Validation of the chinese version of the EORTC QLQ-CR29 in patients with colorectal cancer

AIM To assess the validity and reliability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29(EORTC QLQ-CR29) in Chinese patients with colorectal cancer(CRC). METHODS From March 2014 to January 2015, 356 patients with CRC from four different hospitals in China were enrolled in the study, and all patients self-administered the EORTC QLQ-CR29 and the quality of life core questionnaire(EORTC QLQ-C30). Evaluation of the scores was based on the Karnofsky Performance Scale(KPS). The reliability and validity of the questionnaires were assessed by Cronbach's α coefficient, the Spearman correlation test and Wilcoxon rank sum test.RESULTS The EORTC QLQ-CR29 showed satisfactory reliability(α > 0.7), although the urinary frequency and blood and mucus in stool dimensions had only moderate reliability(α = 0.608). The multitrait scaling analyses showed good convergent(r > 0.4) and discriminant validity. Significant differences were obtained for each item in the different KPS subgroups(KPS ≤ 80; KPS > 80). body image and most single-item dimensions showed statistically significant differences in patients with a stoma compared with the rest of the patients. CONCLUSION The EORTC QLQ-CR29 exhibits high validity and reliability in Chinese patients with CRC, and can therefore be recommended as a valuable tool for the assessment of quality of life in these patients.

Targeting FGFR in non-small cell lung cancer:implications from the landscape of clinically actionable aberrations of FGFR kinases

Objective:Dysfunction in fibroblast growth factor receptor(FGFR)signaling has been reported in diverse cancer types,including non-small cell lung cancer(NSCLC).The frequency of FGFR aberrations in Chinese NSCLC patients is therefore of great clinical significance.Methods:A total of 10,966 NSCLC patients whose tumor specimen and/or circulating cell-free DNA(cf DNA)underwent hybridization capture-based next-generation sequencing were reviewed.Patients'clinical characteristics and treatment histories were also evaluated.Results:FGFR aberrations,including mutations,fusions,and gene amplifications,were detected in 1.9%(210/10,966)of the population.FGFR abnormalities were more frequently observed in lung squamous cell carcinomas(6.8%,65/954)than lung adenocarcinomas(1.3%,128/9,596).FGFR oncogenic mutations were identified in 19 patients(~0.17%),of which,68%were male lung squamous cell carcinoma patients.Eleven out of the 19 patients(58%)had concurrent altered PI3 K signaling,thus highlighting a potential combination therapeutic strategy of dual-targeting FGFR and PI3 K signaling in such patients.Furthermore,FGFR fusions retaining the intact kinase domain were identified in 12 patients(0.11%),including 9 FGFR3-TACC3,1 FGFR2-INA,1 novel FGFR4-RAPGEFL1,and 1 novel fusion between the FGFR1 and SLC20 A25′-untranslated regions,which may have caused FGFR1 overexpressions.Concomitant EGFR mutations or amplifications were observed in 6 patients,and 4 patients received anti-EGFR inhibitors,in whom FGFR fusions may have mediated resistance to anti-EGFR therapies.FGFR amplification was detected in 24 patients,with the majority being FGFR1 amplifications.Importantly,FGFR oncogenic mutations,fusions,and gene amplifications were almost always mutually exclusive events.Conclusions:We report the prevalence of FGFR anomalies in a large NSCLC population,including mutations,gene amplifications,and novel FGFR fusions.

Subdivision of M category for nasopharyngeal carcinoma with synchronous metastasis:time to expand the M categorization system

Introduction:The current metastatic category(M) of nasopharyngeal carcinoma(NPC) is a "catch-all" classification,covering a heterogeneous group of tumors ranging from potentially curable to incurable.The aim of this study was to design an M categorization system that could be applied in planning the treatment of NPC with synchronous metastasis.Methods:A total of 505 NPC patients diagnosed with synchronous metastasis at Sun Yat-sen University Cancer Center between 2000 and 2009 were involved.The associations of clinical variables,metastatic features,and a proposed M categorization system with overall survival(OS) were determined by using Cox regression model.Results:Multivariate analysis showed that Union for International Cancer Control(UICC) N category(N1-3/N0),number of metastatic lesions(multiple/single),liver involvement(yes/no),radiotherapy to primary tumor(yes/no),and cycles of chemotherapy(>4/<4) were independent prognostic factors for OS.We defined the following subcategories based on liver involvement and the number of metastatic lesions:Mia,single lesion confined to an isolated organ or location except the liver;Ml b,single lesion in the liver and/or multiple lesions in any organs or locations except the liver;and M1 c,multiple lesions in the liver.Of the 505 cases,74(14.7%) were classified as Mia,296(58.6%)as M1 b,134(26.5%) as M1 c,and 1 was not specified.The three Ml subcategories showed significant difference in OS[Ml b vs.Mia,hazard ratio(HR) = 1.69,95%confidence interval(CI) = 1.16-2.48,P = 0.007;Ml c vs.Ml a,HR = 2.64,95%CI = 1.75-3.98,P< 0.001],Conclusions:We developed an M categorization system based on the independent factors related to the prognosis of patients with metastatic NPC.This system may be helpful to further optimize individualized care for NPC patients.

Californium-252 neutron brachytherapy combined with external pelvic radiotherapy plus concurrent chemotherapy for cervical cancer: a retrospective clinical study

Background:Cervical cancer is the sixth most common cancer in Chinese women.A standard treatment modal?ity for cervical cancer is the combination of surgery,chemotherapy,external?beam radiotherapy and intracavitary brachytherapy.The aim of this study was to retrospectively assess the long?term treatment outcomes of patients with cervical cancer who were treated with californium?252 neutron brachytherapy combined with external?beam radio?therapy plus concurrent chemotherapy.Methods:We retrospectively analyzed the medical records of 150 patients with primary stages IB?IVB cervical cancer who received neutron brachytherapy combined with external?beam radiotherapy concurrently with cisplatin chemo?therapy.All patients were followed up.Using an actuarial analysis,patient outcomes and treatment?related adverse effects were evaluated and compared.Results:The median overall survival(OS)was 33.2 months.The 3?year progression?free survival rates for patients with stages I–II,III,and IV diseases were 81.0%(68/84),65.0%(39/60),and 0%(0/6),respectively;the 3?year OS rates were 90.5%(76/84),85.0%(51/60),and 16.7%(1/6),respectively.Vaginal bleeding was controlled within the median time of4.0 days.One month after treatment,97.3%of patients achieved short?term local control.The local recurrence rates for patients with stages I–II,III,and IV disease were 4.8%(4/84),11.7%(7/60),and 33.3%(2/6),respectively,and the occurrence rates of distant metastasis were 16.7%(14/84),25.0%(15/60),and 100.0%(6/6),respectively.Cancer stage,tumor size,and lymph node metastasis were identified as prognostic risk factors,but only lymph node metastasis was found to be an independent prognostic factor.The most common adverse effects during treatment were grades 1 and 2 irradiation?related proctitis and radiocystitis.Conclusion:For patients with cervical cancer,neutron brachytherapy combined with external?beam radiotherapy plus concurrent chemotherapy produces a rapid response and greatly improves local control and long?term survival rates with tolerable adverse effects.

Luminescence Properties of Phosphate Phosphor: Barium Tungstate Doped with Dy

A series of barium-tungstate-based phosphors doped with different concentrations of Dy3+ were synthesized by solid-state reaction method. Photoluminescence properties and decay lifetime of Dy3+-doped BaWO4 samples were studied. The results indicated that luminescent properties of BaWO4:Dy3+ depended on the Dy3+ concentration, and the inner energy could transfer from to Dy3+. The quality of the light was checked by estimating CIE parameters, and the results showed that BaWO4:Dy3+ was a potential candidate as blue-green luminescent materials in white LED because of its excellent emission spectrum excited by UV light.

Dosimetric benefit to organs at risk following margin reductions in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy

Introduction:It is important to decrease the radiation exposure of normal tissue in intensity-modulated radiation therapy(IMRT).Minimizing planning target volume(PTV) margins with more precise target localization techniques can achieve this goal.This study aimed to quantify the extent to which organs at risk(OARs) are spared when using reduced margins in the treatment of nasopharyngeal carcinoma(NPC).Methods:Two IMRT plans were regenerated for 40 patients with NPC based on two PTV margins,which were reduced or unchanged following cone beam computed tomography online correction.The reduced-margin plan was optimized based on maximal dose reduction to OARs without compromising target coverage.Dosimetric comparisons were evaluated in terms of target coverage and OAR sparing.Results:Improvements in target coverage occurred with margin reduction,and significant improvements in dosimetric parameters were observed for all OARs(P<0.05) except for the right optic nerve,chiasm,and lens.Doses to OARs decreased at a rate of 1.5%to 7.7%.Sparing of the left parotid and right parotid,where the mean dose(D_(mean)) decreased at a rate of 7.1%and 7.7%,respectively,was greater than the sparing of other OARs.Conclusions:Significant improvements in OAR sparing were observed with margin reduction,in addition to improvement in target coverage.The parotids benefited most from the online imaging-guided approach.

Association between FOXO3A gene polymorphisms and human longevity： a meta-analysis

Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box 03 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios （ORs） and 95% confidence intervals （Cls） were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups, rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity （OR = 1.36, 95% Cl = 1.10-1.69, P= 0.005; OR = 1.20, 95% CI = 1.04-1.37, P= 0.01; OR = 1.27, 95% CI = 1.10-1.46, P= 0.001; OR = 1.14, 95% CI = 1.01-1.27 and OR = 1.24, 95% CI = 1.07-1.43, P= 0.003, respectively）. Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity （OR = 1.54, 95% Cl = 1.33-1.79, P〈 0.001; OR = 1.38, 95% Cl = 1,15-1.66, P= 0.001; and OR = 1.39, 95% Cl = 1.15-1.67, P= 0.001）, but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific, Further investigations are required to confirm these findings.

阿瑞匹坦用于预防女性胃肠道肿瘤患者化疗所致恶心呕吐的疗效研究

背景与目的 预防化疗所致恶心呕吐在肿瘤治疗的全程管理中是十分重要的一环。本研究评价了在高危女性胃肠道肿瘤患者中,在帕洛诺司琼、地塞米松基础上联用阿瑞匹坦能否进一步预防或减轻FOLFIRI方案(氟尿嘧啶、亚叶酸和伊立替康)或FOLFOX方案(氟尿嘧啶、亚叶酸和奥沙利铂)化疗所致恶心呕吐的发生率和严重程度。方法 本研究为随机、双盲、安慰剂对照、Ⅲ期临床研究。纳入患者为年龄≤50岁的年轻女性,既往饮酒较少或无饮酒史,确诊为胃肠道肿瘤且正在接受FOLFOX或FOLFIRI方案化疗。2015年8月4日至2020年3月31日期间共有248例女性患者入组,按1∶1比率随机分配至干预组和对照组。采用意向性分析评价患者的基线特征和疗效。分析日期为2020年10月30日。患者随机分配至阿瑞匹坦组(阿瑞匹坦:化疗第1天125 mg,化疗开始前60 min口服;第2、3天80 mg,每天早上口服;帕洛诺司琼0.25 mg静脉注射;地塞米松:化疗第1天6 mg,化疗开始前30 min口服)或安慰剂组(安慰剂:化疗第1天125 mg,化疗开始前60 min口服;第2、3天80 mg,每天早上口服;帕洛诺司琼0.25 mg静脉注射;地塞米松:化疗第1天12 mg,化疗开始前30 min口服)。主要研究终点为完全缓解(complete response,CR)率,定义为第1周期化疗后全程(overall phase)无呕吐发作或未使用解救性治疗药物的患者的比例。其他疗效指标,如无恶心、无呕吐的患者比例等,作为次要研究终点和探索性研究终点。结果 共有来自中国4个临床研究中心的248例患者入组,其中243例[阿瑞匹坦组125(51.4%)例、对照组118(48.5%)例]患者可进行疗效和安全性分析。所有患者的平均[mean(SD)]年龄为40.1(7.3)岁。阿瑞匹坦组的CR率显著高于对照组,包括全程[107(87.0%)vs. 80(66.7%),P<0.001]、急性期[114(92.7%)vs. 91(75.8%),P=0.001]和延迟期[109(88.6%)vs. 84 (70.0%),P=0.001]。两组不良事件的发生率[100(80.0%)vs. 96(81.3%),P=0.79]相似,未观察到与阿瑞匹坦治疗相关的3或4级不良事件。多因素分析显示阿瑞匹坦的应用是唯一与全程CR相关的独立因素。结论 在较年轻的、少量饮酒或无饮酒史的胃肠道肿瘤的女性患者中,帕洛诺司琼和地塞米松基础上联用阿瑞匹坦可增强FOLFOX或FOLFIRI方案化疗时的止吐疗效,耐受性良好。

Safety and activity of WX-0593(Iruplinalkib)in patients with ALK-or ROS1-rearranged advanced non-small cell lung cancer:a phase 1 dose-escalation and dose-expansion trial

WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)patients with ALK or ROS1 rearrangement.In the dose-escalation phase and dose-expansion phase,patients were treated with WX-0593 until disease progression,unacceptable toxicity,or subject withdrawal.In the dose-escalation phase,the primary endpoints were maximum tolerated dose(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient.MTD was not reached.Overall,140 of the 152(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.

A modified clinicopathological tumor staging system for survival prediction of patients with penile cancer

Background:The 8th American Joint Committee on Cancer tumor-node-metastasis(AJCC-TNM)staging system is based on a few retrospective single-center studies.We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular emboliza-tion could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer.Methods:A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system.The internal validation was analyzed by bootstrap-corrected C-indexes(resampled 1000 times).Data from 436 patients who were treated at 15 centers over four conti-nents were used for external validation.Results:A survivorship overlap was observed between T2 and T3 patients(P=0.587)classified according to the 8th AJCC-TNM staging system.Lymphovascular embolization was a significant prognostic factor for metastasis and survival(all P<0.001).Based on the multivariate analysis,only lymphovascular embolization showed a significant influ-ence on cancer-specific survival(CSS)(hazard ratio=1.587,95%confidence interval=1.253-2.011;P=0.001).T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascu-lar embolization(P<0.001).Therefore,a modified clinicopathological staging system was proposed,with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows:t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion,and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion.The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories(all P<0.005)and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system(C-index,0.739 vs.0.696).These results were confirmed in the external validation cohort.Conclusions:T2-3 penile cancers are heterogeneous,and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system.

New frontiers in proton therapy:applications in cancers

Proton therapy offers dominant advantages over photon therapy due to the unique depth-dose characteristics of proton,which can cause a dramatic reduction in normal tissue doses both distal and proximal to the tumor target volume.In turn,this feature may allow dose escalation to the tumor target volume while sparing the tumor-neighboring susceptible organs at risk,which has the potential to reduce treatment toxicity and improve local control rate,quality of life and survival.Some dosimetric studies in various cancers have demonstrated the advantages over photon therapy in dose distributions.Further,it has been observed that proton therapy confers to substantial clinical advantage over photon therapy in head and neck,breast,hepatocellular,and non-small cell lung cancers.As such,proton therapy is regarded as the standard modality of radiotherapy in many pediatric cancers from the technical point of view.However,due to the limited clinical evidence,there have been concerns about the high cost of proton therapy from an economic point of view.Considering the treatment expenses for late radiation-induced toxicities,cost-effective analysis in many studies have shown that proton therapy is the most cost-effective option for brain,head and neck and selected breast cancers.Additional studies are warranted to better unveil the cost-effective values of proton therapy and to develop newer ways for better protection of normal tissues.This review aims at reviewing the recent studies on proton therapy to explore its benefits and cost-effectiveness in cancers.We strongly believe that proton therapy will be a common radiotherapy modality for most types of solid cancers in the future.