食管鳞癌患者根治性放疗预后列线图模型的构建—泛京津冀多中心回顾分析(3JECROG R-03A)

目的:构建列线图(nomogram)模型以预测食管鳞癌患者的预后情况,指导个体化治疗。方法:回顾性分析2002年1月至2016年12月国内10家放疗中心(泛京津冀食管癌协作组-3JECROG)收治的2680例根治性放疗食管鳞癌患者资料,随机分为训练组和验证组,根据训练组的预后因素构建nomogram模型,并进行训练组内部和验证组外部验证。分别以nomogram模型与AJCC/UICC分期评估两组患者预后及临床获益。结果:全组1、3、5年生存率分别为69.0%、37.7%、31.0%。多因素分析肿瘤部位、TNM分期、原发肿瘤体积和是否同步化疗是影响食管癌的独立预后因素(均P<0.05)。在训练组和验证组中nomogram模型的一致性指数(C-index)、AUC值均高于AJCC/UICC分期(均P<0.001)。基于nomogram模型分为低、中、高风险亚组与AJCC/UICC分期比较,nomogram模型的生存曲线之间具有显著性差异(P<0.001),且1、3、5年的总生存临床决策曲线(decision curve analysis,DCA)下面积均具有显著性差异。结论:本研究构建的nomogram模型较AJCC/UICC分期具有更好的预测能力,有助于食管癌患者的预后判断及指导个体化治疗。

Ag nanoparticles sensitize IR-induced killing of cancer cells

Dear Editor, Nanosized particulate systems combining better cancer diagnosis with therapeutic effect are being designed based on the merging of nanotechnology with cellular and molecular techniques. The surface of these nanoscale carriers is often functionalized with biological molecules for stabilization and targeted delivery. The combinations of nano-core and associated functional molecules can cross the cell membrane [1], and the surface of nanomaterials （including coating and associated functional molecules） plays a critical role in determining the outcome of their interactions with cells [2, 3]. Studying the potential effects of nanomaterials in biological systems often requires the administration of nanoparticles into a cell culture system or into living organisms in vivo. It should be noted, however, that under such conditions nanopaticles are known to adsorb proteins from the biological system,

Targets and molecular mechanisms of triptolide in cancer therapy

Triptolide（TPL/TL） is a natural drug with novel anticancer effects. Preclinical studies indicated that TPL inhibits cell proliferation, induces cell apoptosis, inhibits tumor metastasis and enhances the effect of other therapeutic methods in various cancer cell lines. Multiple molecules and signaling pathways, such as caspases, heat-shock proteins, NF-κB, and deoxyribonucleic acid（DNA） repair-associated factors, are associated with the anti-cancer effect. TPL also improves chemoradiosensitivity in cancer therapy. Phase I trials indicate the potential clinical value of TPL use. However, further trials with larger sample sizes are needed to confirm these results.

Identification and verification of aging-related lncRNAs for prognosis prediction and immune microenvironment in patients with head and neck squamous carcinoma

Aging is highly associated with tumor formation and progression.However,little research has explored the association of aging-related lncRNAs(ARLs)with the prognosis and tumor immune microenvironment(TIME)of head and neck squamous cell carcinoma(HNSCC).RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas.In the training group,we used Pearson correlation,univariate Cox regression,least absolute shrinkage/selection operator regression analyses,and multivariate Cox regression to build a prognostic model.In the test group,we evaluated the model.Multivariate Cox regression was done to screen out independent prognostic factors,with which we constructed a nomogram.Afterward,we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics.Gene set enrichment analysis,immune correlation analysis,and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.The most important LINC00861 in the model was examined in HNE1,CNE1,and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid.In addition,CCK-8,Edu,and SA-β-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells.The signature based on nine ARLs has a good predictive value in survival time,immune infiltration,immune checkpoint expression,and sensitivity to multiple drugs.LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells,and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines.This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC.LINC00861 is a protective factor for the development of HNSCC.

Quality of life and survival outcomes of patients with inoperable esophageal squamous cell carcinoma after definitive radiation therapy:A multicenter retrospective observational study in China from 2015 to 2016

Objectives:To investigate the health-related quality of life(HRQL)of long-term survivors of inoperable esophageal squamous cell carcinoma(ESCC)treated with definitive radiation therapy,the real-world trends in the use of advanced radiation techniques,and their impact on the survival outcomes of ESCC patients.Methods:In this multicenter retrospective observational study,the medical records related to demographics and treatment of ESCC patients who were treated with definitive radiation therapy at 14 provincial hospitals in China from 1 January 2015 to 31 December 2016 were analyzed.A HRQL questionnaire was completed by survivors and collected by doctors at the final follow-up.The difference in quality of life between patients with or without recurrence was compared using the Wilcoxon-Mann-Whitney test.Overall survival(OS)was estimated using the Kaplan-Meier method and the group differences were assessed by unstratified log-rank test.The Cox proportional hazards model with Efron’s method of tie handling was used to calculate the risk factors for OS.Results:The data of a total of 3,308 patients were collected for this study,248 were excluded because of missing data,and a final of 3,060 patients were included in the analysis.Most patients(2,901;94.8%)received intensity-modulated radiotherapy(IMRT)/volumetric-modulated arc therapy(VMAT)/tomotherapy(TOMO).The 5-year OS rate was 30%.Patients who received either two-dimensional radiotherapy(2DRT;HR,2.43[95%CI,1.70-3.47];P<0.001)or three-dimensional radiotherapy(3DRT;HR,1.45[95%CI,1.14-1.84];P=0.003)had a significantly increased risk of death compared to those who received IMRT/VMAT/TOMO.Of the 716(23.4%)long-term survivors who completed the HRQL questionnaire,nearly 70%patients were still able to swallow normally or almost normally,and>80%patients did not experience weight loss.Nearly 80%patients found life very enjoyable or were fairly enjoying life.Conclusions:This large,multicenter retrospective study on ESCC patients who received definitive radiation ther-apy found that most ESCC survivors are satisfied with their quality of life.Most patients received advanced radiation technology.Patients who received either 2DRT or 3DRT had a significantly increased risk of death compared to those who received advanced radiation technology.

Report of China's innovation increase and research growth in radiation oncology

Aims： To investigate the research status of radiation oncology in China through survey of literature in international radiation oncology journals and retrospectively compare the outputs of radiation oncology articles of the three major regions of China--Mainland （ML）, Taiwan （TW） and Hong Kong （HK）. Methods： Radiation oncology journals were selected from ＂oncology＂ and ＂radiology, nuclear ＆ medical image＂ category from Science Citation Index Expand （SCIE）. Articles from the ML, TW and HK were retrieved from MEDLINE. The number of total articles, clinical trials, case reports, impact factors （IF）, institutions and articles published in each journals were conducted for quantity and quality comparisons. Results： A total 818 articles from 13 radiation oncology journals were searched, of which 427 are from ML, 259 from TW, and 132 from HK. Ninety-seven clinical trials and 5 case reports are reported in China. Accumulated IF of articles from ML （1,417.11） was much higher than that of TW （1,003.093） and HK （544.711）, while the average IF of articles from ML is the lowest. Conclusions： The total number of articles from China especially ML increased significantly in the last decade. The number of articles published from the ML has exceeded those from TW and HK. However, the quality of articles from TW and HK is better than that from ML.

Concurrent chemoradiotherapyof different radiation doses and different irradiation fields for locally advanced thoracic esophageal squamous cell carcinoma:A randomized,multicenter,phase Ⅲ clinical trial

Background:Concurrent chemoradiotherapy(CCRT)is the standard treatment for locally advanced esophageal squamous cell carcinoma(ESCC).However,the optimal radiotherapy regimen,particularly in terms of total dose and planned range of irradiation field,remains unclear.This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields.Methods:This trial compared two aspects of radiation treatment,total dose and field,using a two-by-two factorial design.The high-dose(HD)group received 59.4 Gy radiation,and the standard-dose(SD)group received 50.4 Gy.The involved field irradiation(IFI)group and elective nodal irradiation(ENI)group adopted different irradiation ranges.The participants were assigned to one of the four groups(HD+ENI,HD+IFI,SD+ENI and SD+IFI).The primary endpoint was overall survival(OS),and the secondary endpoints included progressionfree survival(PFS).The synergy indexwas used to measure the interaction effect between dose and field.Results:The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field.In comparison to the target field,patients in IFI or ENI showed similar OS(hazard ratio[HR]=0.99,95%CI:0.80-1.23,p=0.930)and PFS(HR=1.02,95%CI:0.82–1.25).TheHDtreatment did not show significantly prolonged OS compared with SD(HR=0.90,95%CI:0.72–1.11,p=0.318),but it suggested improved PFS(25.2 months to 18.0 months).Among the four groups,the HD+IFI group presented the best survival,while the SD+IFI group had the worst prognosis.No significant difference in the occurrence of severe adverse events was found in dose or field comparisons.Conclusions:IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC.The HD demonstrated improved PFS,but did not significantly improve OS.The dose escalation based on IFI(HD+IFI)showed better therapeutic efficacy than the current recommendation(SD+ENI)and is worth further validation.