Small cell lung carcinoma metastatic to the stomach: Commonly overlooked, limited treatment options

Small cell lung carcinoma metastatic to the stomach,whether synchronous or metachronous,is a rare phenomenon accounting for<0.5%of lung cancers.Hence it can be overlooked by clinicians resulting in delayed diagnosis.This manuscript comments on Yang et al’s article which reported 3 such cases.The main diagnostic features are based on routine morphology comprised of small cells with hyperchromatic nuclei,scant cytoplasm,brisk mitoses and necrosis.This can be supplemented by immunohistochemistry demonstrating positivity for cytokeratin,thyroid transcription factor-1 and neuroendocrine markers as well as a high Ki-67 labelling index.Imaging modalities such as positron emission tomography/contrast computed tomography help to confirm lung origin and rule out the possibility of extra-pulmonary small cell carcinoma.The predominant mechanism of spread is most likely hematogeneous.Prognosis is generally poor since this represents stage 4 disease but survival can be improved by chemo/ra-diotherapy and palliative surgery in select cases.Though outcomes have not changed much in the last several decades,the recent Food and Drug Adminis-tration approval of immune checkpoint inhibitors was a significant milestone as was the delineation of small cell lung carcinoma molecular subtypes.Liquid biopsies are increasingly being used for biomarker studies in clinical trials to assess treatment response and prognosis.

Synchronous multiple lung cancers with hilar lymph node metastasis of small cell carcinoma:A case report

BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We report a case of multiple synchronous lung cancers with hilar lymph node metastasis of small cell carcinoma of unknown origin in a 73-year-old man.Transbronchial lung biopsy revealed squamous cell carcinoma.Although enlargement of lymph node 12u was detected,no distant metastases were observed.The patient was preoperatively diagnosed with T1cN0M0 and underwent thoracoscopic right upper lobectomy with nodal dissection(ND2a).Based on histopathological findings,the primary lesion was squamous cell carcinoma.A microinvasive adenocarcinoma was also observed on the cranial side of the primary lesion.Tumors were detected in two resected lymph nodes(#12u and#11s).Both tumors were pathologically diagnosed as small cell carcinomas.The primary lesion of the small cell carcinoma could not be identified even by whole-body imaging;however,chemotherapy was initiated for hilar lymph node metastasis of the small cell carcinoma of unknown origin.CONCLUSION Multiple synchronous lung cancers can be accompanied by hilar lymph node metastasis of small cell carcinomas of unknown origin.

Case Report:Breast metastasis from small cell lung carcinoma

Breast metastases from extramammary neoplasms are very rare. We presented a 66 year-old female with metastasis of small cell lung carcinoma to the breast. She presented with consolidation over the left upper lobe of her lung undetermined after endobronchial or video-assisted thoracoscopic surgery (VATS) biopsy,and this was treated effectively after antibiotic therapy at initial stage. The left breast lumps were noted 4 months later,and she underwent a modified radical mastectomy under the im-pression of primary breast carcinoma. However,the subsequent chest imaging revealed re-growing mass over the left mediastinum and hilum,and cells with the same morphological and staining features were found from specimens of transbronchial brushing and biopsy. An accurate diagnosis to distinguish a primary breast carcinoma from metastatic one is very important because the therapeutic planning and the outcome between them are different.

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.

Review of the treatment of metastatic non small cell lung carcinoma:A practical approach

In recent years,as we have a better knowledge and understanding of the biology of non small cell lung carcinoma(NSCLC),which leads us to targeting biomarkers driving the NSCLC carcinogenesis and metastatic potential,we now have an increased number of options to offer our patients with NSCLC.We also realize the importance of distinguishing squamous and non squamous histology to guide our treatment decisions of NSCLC.The palliative care concomitant with therapies from the very start of the treatment also showed an impact on survival.This review examines the treatment options in all lines of therapy for metastatic NSCLC that have been approved in Canada,the United States,or Europe.

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.

Glabridin and Anti-Non-Muscle Myosin IIA Therapy Disrupts Non-Small Cell Lung Carcinoma Motility

Lung cancer is the leading cause of cancer related death in the United States killing over 130,000 people each year. While a combination of chemo and radiation therapy may be effective, surgery is still required for many patients. Without surgery, the disease may progress and lead to metastases. We sought to determine if treatment with anti-non-muscle myosin IIA antibody would inhibit movement of the cells in the presence and absence of glabridin (an isoflavonoid compound shown to inhibit cell migration by inhibiting myosin). We compared inhibition by glabridin to that of an anti-non-muscle myosin IIA antibody and a combination therapy of both at 12 and 24 hours post wound creation. Cells that took up the anti-non-muscle myosin IIA antibody were greatly inhibited in motility and exhibited no significant change in wound healing. Glabridin treatment resulted in a dramatic increase in wound size within 12 hours and regeneration within 24 hours. The greatest decrease in motility was observed in cells treated with the combination of both glabridin and anti-non-muscle myosin IIA antibody. By 24 hrs, cell migration had halted due to death of the cells resulting from this combination. Further testing needs to be done to determine a safe mode of delivery of the combination therapy to ensure only local distribution. Controlled release drug delivery depot systems have been used as a means to provide local release of drugs intra-tumorally or adjacent to the cancerous tissue after surgical resection and have great potential.

Primary small cell esophageal carcinoma,chemotherapy sequential immunotherapy:A case report

BACKGROUND Primary small cell esophageal carcinoma(PSCEC)is aggressive and rare,with a worse prognosis than other subtypes esophageal carcinoma.No definitive and optimum standard guidelines are established for treating it.Herein,we report a case of PSCEC,including a current literature review of PSCEC.CASE SUMMARY A 79-year-old male was diagnosed PSCEC with multiple lymph node metastasis thorough computed tomography,positron emission tomography-computed tomography,endoscopy and pathology.Surgery was not suitable for this patient.He was treated with etoposide 100 mg/m2 and cisplatin 25 mg/m2 on days 1-3,every 3 wk for 4 cycles.The tumor and lymph nodes became smaller and dysphagia and vomiting symptoms improved.The patient could not tolerate subsequent chemotherapy(CT)because of hematological toxicity;therefore,we performed immunotherapy(durvalumab,1500 mg)every 4 wk.At present the patient has received 12 cycles immunotherapy over about 1 year.He is still receiving treatment and follow-up.CONCLUSION PSCEC with multiple lymph nodes metastasis does not always indicate surgery.CT may extend survival time and improve the quality of life in the absence of surgery.Immunotherapy or immunotherapy plus CT may also work as a treatment for PSCEC.

Expressions of FEZ1 and Survivin, and their significance in small cell lung cancer and squamous cell lung carcinoma

Objective： To detect the expressions of FEZ1 and Survivin in small cell lung cancer （SOLO） and poorly differentiated squamous cell carcinoma （PDSCC）, and to approach a theoretical basis for clinical diagnosis and treatment. Methods： Immunohistochemical and flow cytometry method were used to detect the expressions of FEZ1 and Survivin. Apoptosis ratio and cell proliferation index in normal lung tissue, SCLC and PDSCC were analyzed. Results： The expressions of FEZ1 and Survivin were significantly different between SCLC and PDSCC （P 〈 0.05）. The apoptosis ratio and proliferation index of normal lung tissue were lower than those of PDSCC and SOLO, with a significant difference （P 〈 0.05）. Conclusion： The expressions of FEZ1 and Survivin are significantly different between SCLC and PDSCC, indicating that detecting the expressions of the two indexes may be helpful for clinical diagnosis.

Sequential occurrence of T790M mutation and small cell lung cancer transformation in EGFR-positive lung adenocarcinoma:A case report

BACKGROUND The emergence of secondary drug resistance when treating epidermal growth factor receptor(EGFR)mutated non-small cell lung cancer(NSCLC)using EGFRtyrosine kinase inhibitors(EGFR-TKIs),seriously affects the therapeutic efficacy and survival of patients.Here,we report a case of advanced NSCLC focusing on the application of multiple biopsy modalities to reveal the development of multiple resistance mechanisms during targeted therapies.CASE SUMMARY A 54-year-old male patient presented with EGFR 19Del-mutated advanced lung adenocarcinoma,and exhibited the development of a T790M mutation during initial TKI treatment.Following 3 mo of Osimertinib treatment,a mixed response was observed.Tissue biopsy of the progressive lesion showed transformation to small cell lung cancer(SCLC)harboring RB1 and TP53 mutations,with loss of the original T790M mutation.A standard chemotherapy regimen with Anlotinib for SCLC was administered.Repeat biopsy revealed adenocarcinoma combined with SCLC after tumor progression.The patient’s overall survival was 24 mo.CONCLUSION Multiple biopsy modalities can reveal the development of multiple resistance mechanisms which help with treatment decision-making.Comprehensive treatment regimens according to the drug resistance mechanism significantly improved the prognosis of such patients.

A Novel Peptide from T-Cell Leukemia Translocation-Associated Gene (TCTA) Protein Inhibits Proliferation of a Small-Cell Lung Carcinoma

In 2009, we demonstrated that a peptide, which we named “Peptide A”, derived from the extracellular domain of T-cell leukemia translocation-associated gene (TCTA) protein, inhibited both RANKL-induced human osteoclastogenesis and pit formation of mature human osteoclasts. Here, we examined the effect of Peptide A on the cell proliferation of cell lines of small-cell lung carcinoma, breast cancer, and prostate cancer: RERF-LC-MA, MCF-7, and PC-3, respectively. Peptide A inhibited the proliferation of RERF-LC-MA, but not MCF-7 or PC-3. TCTA protein was immunohistologically detected in RERF-LC-MA and MCF-7. Thus, Peptide A may provide a novel strategy for the therapy of the patients with small-cell lung carcinoma, especially with bone metastasis. In addition, Peptide A may be useful for the treatment of various cancer patients with bone metastasis.

Primary Ovarian Small Cell Carcinoma of Pulmonary Type: Analysis of 6 Cases and Review of 31 Cases in the Literatures

Objective Primary ovarian small cell carcinoma of pulmonary type(SCCOPT)is a rare ovarian tumor with a poor prognosis.The platinum-based chemotherapy is the standard treatment.However,there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence.The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical,imaging,laboratorical and pathological characteristics of 37 SCCOPT cases,in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases(n=37)was 56.00(range,22-80)years.Almost 80%of them had a stageⅢorⅣtumor.All patients underwent an operation and postoperative chemotherapy.Nevertheless,all cases had a poor prognosis,with a median overall survival time of 12 months.Immunohistochemical y,the SCCOPT of all patients showed positive expressions of epithelial markers,such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2(SOX-2),and negative expressions of estrogen receptor,progesterone receptor,vimentin,Leu-7,and somatostatin receptor 2.The tumor of above 80%cases expressed synaptophysin.Only a few cases expressed neuron-specific enolase,chromogranin A,and thyroid transcription factor-1.Conclusions SCCOPT had a poor prognosis.SOX-2 could be a biomarker to be used to diagnose SCCOPT.

The ^(18)F-FDG uptake in non small cell lung carcinoma correlates with the DNA-grading of malignancy

In order to evaluate correlation of glucose metabolism and DNA ploidity of tumors, the uptake of 18F-Deoxyglucose (FDG) by PET prior to surgery and the DNA cotent and DNA-grading of malignancy (DNA-MG) of Schiff-stained nuclei obtained from fresh tumor fragments by means of image cytometry were studied, and thereafter the correlation between standardized uptake value (SUV) and (DNA-MG) was analysed in forty-nine patients with histologically proven non-small cell lung carcinoma (NSCLC). As a result of the DNA histograms of these 49 patients, 46 (93.88%) were aneuploid and only 3(6.12%) were tetraploid. A linear correlation of the SUV versus the (DNA-MG) (r=0.336, p=0.024) was found, demonstrating that 18F-FDG PET as a non-invasive metabolic imaging technique, may also provide inforrnation correlated to malignant DNA patterns which may be valuable in malignant differentiation and prognostic prediction.

EGFR mutation identifies distant squamous cell carcinoma as metastasis from lung adenocarcinoma

Lung cancer metastasis is typically determined by histologic similarity between distant and primary lesions. Herein, we present a 70-year-old Japanese woman with an adenocarcinoma in her lung and a squamous cell carcinoma in her femur; both tumors had an identical epidermal growth factor receptor mutation, G719 S. This indicated that both tumors had a common origin, despite their histologic dissimilarity. The tumor in the femur was thus identified genetically as a lung cancer metastasis. This case suggests that genetic analysis can determine whether a distant lesion is a lung cancermetastasis, particularly when the histology differs from that of the primary lesion.

Colonic metastasis after resection of primary squamous cell carcinoma of the lung:A case report and literature review

Lung cancer is a common malignancy in the world; however symptomatic colonic metastasis from primary lung cancer is rare. A 64-year-old man was originally found poorly differentiated squamous cell carcinoma of right lung and received right lower lobectomy and lymph node dissection. Three years later, the patient presented to our emergency room with the symptom of upper abdominal pain and weight loss. Abdominal palpation and computed tomography scan of the abdomen revealed a large mass measuring 7.6 cm &#x000d7; 8.5 cm in the ascending colon. Colonoscopy and biopsy revealed poorly differentiated squamous cell carcinoma with similar morphological pattern to that of the previous lung cancer. Chemotherapy was given and the patient died 5 mo later. Lung cancer metastatic to the colon confers a poor prognosis: overall survival ranged from 5 wk to 1 year, with a median survival of 3 mo after the diagnosis of the colonic metastasis.

Extrapulmonary small cell carcinoma of lymph node: Pooled analysis of all reported cases

AIM: To study clinical outcomes and management of lymph nodes extrapulmonary small cell carcinoma(LNEPSCC). METHODS: Herein, we perform a systematic search of published literature in the PubMed and EMBASE databases for studies describing LNEPSCC. For uniformity of reporting, LNEPSCC was staged as limited if it involved either single lymph node station or if surgery with curative intent had been undertaken. The disease was staged extensive if it involved two or more lymph node regions.RESULTS: The systematic literature review yielded eight descriptions(n = 14) involving cervical, submandibular and inguinal lymph nodes. Eleven(64.7%) patients had limited disease(LD) and six(35.3%) had extensive disease(ED) at presentation. Chemotherapy(n = 6, 35.3%) or surgery(n = 4, 23.5%) were the most common form of treatment given to these patients. Complete response was achieved in 12(70.6%) of the patients. Median(interquartile range) progression free survival and overall survival was 15(7-42) mo and 22(12.75-42) mo respectively. Of the three illustrative cases, two patients each had ED at presentation and achieved complete remission with platinum based combination chemotherapy.CONCLUSION: LNEPSCC is a rare disease with less than 15 reported cases in world literature. Surgical resection with curative intent is feasible in those with LD while platinum based combination chemoradiation is associated with favorable outcomes in patients with ED. Prognosis of LNEPSCC is better than that of small cell lung cancer in general.

Primary small cell oesophageal carcinoma: A retrospective study of different treatment modalities

BACKGROUND Primary small cell of esophageal carcinoma is an aggressive tumor with no established treatment guidelines.A treatment strategy was adopted based on small cell carcinoma of the lung because of many similar clinicopathological features.Here,we report one of the largest case series in a western population.AIM To review the practice of treating small cell oesophageal cancer(SCOC)with different treatment modalities treated at our institution between 2001 and 2014.METHODS A total of 28 cases of SCOC have been identified.All cases were identified with a ten-digit code known as the CHI number.Data was collected using a combination of an electronic database,case notes and the chemotherapy electronic prescribing system(chemocare).We collected information on age,gender,performance status,staging of the disease(limited stage vs extensive stage).RESULTS The results showed 17 patients(61%)were diagnosed with limited stage small cell oesophageal cancer(LS-SCOC),while 11 patients(39%)were diagnosed with extensive stage small cell oesophageal cancer(ES-SCOC).The median age at diagnosis of SCOC was 72 years(range 52-86).The median survival for patients with ES-SCOC was 7 mo(95%CI:1-12)vs LS-SCOC[median 23 mo(95%CI:14-40)],P<0.0001.Subgroup analysis of those who received treatment showed the median survival for patients who received palliative chemotherapy was 7 mo(95%CI:1.5-12),concurrent chemoradiation 45 mo(95%CI:38-)and sequential chemoradiation 20 mo(95%CI:17-25),P<0.0001.CONCLUSION Our data strongly support the use of concurrent chemoradiation in the treatment of LS-SCOC in patients who are fit with no significant comorbidity.

The 2002 AJCC TNM classification is a better predictor of primary small cell esophageal carcinoma outcome than the VALSG staging system

Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant tumor with a poor prognosis. The optimal disease staging system and treatment approaches have not yet been defined. This study aimed to evaluate the prediction of different staging systems for prognosis and treatment options of SCCE. We retrospectively accessed the clinicopathologic characteristics, treatment strategy, and prognosis of 76 patients diagnosed with primary SCCE between 2001 and 2011. The 1-, 2-, 3-, and 5-year overall survival rates were 58%, 31%, 19%, and 13%, respectively. Univariate analysis showed that the 2002 American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) classification (P=0.002), Veterans Administration Lung Study Group (VALSG) stage (P=0.001), predisposing factors (P<0.001), T category (P=0.023), and M category (P<0.001) were prognostic factors for overall survival. Multivariate analysis showed that the 2002 AJCC TNM stage (P<0.001) was the only independent prognostic factor for survival. The value of the area under the receiver operator characteristic (ROC) curve (AUC) of the 2002 AJCC TNM staging system was larger than that of VALSG staging system with regard to predicting overall survival (0.774 vs. 0.620). None of the single treatment regimens showed any benefit for survival by Cox regression analysis. Thus, the 2002 AJCC TMN staging system improved the prediction of SCCE prognosis; however, the optimal treatment regimen for SCCE remains unclear.

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

Pang Fuwan Uses Yao Medicine to Observe the Therapeutic Effects on the Physical and Mental Symptoms of Patients with Advanced Non-Small Cell Lung Cancer

Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July 2022, 84 patients with advanced non-small-cell lung carcinoma were selected and randomly divided into the Observation Group and control group, and the control group was treated with routine Western medicine, with 42 cases in each group. The activity of daily living (ADL) was assessed before and after treatment, meanwhile, the self-rating depression scale (SDS) and self-rating anxiety SAS (SAS) were used to assess the improvement of a bad mood, and quality of life SF-36 was used to assess the quality of life, to judge the efficacy and safety. Results: The effective rate of observation group was 91.67%. The effective rate of the control group was 76.19%. The effective rate of the observation group was significantly higher than that of the control group (P 0.05). There were no significant differences in the scores of SDS, SAS and quality of life between the two groups before treatment (P > 0.05), and after treatment, the scores of SDS, SAS and quality of life in the two groups were compared with those in the control group (P > 0.05), the scores of VAS, SDS and SAS decreased significantly, while ESCV, angle of straight leg elevation, ADL, physiological score, emotional score, social score and health status score increased significantly, the difference was statistically significant (P 0.05). Conclusion: Yao Medicine can improve the psychosomatic symptoms of patients with advanced non-small-cell lung carcinoma better, with better efficacy and higher safety.