed and validated an S3 peptide-based radiotracer 18F-ALF-NOTA-S3 for PET (Positron Emission Tomography) imaging of breast cancer and other NKA α1-overexpressing cancers, including hepatocellular carcinoma and non-small cell lung cancer, in mouse models. Our findings demonstrated the potential application of 18F-ALF-NOTA-S3 for visualization of NKA α1-positive lesions, which provide a new approach to character tumor phenotypic imaging.

Purpose: Investigating surrogate endpoints shortening the time of therapeutic evaluation in nasopharyngeal carcinoma (NPC) after radical treatment. Patients and Methods: We retrospectively analyzed 830 patients receiving intensity-modulated radiotherapy (IMRT) from 2008 to 2010 and being stratified by the 8th edition of UICC/AJCC staging system and the plasma Epstein-Barr virus DNA (EBV DNA). The annual rates of overall survival (OS), progression-free survival (PFS), loco-regional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were sequentially calculated using the life table and compared by the McNemar method. Results: The time of shortening therapeutic evaluation by surrogate endpoints: OS, PFS, LRFS and DMFS could be shortened to 1-year (100% vs 100%, P=1) in patients with stage I; OS, PFS, LRFS and DMFS could be shortened to 3-year (96.9% vs 96.1%, P = 1; 94.6% vs 92.2%, P = 0.125; 96.9% vs 95.3%, P = 0.5) and 4-year (92.2% vs 91.2%, P = 0.125) in stage II; In the high EBV DNA group , OS and DMFS could be shortened to 1-year (100% vs 100%, P = 1;100% vs 100%, P = 0.25) in stage II; OS and PFS could be shortened to 3-year (94.3% vs 91.4%, P = 1;82.9% vs 74.3%, P = 0.25) in stage III; OS could be shortened to 4-year (75% vs 72.7%, P = 1) in stage IVA. Conclusions: The time of therapeutic evaluation could be shortened to

Objective The radioprotective effects of amifostine remain uncertain in patients with nasopharyngeal carcinoma (NPC), and adverse effects and cost limit generalization of its classical everyday regimen. This phase II multicenter randomized controlled trial aimed to explore whether amifostine could ameliorate the toxicities of NPC patients in the era of intensity-modulated radiotherapy (IMRT), and to compare different regimens of amifostine on effectiveness and safety. Methods Patients with stage I-IVB NPC were involved prospectively from January 1st, 2013. All patients received radical treatment based on IMRT. After a randomization stratified by their stage, these patients were allocated into 3 groups: the group treated without amifostine, the group treated with the everyday regimen of amifostine, and the group treated with the every-other-day regimen. The 3 groups of patients were compared on radiotherapy-related acute toxicities, treatment effects of NPC, and amifostine-related complications. This trial was registered on the clinicaltrials.gov (ID: NCT01762514). Results Until August 31st, 2017, totally 187 patients completed experimental intervention. Only amifostine of everyday regimen appeared to reduce the patient proportion of mucositis (79.1% vs. 96.8%, P=0.002). Hypocalcemia was less common in patients treated without amifostine than in those treated with amifostine (22.6% vs. 53.4% vs. 41.8%, P=0.002). Neither complete remission rates nor the survivals were affected by amifostine. Conclusions Amifostine of everyday regimen could reduce mucositis in NPC patients who received IMRT, though it also had the possibility to cause more hypocalcemia.

Ependymomas are glial brain tumors accounting for approximately 2~3% of all primary tumors of the central nervous system (CNS), and 12% of all pediatric intracranial tumors. To better understand the evolution process of ependymomas, we studied the clinical, pathological and genetic development of a rare girl case with repeatedly recurrent ependymoma. This girl was diagnosed as ependymoma at age of 9 years old, and experienced 7 times tumor relapse and received 9 times surgeries but finally ceased at 19 years old with multiregional recurrences. The pathological characteristics, radiographic images and therapeutic strategies of the patient were all retrieved. Molecular markers confirmed the diagnosis of anaplastic ependymoma based on the updated WHO guideline for CNS tumors. Whole-genome sequencing (WGS) was performed to elucidate the landscape of mutation signatures and to identify potential driver mutations along the tumor progression. The seven tumor specimens showed a highly branched evolutionary pattern. There were six gene mutations found in 5 of the 7 specimens (PCDHA4, PCDHA8, SEC14L6, SETD2, RIOK2, and SLCO2A1) and three in 6 of 7 the samples (RYR1, SNX25, DSC2). Strikingly, there was one gene, ADGRL3, which was found to be consistently mutated in the entire disease progression process. Our findings therefore suggest that ADGRL3 might play roles in the disease progression of ependymoma patient.

Extradomain-B fibronectin (EDB-FN), an oncofetal isoform of FN, is a promising diagnostic and therapeutic target of tumors, including breast cancer. Many EDB-FN-targeted drugs have been developed and have shown therapeutic effects in clinical trials. Molecular imaging to visualize EDB-FN-positive cancers may help select the right patients who will be benefit from EDB-FN-targeted therapy. Although a few EDB-FN-targeted imaging probes have been developed, the complicated manufacturing procedure and expensive material and equipment required limit their application for large-scale screening of EDB-FN-positive cancer patients. Thus, more simple and economic EDB-FN-targeted imaging probes are still urgently needed. Previously, we have identified a breast cancer-targeted peptide, CTVRTSADC. Coincidently, it was later identified as an EDB-FN-targeted peptide and named ZD2. In this study, we found a positive correlation between the binding activity of the ZD2 phage and the expression level of EDB-FN in breast canc...

Objective: Great heterogeneity exists in clinical behavior and survival outcome in patients with stage IE/IIE extranodal natural killer/T-cell lymphoma, nasal type (ENKTL). In this study, we proposed lymphocyte/monocyte ratio (LMR) as a new prognostic factor for these early stage ENKTL. Methods: We retrospectively examined the LMR as a prognostic variable in a cohort of 379 patients with newly diagnosed stage IE/IIE ENKTL. The relationship between the LMR and clinicopathologic variables were analyzed in Kaplan-Meier log-rank survival analysis, and the Cox proportional hazards model was used to determine the survival significance of the LMR for both progression-free survival (PFS) and overall survival (OS). Results: Patients were categorized into two different groups based on the LMR using cut-off value of 2.0. The 5-year PFS rates in the low and high LMR group were 43.9% and 62.7%, respectively, and the 5-year OS rates in the two groups were 59.1% and 77.7%, respectively. In multivariate analysis, low LMR at diagnosis was associated with worse PFS (hazard ratio 1.611, 95% confidence interval: 1.027-2.525, P =0.038) independent of age (P=0.033) and treatment stratagem (P

// Yi-Yang Li 1, 2, 3, * , Ling-Ling Feng 2, 3, * , Shao-Qing Niu 4 , Han-Yu Wang 2, 3 , Lu-Lu Zhang 2, 3 , Liang Wang 2, 5 , Zhong-Jun Xia 2, 5 , Hui-Qiang Huang 2, 6 , Yun-Fei Xia 2, 3 , Yu-Jing Zhang 2, 3 , Xi-Cheng Wang 1 1 Department of Oncology, the First affiliated Hospital of Guangdong Pharmaceutical University, Guangdong 510080, People’s Republic of China 2 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, People’s Republic of China 3 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China 4 Department of Radiation Oncology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510060, People’s Republic of China 5 Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 5100600, People’s Republic of China 6 Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Xi-Cheng Wang, email: 13902400598@126.com Yu-Jing Zhang, email: yujing_zhang1969@163.com Keywords: extranodal natural killer/T cell lymphoma, non-Hodgkin lymphoma, asparaginase, radiotherapy, chemotherapy Received: September 18, 2016 Accepted: November 23, 2016 Published: December 17, 2016 ABSTRACT This study retrospectively investigated asparaginase-based chemotherapy treatment outcomes with or without radiotherapy in 143 patients with stage I E –II E extranodal natural killer/T cell lymphoma (ENKTCL). All patients received a median of three cycles of asparaginase-based chemotherapy, while 121 patients received radiotherapy following the chemotherapy. The complete remission (CR) rate for all patients post-chemotherapy was 58.7%, and rose to 73.4% by the end of treatment. Patients who received radiotherapy achieved better survival outcomes than those who did not (89.7% vs. 49.0% for 2-year overall survival (OS), P

Chronic inflammation plays an important role in tumor progression. The aim of this analysis was to evaluate whether inflammatory biomarkers such as the Glasgow prognostic score (GPS), the neutrophil‐lymphocyte ratio (NLR), the platelet‐lymphocyte ratio (PLR), and the lymphocyte‐monocyte ratio (LMR) could predict the prognosis of nasopharyngeal carcinoma (NPC). In this analysis, pretreatment GPS, NLR, PLR, LMR of 388 patients who were diagnosed as nonmetastatic NPC and recruited prospectively in the 863 Program No. 2006AA02Z4B4 were assessed. Of those, the 249 cases enrolled between December 27th 2006 and July 31st 2011 were defined as the development set. The rest 139 cases enrolled between August 1st 2011 and July 31st 2013 were defined as the validation set. The variables above were analyzed in the development set, together with age, gender, Karnofsky performance score, T stage, and N stage, with respect to their impact on the disease‐specific survival (DSS) through a univariate analysis. The candidate prognostic factors then underwent a multivariate analysis. A nomogram was established to predict the DSS, by involving the independent prognostic factors. Its predction capacity was evaluated through calculating Harrell's concordance index (C‐index) in the validation set. After multivariate analysis for the development set, age (≤50 vs. >50 years old), T stage (T1–2 vs. T3–4), N stage (N0–1 vs. N2–3) and pretreatment GPS (0 vs. 1–2), NLR (≤2.5 vs. >2.5), LMR (≤2.35 vs. >2.35) were independent prognostic factors of DSS (P values were 0.002, 0.008

Wei Yi,1,* Zhi-Gang Liu,2,3,* Xian Li,4 Jiao Tang,2,3 Chang-Bin Jiang,1 Jing-Ye Hu,5 Zi-Wei Tu,5 Hui Wang,2,3 Dao-Li Niu,1 Yun-Fei Xia5 1Department of Radiotherapy, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 2Department of Radiotherapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 3Key Laboratory of Translational Radiation Oncology, Hunan Province, 4Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, 5State Key Laboratory of Oncology in Southern China, Department of Radiotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Bone metastasis is the most frequent type of distant metastasis in nasopharyngeal carcinoma (NPC). In this study, we investigated the correlation between the skull base bone destruction and the distant bone metastasis in patients with NPC. A total of 449 cases with NPC who were diagnosed and had definitive radiotherapy from 2001 to 2006 were enrolled in this study. The skull base bone destruction was diagnosed by computed tomography (CT) in all cases, and 191 patients also underwent magnetic resonance imaging scan. Kaplan–Meier method was adopted to perform the univariate analysis; Cox regression model was used to perform multivariate analysis to determine whether the skull base bone destruction when diagnosed by CT was an independent impact factor of the distant bone metastases. The group with skull base bone destruction had a distant bone metastases rate of 9.0% (14/155), whereas the group without skull base bone destruction had rate of 4.1% (12/294). The multivariate analysis showed that the skull base bone destruction, when diagnosed by CT, was an independent impact factor of the distant bone metastases-free survival in the early N-staging cases, but was not an independent impact factor when diagnosed by MRI. The skull base bone destruction diagnosed by CT in patients with NPC had predictive value for the distant bone metastases, especially for the early N-staging cases. Keywords: bone metastasis, skull base bone destruction, radiotherapy, nasopharyngeal carcinoma

Distant metastasis is the leading cause of death in patients with N2-3 nasopharyngeal carcinoma (NPC). And aspirin is found to reduce metastasis and improve prognosis in some other malignancies, such as colorectal cancer. This study aimed to evaluate the clinical value of regular aspirin intake (RAI) in N2-3 NPC treated with standard chemoradiotherapy.Totally 2064 patients diagnosed with TxN2-3M0 NPC from Jan. 2008 to Dec. 2015 and treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy were involved. According to RAI, these patients were divided into 2 groups between which a propensity score matching was made, with a ratio of 1:3 and a series of clinical characteristics (age, gender, T stage, N stage and EBV DNA) as covariates. Then survivals and acute toxicities were compared in the 464 matched patients.RAI appeared to bring better overall (87.7% vs. 79.6%, P = 0.031), metastasis-free (87.8% vs. 76.5%, P = 0.017) and disease-free (85.9% vs. 75.5%, P = 0.033) survivals. It simultaneously increased total incidences of myelosuppression (55.2% vs. 32.2%, P 0.001), oral mucositis (60.3% vs. 38.2%, P 0.001), cervical dermatitis (60.3% vs. 38.5%, P 0.001) and xerostomia (49.1% vs. 33.3%, P = 0.002). But RAI failed to affect incidence of any grade 3/4 toxicity.Post-diagnosis RAI might be a tolerable approach to control distant metastasis and provide survival benefit for N2-3 NPC in combination with standard chemoradiotherapy.

BACKGROUND: Acute xerostomia is the most common side effect of radiation therapy (RT) for head and neck (H&N) malignancies. Investigating radiation-induced changes of computed tomography (CT) radiomics in parotid glands (PGs) and saliva amount (SA) can predict acute xerostomia during the RT for nasopharyngeal cancer (NPC). METHODS: CT and SA data from 35 patients with stages I–IVB were randomly collected from an NPC clinical trial registered on the clinicaltrials.gov (ID: NCT01762514). All patients received radical treatment based on intensity-modulated RT (IMRT) with a prescription dose of 68.1 Gy in 30 fractions. The patients’ ages ranged 24–72 years, and each patient had five CT sets acquired at treatment position: at the 0(th), 10(th), 20(th), 30(th) fractions during the RT, and at 3-month later after the RT. The PGs for each CT set were delineated by a radiation oncologist and verified independently by another. Patients’ saliva was collected every other 10 days during the RT. Acute xerostomia was evaluated based on the RTOG acute toxicity scoring and the SA. In total, 1,703 radiomics features were calculated for PGs from each CT set, including feature value at 0(th) fraction (FV(0F)), FV(10F), and delta FV (ΔFV(10F-0F)), respectively. Extensive experiments were conducted to achieve the optimal results. RidgeCV and Recursive Feature Elimination (RFE) were used for feature selection, while linear regression was used for predicting SA(30F). Four more patients were added for independent testing. RESULTS: Substantial changes in various radiomics metrics of PGs were observed during the RT. Eight normalized feature value (NFV), selected from NFV(0F), predicted SA(10F) with a mean square error (MSE) of 0.9042 and a R(2) score of 0.7406. Fourteen NFV, selected from ΔNFV(10F-0F), NFV(0F), and NFV(10F) to predict SA(30F), showed the best predictive ability with an MSE of 0.0569. The model predicted the level of acute xerostomia with a precision of 0.9220 and a sensitivity of 100%, compared to the clinical observed SA. For the independent test, the MSE of PSA(30F) was 0.0233. CONCLUSIONS: This study demonstrated that radiation-induced acute xerostomia level could be early predicted based on the SA and radiomics changes of the PGs during IMRT delivery. SA, NFV(0F), NFV(10F), and especially ΔNFV(10F-0F) provided the best performance on acute xerostomia prediction for individual patient based on RidgeCV_RFE_LinearRegression method of delta radiomics.

Background Whether PD-L1/PD-1 expression plays a significant role in the prognosis of NPC is still controversial. The present study mainly aimed to investigate the prognostic significance of PD-L1/PD-1 expression in patients with NPC. Methods A systematical research was performed in the PubMed, Web of Science, EMBASE, and the Cochrane Library databases up to January 06, 2019. Eighteen studies met eligible criteria were included in the meta-analysis. Quality assessment of included articles was evaluated by Newcastle–Ottawa quality assessment scale (NOS). Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were used to elucidated the primary endpoint, overall survival (OS), and the secondary endpoints. Furthermore, the relationship between clinicopathological features of NPC and PD-L1/PD-1 expression was estimated by relative ratios (RRs) and 95% CIs. Results A total of 1836 patients from 15 included studies concerning PD-L1 and 678 patients from six studies regarding PD-1 were included in the meta-analysis. Pooled results revealed that PD-L1 expression in NPC did not correlate with OS (HR 1.34 95% CI 0.93–1.93, p = 0.11), DFS (HR 1.82, 95% CI 0.86–3.85, p = 0.12), PFS (HR 1.19, 95% CI 0.46–3.08, p = 0.72), and DMFS (HR 2.26, 95% CI 0.60–8.56, p = 0.23). Meanwhile, no statistically significant differences existed between the expression level of PD-1 in tumor infiltrating lymphocytes (TILs) and the OS in NPC, with the pooled HR 1.29 (95% CI 0.68–2.42, p = 0.44). In subgroup analysis, higher expression of PD-L1 in immune cells correlated with better OS in patients with NPC, with a pooled HR 0.68 (95% CI 0.47–0.99, p = 0.04). Among the clinicopathological features included in our study, we found that the positive expression of PD-L1 in NPC associated with the higher expression of PD-1 (RR 1.25, 95% CI 1.02–1.52, p = 0.03). Conclusions Our meta-analysis indicated that higher/positive expression of PD-L1/PD-1 may not serve as suitable biomarkers for the prognosis of NPC, which was not in consistent with some previous studies about the prognostic value of PD-L1/PD-1 in other types of tumors. Despite the positive results in subgroup analysis and study about clinicopathological features, it may still need corroboration of prospective and large-scale studies. Electronic supplementary material The online version of this article (10.1186/s12935-019-0863-5) contains supplementary material, which is available to authorized users.

Purpose: The purpose of our meta-analysis is to clarify whether the biomarker of programmed cell death ligand-1 (PD-L1) could predict the treatment efficacy and prognosis of programmed cell death protein-1 (PD-1)/PD-L1 immune-checkpoint inhibitors (ICIs) in head and neck cancer (HNC) patients. Materials and Methods: We performed the article search in four main online databases. The search deadline was September 8, 2020. To elucidate whether a positive or negative PD-L1 expression correlates with different efficacy and prognosis of PD-1/PD-L1–related therapy in HNC, the relative risk (RR) and 95% confidence interval (95% CI) were pooled. Our meta-analysis assigned the overall survival (OS) at 6 and 12 months and the objective response rate (ORR) for the primary end points. Results: The present meta-analysis included 11 relevant studies, which have 1663 HNC cases who received the treatment of PD-1/PD-L1 ICIs. The pooled results revealed that the high or positive expression of PD-L1 predicted better 6- and 12-month OS in head and neck squamous cell carcinoma (HNSCC) (RR 1.30, 95% CI: 1.02–1.65, P = 0.03; and RR 1.31, 95% CI: 1.05–1.62, P = 0.01). PD-L1 expressors were also relevant with higher ORR in HNC patients who had treatment of PD-1/PD-L1 inhibitors compared to PD-L1 nonexpressors (RR 1.84, 95% CI: 1.41–2.41, P Conclusions: In summary, PD-L1–positive HNSCC patients portend favorable OS at 6 and 12 months from PD-1/PD-L1 ICIs. Increased ORR also favored to appear in PD-L1 expressors of HNC or recurrent/metastatic HNSCC who received PD-1/PD-L1 ICIs. Therefore, PD-L1 proved to be an appropriate biomarker to predict the clinical efficacy and prognosis of PD-1/PD-L1 ICIs in HNC.

// Zhi-Gang Liu 1, * , Guanmin Jiang 2, * , Jiao Tang 1, * , Hui Wang 1, * , Guokai Feng 3 , Furong Chen 3 , Ziwei Tu 3 , Guiyun Liu 1 , Yu Zhao 1 , Ming-Jing Peng 4 , Zheng-Wen He 5 , Xiao-Yan Chen 6 , Holly Lindsay 7 , Yun-Fei Xia 3 , Xiao-Nan Li 7 1 Key Laboratory of Translational Radiation Oncology, Hunan Province, Department of Radiotherapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China 2 Department of Clinical Laboratory, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China 3 State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P.R. China 4 Translational Medicine Center, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China 5 Department of Neurosurgery, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China 6 Department of Pathology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China 7 Laboratory of Molecular Neuro-Oncology, Texas Children’s Cancer Center, Baylor College of Medicine, Houston TX, 77030, USA * These authors have contributed equally to this work Correspondence to: Zhi-Gang Liu, email: zhigangliu1983@hotmail.com Keywords: malignant glioma, radioresistance, c-Fos , prognosis Received: January 06, 2016 Accepted: August 22, 2016 Published: September 01, 2016 ABSTRACT c-Fos is a major component of activator protein (AP)-1 complex. It has been implicated in cell differentiation, proliferation, angiogenesis, invasion, and metastasis. To investigate the role of c-Fos in glioma radiosensitivity and to understand the underlying molecular mechanisms, we downregulated c-Fos gene expression by lentivirus-mediated shRNA in glioma cell lines and subsequently analyzed the radiosensitivity, DNA damage repair capacity, and cell cycle distribution. Finally, we explored its prognostic value in 41 malignant glioma patients by immunohistochemistry. Our results showed that silencing c-Fos sensitized glioma cells to radiation by increasing radiation-induced DNA double strand breaks (DSBs), disturbing the DNA damage repair process, promoting G2/M cell cycle arrest, and enhancing apoptosis. c-Fos protein overexpression correlated with poor prognosis in malignant glioma patients treated with standard therapy. Our findings provide new insights into the mechanism of radioresistance in malignant glioma and identify c-Fos as a potentially novel therapeutic target for malignant glioma patients.

Background With the improved overall survival (OS) of nasopharyngeal carcinoma (NPC) patients, the importance of quality of life (QoL) is increasingly being recognized. For some radiosensitive NPC patients, whether low-dose radiotherapy can improve the QoL without affecting clinical efficacy is unknown. This study aimed to assess the survival rates and QoL of NPC patients treated with 50 Gy radiotherapy plus hematoporphyrin derivative (HPD). Methods Forty-six newly diagnosed NPC patients treated with 50 Gy radiotherapy plus HPD between June 1988 and July 1992 were analyzed. All patients were restaged according to the 7th edition of the American Joint Committee on Cancer staging system. The radiotherapy plan was designed on the basis of pretreatment computed tomography. The OS, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) rates were estimated using the Kaplan–Meier method. QoL was assessed using the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group. Results The 5-year OS, LRFS, DMFS, and DFS rates were 74.3%, 72.6%, 82.1%, and 61.2%, respectively. The corresponding 10-year rates were 38.4%, 62.9%, 78.5%, and 49.8%, respectively, and the 20-year rates were 27.7%, 51.4%, 78.5%, and 40.7%, respectively. None of the patients developed severe radiation-related complications, such as radiation-induced temporal lobe necrosis, hearing loss, trismus, and dysphagia. Conclusion Some NPC patients were sensitive to 50 Gy radiotherapy plus HPD, and this sensitivity was characterized by long-term survival without significant late treatment morbidities.

Objective In our previous work, we incorporated complete blood count (CBC) into TNM stage to develop a new prognostic score model, which was validated to improve prediction efficiency of TNM stage for nasopharyngeal carcinoma (NPC). The purpose of this study was to revalidate the accuracy of the model, and its superiority to TNM stage, through data from a prospective study. Methods CBC of 249 eligible patients from the 863 Program No. 2006AA02Z4B4 was evaluated. Prognostic index (PI) of each patient was calculated according to the score model. Then they were divided by the PI into three categories: the low-, intermediate-and high-risk patients. The 5-year disease-specific survival (DSS) of the three categories was compared by a log-rank test. The model and TNM stage (7th edition) were compared on efficiency for predicting the 5-year DSS, through comparison of the area under curve (AUC) of their receiver-operating characteristic curves. Results The 5-year DSS of the low-, intermediate-and high-risk patients were 96.0%, 79.1% and 62.2%, respectively. The low-and intermediate-risk patients had better DSS than the high-risk patients (P

Background Promising efficacy and manageable toxicity of docetaxel-based concurrent chemoradiotherapy (CCRT) were reported in head and neck cancer. In addition, the effect of CCRT in combination with cisplatin and/or 5-fluorouracil on both locoregionally advanced and metastatic/recurrent nasopharyngeal carcinoma (NPC) was verified. However, CCRT with docetaxel for locoregionally advanced NPC are not well studied. This study aimed to compare effectiveness and toxicities of CCRT with weekly docetaxel versus tri-weekly cisplatin for locoregionally advanced NPC. Methods Clinical data of patients with locoregionally advanced NPC newly diagnosed between January 2010 and December 2014 receiving CCRT with either weekly docetaxel (15 mg/m2) or tri-weekly cisplatin (80–100 mg/m2) were reviewed. Propensity score matching at a 1:1 ratio was performed to balance baseline characteristics. Adverse events and survival were compared between the two groups. Results A total of 962 patients were included as the whole cohort, and 448 patients were matched and were regarded as the matched cohort. The median follow-up duration was 48 months for the whole cohort. The 3-year nodal recurrence-free survival rate was significantly increased for patients treated with docetaxel in both the whole (hazard ratio [HR] = 0.37, 95% confidence interval [CI] 0.19–0.72, P = 0.030) and matched cohorts (HR = 0.33, 95% CI 0.14–0.79, P = 0.023). However, no significant differences were observed in overall survival, local recurrence-free survival, and distant metastasis-free survival between the two groups in both cohorts. Significantly higher rates of grade 3 radiodermatitis (6.7% vs. 1.8%, P = 0.001), mucositis (74.5% vs. 37.9%, P

Background: The conventional way of patient treatment should be following guidelines. While in clinical practice, patients received treatments very often away from suggested guideline. In this report, we reviewed glioma patients received real world treatment at Sun Yat-sen University Cancer Center (SYSUCC) and results of this patient series. Methods: Total of 1215 glioma patients received surgery at SYSUCC from 2000 to 2017 were enclosed for analysis. The pathologic diagnosis of patients has followed WHO classification (initially 2007 standard, than 2016 standard). Results: A total of 1001 newly diagnosed brain glioma patients were analyzed, including 90 cases WHO grade I, 307 grade II, 239 grade III and 365 grade IV. The median age of onset was 14 (1–75), 35 (2–69), 41 (8–82) and 50 (2–86) years old, respectively, for grade I, II, III and IV glioma patients. Tumor total resection was achieved in 567 patients (57.5%). Among all patients, 331 high-grade gliomas (54.8%) and 159 low-grade glioma (40.1%) received radiotherapy, whereas 285 high-grade gliomas (47.1%) and 80 low-grade tumors (20.2%) received chemotherapy. Among high-grade gliomas, the median OS of glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglial tumors were 17.7 months (15.7–19.7 months), 33.7 months (24.0–43.4 months) and 110.6 months (43.5–177.7 months), respectively, whereas the median OS of low-grade gliomas was not reach. The 5-year survival rate of grade I, II, III and IV gliomas was 94.7%, 73.7%, 45.1% and 18.6%, respectively. Multivariate analysis identified that onset age, Karnofsky performance status, tumor location, preoperative seizure, pathological subtype, resection extent and post-surgical treatment were independent predictors of OS for patients with high-grade gliomas. Patients received post-surgical radiotherapy and (or) chemotherapy had better survival than those without adjuvant treatment (grade III: 53.3 vs. 20.6 months, p =0.012; grade IV: 22.9 vs. 12.3 months, p < 0.001). For low-grade gliomas, patients’ age, Ki-67 index, tumor subtype and resection extent were associated with clinical outcomes. Conclusions: Glioma patients received treatments do not always following guidelines in clinical practice. Although standard care for patients may beneficial for prognosis, personalized treatment may more acceptable for patients and even resulting better outcome which should keep in mind in routine clinical practice.

Background: A moderate dose of radiation is the recommended treatment for solitary plasmacytoma (SP), but there is controversy over the role of surgery. Our study aimed at comparing different treatment modalities in the management of SP. Materials and Methods: Data from 38 consecutive patients with solitary plasmacytoma, including 16 with bone plasmacytoma and 22 with extramedullary plasmacytoma, were retrospectively reviewed. 15 patients received radiotherapy alone; 11 received surgery alone, and 12 received both. The median radiation dose was 50Gy. All operations were performed as radical resections. Local progression-free survival (LPFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS) and overall survival (OS) were calculated and outcomes of different therapies were compared. Results: The median follow-up time was 55 months. 5-year LPFS, MMFS, PFS and OS were 87.0%, 80.9%, 69.8% and 87.4%, respectively. Univariate analysis revealed, compared with surgery alone, radiotherapy alone was associated with significantly higher 5-year LPFS (100% vs 69.3%, p=0.016), MMFS (100% vs 51.4%, p=0.006), PFS (100% vs 33.7%, p=0.0004) and OS (100% vs 70%, p=0.041). Conclusions: Radiotherapy alone can be considered as a more effective treatment for SP over surgery. Whether a combination of radiotherapy and surgery improves outcomes requires further study.

This paper first introduces PAC dosing system, then research the feasibility of the project goal. confirmed the goal can be achieved. Research on the project, and analysis the process of this project, and implementation finally. After the PAC dosing filter automatic cleaning device completed, control charts are used to verify the device, results show that, PAC amount is controlled in the range of 1.8~2.2mg/L, COD is above 35mg/L.

The COD of the sewage in the cigarette factory is often exceeded. This article through observation and analysis find out that the high COD is because of monitoring probe dirty. This article through comparison and analysis, the team members designed a probe cleaning method, and finally completed the water quality monitoring vehicle construction, though the use of the actual use of the probe clean method, we found that the device ensures that the water quality monitoring probe is stable and reliable, ensuring that the dosing system is working properly. Through the implementation of this project, the probe cleaning time savings of 91.6%, the effect is significant.

To meet the special demands in China and the particular needs for the radiotherapy department, a MOSAIQ Integration Platform CHN (MIP) based on the workflow of radiation therapy (RT) has been developed, as a supplement system to the Elekta MOSAIQ. The MIP adopts C/S (client-server) structure mode, and its database is based on the Treatment Planning System (TPS) and MOSAIQ SQL Server 2008, running on the hospital local network. Five network servers, as a core hardware, supply data storage and network service based on the cloud services. The core software, using C# programming language, is developed based on Microsoft Visual Studio Platform. The MIP server could offer network service, including entry, query, statistics and print information for about 200 workstations at the same time. The MIP was implemented in the past one and a half years, and some practical patient-oriented functions were developed. And now the MIP is almost covering the whole workflow of radiation therapy. There are 15 function modules, such as: Notice, Appointment, Billing, Document Management (application/execution), System Management, and so on. By June of 2016, recorded data in the MIP are as following: 13546 patients, 13533 plan application, 15475 RT records, 14656 RT summaries, 567048 billing records and 506612 workload records, etc. The MIP based on the RT workflow has been successfully developed and clinically implemented with real-time performance, data security, stable operation. And it is demonstrated to be user-friendly and is proven to significantly improve the efficiency of the department. It is a key to facilitate the information sharing and department management. More functions can be added or modified for further enhancement its potentials in research and clinical practice.

Breast cancer is the most common malignant cancer and is the leading cause of cancer death among females. Molecular imaging is a promising approach for the early detection and staging of breast cancer as well as for assessing therapeutic responses. Tumor-targeting peptides are effective targeting vehicles for molecular imaging. Here, we identified a breast cancer-targeting peptide CLKADKAKC (CK3) contains a cryptic C-end rule motif that may mediate its binding to neuropilin-1 (NRP-1), an attractive therapeutic target which expression was associated with poor outcome of the patients with breast cancer. Phage CK3 bound to NRP-1-positive breast cancer cells, which could be inhibited by peptide CK3 in a dose-dependent manner or by knock-down NRP-1 expression. Consistently, NRP-1 overexpression in cells increased the binding of phage CK3. Furthermore, peptide CK3 co-localized with NRP-1. Importantly, unlike previously reported NRP-1-targeting peptides with exposed C-end rule motifs, peptide CK3 did not penetrate into lungs and heart in vivo, which could make it more clinically applicable. Single-photon emission CT (SPECT) and near-infrared fluorescence (NIRF) imaging showed enrichment of peptide CK3 to the xenograft tumors in nude mice. In conclusion, as a novel NRP-1-targeting peptide, peptide CK3 could be used for breast cancer molecular imaging, which may represent a new avenue for breast cancer diagnostics, staging and assessments of therapeutic response.

The aim of the present study was to develop a metastatic risk score model of neck level Ib lymph nodes in primary nasopharyngeal carcinoma (NPC) to guide the level Ib radiotherapy. There were a total of 1,557 patients enrolled in the study, and of these patients, 1,145 were included in the training set. Univariate χ2 analysis and multivariate logistic regression analyses were used to screen the independent risk factors to construct the risk score model. A total of 85 patients in the validating set underwent a pathology biopsy of level Ib lymph nodes to test the model. The remaining 327 patients from the prognostic-research set were used to evaluate the prognostic impact of level Ib irradiation in high- and low-risk groups. The independent risk factors in the model were carotid sheath involvement, the maximal diameter of the neck lymph nodes (≥20 mm) and the involvement of the level II/III/IV lymph nodes. The involvement of level IV was assigned score 2 and the other risk factors were assigned score 1. According to the total scores, the patients were divided into the low- (total score, 0–1; level Ib metastasis rate, 0.5%) and high-risk groups (total score, 2–4; level Ib metastasis rate, 8.5%). In the validating set, the metastatic rate of level Ib in 43 low-risk patients was 0%, and the rate was 31.0% (13/42) in 42 high-risk patients. In the prognostic-research set, the prognosis of 137 low-risk patients was not affected by level Ib irradiation. However, level Ib unirradiation was an independent prognostic factor for the locoregional recurrence in 190 high-risk patients. According to the data, the novel score model could help assess the metastatic risk of level Ib in primary NPC, and the radiotherapy on level Ib may impact the locoregional recurrence in high-risk patients.

To evaluate the effect of smoking on prognosis of male nasopharyngeal carcinoma by comparing the treatment outcomes between smokers and non-smokers.A total of 2450 nasopharyngeal carcinoma patients were enrolled, including 1865 male patients. Matching was performed between smokers and non-smokers in male patients according to age, UICC clinical stage, T stage, N stage and treatment. Survival outcomes were compared using Kaplan-Meier analysis and Cox regression. Smoking index was calculated by multiplying cigarette packs per day and smoked time (year).In male patients, smokers had significantly lower 5-year overall survival (70.1% vs. 77.5%, P0.001) and locoregional recurrent free survival (76.8% vs.82.4%, P = 0.002) compared with non-smokers. Matched-pair analysis showed that smokers kept a high risk of death compared with non-smokers (HR = 2.316, P0.001). High degree of smoking index (15 pack-years) had a poor effect on overall survival (HR = 1.225, P = 0.016). When smoking index was more than 45 and 60 pack-years, the risk for death increased to 1.498 and 1.899 fold compared with non-smokers (P = 0.040, 0.001), respectively.Smoking was a poor prognostic factor for male nasopharyngeal carcinoma. The heavier the patients smoked, the poorer prognosis they suffered.

Firstly, through the fishbone diagram and Causal table method to find the factor which effect the time of temperature and humidity reach standard. Secondly, collect various time, temperature and humidity data of every time air conditioning boot, analysis and arrange the data, build the three-dimensional relationship between workshop temperature, humidity and the reach standard time, and fitting, finally, find the regular pattern between environmental factors and the time of temperature and humidity reach standard.

Background The purpose of this study was to investigate the relationship between pretreatment nutritional status and prognosis of nasopharyngeal carcinoma (NPC). Methods Pretreatment nutritional status was evaluated by ideal body weight percentile (IBW%) and serum albumin for 512 patients with NPC who underwent radical radiotherapy. Kaplan–Meier methods, log-rank test, and a Cox model were applied for survival analysis. Results Before radiotherapy, IBW%

Background: Weight loss during radiotherapy has been known as a negative prognostic factor for nasopharyngeal carcinoma (NPC) patients, but the factors related to weight loss during radiotherapy were not fully understood. Methods: A total of 322 newly diagnosed NPC patients receiving intensity modulated radiotherapy (IMRT) in Sun Yat-sen University Cancer Center between June 2002 and August 2006 were enrolled. Kaplan-Meier methods and log-rank test were applied for survival analysis; a multiple regression was used to identify the factors related to weight loss during radiotherapy. Results: The mean and median values of weight loss (%) during radiotherapy were 6.85% and 6.70%. NPC patients with critical weight loss (> 5.4%) have poorer overall survival (OS) and distant metastasis-free survival (DMFS) than the patients without critical weight loss (p = 0.002 and 0.021, respectively). Pre-radiotherapy weight, acute mucosal toxicity, acute pharynx and esophagus toxicity, and acute upper gastrointestinal toxicity were related to the weight loss during radiotherapy independently (p = 0.01, p < 0.001, p < 0.001, and p = 0.009, respectively). Conclusions: Acute radiation toxicities had significant and independent impact on weight loss during radiotherapy. The vicious circle of acute radiation toxicities and weight loss had bad effect on prognosis of NPC patients.

The X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism (rs861539, C > T) has drawn wide attentions as its association with cancer risk and its involvement in DNA repair. Several studies have attempted to link rs861539 to nasopharyngeal cancer (NPC) risk; however, the sample sizes of these studies are small and the results are controversial. To investigate the relationship of rs861539 and NPC susceptibility, we conducted a large-scale case-control study involving 4001 NPC cases and 2967 controls of southern Chinese. Logistic regression analysis revealed significant association for rs861539 and NPC risk under the recessive model (TT vs. CT + CC) with adjustment of age and gender (odds ratio, OR = 2.72; 95 % CI 1.10–6.72; P = 0.03). Further, meta-analysis involving 4457 NPC cases and 4132 controls from four studies showed consistent association of TT carriers and NPC risk (OR = 3.12; 95 % CI 1.58–6.13; P = 0.001). Taken together, our findings based on large-scale sample size suggested rs861539 at XRCC3 to be associated with NPC risk through recessive model.