基于传感器阵列和LightGBM-SR模型的危化品泄露监测方法研究

探索了使用传感器阵列和LightGBM-SR模型的危化品泄露监测方法,采用多个传感器实时获取危化品监测数据,并且采用非线性随机共振(stochastic resonance,SR)模型对监测数据调整获取特征信息。选取ExtraTrees、XGBoost、KNN和LightGBM模型作为研究对照模型,分别使用传感器阵列原始数据和SR调理数据对四种模型进行自主学习拟合,然后对测试集数据进行回归预测。研究结果证明未经非线性模型调理的原始传感器阵列监测数据与四种模型的匹配度有所不足。数据经非线性SR算法处理后代入训练,LightGBM-SR模型准确率由LightGBM模型的78.75%提升至98.34%,ExtraTrees-SR稳定性最佳但实际依然存在用时较长,XGBoost-SR和KNN-SR泛化能力与稳定性良好,但是平均准确率不高。LightGBM-SR模型展现了较高的平均准确率,更适合危化品泄露监测的应用场景。

Application and Promotion of Non-pesticide Replacing High-toxic Pesticide Techniques and Its Benefit Analysis in Kunming City

[ Objective] The paper was to operate the application and promotion of non-pesticide replacing high-toxic pesticides techniques in Kunming City, and to analyze its benefit. [ Method ] Through application and promotion of frequency trembler grid lamps, sticking plate trapping technology, construction of treatment ponds for field waste vegetable leaves, standardized （accurate） cultivation techniques, cultivation techniques of disease-resistant varieties and diverse cultivation technologies, the promotion benefit of non-pesticide replacing high-toxic pesticides techniques was comprehensively investigated and evaluated. [ Result ] The appli- cation and promotion area of non-pesticide replacing high-toxic pesticides techniques in Kunming City during 2006 -2010 reached 94 667 hm2. The investigation on control efforts and quantitative analysis of cost/benefit showed that the beneficial result of application and promotion of non-pesticide replacing high-toxic pesticides techniques was higher than the direct benefit of application and promotion of traditional pesticide replacing techniques. This improvement innovated the traditional pesticide replacing method in replacement work of high-toxic pesticides, reducing the usage volume of pesticide in Kunming City. [ Conclusion] The application and promotion of non-pesticide replacing high-toxic pesticides techniques improved the economic, social and ecological benefit of replacement work of high-toxic pesticides, protected the agricultural ecological environment and promoted the sustainable development of agricultural production.

Complete stabilization of severely As-contaminated soil by a simple H2O2 pre-oxidation method combined with non-toxic TMT-15 and FeCl3·6H2O

The stabilization of severely As-polluted soil has been a challenge, especially for the extremely toxic As(Ⅲ) contaminants. In this study, soil with a high As concentration(26084 mg/kg) was availably stabilized by a H2O2 pre-oxidation assisted TMT-15(Na3S3C3N3 solution with a mass fraction of 15%) and FeCl3·6 H2O stabilization method. The results showed that the combination of the two stabilizers(i.e., TMT-15 and FeCl3·6 H2O) presented a better stabilization behavior than either stabilizer used individually. The use of the H2O2 pre-oxidation assisted TMT-15 and FeCl3·6 H2O stabilization approach not only converted the As(Ⅲ) to As(Ⅴ) but also reduced the toxic leaching concentration of As to 1.61 mg/L, which is a safe level, when the additions of TMT-15 and FeCl3·6 H2O were 2 mL and 0.20 g, respectively. Thus, using only a simple H2O2 pre-oxidation to combine clean stabilization with non-toxic stabilizers TMT-15 and FeCl3·6 H2O could render the severely As-contaminated soil safe for disposal in a landfill.

培美曲塞维持化疗联合PD-1/PD-L1抑制剂对晚期非小细胞肺癌的临床疗效分析

目的研究晚期非小细胞肺癌(NSCLC)治疗中培美曲塞维持化疗联合程序性死亡受体-1(PD-1)/程序性死亡受体配体-1(PD-L1)抑制剂的应用效果。方法研究对象为58例晚期NSCLC患者,根据治疗方式不同分为对照组及研究组,各29例。对照组单用培美曲塞维持化疗,研究组在对照组基础上联用培美曲塞维持化疗与PD-1/PD-L1抑制剂(纳武利尤单抗注射液)治疗。对比两组治疗前后T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))及血清肿瘤标志物[神经元特异性烯醇化酶(NSE)、癌胚抗原(CEA)、血清癌抗原125(CA125)、血清细胞角蛋白19片段(CY-FRA21-1)]水平,治疗效果,毒副反应发生率。结果研究组治疗后较治疗前CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)^(+)水平更高,CD8水平更低(P<0.05);且研究组治疗后CD8^(+)(26.24±4.06)%低于对照组的(34.97±4.25)%,CD3^(+)(62.93±4.87)%、CD4^(+)(37.35±4.18)%、CD4^(+)/CD8^(+)(1.41±0.22)高于对照组的(52.16±4.43)%、(30.11±4.04)%、(0.86±0.19)(P<0.05)。两组治疗后较治疗前NSE、CEA、CA125、CY-FRA21-1水平更低(P<0.05);研究组治疗后NSE(16.21±4.04)ng/ml、CEA(29.96±4.52)ng/ml、CA125(49.91±6.63)U/ml、CY-FRA21-1(6.76±3.15)ng/ml低于对照组的(20.94±4.09)ng/ml、(60.08±5.34)ng/ml、(79.85±7.08)U/ml、(11.08±3.27)ng/ml(P<0.05)。研究组治疗后总有效率93.10%高于对照组的65.52%(P<0.05)。两组治疗后毒副反应发生率无差异(P>0.05)。结论晚期NSCLC治疗中培美曲塞维持化疗联合PD-1/PD-L1抑制剂的应用效果显著,可有效降低患者血清肿瘤标志物水平,增强其免疫功能,且毒副反应少。

Toxic epidermal necrolysis related to AP(pemetrexed plus cisplatin)and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer

Toxic epidermal necrolysis(TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related(80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen(pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer(NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21 st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.

Insilico structural analysis of parasporin 2 protein sequences of non-toxic bacillus thuringiensis

The unusual and remarkable property of parasporin 2 of non-insecticidal Bacillus thuringiensis is specifically recognizing and selectively targeting human leukemic cell lines. The 37-kDa inactive nascent protein is proteolytically cleaved to the 30-kDa active form that loses both the N-terminal and the C-terminal segments. Accumulated cytological and biochemical observations on parasporin-2 imply that the protein is a pore-forming toxin. To confirm the hypothesis, insilico analysis was performed using homology modeling. The resulting model of parasporin 2 protein is unusually elongated and mainly comprises long β-strands aligned with its long axis. It is similar to aerolysin-type β-pore-forming toxins, which strongly reinforce the pore-forming hypothesis. The molecule can be divided into three domains. Domain 1, comprising a small β-sheet sandwiched by short α-helices, is probably the target-binding module. Two other domains are both β-sandwiches and thought to be involved in oligomerization and pore formation. Domain 2 has a putative channel-forming β-hairpin characteristic of aerolysin-type toxins. The surface of the protein has an extensive track of exposed side chains of serine and threonine residues. The track might orient the molecule on the cell membrane when domain 1 binds to the target until oligomerization and pore formation are initiated. The β-hairpin has such a tight structure that it seems unlikely to reform as postulated in a recent model of pore formation developed for aerolysin-type toxins. Parasporin 2 (Accession no: BAD35170) protein sequence analysis indicated two different domains namely, aerolysin toxin and clostridium toxin domain based on different database searches (CDD and Pfam). It showed a close similarity with the available PDB template (PDB id: 2ZTB) of parasporin which has cytocidal activity against MOLT-4, HL60 and Jurkat cell lines. Based on the PSI Blast analysis, 3D structures of the domains were predicted by using Swiss model server. Accuracy of the prediction of 3D structure of different domains of parasporin protein was further validated by Ramachandran plot and PROCHECK (G-value). The structure is dominated by β-strands (67%, S1-12), most of which are remarkably extensive, running all or most of the longer axis of the molecule. This study helped to elucidate the 3D structure of parasporin 2 (Acc. No. BAD35170) which might enable to probe further its specific mechanism of action. Though the similarity is observed in the domain architecture, there is variation in the regions of the domains even among the same group of parasporin 2. Docking of this model structure and experimental structure with specific receptors of the cancer cells will facilitate to explore mechanism of parasporin 2 action and also provide information about its evolutionary relationship with toxic Cry proteins.

螺旋断层调强放疗联合顺铂治疗中晚期非小细胞肺癌的效果及对miR-532-3p、MAPK表达的影响

目的:探讨与分析螺旋断层调强放疗联合顺铂治疗中晚期非小细胞肺癌(non-small-cell lung cancer,NSCLC的效果及对微小RNA-532-3p(micro RNA-532-3p,miR-532-3p)、丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)表达的影响。方法:选择2017年5月—2022年4月于天水市第二人民医院诊治的60例中晚期NSCLC患者作为研究对象,根据1∶1随机数表法分组原则将患者分为断层组30例与对照组30例。对照组给予顺铂化疗治疗,断层组在对照组治疗基础上给予螺旋断层调强放疗,比较两组疗效、毒副反应及治疗前后外周血CD3^(+)T淋巴细胞、CD4^(+)T淋巴细胞相对含量、血液miR-532-3p、MAPK相对表达水平。结果:断层组总有效率为90.0%,高于对照组的60.0%,差异有统计学意义(P<0.05)。断层组治疗期间胃肠道反应、血液学毒性、肝肾功能损害、神经系统毒性等毒副反应发生率与对照组比较,差异无统计学意义(P>0.05)。治疗后,两组外周血CD3^(+)T淋巴细胞、CD4^(+)T淋巴细胞相对含量高于治疗前,且断层组高于对照组,差异有统计学意义(P<0.05)。治疗后,两组血液miR-532-3p、MAPK相对表达水平低于治疗前,且断层组低于对照组,差异有统计学意义(P<0.05)。结论:螺旋断层调强放疗联合顺铂治疗中晚期NSCLC患者能提高临床效果,不会增加毒副反应发生率,还可提高外周血CD3^(+)T淋巴细胞、CD4^(+)T淋巴细胞相对含量,降低血液miR-532-3p、MAPK相对表达水平。

Predictive Factors of Severe Toxicities of Pemetrexed-Containing Chemotherapy in Patients with Non-Squamous Non-Small Cell Lung Cancer

Background: Pemetrexed (PEM) is an efficacious multi-targeted antifolate with acceptable toxicities for non-squamous non-small cell lung cancer (non-Sq NSCLC). However, in the clinical setting, PEM has more severe adverse effects than those reported. The aim of this study was to identify the factors for the toxicities of PEM-containing chemotherapy in non-Sq NSCLC patients in the clinical setting. Patients and Methods: We retrospectively evaluated the factors related to PEM toxicities in chemotherapy-naive patients with non-Sq NSCLC from September 2009 to July 2013 at our hospital. Logistic regression model was used in the univariate and multivariate analyses. Results: In total, 104 patients were analyzed. Grades 3 to 5 hematologic toxicities were frequent and included neutropenia (42%), febrile neutropenia (7%), anemia (18%), thrombocytopenia (17%), and disseminated intravascular coagulation (2%). On multivariate analyses, the predictors were poor performance status (PS) [odds ratio (OR): 4.89, 95% confidence interval (CI): 1.22 - 19.4] and low body mass index (OR: 1.44, 95% CI: 1.05 - 1.98) for febrile neutropenia;concomitant chronic infectious disease (OR: 6.63, 95% CI: 1.59 - 27.5) and bevacizumab use (OR: 3.57, 95% CI: 1.36 - 9.32) for neutropenia;poor PS (OR: 3.02, 95% CI: 1.33 - 6.85) for thrombocytopenia;and low serum albumin level (OR: 0.22, 95% CI: 0.08 - 0.63) for non-hematologic toxicities. Conclusions: In addition to the previously reported predictors of PEM toxicities, the presence of concomitant chronic infectious disease was associated with hematologic toxicities. Patient groups who are not sufficiently evaluated in clinical trials should be carefully monitored for the development of more toxicities than expected.

肥胖儿童non-HDL-C、remnant cholesterol与亚临床动脉粥样硬化的关系

目的:了解non-HDL-C和remnant cholesterol与肥胖儿童亚临床动脉粥样硬化(AS)的关系。方法:根据甘油三酯(TG)水平将65例肥胖儿童(肥胖组)分为I组(TG≥2.3 mmol/L)32例,II组(TG<2.3 mmol/L)33例,与肥胖组儿童性别年龄相匹配的正常体质量儿童30例为III组(对照组)。比较3组儿童血脂指标,对肥胖组各项血脂指标与血浆致动脉粥样硬化指数(AIP)进行相关性分析,肥胖患儿体质指数、血脂指标与颈动脉内径、内膜-中层厚度(c-IMT)、血流参数进行相关性分析。结果:I组、II组的TG、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、non-HDL-C、remnant cholesterol、AIP均较对照组升高,高密度脂蛋白胆固醇(HDL-C)较对照组降低,且I组的remnant cholesterol、AIP均较II组升高。肥胖组儿童AIP与TG、non-HDL-C、remnant cholesterol呈正相关,与HDL-C呈负相关。37例行颈动脉超声检查的肥胖儿童的c-IMT较正常儿童的增厚。结论:non-HDL-C、remnant cholesterol在肥胖儿童亚临床AS中有重要作用,在肥胖儿童血脂异常的治疗中应关注non-HDL-C、remnant cholesterol的变化。

Phase I Study to Determine MTD of Docetaxel and Cisplatin with Concurrent Radiation Therapy for Stage Ⅲ Non-Small Cell Lung Cancer

Objective： To evaluate the maximum tolerated dose （MTD） of docetaxel （DCT） and cisplatin （DDP） concurrently with three dimensional （3D） conformal radiotherapy or IMRT for patients with locally advanced non-small cell lung cancer （stage IIIa and IIIb） after 2–4 cycles of induction chemotherapy. Methods： Fourteen patients with histological/cytological proven stage III non–small-cell lung cancer were eligible. 3D or IMRT radiotherapy （60-70Gy in 30-35 fractions, 6-7weeks, 2 Gy/fraction） was delivered concurrently with cisplatin and docetaxel, 2 cycles during concurrent chemoradiotherapy （CCRT）. The level I dosage was composed of 56 mg/m2 DCT, on day 1 and 28mg/m2 DDP, on day 1 and day 2. The level II was composed of 60 mg/m2 DCT, on day 1 and 30 mg/ m2 DDP, on day 1 and day 2. The level III was composed of 64 mg/m2 DCT, on day 1 and 32 mg/ m2 DDP, on day 1 and day 2. Results： Fourteen patients were allocated and finished concurrent chemoradiotherapy. The dose-limiting neutropenia was at the dose Level III （64 mg/m2） and occurred in 2 of 5 patients. No dose limiting non-hematologic or hematologic toxicity occurred in the other patients. Conclusions： Patients with locally advanced non-small cell lung cancer may tolerate 60mg/m2 docetaxel and 60mg/m2 cisplatin for 2 cycles during concurrent radiotherapy after 2-3 cycles of induction chemotherapy.

Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced non-small cell lung cancer： a meta-analysis

Objective： To evaluate the clinical efficacy of Shenqi Fuzheng injection combined with gemcitabine plus cisplatin（GP） in the treatment of advanced non-small cell lung cancer （NSCLC）. Methods： we performed a systematicsearch in the electronic databases such as Cochrane Library, Pubmed, Embase, Chinese Journal Full-text Database,Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Full-text Database andWanfang Database up to 30 January 2017. Randomized controlled trials （RCT） of Shenqi Fuzheng Injectioncombined with GP chemotherapy in the treatment of advanced NSCLC were searched, and all the RCTs wereconducted on methodological quality assessment. Data extraction and data analysis were according to standards ofCochrane systematic review. Results： Eight trials were included including a total of 701 patients. Meta-analysisresults： Shenqi Fuzheng injection combined with GP chemotherapy could significantly improve the functionalstatus of patients with NSCLC （OR = 3.44, 95% CI [2.26, 5.25], P 〈 0.0001） and clinical treatment efficacy （OR =（OR = 0.31, 95%CI [0.20, 0.47], P 〈 0.0001. The rate of leukopenia （OR = .31, 95%CI [0.20,0.47], P 〈 0.0001）,thrombocytopenia （OR = 0.58, 95%CI [0.37, 0.91], P = 0.020）, hemoglobin decline （（OR = 0.31, 95%CI [0.16,0.59], P = 0.0004） and incidence of gastrointestinal reactions （OR = 0.58,P 〈 0.05） could be reduced. Conclusion：Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced NSCLC obtainedsignificantly clinical efficacy. The quality of the literature incorporated is low, the conclusion requires high-qualityresearch to further prove.

安罗替尼胶囊联合AP方案治疗晚期非小细胞肺癌的效果及对毒副反应发生情况、CTC、Her-2与P-Akt的影响

目的探讨安罗替尼胶囊联合AP方案治疗晚期非小细胞肺癌的效果及对毒副反应发生情况、循环肿瘤细胞(CTC)、人表皮生长因子受体2(Her-2)与磷酸化丝氨酸苏氨酸蛋白激酶(P-Akt)的影响。方法选取2018年1月至2021年1月我院收治的84例晚期非小细胞肺癌患者,以随机数字表法将其分为对照组(AP方案治疗)和观察组(AP方案联合安罗替尼胶囊治疗),各42例。比较两组的治疗效果。结果观察组的疾病控制率显著高于对照组(P<0.05)。两组的胃肠道反应、白细胞减少、骨髓抑制、肝功能损害及肾功能损害发生率无明显差异(P>0.05)。治疗后,观察组的CTC阳性率以及Her-2、P-Akt表达水平均低于对照组(P<0.05)。治疗后,观察组的红细胞免疫黏附促进因子(FEER)、协同肿瘤红细胞花环(ATER)均高于对照组(P<0.05)。结论安罗替尼胶囊联合AP方案治疗晚期非小细胞肺癌有助于提高治疗效果,降低CTC阳性率,下调Her-2、P-Akt表达,且不会增加毒副反应。

Maligned non-steroidal anti-inflammatory drugs:Misunderstanding of their safety profile in patients with renal insufficiency

Non-steroidal anti-inflammatory drugs have a fundamental and pivotal position in management of many of the disorders managed by rheumatologists.Promulgation of a false perspective of their toxicity has compromised our ability to advise our patients and participate in the management of their disorders. The literature sources, from which the false perspective derives, do not accurately reflect safety and fail to address the value of appropriate drug use monitoring.We, as rheumatologists, must stand up and proactively address engrained misconceptions-if we are to be able to continue to provide safe, effective care for our patients.

Fixed Dose Rate versus Standard Dose Rate Infusion of Gemcitabine and Cisplatin in Advanced Stage Non-Small Cell Lung Cancer

Background: Comparing the efficacy and safety of gemcitabine at a fixed-dose rate (FDR) infusion (10 mg/m2/min) with the standard dose rate infusion in patients with locally advanced and metastatic non-small squamous cell carcinoma (NSCLC). Methods: The study randomized 60 patients with confirmed diagnosis of NSCLC to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 given as a 30-min infusion (Arm A) or at a rate of 10 mg/m2/min (Arm B). Cisplatin 75 mg/m2 was administered intravenously on day 2 in both arms. Results: No difference in overall response rate (46.6% versus 43.3%). Median time to progression for Arm A was 7 months (95% CI, 6.207 - 7.793 months), versus 6 months for Arm B (95% CI, 4.990 - 7.010 months). Median survival time was comparable [12 months (95% CI, 8.588 - 15.412 months) versus 11 months (95% CI, 9.066 - 12.934 months)] respectively. Two-year survival (18% versus 11%, p = 0.38) was detected. No treatment related deaths occurred. Main hematological toxicities were grade I and II neutropenia, in 36.7% and 53.3% respectively (p = 0.044). Grade III anemia was observed in 10% and 6.7% in both arms respectively (p = 0.024). Grade I and II nausea and vomiting was observed in 50% and 46.7%. Conclusions: FDR gemcitabine in combination with cisplatin had equivalent efficacy and more severe hematologic toxicities compared to the standard 30-min gemcitabine infusion with cisplatin in patients with advanced NSCLC.

Analysis of Numerical Results in High Temperature Congealment and Chemistry Non-equilibrium Flow Field

Using the air plasma ignition technique, physicochemical process of burning can be accelerated; concentration limit ofretrofires both can be extended; reliability of retrofires and stability of burning can be improved. In this paper, using internalequivalent heat area in place of electric are that created Ohm heat, the flow fields of thermodynamic equilibrium chemistry con-gealment and chemistry non-equilibrium in the plasma generator were simulated. The influences of the inlet prerotation angleof air, the inlet total pressure of air and the airflow compression angle of spray nozzle on the temperature on the surface of elec-

Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration

Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotrophic factor(BDNF)are believed to be associated with the neurotoxic effects of Aβpeptide.To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ_(1-40)-induced retinal injury in Sprague-Dawley rats,we treated rats by intravitreal administration of phosphate-buffered saline(control),Aβ_(1-40)(5 nM),or Aβ_(1-40)(5 nM)combined with BDNF(1μg/mL).We found that intravitreal administration of Aβ_(1-40)induced retinal ganglion cell apoptosis.Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ_(1-40)group than in the control and BDNF groups.In the Aβ_(1-40)group,low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression.BDNF abolished Aβ_(1-40)-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression.These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ_(1-40)by activating the BDNF-TrkB signaling pathway in rats.

Turbulent Flow Action of Pulp in Wet - Laid Non - Woven Processes

The paper deals with the fluid field of web forming in wet-laid non-woven production.The influence of the turbulent flow on blending fiber and occluded fluid produced in pulp flow has been discussed in theory and practice.The suitable use of the imported velocity of pulp is very important in producing wet-laid products of good quality.

CYFRA 21-1 as an early predictor of first line chemotherapy response in advanced non small cell lung cancer

Objective： In an era of ever evolving, promising new therapies for advanced non small cell lung cancer （NSCLC）, early predictors of response to therapy, are needed. We evaluated early variations in CYFRA 21-1 serum levels of patients with advanced NSCLC receiving first line chemotherapy and correlated the results with objective tumor response. Methods： 29 consecutive, previously untreated, patients of advanced non small cell lung cancer, with measurable disease on CT scan were evaluated. All patients were treated with conventional systemic chemotherapy, although the choice of chemotherapy was left to the discretion of the treating physicians. Serum samples were obtained immediately before the start of 1st and 2nd cycles of chemotherapy. CYFRA 21-1 was measured with an electrochemiluminescense immunoassay on an automatic analyzer （Elecsys 2000; Roche Diagnostics）. Response was evaluated using Response evaluation criteria in solid tumors （RECIST） criteria. Results： 10 patients had partial response, 9 patients had stable disease and 9 had progressive disease. None of the patients had complete response. 21/29 （72%） patients had an elevated baseline value of CYFRA 21-1.62% patients （18/29） had a decrease in CYFRA 21-1 after 1 cycle of chemotherapy. The average reduction in the 2nd reading was irrespective of whether baseline value was normal or not. The average reduction was statistically significant （P = 0.002; 95% CI, from 0.8369 to 3.49464; t test）. 8 out of 10 （80%） patients with partial response had a reduction in their 2nd reading of. CYFRA （P = 0.019; 95% CI, from 0.81965 to 7.20035; t test） which was significant. We also observed that 6/9 （66%） patients whose disease remains stable also had a decrease in their subsequent reading （P = 0.0106; 95% CI, from -0.44942 to 3.82720; t test）, though it was not significant statistically. Although 5 out of 9 （55%） patients, who had an increase in their CYFRA 21-1 level, had progressive disease, but it was not statistically significant （P = 0.537; 95% CI, from -1.20021 to 2.13354; ttest）. 14 out of 19 （73%） who either had partial response or had stable disease, had a reduction in their 2nd value of CYFRA 21-1 and was significant statistically （P = 0.004; 95% CI, from 0.74792 to 3.50208; t test）. We also observed that except for 1 patient, all patients who had a decrease of 42% or more in their subsequent CYFRA 21-1 level, were those who had either responded to chemotherapy or had stable disease （P = 0.001）, which was statistically significant. Conclusion： We can conclude that monitoring of serum marker CYFRA 21-1, early dudng first-line chemotherapy may be a useful prognostic tool for evaluation of early tumor response in patients with advanced NSCLC.

Using Novel Statistical Techniques to Accurately Determine the Predictive Dose Range in a Study of Overall Survival after Definitive Radiotherapy for Stage III Non-Small Cell Lung Cancer in Association with Heart Dose

Purpose: Recent studies of radiotherapy (RT) for stage III non-small-cell lung cancer (NSCLC) have associated high dose to the heart with cardiac toxicity and decreased overall survival (OS). We used advanced statistical techniques to account for correlations between dosimetric variables and more accurately determine the range of heart doses which are associated with reduced OS in patients receiving RT for stage III NSCLC. Methods: From 2006 to 2013, 119 patients with stage III NSCLC received definitive RT at our institution. OS data was obtained from institutional tumor registry. We used multivariate Cox model to determine patient specific covariates predictive for reduced overall survival. We examined age, prescription dose, mean lung dose, lung V20, RT technique, stage, chemotherapy, tumor laterality, tumor volume, and tumor site as candidate covariates. We subsequently used novel statistical techniques within multivariate Cox model to systematically search the whole heart dose-volume histogram (DVH) for dose parameters associated with OS. Results: Patients were followed until death or 2.5 to 81.2 months (median 30.4 months) in those alive at last follow up. On multivariate analysis of whole heart DVH, the dose of 51 Gy was identified as a threshold dose above which the dose volume relationship becomes predictive for OS. We identified V55Gy (percentage of the whole heart volume receiving at least 55 Gy) as the best single DVH index which can be used to set treatment optimization constraints (Hazard Ratio = 1.044 per 1% increase in heart volume exposed to at least 55 Gy, P = 0.03). Additional characteristics correlated with OS on multivariate analysis were age, stage (IIIA/IIIB), and administration of chemotherapy. Conclusion: Doses above 51 Gy, applied to small volumes of the heart, are associated with worse OS in stage III NSCLC patients treated with definitive RT. Higher stage, older age and lack of chemotherapy were also associated with reduced OS.

A phase I study with Satraplatin and simultaneous chest radiation for non-small cell lung cancer

Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advanced non-small cell lung cancer (NSC-LC) has not been defined. This phase I trial attempts to identify a maximally tolerated dose (MTD) and dose limiting toxicity (DLT) for Satraplatin given con-currently with radiation for locally advanced N-SCLC. Patients and Methods: 15 patients with histologically confirmed Stage IIIA/B NSCLC entered onto this study with four dose escalations (10 to 40 mg daily) of Satraplatin. Eligibility included patients with NSCLC and one of the following criteria: 1) previously untreated, inoperable disease and planned to receive radiation therapy to primary disease site;2) previously resected disease with mediastinal relapse;or 3) metastatic disease in no more than one distant site. Results: The most common toxicities reported were all grades of fatigue (n = 9), nausea (n = 9), constipation (n = 7), fever (n = 7), and vomiting (n = 6). No DLT at the 1st, 2nd, and 3rd dose levels was identified. At the 4th dose level, one patient developed grade III elevation of liver function tests (LFTs) and a second patient developed grade III diarrhea with fever requiring hospitalization. There were 8 partial responses out of 11 evaluable patients for response (RR 67%). Conclusion: Elevated LFTs and diarrhea appear to be the principal DLTs of concurrent daily oral Satraplatin and thoracic radiation in the outpatient setting. The MTD of concurrent Satraplatin with thoracic radiation therapy appears to be 40 mg daily.