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.

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.

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.

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.

Complete pathological response in locally advanced non-small-cell lung cancer patient: A case report

BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally advanced node-positive NSCLC(LA-NSCLC)treated in a phase II prospective protocol with chemotherapy,accelerated hypofractionated radiotherapy(AHRT)and surgery in the preimmunotherapy era.CASE SUMMARY A 69-year-old male,ex-smoker(20 PY),with a Karnofsky performance status of 90,was diagnosed with locally advanced squamous cell lung carcinoma.He was staged by total body computed tomography(CT)scanning,and integrated 18Ffluorodeoxyglucose positron emission tomography/CT scan[cT4 cN3 cM0,stage IIIC according to TNM(tumor-node-metastasis)8th edition]and received AHRT between chemotherapy cycles,in accordance with the study protocol(EudractCT registration 2008-006525-14).At the end of the study the patient underwent surgery,which was not part of the protocol,and showed a complete pathological response.CONCLUSION This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement.Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications.We hypothesize that this radiotherapeutic approach,with its proven efficacy,could be delivered as a short course reducing treatment costs,increasing patient compliance and reducing toxicity.We are currently investigating the possibility of combining hypofractionation,chemotherapy and immunotherapy for patients with LA-NSCLC.

Therapeutic Effects of Kanglaite Injection Combined with Chemotherapy on Advanced Non-small-cell Lung Cancer

The objective of this study was to study the therapeutic effect of Kanglaite injection combined with chemotherapy in the treatment of late-stage nonsmall-cell lung cancer(NSCLC)and also to observe the effect of the combination treatment on immune function.92 patients with advanced stage of NSCLC who admitted to First Hospital of Zibo city hospital from May 2017 to October 2018 were randomly divided into experimentagroup and control group,with 46 cases,respectively.The control group was treated with chemotherapy only while the experimental group was treated with Kanglaite injection combined with chemotherapy which was the basic treatment for patients,and the total treatment effective rate,adverse reaction rate,and immune index of the treatments on two groups were compared.The total treatment effective rate of the experimental group was 80.43%,which was significantly higher than that of the control group,which was 63.04%.The incidence of adverse reactions in the experimental group was 36.96%,which was lower than that of the control group(78.26%).The immune indexes of the experimental group(CD3+,CD4+,IgG,and IgA)were better than that of the control group,respectively.The differences between the two groups were statistically significant(P<0.05).During the chemotherapy of late-stage or advanced NSCLC,the addition use of Kanglaite injection has a significant effect on improving tumor control and reducing the side effects of chemotherapy,and helps to improve the immune function of patients;thus,it is worth promoting.

Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment:A phase 2 clinical trial(BG01-1801)

Background:Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer(NSCLC),but acquired resistance presents challenges.The aim of this open-label,multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone,a novel genetically engineered epothilone analog and microtubule-stabilizing agent,as a third-or later-line treatment for locally advanced ormetastatic NSCLC.Methods:Patients who had failed standard second-line treatment(including platinum-containing chemotherapy or targeted therapy)received utidelone(40 mg/m?via intravenous injection daily,day 1-5)every 21 days.The primary endpoint was the objective response rate(ORR).Secondary endpoints were the duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.Results:From March 12,2019 to January 18,2021,26 pretreated patients with locally advanced or metastatic NSCLC(100%of patients had received prior platinum and 65.4%patients had received prior taxane treatment)were enrolled(80.8%of patients had adenocarcinoma).At baseline,nine(34.6%)patients had received secondline treatment,10(38.5%)patients had received third-line treatment,and seven(26.9%)patients had received fourth-or later-line treatment.By the data cut-off date of August 10,2021,the median follow-up was 7.49 months(range,1.4-26.7 months).The ORR was 15.4%(95%confidence interval[CI],4.4%-34.9%)in the intention-totreat(ITT)cohort(N=26)and 19.0%(95%CI,5.4%-41.9%)in the per-protocol(PP)cohort(N=21).The disease control rate was 69.2%(95%CI,48.2%-85.7%)and 81.0%(95%CI,58.1%-94.6%)in the ITT and PP cohorts,respectively.The median DoR was 4.1 months(95%CI,3.1-5.1 months)in the ITT cohort.The median PFS was 4.37 months(95%CI,2.50-5.29 months)in the ITT cohort and 4.37 months(95%CI,2.50-9.76 months)in the PP cohort.The median OS was not reached,and the 12-month OS rate was 69%(95%CI,45.1%-84.1%).Grade 3/4 treatment-emergent adverse events occurred in 38.5%of patients,and the most common was peripheral neuropathy(23.1%,all Grade 3),which was manageable with dose modifications.Conclusions:In this clinical trial,utidelone showed promising efficacy and had a manageable safety profile.Furtherclinical studies arewarranted to confirm its role in NSCLC treatment.Trial registration:No.NCT03693547;https://classic.clinicaltrials.gov.

Efficacy and safety of anlotinib plus S-1as thirdly-line or later-line treatmentin advanced non-small cell lung cancer

Objective Anlotinib,an oral vascular endothelial growth factor receptor 2(VEGFR2)inhibitor,has confirmed antitumor activity in lung cancer in both in vitro and in vivo assays,and has been recommended as third-line treatment agent in non-oncogene driven non-small cell lung cancer(NSCLC).This prospective study aimed to investigate the efficacy and safety of anlotinib plus S-1 for third-or later-line treatment in patients with advanced NSCLC.Methods Patients with histologically or cytologically confirmed NSCLC,and documented disease progression following second-line chemotherapy,and/or epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)treatment were enrolled in this study.The patients were treated anlotinib(8 mg daily d 1–14)and S-1(60 mg/m^2 d 1–14)and the treatment was repeated every 3 weeks.Treatment was continued until disease progression or unacceptable toxicity occurred.The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and adverse events(AEs)were reviewed and evaluated.Results Forty-one patients were enrolled in the study between June 2018 and December 2018.The total ORR and DCR were 26.8%and 80.5%,respectively.The median PFS was 5.2 months[95%confidence interval(CI),3.9 to 6.6 months].In the univariate analysis,there was a significant difference in the median PFS between patients with brain metastases and those without brain metastases(4.8 months vs 5.9 months,respectively;P=0.039).The Eastern Cooperative Oncology Group(ECOG)performance status(P=0.002),lines of therapy(P=0.015),and therapeutic evaluation(P=0.014)were independent factors that influenced PFS.The most common AEs were hypertension,proteinuria,myelosuppression,gastrointestinal reactions,fatigue,and mucositis.Conclusion Anlotinib plus S-1 is an effective and safe regimen for advanced NSCLC as third-or later-line 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.

Biomarker Testing Rates in Patients with Advanced Non-Small Cell Lung Cancer Treated in the Community

Introduction: Over the past few years, molecular targeted therapies have been?emerging for the treatment of metastatic non-small cell lung cancer (NSCLC).?Targeted therapy is associated with improved outcomes in patients with identified gene alterations, and national guidelines recommend routine biomarker testing. This study evaluated real-world rates of documented epidermal growth factor receptor (EGFR) mutation and other biomarker testing in patients with advanced NSCLC over time.?Methods: Adult patients with Stage IV NSCLC were identified between January 1, 2012 and May 31, 2017 from the US Oncology Network iKnowMedTM?electronic health records. Patients were examined overall and by histology. Rates of documented EGFR mutation and other biomarker testing were calculated. Multivariable regression analyses were conducted to identify characteristics associated with documented biomarker testing. Results: A total of 14,461 patients were identified: median age was 69.3 years, 52.3% were male, 14.6% were nonsmokers, and 64.7% had non-squamous histology.?EGFR mutation testing rates were 35.5%?overall, with an increase in rates seen over time: 30.0% in 2012 to 44.0% in 2016?(p??0.001).?Anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and programmed death-ligand 1 (PD-L1) mutation testing rates were 32.9%, 5.7%, and 5.7%, respectively. More recent diagnosis year, non-squamous histology, larger practice size, and nonsmoking status were strongly associated with higher documented EGFR and ALK mutation testing rates.?Conclusions: EGFR mutation testing rates steadily increased over time, but remained less than 50%, with lower mutation testing rates reported for ALK, ROS1, and PD-L1, suggesting that opportunities exist to improve education on testing for biomarkers in NSCLC.

Effect of etoposide plus thalidomide as maintenance therapy on progression-free survival of elderly patients with advanced non-small cell lung cancer

Objective The aim of the study was to evaluate the efficacy and safety of etoposide plus thalidomide as maintenance therapy for elderly patients with advanced non-small cell lung cancer(NSCLC) without disease progression after first-line chemotherapy.Methods After four to six cycles of platinum-based first-line therapy, 64 elderly patients with advanced NSCLC without disease progression who were treated in the General Hospital of Shenyang Military Region(China) from 2014 to 2016 were enrolled in this study. According to the different maintenance treatment methods, patients were divided as having received etoposide plus thalidomide therapy(treatment group, n = 32) and best supportive care(control group, n = 32). Disease control and progression-free survival(PFS) were compared between the two groups. Results The recent curative effect objective response rates of the treatment group and the control group were 31.3% and 3.1%, respectively, and the disease control rates were 71.9% and 31.3%, respectively. The Kaplan-Meier survival curves of the two groups were significantly different(χ2 = 26.532, P = 0.001). The median PFS for the treatment group and control group was 6.0 months [95% confidence interval(CI) = 4.3–7.9 months] and 3.2 months(95% CI = 2.6–3.8 months), respectively. The side effects in the treatment group included hematologic abnormalities, gastrointestinal toxicity, and impaired liver function, which were relieved after symptomatic support therapy and drug withdrawal.Conclusion Etoposide plus thalidomide as maintenance therapy is associated with a significantly longer PFS with tolerable toxicity for elderly patients with advanced NSCLC.

Cetuximab Combination with Chemotherapy in Advanced Non-Small Cell Lung Cancer

Objective： To observe the efficacy and safety of cetuximab combined with chemotherapy in advanced non-small-cell lung cancer （NSCLC）, and to investigate the association of status of K-RAS gene mutation and epidermal growth factor receptor （EGFR） genotype with clinical outcome. Methods： Between Jan. 2006 and Sep. 2009, nineteen patients with advanced NSCLC received cetuximab （〉4 weeks） combined with chemotherapy in Department of Thoracic Oncology at Beijing Cancer Hospital. Response, survival and toxicity were retrospectively assessed, epidermal growth factor receptor （EGFR） protein expression was evaluated by ELISA Kit. The status of K-RAS gene mutation was tested by PCR-RFLP and EGFR gene amplification was measured by EGFR fluorescence in situ hybridization （FISH）. Results： Partial response（PR） was observed in 26.3%（5/19） of the patients and stable disease（SD） in 52.6%（10/19）. Median progression free survival（PFS） was 6 months （95% CI： 3.6-8.4）. Median overall survival （MST） and 1-year survival rate（SR） were 10.6 months （95% CI： 6.6-14.6） and 47.6%, respectively. Mild or moderate skin rash was the most common toxicity related with cetuximab. K-RAS gene mutation, EGFR protein level and amplification have little correlation with prognosis. Conclusion： Cetuximab combined with chemotherapy was tolerable and the skin rash related with cetuximab was mild to moderate. Cetuximab may prolong survival of the patients who failed to previous chemotherapy.

Inhibition of non-small-cell lung cancer cell proliferation by Pbx1

Lung cancer is one of the most deadly human cancers and continues to be a major unsolved health problem worldwide. Here, we evaluate the function of Pbx1 in the proliferation of non-smallcell lung cancer（NSCLC）. In contrast with its known proliferative function, we found that Pbx1 inhibits the proliferation of lung cancer cells. In particular, Pbx1-specific RNA interference resulted in increased proliferation in lung cancer cells. In addition, histone H3 phosphorylation was also increased following inhibition of Pbx1 expression. In contrast, Pbx1 overexpression repressed the proliferation of lung cancer cells and inhibited DNA synthesis. Collectively, our data indicate that Pbx1 inhibits proliferation in lung cancer cells, suggesting a complex role for Pbx1 in modulating the proliferation of cancer cells and making this protein a potential new target for lung cancer therapy.

In Surgical Treatment of Non-Small-Cell Lung Cancer a Minimum Number of Resected Mediastinal Lymph Nodes Is Mandatory for Accurate Staging

Objective: Increased numbers of removed lymph nodes (LN) are resulting in more accurate staging of the patient (Will-Rogers-Phenomenon). This study evaluates dependence of lymph node sample size to 1) Will-Rogers-Phenomenom, 2) influence of sample size on overall survival and in?terms of 3) morbidity and mortality. Methods: 131 patients after pulmonary resection were?retrospectively analysed concerning surgery, number of removed lymph nodes, stage, complications and survival. Patients were stratified according to the median number of lymph nodes in two groups (A <12 lymph nodes and B ≥12 lymph nodes). Results: 5% of the patients had only local lymphadenectomy and in 14% a systematic lymphadenectomy was performed. 17% of the patients showed skip metastasis. Lymph node positivity was correlated to the number of removed lymph nodes (p = 0.003). The approximated median survival for UICC (Union internationale contre le cancer) stage I was 511, stage II 521 and stage III 290 days. Subgroup analysis of survival data showed in group A an approximated median survival at stage I of 495 days, at II 537 days and at III 451.5 days. Group B showed at stage I 675 days, at II 521 days and at III 221 days. There was no difference in complications and mortality. Conclusion: A too low sample size leads to understaging due to skip metastasis. Obligatory mediastinal lymph node sampling would decrease the risk of understaging due to skip metastasis and does not increase morbidity or complications. Lymph node sampling is not inferior concerning morbidity and survival in our patient collective. This study cannot recommend a minimum number of LN to be resected. The evaluated limit of 12 LN proves to be suitable as a guideline.

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.

RRM1 gene expression in peripheral blood is predictive of shorter survival in Chinese patients with advanced non-small-cell lung cancer treated by gemcitabine and platinum

Objective:To evaluate the predictive values of gene expressions of ribonucleotide reductase M1(RRM1) and breast cancer susceptibility gene 1(BRCA1) in peripheral blood from Chinese patients with non-small-cell lung cancer(NSCLC) treated with gemcitabine plus platinum.Methods:Forty Chinese patients with advanced NSCLC were recruited and received gemcitabine 1200 mg/m 2 on Days 1 and 8 plus carboplatin AUC 5 on Day 1.RRM1 and BRCA1 expression levels in peripheral blood were detected by quantitative reverse transcription-polymerase chain reaction(RT-PCR) .Kaplan-Meier survival curve and log-rank test were performed to evaluate the correlation between gene expression and overall survival for these subjects.Results:No correlation was observed between gene expression of RRM1 and that of BRCA1(P>0.05) ,but there was a strong correlation between the expression of RRM1 and the response to chemotherapy(P=0.003) .Subjects with low RRM1 expression levels in peripheral blood had longer sur-vival time than those with high RRM1 expression levels(16.95 vs.12.76 months,log-rank 3.989,P=0.046) .However,no significant association between BRCA1 expression levels and survival time was found(16.80 vs.13.77 months,log-rank 0.830,P=0.362) .Conclusions:Patients with low RRM1 expression levels in peripheral blood have a greater response to chemotherapy and longer survival time.Advanced NSCLC patients with low RRM1 expression levels may benefit from gemcitabine plus platinum therapy.RRM1 mRNA expression in peripheral blood could be used to predict the prognosis of NSCLC treated by gemcitabine and platinum.

Partial removal of the pulmonary artery in video-assisted thoracic surgery for non-small cell lung cancer

Lobectomy with partial removal of the pulmonary artery in video-assisted thoracic surgery （VATS） currently remains a challenge for thoracic surgeons. We were interested in introducing pulmonary vessel blocking techniques in open thoracic surgery into video-assisted thoracic surgery （VATS） procedures. In this study, we reported a surgical technique simultaneously blocking the pulmonary artery and the pulmonary vein for partial removal of the pulmonary artery under VATS. Seven patients with non-small-cell lung cancer （NSCLC） received lobectomy with partial removal of the pulmonary artery using the technique between December 2007 and March 2012. Briefly, rather than using a small clamp on the distal pulmonary artery to the area of invading cancer, we replaced a vascular clamp with a ribbon and Hem-o-lock clip to block the preserved pulmonary veins so as to prevent back bleeding and yield a better view for surgeons. The mean occlusion time of the pulmonary artery and pulmonary veins were 44.0±10.0 and 41.3±9.7 minutes, respectively. The mean repair time of the pulmonary artery was 25.3±13.7 minutes. No complications occurred. No patients showed abnormal blood flow through the reconstructed vessel. There were no local recurrences on the pulmonary artery. In conclusion, the technique for blocking the pulmonary artery and veins is feasible and safe in VATS and reduces the risk of abrupt intraoperative bleeding and the chance of converting to open thoracotomy, and extends the indications of VATS lobectomy.

Debulking surgery and hyperthermic intrathoracic chemotherapy(HITHOC)for lung cancer

One hundred years ago, the first patients with lung cancer have been reported （1）. Since then long term survival in patients with lung cancer remains disappointing, and this is not only due to the delayed diagnosis but also to the dismal survival of the 70%-75% inoperable patients.

Feasibility of cetuximab and chemoradiotherapy combination in Chinese patients with unresectable stage Ⅲ non-small cell lung cancer:a preliminary report

Objective： In recent years, the combination of cetuximab and chemoradiotherapy （CRT） has been used to treat stage III non-small cell lung cancer （NSCLC）; however, limited data are available for Chinese patients. Herein, we report preliminary data from a phase I/II study testing the combination of cetuximab with inductive chemotherapy, followed by concurrent CRT （CCRT） in Chinese patients with stage III NSCLC. Methods： Eligibility criteria were Zubrod performance status （PS） 0-1, forced expiratory volume in 1 second （FEV1） 〉_1.2 L and adequate organ function. Enrolled patients received weekly cetuximab （initial dose of 400 mg/m2 on day 1 of week 1 and a maintenance dose of 250 mg/m2 on week 2 to the end of CCRT） with cisplatin/vinorelbine （NP） chemotherapy （every 3 weeks for 2 cycles from week 2, followed by two cycles of concomitant NP chemotherapy and intensity-modulated thoracic radiotherapy （TRT） （60-66 Gy/2 Gy）. The primary endpoints were toxicity and feasibility. All patients received positron emission tomography- computerized tomography （PET-CT） scans within the 2 weeks prior to enrollment. Univariate analyses were used to assess the correlation between SUV-T, SUV-N, SUV-TOTAL, gender, age, histology, tumor-node- metastasis （TNM） stage, PS and smoking status and survival. Survival curves were generated for different populations using the Kaplan-Meier method and compared using a log-rank test. Results： Seventeen patients were enrolled and 16 completed the full regime. The overall response rate （ORR） was 58.8% and 82.3% after the induction and CCRT phases, respectively. With a median follow-up duration of 27.6 months, the median survival was 27.6 months [95% confidence interval （CI）： 11.3-43.9 months] with 1- and 2-year survival rates of 88.2% （95% CI, 60.6-96.9%） and 58.8% （95% CI, 60.6-77.8%）, respectively. Three patients remain progression-free to date, and the median progression-free survival （PFS） was 13.5 months （95% CI, 6.8-20.2 months）. No treatment-related death occurred; however, 76% of the patients experienced grade 3＋ adverse events （AEs）, including nansea/vomiting, intestinal obstruction, and esophagitis （〈6%）, while other AEs were mostly of hematological nature （71%）. The cut-off values for SUV-T and SUV-TOTAL were 11 and 20, respectively. Univariate analyses revealed SUV-TOTAL （P=0.027）, SUV-T （P=0.025）, and PS （P=0.006） as potential survival predictors, with a hazard ratio （HR） of 3.4, 3.7, and 9.9, respectively. Conclusions： The combination of cetuximab with induction chemotherapy followed by CCRT appears feasible and promising. Local and locoregional maximal SUVs, defined by 18F-FDG PET-CT scanning, may represent a prognostic indicator for long-term survival for these patients, which warrants further study.