Nab-paclitaxel(abraxane)-based chemotherapy to treat elderly patients with advanced non-small-cell lung cancer:a single center,randomized and open-label clinical trial

Background： The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer （NSCLC）. Materials and methods： From October 2009 to January 2013, 48 elderly patients （≥65 years） with NSCLC were investigated in this clinical trial. The patients were randomized and equally allocated into arms A and AP- （A） abraxane （130 mg/m2, days 1, 8）; （B） abraxane ＋ nedaplatin （20 mg/m2 days 1-3, q3w）. The parameters of objective response rate （ORR）, disease control rate （DCR）, progression-free survival （PFS）, overall survival （OS） and side effects were evaluated between two arms. Results： Over 80% of the patients completed four cycles of chemotherapy. The total ORR was 21.3 %, DCR was 55.3%, PFS 4.5 months and OS 12.6 months. No significant difference was found between arms A and AP in terms of ORR （16.7% vs. 26.1%, P=0.665） or DCR （55.3% vs. 56.5%, P=0.871）. The median PFS in arm A was 3.3 months [25-75% confidence interval （CI）： 3.1-7.2] and 5.5 months （25-75% CI： 3.2-7.0） in arm AP with no statistical significance （P=0.640）. The median OS in arm A was 12.6 months （25-75% CI： 5.7-26.2） and 15.1 months （25-75% CI： 6.4-35.3） in arm AP with no statistical significance （P=0.770）. The side effects were mainly grade 1-2. The incidence of grade 3-4 toxicities was 29.1% in arm A and 62.5% in arm AP with a statistical significance （P=0.020）. Conclusions： Compared with combined therapy, abraxane alone chemotherapy was beneficial for elderly NSCLC patients with better tolerability and less adverse events, whereas did not significantly differ in terms of ORR, DCR, PFS or OS.

Inhibitory Effect of MiR-449b on Cancer Cell Growth and Invasion through LGR4 in Non-Small-Cell Lung Carcinoma

Non-small-cell lung carcinoma （NSCLC） is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b （miR-449b） functions as a tumor suppressor in many cancers. However, the role of miR- 449b in NSCLC is still unknown. In the present study, miR-449b was significantly down- regulated in NSCLC samples and cell lines. Bioinformatics analysis revealed that 3＇-UTR region of leucine rich repeat containing G protein-coupled receptor 4 （LGR4） mRNA had putative complementary sequences to miR-449b, which was further confirmed by the luciferase assay. Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4. Interestingly, over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro. Furthermore, ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells. Therefore, the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.

Weekly intravenous nanoparticle albumin-bound paclitaxel for elderly patients with stage IV non-small-cell lung cancer:a series of 20 cases

The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m2 in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.

Low Correspondence of EGFR Mutations in Tumor Tissue And Paired Serum of Non-Small-Cell Lung Cancer Patients

Objective： Epidermal growth factor receptor （EGFR） mutations are strong determinants of tumor response to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer （NSCLC） patients. The aim of this study was to evaluate the correspondence between EGFR mutations in non-small-cell lung cancer tissues and in circulating DNA. Methods： The research was conducted in 50 non-small-cell lung cancer patients who had undergone curative surgery, and in whom both serum and neoplastic tissues were available. Meanwhile sera of 33 cases of advanced NSCLC patients were also analyzed. DNA were extracted from each sample. Mutations of EGFR in exonl8-21 were examined by PCR amplification method and direct sequencing. Results： EGFR mutations were detected in 15 （30%） of 50 neoplastic tissue samples, 6 cases were in-frame deletion del E746-A750 in exonl9, 9 cases were substitution in exon 21 （all were L858R except one was L861Q）, but no mutated DNA resulted in paired serum circulating DNA samples of 50 resectable patients. As the 33 advanced NSCLC patients, EGFR mutations were detected in only 2 serum circulating DNA samples, all were L858R mutation in exon 21. Conclusion： These data indicated that it was difficult to identify EGFR mutations in circulating DNA of NSCLC patients. The use of EGFR mutation in serum as a clinical method for decision making of TKI therapy is unsatisfactory.

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

A phase I study of nimotuzumab plus docetaxel in chemotherapy- refractory/resistant patients with advanced non-small-cell lung cancer

Background： To determine the safety and therapeutic efficacy of nimotuzumab （h-R3） combined with docetaxel in advanced non-small-cell lung cancer （NSCLC） patients who have failed to respond to prior first-line chemotherapy. Methods： In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor （EGFR）-expressing stage IV NSCLC were treated with nimotuzumab plus doeetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed.Results： There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade Ⅲ-Ⅳ toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients （66.7%）. The median progression-free survival （PFS） was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR （EGFR WT）. The median survival time （MST） was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT. Conclusions： Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients.

Sequential therapy according to distinct disease progression patterns in advanced ALK-positive non-small-cell lung cancer after crizotinib treatment

Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.

Advances in adjuvant systemic therapy for non-small-cell lung cancer

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.

Relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma

Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.

Achievable complete remission of advanced non-small-cell lung cancer: Case report and review of the literature

Surgery is the first choice of treatment for patients with non-small-cell lung cancer(NSCLC), but few patients can be treated surgically because of either advanced disease or poor pulmonary function. Other therapies include radiotherapy and chemotherapy, as well as complementary and alternative therapies, usually with disappointing results. Bronchial artery infusion(BAI) is a manageable and effective method for treating advanced NSCLC. Outcome is good by BAI due to its repeatability and low toxicity. Icotinib hydrochloride is a newly developed and highly specific epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor and has been safely and efficiently used to treat advanced NSCLC. We herein report a 73-year-old patient with chronic cough, who was diagnosed with advanced NSCLC with the EGFR mutation of L858 R substitution in exon 21, and treated with the combination of oral icotinib and BAI chemotherapy as the first-line therapy, which resulted in a satisfactory clinical outcome. Complete remission of advanced NSCLC can be achieved using the combination of oral icotinib and BAI chemotherapy.

Prognostic role of multiple abnormal genes in non-small-cell lung cancer

BACKGROUND Non-small-cell lung cancer(NSCLC)has the highest morbidity and mortality rates among all malignant tumor types.Although therapies targeting the mutated genes such as KRAS have been used in the clinic for many years,the prognosis remains poor.Therefore,it is necessary to further study the aberrant expression or mutation of non-target genes affecting the survival and prognosis.AIM To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients.METHODS We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas(TCGA)database.We also collected samples from 85 NSCLC patients from the First People’s Hospital of Jingzhou City and retrospectively followed the patients.Multivariate Cox regression analysis and survival analysis were performed.RESULTS Analysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival:TP53(P=0.79),PTEN(P=0.94),RB1(P=0.49),CTNNB1(P=0.24),STK11(P=0.32),and PIK3CA(P=0.013).However,the probability of multiple genes(TP53,PTEN,RB1,and STK11)affecting survival was 0.025.Retrospective analysis of clinical data revealed that sex(hazard ratio[HR]=1.29;[95%CI:0.64-2.62]),age(HR=1.05;[95%CI:1.02-1.07]),smoking status(HR=2.26;[95%CI:1.16-4.39]),tumor histology(HR=0.58;[95%CI:0.30-1.11]),cancer stage(HR=16.63;[95%CI:4.8-57.63]),epidermal growth factor receptor(EGFR)mutation(HR=1.82;[95%CI:1.05-3.16]),abundance(HR=4.95;[95%CI:0.78-31.36]),and treatment with tyrosine kinase inhibitors(TKIs)(HR=0.58;[95%CI:0.43-0.78])affected patient survival.Co-occurring mutations of TP53,PTEN,RB1,and STK11 did not significantly affect the overall survival of patients receiving chemotherapy(P=0.96)but significantly affected the overall survival of patients receiving TKIs(P=0.045).CONCLUSION Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients.Combined with TKI treatment,the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.

Immediate Versus Delayed Treatment with EGFR Tyrosine Kinase Inhibitors after First-line Therapy in Advanced Non-small-cell Lung Cancer

Objective： To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment （immediate group） vs. those received delayed treatment upon disease progression as second-line therapy （delayed group）. Methods： The study included 159 no-small-cell lung cancer （NSCLC） patients who received gefitinib or erlotinib as maintenance treatment in the immediate group （85 patients） or as second-line therapy in the delayed group （74 patients）. The primary end point was progression-free survival （PFS）. EGFR mutation status was detected using denaturing high-performance liquid chromatography （DHPLC）. Results： PFS was 17.3 and 16.4 months in the immediate and delayed groups, respectively （hazard ratio [HR], 0.99; 95% Confidence Interval [CI]： 0.69-1.42; P=0.947）. In a subgroup analysis that included only patients with EGFR mutation, however, PFS was significantly longer in the immediate group than in the delayed group （HR, 0.48; 95% CI： 0.27-0.85; P=0.012）. In patients with wild type EGFR, the risk for disease progression was comparable between the two groups （HR, 1.23; 95% CI： 0.61-2.51; P=0.564）. No significant difference was demonstrated between the immediate and delayed group in terms of the overall survival （OS） （26.1 months vs. 21.6 months, respectively; HR=0.53; 95% CI： 0.27 to 1.06; P=0.072）. There was also no difference in the incidence of adverse events between the two groups. Conclusions： EGFR TKI maintenance improves PFS in patients with EGFR mutation. Prospectively designed clinical studies that compare TKI immediate vs. delayed treatment after first-line chemotherapy upon disease progression are needed.

Impact of crizotinib on long-term survival of ALK-positive advanced non-small-cell lung cancer: A Chinese multicenter cohort study

Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC) in clinical trials. We conducted this retrospective multicenter study to assess the outcomes of crizotinib therapy in, to our knowledge, a large sample cohort of patients with ALKpositive advanced NSCLC.Methods: We reviewed the medical records of 484 unselected ALK-positive NSCLC patients treated with crizotinib at 5 cancer centers in China from January 2013 to November 2017. Clinical data were collected from the initiation of crizotinib therapy to Response Evaluation Criteria in Solid Tumors(RECIST)-defined progressive disease(PD).Results: A total of 428 eligible ALK-positive NSCLC patients were enrolled, 273(63.8%) of whom received crizotinib as first-line treatment. The median progression-free survival(PFS) and overall survival(OS) from the initiation of crizotinib treatment were 14.4 [95% confidence interval(95% CI), 12.4-16.4] months and 53.4(95%CI, 33.7-73.1) months, respectively. In subgroup analyses, patients who received crizotinib as first-line treatment showed a higher disease control rate(DCR) and a longer median OS compared with second-/later-line crizotinib treatment(94.8% and OS not reached vs. 89.0% and 40.5 months, respectively). For 261 patients with RECISTdefined PD, multivariate Cox analysis revealed that in patients who received first-line crizotinib therapy, continued crizotinib beyond progressive disease(CBPD) and next-generation ALK inhibitors after crizotinib failure were associated with improved survival.Conclusions: This study has demonstrated the clinically meaningful benefit of crizotinib treatment in a large cohort of Chinese ALK-positive NSCLC patients. CBPD and next-generation ALK inhibitor treatment may provide improved survival after RECIST-defined progression on crizotinib.

Review of epidermal growth factor receptor-tyrosine kinase inhibitors administration to non-small-cell lung cancer patients undergoing hemodialysis

Non-small-cell lung cancer(NSCLC)causes significant mortality worldwide.Patients with chronic renal failure have an increased risk of developing lungcancer.NSCLC Patients with chronic renal failure undergoing hemodialysis(HD)often exhibit poor performance,and chemotherapy is generally contraindicated.Oral epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective treatment agents for NSCLC patients.However,the benefits andadverse effects of EGFR-TKIs in NSCLC undergoing HD are known.There are noclinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD.We reviewed all previous case reports about EGFR-TKIs in NSCLC patientsundergoing HD.It is difficult to design studies about the effects of EGFR-TKIs inpatients undergoing HD,and this review is quite important.EGFR-TKIs are welltolerated in patients undergoing HD.The main routes of elimination of EGFRTKIsare metabolism via the liver,and renal elimination is minor.Therecommended doses and pharmacokinetics of these EGFR-TKIs for patientsundergoing HD are similar to those for patients with normal renal function.Theplasma protein binding of EGFR-TKIs is very high,and it is not necessary toadjust the dose after HD.In conclusion,EGFR-TKIs are effective and welltolerated in patients undergoing HD.

Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer

Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.

Review of the current targeted therapies for non-small-cell lung cancer

The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer(NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor(EGFR), and crizotinib which targets anaplastic lymphoma kinase(ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790 Mtargeted agents CO-1686 and AZD9291, and the ALKtargeted agents ceritinib(LDK378), AP26113, alectinib(CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come.

LungPoint导航联合吲哚菁绿荧光成像在Ⅰa期非小细胞肺癌淋巴结采样中的应用价值

目的:寻找一种准确定位Ⅰa期非小细胞肺癌患者(NSCLC)前哨淋巴结(SLN)的方法,验证SLN作为淋巴结取样样本的合理性。方法:采用前瞻性研究方法,参照入组标准纳入2021年1月至2023年12月在山东省公共卫生临床中心胸外科临床分期为Ⅰa期NSCLC住院患者50例,术前借助LungPoint导航气管镜下肿瘤周围注射示踪剂吲哚菁绿,通过荧光胸腔镜成像完成SLN定位,并对包括SLN在内的区域淋巴结行病理学检查,使用该方法对SLN的识别率、准确率与假阴性率等验证其作为淋巴结取样样本的合理性。结果:50例患者中,41例检测到SLN,识别率为82.0%(41/50),经病理检测发现3例共计9枚SLN有淋巴结转移(阳性),其中1例亦检出非前哨淋巴结(N-SLN)阳性2枚。9例患者未检测到SLN,清扫淋巴结54枚,未发现转移淋巴结,故SLN准确率为100.0%(41/41),假阴性率为0(0/3)。结论:借助LungPoint气管镜在肿瘤周围注射示踪剂吲哚菁绿,通过荧光胸腔镜成像探寻SLN技术具有较高的区域淋巴结转移预测性,有望成为指导Ⅰa期NSCLC系统性淋巴结采样的依据。

Antitumor and vascular effects of apatinib combined with chemotherapy in mice with non-small-cell lung cancer

Objective The aim of this study was to investigate the antitumor and vascular effects of apatinib use combined with chemotherapy on mice with non-small-cell lung cancer(NSCLC).Methods First,60 tumor-bearing nude mice were randomly divided into control,low-dose,and high-dose groups.Four nude mice per group were sacrificed before administration and on days 1,3,7,and 10 after administration.HIF-1αexpression in tumor tissues was detected.Second,32 nude mice were randomly divided into control,premetrexed,synchronous,and sequential groups.The weights and tumor volumes of mice were recorded.Results(1)HIF-1αexpression decreased significantly on days 3 and 7 after low-dose apatinib treatment.There was no significant difference in HIF-1αexpression in the high-dose apatinib group(P>0.05).MMP-2 and MMP-9 expression levels in the low-dose apatinib group were significantly lower than those in the control group(P<0.05).(2)In the low-dose apatinib group,the microvessel density increased gradually from days 3 to 7 post-treatment,while that in the high-dose apatinib group decreased significantly.(3)The inhibitory effect of sequential therapy using low-dose apatinib and pemetrexed was optimal,while that of synchronous treatment was not better than that of pemetrexed usage alone.Sequential treatment using low-dose apatinib and pemetrexed exerted the best antitumor effect.(4)The expression levels of p-AKT,p-mTOR,p-MEK,and p-ERK in the sequential group were significantly lower than those in the other three groups(P<0.05).Conclusion Apatinib usage involves certain considerations,such as dose requirements and time window for vascular normalization during lung cancer treatment in nude mice,suggesting that dynamic contrast-enhanced magnetic resonance imaging and other tests can be conducted to determine the vascular normalization window in patients with lung cancer and to achieve the optimal anti-vascular effect.

Verification and Dosimetric Impact of Acuros XB Algorithm for Stereotactic Body Radiation Therapy (SBRT) and RapidArc Planning for Non-Small-Cell Lung Cancer (NSCLC) Patients

Purpose: The experimental verification of the Acuros XB (AXB) algorithm was conducted in a heterogeneous rectangular slab phantom, and compared to the Anisotropic Analytical Algorithm (AAA). The dosimetric impact of the AXB for stereotactic body radiation therapy (SBRT) and RapidArc planning for 16 non-small-cell lung cancer (NSCLC) patients was assessed due to the dose recalculation from the AAA to the AXB. Methods: The calculated central axis percentage depth doses (PDD) in a heterogeneous slab phantom for an open field size of 3 ×3 cm2 were compared against the PDD measured by an ionization chamber. For 16 NSCLC patients, the dose-volume parameters from the treatment plans calculated by the AXB and the AAA were compared using identical jaw settings, leaf positions, and monitor units (MUs). Results: The results from the heterogeneous slab phantom study showed that the AXB was more accurate than the AAA;however, the dose underestimation by the AXB (up to ?3.9%) and AAA (up to ?13.5%) was observed. For a planning target volume (PTV) in the NSCLC patients, in comparison to the AAA, the AXB predicted lower mean and minimum doses by average 0.3% and 4.3% respectively, but a higher maximum dose by average 2.3%. The averaged maximum doses to the heart and spinal cord predicted by the AXB were lower by 1.3% and 2.6% respectively;whereas the doses to the lungs predicted by the AXB were higher by up to 0.5% compared to the AAA. The percentage of ipsilateral lung volume receiving at least 20 and 5 Gy (V20 and V5 respectively) were higher in the AXB plans than in the AAA plans by average 1.1% and 2.8% respectively. The AXB plans produced higher target heterogeneity by average 4.5% and lower plan conformity by average 5.8% compared to the AAA plans. Using the AXB, the PTV coverage (95% of the PTV covered by the 100% of the prescribed dose) was reduced by average 8.2% than using the AAA. The AXB plans required about 2.3% increment in the number of MUs in order to achieve the same PTV coverage as in the AAA plans. Conclusion: The AXB is more accurate to use for the dose calculations in SBRT lung plans created with a RapidArc technique;however, one should also note the reduced PTV coverage due to the dose recalculation from the AAA to the AXB.

Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer

Objective： To observe the efficacy and safety of albumin-bound paclitaxel （ABP） monotherapy in treating recurrent advanced non-small-cell lung cancer （NSCLC）. Methods： We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results： Of these 21 patients, the best overall response was partial response （PR） in 6 patients （28.6%）, stable disease （SD） in I0 patients （47.6%）, and progressive disease （PD） in 5 patients （23.8%）. The overall response rate （ORR） was 28.6% and the disease control rate （DCR） （PR ＋ SD） was 76.2%. The median progression-flee survival （PFS） was 4.0 months （95% CI, 5.0-7.0 months）. The main grade 3/4 toxicities included neutropenia （11.1%）, peripheral nerve toxicity （5.6%）, muscle and joint aches （5.6%）, and fatigue （5.6%）. Conclusions： The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.