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 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.

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.

Clinical observation of pemetrexed on advanced non-small-cell lung cancer

Objective： The aim of our study was to observe the efficacy and toxicity of 50 cases of advanced non-small cell lung cancer （NSCLC） patients treated by pemetrexed. Methods： Fifty patients, including 29 females and 21 males, with a median age 62 years （35–82 years）, 13 of whom were treated with pemetrexed only and the left 37 cases were treated with pemetrexed combined with platinum in the Department of Oncology, Renmin Hospital of Wuhan University from June 2006 to March 2009. Single agent regimen： patients received pemetrexed 500 mg/m2 on day 1 with every 21 days. Combination regimen： patients received pemetrexed 500 mg/m2 on day 1 and carboplatin 300 mg/m2 on day 1 or cisplatin 35 mg/m2 on day 1 to day 3 or nedaplatin 80 mg/m2 on day 1 by intravenous infusion with 21 days as one cycle. RECIST 1.0 standard was used to evaluate the clinical efficiency, and the WHO toxicity standard was used to evaluate toxic reaction, and the QOL was used to evaluate the quality of life. Results： All patients were given 162 cycles （at least 2 cycles, at most 6 cycles） and the response rate of all the patients were evaluated. There were 2 complete remission （CR）, 7 partial remission （PR）, 22 stable disease （SD） and 19 progressive disease （PD） in the group, the overall response rate was （RR） was 18.0% and disease control rate （DCR） 62.0%. The quality of life improvement rate reaches 58.0%. The major toxic reaction included neutropenia, thrombocytopenia, hypemia, nausea, and vomiting. Most of the severity of these effects was grade I–II and well tolerated. Conclusion： Chemotherapy with pemetrexed or pemetrexed combined with platinum in the treatment of advanced non-small cell lung cancer is effective, safe and well-tolerable, which can improve quality of life of the patient.

Pharmacokinetics of gemcitabine in Chinese patients with non-small-cell lung cancer

To determine the pharmacokinetics of gemcitabine (2′,2′-difluorodeoxycytidine) in Chinese non-small-cell lung cancer (NSCLC) patients. Six study subjects were administered gemcitabine at a fixed dose rate of 10 mg/m2 per min (1200 mg/m2, two hours infusion) and carboplatin, and plasma gemcitabine concentrations were measured by ion-pair reversed-phase high-performance liquid chromatography (HPLC). 3P97 Pharmaceutical Kinetics Software was used for the calculation of pharmacokinetic parameters. The obtained mean parameters, elimnation half life (t1/2) (10.67±3.38 min), area under the curve (AUC) (7.55±1.53 (μg·h)/ml), and clearance (CL) (3940.05±672.08 ml/min), were consistent with those reported in literature. The hematologic toxicology result showed that the regimen was effective on and tolerated by the patients.

Clinical application value of bone turnover markers in non-small-cell lung cancer patients with bone metastases

Objective:The purpose of this study was to assess the clinical application value of bone turnover markers in non-small-cell lung cancer(NSCLC) patients with bone metastases.Including diagnosing bone metastases,detecting bone metastatic spread.Methods:Alkaline phosphatase(AKP),β-C-terminal telopeptide of type I collagen(β-CTx),osteocalcin(OST) and bone alkaline phosphatase(BALP) were measured in 76 patients with bone metastases from NSCLC and 44 normal people.Results:The level of AKP,β-CTx and BALP in patients with bone metastasis was significantly higher than in the normal people.Significant correlation was observed among bone turnover markers.The levels of BALP and OST were significantly correlated with the extent of bone metastasis.The patients with high-level CTx and low-level BALP had higher risk of pathologic fracture.Conclusion:In NSCLC patients with bone metastases,bone turnover markers can help to make diagnosis and evaluate the severity.It will have a wide range of use in clinical practice.

The expression of Elf-1 and Ki-67 and their correlations in non-small-cell lung cancer

Objective: Elf-1 is a member of the proto-oncogenes Ets-related transcription factor family and over-expressed in many human tumors, Ki-67 is an important nuclear antigen associated with cell proliferation. This study investigated the expression of Elf-1 and Ki-67 in non-small-cell lung cancer(NSCLC) and studied their correlation with the clinicopathological features. Methods: Tissue microarray from 64 cases lung cancer tissue and 10 cases normal lung tissue was constructed, immunohistochemical method was used to evaluate the protein expressions of Elf-1 and Ki-67, correlations of the expression of Elf-1 and Ki-67 to clinicopathological features of NSCLC were analyzed. Results: Expression of Elf-1 and Ki-67 in NSCLC tissues were significantly higher than in normal lung tissues(P < 0.05), the positive rate of Elf-1 and Ki-67 was 73.44% and 64.06% in NSCLC group, Overexpression of Elf-1 in NSCLC was significantly related to histopathological grading, different clinical staging and the intensity of ELF-1 expression was significantly higher in the group with lymph node metastasis than that without(P < 0.05). Overexpression of Ki-67 was also closely related to tumor differentiation, clinical stages and lymph node metastasis(P < 0.05). In addition positive correlation was found between the expressive intensity of Elf-1 and Ki-67(τ = 0.295, P = 0.018). Conclusion: The high expression and positive correlation of Elf-1 and Ki-67 in NSCLC suggest that they probably play a role in onset and progression of lung cancer, united detecting their expression could be used as an valuable molecular biological index for predicting the malignant behavior and early diagnosis of NSCLC.

Comparison of pharmacokinetics,efficacy and toxicity profile of gemcitabine using two different administration regimens in Chinese patients with non-small-cell lung cancer

Objective： To conduct a randomized comparative trial of pharmacokinetics, efficacy and toxicity profile treatment with 1200 mg/m^2 gemcitabine using standard 30-min infusion or fixed dose rate （FDR） infusion [10 mg/（m^2-min）] on days 1 and 8 plus carboplatin AUC （area under curve） 5 on day 1 in Chinese non-small-cell cancer patients. Twelve patients were enrolled in this study. Methods： Plasma gemcitabine concentrations were measured by ion-pair reversed phase high performance liquid chromatography. Antitumoral activity and toxicity of gemcitabine was assessed according to World Health Organization criteria. Results： The obtained mean parameters, such as T1/2 （elimination half time）, AUC, and CL （clearance）, were consistent with those reported in literature. Qualified response rate in our study was 33.3% for standard arm and 50% for FDR ann. Additional 50% and 33.3% patients contracted stable disease （SD） in standard arm and FDR arm, respectively. The predominant toxicity was hematologic, and patients in the standard infusion ann experienced consistently more hematologic toxicity, Conclusion： Pharmacokinetic and clinical data in this trial support the continued evaluation of the FDR infusion strategy with gemcitabine.

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.

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.

Therapy for non-small-cell lung cancer patients with brain metastasis

Brain metastasis is a major cause of poor prognosis and high mortality for non-small cell lung cancer patients. The prognosis of non-small-cell lung cancer(NSCLC) patients with brain metastasis is generally poor and more effective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.

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.

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.

EXPRESSION OF P120ctn IN NON-SMALL-CELL LUNG CANCER: A CLINICOPATHOLOGICAL STUDY

Objective: To investigate the expression of p120ctn in non-small-cell lung cancer (NSCLC) and its relationship with clinicopathological factors and prognosis. Methods: p120ctn expression was tested by immunohistochemistry for 80 tumors from patients with non-small-cell lung cancer. Correlations were investigated between p120ctn immunostaining in primary tumors and clinicopathological characteristics and survival. Results: Abnormal expression of p120ctn was found in 68/80(85%) tumors in which 43 cases had cytoplasmic staining. Abnormal staining of p120ctn was related with high TNM stage (P=0.003) and nodal metastasis (P=0.024). However, there was no correlation between altered expression with poor differentiation and histological type. According to Kaplan-Meier survival estimate, the expression of p120ctn was related to the poor survival (P=0.015) of patients. A Cox regression analysis revealed that p120ctn expression was a significant independent factor in the prediction of survival for patients with non-small-cell lung cancer (P=0.008). Conclusion: altered expression of p120ctn was found in non-small-cell lung cancers and was correlated with lymph node metastasis and prognosis. From a practical point of view, the expression of p120ctn can be of prognostic value for patients with non-small-cell lung cancer.

Multisegmental Lobe Bronchoplasty for the Treatment of Non-small-cell Lung Cancer

Bronchoplasty was extended to the segmental level and the effect of the multi-segmental surgery for the central non-small lung cancer was observed. The involved lobular bronchi and part of main bronchi were resected and single-layer continuous suture with 5-0 Prolene was used for suturing of the carina of the reconstructed segmental bronchi to form lobular bronchi. Then, single-layer continuous suture with 4-0 Prolene was employed to anastomose the ＂lobular bronchi＂ with main bronchi Our results showed that the 15 bronchoplasties were successfully performed. The tumors were completely removed and postoperatively, the pulmonary functions of the patients were substantially improved. No broncho-pleural fistula and stomal stenosis took place in all the cases. The quality of life of the patients were obviously improved. It is concluded that multisegmental bronchoplasty can completely remove the tumor of central non-small-cell lung cancer and conserve more non-involved lung. The procedure is especially suitable for those patients with severely impaired lung functions and it expands the indications of surgical resection of lung cancer.

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.

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.

Response to dacomitinib in advanced non-small-cell lung cancer harboring the rare delE709_T710insD mutation:A case report

BACKGROUND Tyrosine kinase inhibitors(TKI)have been the standard first-line therapy for advanced non-small cell lung cancer(NSCLC)of epidermal growth factor receptor(EGFR)sensitive mutations.Uncommon EGFR mutations are increasingly reported with the development of next-generation sequencing.However,their sensitivity to TKIs is variable with limited clinical evidence.CASE SUMMARY Here,we report a patient with the rare delE709_T710insD mutation,who showed the favorable efficacy of dacomitinib and achieved a partial response with a progression-free survival of 7.0 mo.CONCLUSION To our knowledge,this is the first report displaying the clinical efficacy of dacomitinib for patients with delE709_T710insD,which may help to provide alternatives in non-classical variant NSCLC patients.Further studies are warranted to make the optimal choice of EGFR-TKI for rare mutations.