Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Analysis and Review of Downregulated Actin Cytoskeletal Proteins in Non-Small Cell Lung Cancer

Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.

Envafolimab combined with chemotherapy in the treatment of combined small cell lung cancer: A case report

BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy combined with first-line chemotherapy to treat extensive-stage C-SCLC to explore its antitumor activity and safety.CASE SUMMARY We report a case of C-SCLC that presented early with adrenal, rib, and mediastinal lymph node metastases. The patient received carboplatin and etoposide with concurrent initiation of envafolimab. After 6 cycles of chemotherapy, the lung lesion was significantly reduced, and the comprehensive efficacy evaluation showed a partial response. No serious drug-related adverse events occurred during the treatment, and the drug regimen was well tolerated.CONCLUSION Envafolimab combined with carboplatin and etoposide in the treatment of extensive-stage C-SCLC has preliminary antitumor activity and good safety and tolerability.

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.

A Review of the Impact of PD-L1 Expression on the Prognosis of Small Cell Lung Cancer

Small cell lung cancer is an invasive neuroendocrine carcinoma with early metastasis potential. It tends to grow rapidly and metastasize early, with the majority of patients diagnosed as advanced stage small cell lung cancer (ES-SCLC). Systemic treatment consisting of platinum drugs and etoposide chemotherapy is the main treatment method, although the objective effective rate of this combination is 60% - 80%. However, most SCLC patients experience disease progression shortly after initial treatment, with a median overall survival of 10 months. There are few second-line treatment drugs available, and immunotherapy using checkpoint inhibitors has completely changed the treatment of many cancer types. Adding immune checkpoint inhibitors (ICI) to conventional chemotherapy as first-line treatment can improve the survival rate of widespread small cell lung cancer (ES-SCLC), but so far, there are no definitive factors to determine patients who are more likely to benefit from immunotherapy. This review summarizes the results of immunotherapy trials for small cell lung cancer. And a review was conducted on the predictive factors of these trials, with special emphasis on the expression of PD-L1 in small cell lung cancer to determine its clinical value.

Research Progress of Anti-Angiogenic Drugs in First-Line Treatment of Small Cell Lung Cancer

Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effective treatment now. As an active research direction at present, anti-angiogenic drugs are not only widely used in non-small cell lung cancer and other tumors, but also have certain effects in small cell lung cancer combined with chemotherapy. As one of the effective treatment methods for small cell lung cancer, related research is not rare, but there is still inadequacy, such as side effects can not be tolerated, and the timing of treatment can not be accurately assessed. This article will briefly describe the research progress of anti-angiogenic drugs combined with chemotherapy in the first-line treatment of extensive small cell lung cancer.

Therapy-Induced Changes of Gene Expression in a Matched Pair of Small Cell Lung Cancer (SCLC) Cell Lines

Extended stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses early as drug-resistant tumor associated with a dismal prognosis. A pair of SCLC cell lines obtained from a single patient at different time points during treatment allows for the investigation of the changes in gene expression prior to (GLC14) and following cycles of chemotherapy and irradiation (GLC19). GLC19 cells were reported to reveal an increased doubling time and exhibit increased chemoresistance to doxorubicin, etoposide, melphalan and vinblastine. Upregulated transcripts in GLC19, as assessed by microarray analysis, comprised proteins involved in regulation of cellular growth (NGFRAP1/BEX3), adhesion, glutathione metabolism and, in particular, WNT/Notch pathways and the putative cancer stem cell phenotype (CD44, ALDH1A1, and AKR1C1/13). Metallothioneins, tubulins TUBA3/4 and tumor protein p53 inducible protein 11 (TP53IP11) were downregulated in this cell line compared to GLC14. Except increased expression of glutathione transferases no classical markers of chemoresistance were found, pointing to a role of altered growth control/differentiation and reduced accessibility of this SCLC tumor cells growing as multicellular spheroids. In conclusion, treatment of this single SCLC with cyclophosphamide, doxorubicin and etoposide (CDE) followed by radiotherapy ultimately resulted in an enrichment of tumor cells displaying the typical signature of tumor-initiating or cancer stem cells (CIC/CSC).

Synergistic Anticancer Activity of Topotecan— Cyclin-Dependent Kinase Inhibitor Combinations against Drug-Resistant Small Cell Lung Cancer (SCLC) Cell Lines

Extended-stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses rapidly as drug-resistant tumor. Topotecan (TPT) is the single chemotherapeutic agent approved for second-line treatment of SCLC. However, the response to TPT is short-lived and novel treatment modalities need to be developed. Sequential treatment of cytotoxic drugs and inhibitors of cyclin-dependent kinases (CDKs) showed promising preclinical anticancer activity and, in the present work, combinations of TPT with CDK inhibitors olomoucine, roscovitine and CDK4I are shown to exhibit synergistic cytotoxic activity against SCLC cell lines. Highest activity was found against TPT-resistant NCI-H417 and DMS153 cell lines and moderate chemosensitizing effects against a primary SCLC cell line and sensitive GLC19 cells at levels of CDK inhibitors which exerted low toxicity. A combination of 0.6 μM TPT with 0.6 μM roscovitine, exhibiting no significant cytotoxicity as single agents, reduced viability of the TPT-resistant NCI-H417 line (IC50 > 10 μM) by 50%. In the TPT resistant cell lines olomoucine and roscovitine, targeting CDK1,2,5,7, were highly effective, whereas in the more sensitive cell lines CDK4I, inhibiting mainly CDK4/6, showed activity. In NCI-417 cells, preincubation with roscovitine for one day proved synergistic with TPT. Thus, in good accordance with previous findings, CDK inhibitors are able to convert SCLC cancer cells which are cell-cycle arrested by a blockade of topoisomerase I by TPT to apoptotic cells. Since nowadays several CDK inhibitors are at various phases of clinical testing their combination with TPT seems to constitute a promising approach to improve second-line chemotherapy in SCLC.

A Clinic-Epidemilogical Study of Cases of Locally Advanced Non Small Cell Lung Cancer (NSCLC) That Received Radiotherapy at NCI Cairo in the Period from 2001-2010

Purpose: This work was to study the clinic-epidemiological characteristics of patients with locally advanced NCSLC and to analyze their prognostic factors and also the results of different treatment modalities for local control and their effect on overall survival (OAS). Materials and Methods: This is a retrospective study including 121 patients with primary locally advanced NSCLC diagnosed between 2001 and 2010 at the radiotherapy department , National Cancer Institute, Cairo University, Egypt. Results: The study showed significant correlation between the tumor size 60, moderately differentiated tumors G2 and treatment outcomes;better locoregional control and better survival rates. On the opposite side poorly differentiated tumors G3, tumor size > 7 cm had the worst locoregional control and survival rates. The study also showed significant statistical correlation between treatment modality, locoregional control and survival rates. Patients who were treated by either concommitent chemo-radiotherapy or sequential chemo-radiotherapy had better local control compared to other patients who were treated by radical radiotherapy, and they also had the best survival rates among all the other treatment groups. The average 6 months OAS rates for all studied patients were 60.3% while 12 months survival rates were 38.8%. The median OAS was 7 months. Conclusions: From the present study, we concluded that concomitant chemo-radiotherapy is the treatment of choice for locally advanced non small cell lung cancer;also we concluded that better performance status and higher hemoglobin levels have better treatment outcome in these cases.

Tumor response assessment by the single-lesion measurement per organ in small cell lung cancer

Background： The criterion of two target lesions per organ in the Response Evaluation Criteria in Solid Tumors （RECIST） version I. 1 is an arbitrary one, being supported by no objective evidence. The optimal number of target lesions per organ still needs to be investigated. We compared tumor responses using the RECIST 1.1 （measuring two target lesions per organ） and modified RECIST I. 1 （measuring the single largest lesion in each organ） in patients with small cell lung cancer （SCLC）. Methods： We reviewed medical records of patients with SCLC who received first-line treatment between January 2004 and December 2014 and compared tumor responses according to the two criteria using computed tomography. Results： There were a total of 34 patients who had at least two target lesions in any organ according to the RECIST 1.1 during the study period. The differences in the percentage changes of the sum of tumor measurements between RECIST 1.1 and modified RECIST 1.1 were all within 13%. Seven patients showed complete response and fourteen showed partial response according to the RECIST I.I. The overall response rate was 61.8%. When assessing with the modified RECIST 1.1 instead of the RECIST 1.1, tumor responses showed perfect concordance between the two criteria （k= 1.0）. Conclusions： The modified RECIST 1.I showed perfect agreement with the original RECIST 1.I in the assessment of tumor response of SCLC. Our result suggests that it may be enough to measure the single largest target lesion per organ for evaluating tumor response.

Clinical Biomarkers and Prognosis in Taiwan Residents Patients with Non-Small Cell Lung Cancer (NSCLC)

Introduction: Lung cancer is the leading cause of cancer death worldwide with poor survival rates. However, the prognostic factors for survival of patients with lung cancer are not well-established. In this study, we examined the impact of routine laboratory biomarkers and traditional factors on survival of patients with non-small cell lung cancer (NSCLC). Method: Secondary data analysis was conducted from a retrospective study of 404 patients with newly diag-nosed lung cancer in 2005-2007 in Taiwan. There were eight routine laboratory biomarkers and eight traditional factors investigated in the analyses. Cox proportional hazards model was used to assess the hazard ratios for the association between risk factors and patient overall survival. The Kaplan-Meier method was used to compare survival curves for each prognostic indicator. Results: High WBC counts (HR = 1.798, 95%CI: 1.225 - 2.639), low Hgb level (HR = 1.437, 95%CI: 1.085 - 1.903), and low serum albumin level (HR = 2.049, 95%CI: 1.376 - 3.052) were significant laboratory prognostic biomarkers for poor NSCLC survival. Additionally we confirmed the traditional prognostic factors for poor overall survival among NSCLC patients, including older age, comorbidity conditions, advanced cancer stage, and non-surgical treatment. Conclusions: This study identified three available laboratory biomarkers, high WBC counts, low Hgb level, and low serum albumin level, to be significant prognostic factors for poorer overall survival in NSCLC patients. Further prognostic evaluation studies are warranted to compare different ethnic groups on the prognostic values of these clinical parameters in NSCLC survival outcomes. These identified prognostic biomarkers should be included in early risk screening of hospitalized lung cancer patient population.

Non-platinum doublets versus single agents in non-small cell lung cancer （NSCLC） patients with elderly age and/or poor performance status： a meta-analysis

学习的目的是在以前未经治疗的先进非小的房间肺癌症(NSCLC ) 把非铂马甲(马甲组) 的功效和毒性与一个非铂单身者代理人(单个代理人的组) 作比较的目的有老年龄或差的表演地位(PS ) 的病人。PubMed 数据库被屏蔽的方法。随后，为全面幸存( OS )的危险比率( HR )和没有前进的幸存( PFS )，为全面反应的相对风险( RR )评价( ORR )并且一个年幸存，并且为毒性的不同类型的机会比率( ORs )用评论经理 5.0 包裹被分享。这研究 1427 个病人包括了的结果在四注册了使随机化的控制试用。分享的 HR 证明马甲组能增加 ORR (P = 0.002 ) 没有异质(P = 0.64 ) ，并且可能改进 OS (P = 0.01 / P = 0.06 ) 与异质(P < 0.001 ) 。在 PFS 没有重要差别(P = 0.16 ) 并且一个年幸存(P = 0.25 ) 在二个治疗组之间。马甲组比单个代理人的组导致了更多的等级 3/4 嗜中性白血球减少症和 thrombocytopenia (P = 0.02 并且 P = 0.000，分别地) 。等级 3/4 贫血症的发生，呕吐，在二个治疗组之间的 mucositis，便秘，腹泻， neurotoxicity，过敏症，和疲劳是不足道的。结论除了嗜中性白血球减少症和 thrombocytopenia，非铂马甲能增加 ORR，和力量没有更多的副作用的增加，与老年龄或差的 PS 为 NSCLC 病人改进 OS；然而，马甲显示出嗜中性白血球减少症和 thrombocytopenia 的增加的率。马甲的增加不能改进 PFS 和一个年幸存。

Single nucleotide polymorphisms of MAGE-A3 gene and its clinical implications in Chinese patients with non-small cell lung cancer(NSCLC)

Background： Available study revealed advanced tumors have a higher expression rate of MAGE-A3 gene which has a lot of single nucleotide polymorphism（SNP） loci with polymorphisms. This study aimed to analyze the allele frequency of SNP loci in MAGE-A3 gene and investigate the relationship between MAGE-A3 gene polymorphisms and clinical factors.Methods： Tumor samples of a cohort of 191 NSCLC patients were collected. EGFR m RNA expression were detected by q RT-PCR. SNPs in whole length of MAGE-A3 gene were detected by direct sequencing. Frequencies of the SNPs were correlated to gene expression, mutation status of EGFR and clinical factors.Results： Sequencing analysis confirmed that allele frequencies of genotypes on SNP loci rs5970360, rs5925210, rs5970361, rs5925211 and rs35123853 were CC（0.681）/CT（0.319）, CC（0.660）/CG（0.340）, CC（0.681）/CA（0.319）, AA（0.984）/AT（0.016） and GG（1.000）/GA（0.000）, respectively, which were different from the frequencies and genotypes of MAGE-A3 in SNP database. Chi-square tests showed the EGFR mR NA expression level had significant correlation with the genotypes of SNP loci rs5970360 and rs5925210. But all frequencies of each MAGE-A3 SNPs were not found significantly different between EGFR mutant and wild type patients. MAGE-A3 gene polymorphisms had no significant effects on survival of NSCLC patients.Conclusions： Chinese patients with NSCLC had different SNP patterns of MAGE-A3 in comparison with those in international SNP database. These MAGE-A3 SNP loci might have not prognostic significance. MAGE-A3 SNP loci rs5970360 and rs5925210 might be predictive for EGFR m RNA expression levels and helpful to the selection of patients for epidermal growth factor receptor（EGFR） targeted immunotherapy.

Impact of Cardiac Dose on Overall Survival in Lung Stereotactic Body Radiotherapy (SBRT) Compared to Conventionally Fractionated Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)

Purpose: To examine possible association between heart irradiation and Overall Survival (OS) in lung SBRT patients and to compare observed associations with cardiac toxicity models previously derived in LA-NSCLC patient studies. Materials and Methods: 197 Patients treated with lung SBRT at Mayo Clinic Arizona were selected for this IRB-approved study. Multivariate Cox model with Akaike Information Criterion (AIC) was used to select patient specific covariates associated with OS. Heart dosimetry was represented by VD indices, which is a percentage of volume exposed to dose D or greater. Multivariate Cox models with patient specific covariates and single VD index per model was used to find a range of doses which were predictive for OS. A digital subdivision of the heart was further used to determine the spatial distribution of doses which were predictive for OS. A coarse subdivision divided heart into 4 segments, while the fine subdivision divided heart into 64 segments. Knowledge constrained Fused Lasso operator was used to derive a more complete model which correlated heart dosimetry with OS. Results of statistical analysis were compared to predictions of a model of cardiac toxicity in LA-NSCLC patients. Results: Higher age (p < 0.001), higher stage (p < 0.001) and squamous cell histology (p = 0.001) were associated with reduced OS. Whole heart DVH analysis did not reveal associations between heart irradiation and reduced OS. Coarse subdivision of the heart into four segments revealed that the irradiation of two inferior segments of the heart with low doses was associated with reduced OS, V2Gy in the right-inferior segment (HR = 1.012/1%, p = 0.02), and V1Gy in the left-inferior segment (HR = 1.01/1%, p = 0.04). Maximum dose in the right-inferior segment of the heart was also associated with reduced OS (HR = 1.02/Gy, p = 0.02). Fine subdivision of the heart into 64 segments revealed that approximately 25% of heart volume in the inferior part of the heart (15/64 segments), when irradiated to doses in the 1 Gy - 5 Gy range, were predictive for reduced OS (HR = 1.01/1%, p = 0.01). A previously derived model of cardiac toxicity in LA-NSCLC patients did not predict a reduction of OS due to heart irradiation in lung SBRT patients, because of relatively low doses to the heart in most lung SBRT patients. Conclusions: Doses lower than 5 Gy in the inferior segments of the heart may be associated with reduced overall survival in patients treated for lung lesions with SBRT. Stage and histology of the disease, as well as patients’ age, were also associated with overall survival. Comparisons of cardiac toxicity patterns in LA-NSCLC patients and lung SBRT patients suggest different etiology of cardiac toxicity in the two groups.

Treatment of Non-Small Cell Lung Cancer (NSCLC) Using CT in Combination with a PET Examination to Minimize the Clinical Target Volume of the Mediastinum

OBJECTIVE To decrease radiation injury of the esophagus and lungs by utilizing a CT scan in combination with PET tumor imaging in order to minimize the clinical target area of locally advanced non-small cell lung can-cer, without preventive radiation on the lymphatic drainage area. METHODS Of 76 patients with locally advanced non-small cell lung cancer (NSCLC), 32 received a PET examination before radiotherapy. Preventive radiation was not conducted in the mediastinum area without lymphatic metastasis, which was confirmed by CT and PET. For the other 44 patients, preventive radiation was performed in the lymphatic drainage area. PET examinations showed that the clinical target volume of the patients was decreased on average to about one third. The radiation therapy for patients of the two groups was the same, i.e. the dose for accelerated fractionated irradiation was 3 Gy/time and 5 time/week. The preventive dose was 42 to 45 Gy/time, 14 to 15 time/week, with 3-week treatment, and the therapeu- tic dose was 60 to 63 Gy/time, 20 to 21 time/week, with a period of 4 to 5 weeks. RESULTS The rate of missed lymph nodes beyond the irradiation field was 6.3% and 4.5% respectively in the group with and without PET exami- nation (P = 0.831). The incidence of acute radioactive esophagitis was 15.6 % and 45.5% in the two groups respectively (P = 0.006). The incidence of acute radiation pneumonia and long-term pulmonary fibrosis in the two groups was 6.3% and 9.1%, and 68.8% and 75.0%, respectively (P = 0.982 and P = 0.547). CONCLUSION The recurrence rate in the lymph nodes beyond the tar-get area was not increased after minimizing the clinical target volume (CTV), whereas radioactive injury to the lungs and esophageal injury was reduced, and especially with a significant decrease in the rate of acute radioactive esophagitis. The method of CT in combination with PET for minimizing the mediastinal CTV is superior to the conventional preventive radiation of the mediastinum.

A Prospective Study of the Effect of Different Palliative Radiotherapy Fractionation Schedules on Tumor Response and Toxicity in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients

Background: The optimal dose of palliative radiotherapy (RT) in symptomatic advanced lung cancer is unclear. Patients and methods: Patients with advanced NSCLC who were indicated for thoracic palliative RT with age up to 65 y and Performance Status (PS) 0 - 2 and no significant cardiac or lung co-morbidities were randomized into two fractionation arms: arm A: 30 Gy/10 over 2 weeks and arm B: 27 Gy/6 over 3 weeks (2 fractions per week) using 2 anterior posterior (AP-PA) fields in both arms. Primary end points were symptomatic and radiological tumor response, respiratory functions assessment. Secondary end point was toxicity. Results: From December 2014 to October 2015, 40 patients were randomized, 20 patients in each arm. There was statistically insignificant higher symptomatic improvement in arm B. Four weeks after treatment, 12 out of 40 patients (30%), 6 patients in each arm, had radiological Partial Response (PR) of the primary thoracic lesion without significant difference between the two arms. There was a tendency for improvement in the post treatment mean Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) in each arm without statistical significance. There were no reported skin reactions or esophagitis in both arms up to 4 weeks after treatment. Eleven out of the 40 patients (27.5%), 6 in arm B and 5 in arm A, had radiological signs of radiation pneumonitis without significant difference between both arms. Conclusion: The two RT fractionation schedules showed equal efficacy in terms of symptoms relief, radiological response of the primary thoracic tumor, respiratory functions and toxicity. Thus the 27 Gy/6 fractionation arm appears preferable compared to 30 Gy/10 arm to minimize the patients’ visits and load on the machines.

Advances and challenges in immunotherapy of small cell lung cancer

Small cell lung cancer(SCLC) is a highly lethal disease, characterized by early metastasis and rapid growth, and no effective treatment after relapse. Etoposide-platinum(EP) combination has been the backbone therapy of SCLC over the past 30 years. It is extremely urgent and important to seek new therapies for SCLC. In the past 5 years,immunotherapy, such as immune checkpoint inhibitors programmed cell death protein-1(PD-1), cytotoxic T lymphocyte associatedprotein-4(CTLA-4), has made remarkable achievements in the treatment of patients with SCLC, and it has become the first-line option for the treatment of some patients. Some traditional chemotherapeutic drugs or targeted drugs, such as alkylating agent temozolomide and transcription inhibitor lurbinectedin, have been found to have immunomodulatory effects and are expected to become new immunotherapeutic agents. In this study, we aimed to review the efficacy of new treatments for SCLC and discuss the current challenges and application prospect in the treatment of SCLC patients.

Improvement of Quality of Life with Shenfu Injection (参附注射液) in Non Small Cell Lung Cancer Patients Treated with Gemcitabine plus Cisplatin Regimen

Objective： To observe the effect of Shenfu injection （参附注射液, SFI） in treating non small cell lung cancer （NSCLC） patients on quality of life with gemcitabine （GEM） plus cisplatin （GP） regimen. Methods： Thirty-four patients were ready to receive GP regimen chemotherapy for treating NSCLC disease, according to lot-drawing, they were divided into SFI pre-treatment group （18 cases） and SFI post-treatment group （ 16 cases）. SFI pre-treatment group： During the first treatment course, chemotherapy was begun with SFI 60 ml, intravenous dripping on the 3rd day, once daily, consecutively for 10 days; on the 1st day, GP regimen （GEM 1250 mg/m^2 , intravenous dripping, on the 1st and 8th day; cisplatin 70 mg/m^2 on the 2nd day; 21 days as one cycle） was carried out; in the second treatment course GP regimen was merely given to serve as the self-control. SFI post-treatment group： the medicament sequence order was reversed from that of pre-treatment group. Using dual international quality of life （QOL） scores, the effect of SFI on the patients＂ QOL was observed through randomized self pre- and post- crossover control. Results： The QOL in the 34 patients after being treated by SFI in combination with GP chemotherapy regimen in one group, and GP chemotherapy regimen alone in the other, was improved in different degrees, with significant difference （P〈0.01）; comparision of SFI combined with GP chemotherapy regimen with GP chemotherapy alone showed that QOL in patients was significantly different （P〈0.01）. Conclusion： SFI could improve QOL in patients with NSCLC who were treated with GP regimen.

Prognostic value of chemotherapy-induced leukopenia in small-cell lung cancer

Objective: Chemotherapy is the standard treatment for small-cell lung cancer (SCLC), and leukopenia is a common side effect. This study assesses whether chemotherapy-induced leukopenia is a predictor of efficacy and whether it is associated with the survival of SCLC patients. Methods: A retrospective analysis was conducted on data from 445 patients with SCLC who received standard chemotherapy for 4 to 10 cycles. The World Health Organization grading system classifies leukopenia during chemotherapy as follows: absent (grade 0), mild (grades 1 and 2), or severe (grades 3 and 4). The primary endpoint is overall survival (OS). Results: The association between chemotherapy-induced leukopenia and OS was assessed. According to a multivariate Cox model with time-varying covariates, the hazard ratio of death was significantly lower among patients with mild leukopenia than among patients with severe leukopenia at 0.687 (0.506 to 0.943) and 1.414 (1.147 to 1.744), respectively. The median survival was 13 months (95% CI: 11 to 15 months) for patients who did not experience leukopenia, 17 months (95% CI: 14 to 18 months) for those with mild leukopenia, and 14 months (95% CI: 13 to 16 months) for those with severe leukopenia (absent vs. mild vs. severe leukopenia, P=0.047). Conclusion: Leukopenia during chemotherapy is associated with the survival of SCLC patients. Mild leukopenia is strongly associated with longer survival time.

Flotillin1 promotes EMT of human small cell lung cancer via TGF-β signaling pathway

Objective:Small cell lung carcinoma(SCLC)is considered one of the most aggressive types of lung cancer due to its rapid growth and early metastasis.No tumor markers or therapeutic targets have been demonstrated to be specific or effective in SCLC to date.This study aims to evaluate the potential of Flotillin1(Flot1)as a target of SCLC treatment.Methods:Flot1 expression level in the tissue of SCLC and other tissue of lung disease was detected using immunohistochemical staining.Transwell and Matrigel assays were employed to examine migration and invasion of cancer cells.Flow cytometry and xCELLigence system were used to evaluate cell apoptosis and cell viability,respectively.Expression levels of Flot1,epithelialmesenchymal transition(EMT)marker E-cadherin,vimentin,cyclinD1,TGF-β-Smad2/3,and p-AKT were examined using Western blot.Furthermore,xenograft tumor in nude mice was used to evaluate the growth and metastasis of NCI-H446 cells in vivo.Results:Our results demonstrated that Flot1 is highly expressed in SCLC samples and that its expression correlates strongly with clinical stage,distant metastasis,and poor survival.The knockdown of Flot1 decreased the growth,migration,and invasiveness of SCLC cells and reversed EMT phenotype in vitro and in vivo,while enhanced Flot1 expression exhibited the opposite behavior.Gene expression profile analysis demonstrated that Flot1-regulated genes frequently mapped to the AKT and TGF-β-Smad2/3pathways.Our results further revealed that Flot1 affected the progression of SCLC via regulation of EMT progression.Conclusions:These findings indicated an oncogenic role of Flot1 via promoting EMT in SCLC and suggested its potential as a tumor marker and prognostic indicator.