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.

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.

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.

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.

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.

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.

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.

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.

Further understanding of an uncommon disease of combined small cell lung cancer： clinical features and prognostic factors of 114 cases

Objective： Combined small cell lung cancer （C-SCLC） is an uncommon subgroup of small cell lung cancer （SCLC） and few clinical data can be referred. Our study is to investigate the clinical features and prognostic factors of C-SCLC, as well as the role of multimodality treatment.Methods： Between January 2004 and December 2012, patients with histologically diagnosed C-SCLC were retrospectively analyzed. The survivals were evaluated with the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate potential prognostic factors.Results： One hundred and fourteen patients were enrolled, with a median age of 59 （range： 20-79） years old. The most common combined component was squamous cell carcinoma （52.6%）. Among these patients, the disease was stage I, II, III and IV in 9.6%, 19.3%, 46.5% and 24.6% of the patients, respectively. Eighty patients （70.2%） received at least two of the three modalities containing chemotherapy, radiotherapy and surgery. The median follow-up was 32.5 months. The median time of overall survival （OS） was 26.2 months. On univariate analysis, smoking （P=0.029）, Karnofsky performance score （KPS） 〈80 （P=0.000）, advanced TNM stage （P=0.000）, no surgery （P=0.010）, positive resection margin （P=0.000）, positive lymph nodes ≥4 （P=0.000）, positive lymph node ratio 〉10% （P=0.000） and non-multimodality treatment （P=0.004） were associated with poor OS. Multivariate analysis confirmed that smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉 10% were poor prognostic features. Conclusions： C-SCLC has a relatively early stage and good prognosis, which may due to the underestimated diagnosis in non-surgical patients. Multimodality therapy is recommended, especially for limited disease. Smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉10% are poor prognostic factors.

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.

Relapse of both small cell lung cancer and Lambert-Eaton myasthenic syndrome after a 13-year disease-free survival period

Lambert-Eaton myasthenic syndrome(LEMS) is a paraneoplastic syndrome and only 3%of small cell lung carcinoma(SCLC) patients have LEMS.Moreover,the recurrence of SCLC after a disease-free survival(DFS) of more than 10 years is rare.We report a patient who had a recurrence of both SCLC and LEMS after a 13-year DFS period.A 69-year-old man was diagnosed with LEMS and SCLC(cT0N2M0,stage ⅢA) 13 years ago.Chemoradiotherapy was performed and a complete response was achieved.With anticancer treatment,the LEMS symptoms was alleviated.At the age of 82 years,gait disturbance appeared followed by left supraclavicular lymphadenopathy and further examination revealed the recurrence of SCLC.Careful screening for the recurrence of SCLC might be needed when the patient has recurrent or secondary paraneoplastic neurological syndrome even after a long DFS period.

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.

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.

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.

Progress in the diagnosis and treatment of extensive-stage small cell lung cancer

Lung cancer, being the most common cancer type, accounts for 13% of all newly diagnosed malignant tumors globally each year. Small cell lung cancer(SCLC) accounts for approximately 15% of newly diagnosed lung cancers each year, but its annual death toll accounts for 25% of that of lung cancer. We summarized relevant clinical studies to elaborate the epidemiology, pathological and clinical characteristics and the treatment status of small cell lung cancer. This paper first described the epidemiology and the pathological and clinical characteristics of SCLC and the systematic treatment of extensive-stage SCLC and then introduced the current targeted therapy and immunotherapy for SCLC to provide clinicians and patients with a more systematic, comprehensive, and beneficial treatment regimen. We expect that these studies can provide clinicians with a clear direction in molecularly targeted therapy or immunotherapy, so that a treatment approach with better antitumor effects and longer-lasting clinical benefits can be provided to the patients.

Whole brain radiotherapy concomitant or sequential Vm26/DDP in treating small cell lung cancer patients with brain metastases

Objective： The aim of the study was to compare efficacies and safeties of 2 different treatments of whole brain radiotherapy （WBRT） sequential or concomitant Vm26/DDP for small cell lung cancer （SCLC） patients with brain metastases. Methods： A total of 39 patients were randomly divided into sequential chemoradiotherapy regime （A group, 20 patients） and concomitant chemoradiotherapy regime （B group, 19 patients）. The close of WBRT was 36 Gy in 18-20 fractions, chemotherapy of Vm26/DDP regimen with teniposide 60 mg/m^2 on dl to d3 and cisplatin 20 mg/m^2 on dl to d5, repeating every 3 weeks. The response was evaluated after WBRT and 2 cycles of chemotherapy. Results： Total response rates of A and B groups were 70.0% and 78.9% respectively （P = 0.520）. The median survival was 11 months in A group and 10 months in B group. Six, twelve and eighteen months cumulative survival rates of A and B groups were 75.0%, 42.5%, 26.2%, and 81.6%, 26.4%, 10.5%, respectively （χ^2 = 0.383, P 〉 0.05）. Response rate and the number of brain metastases were independent prognostic factors. Conclusion： Both sequential and concomitant chemoradiotherapy groups are effective, and the main toxicity with myelosuppression is tolerable after therapy. It can be applied firstly and effectively to the SCLC patients with brain metastases in clinic.

Comparative study of induction chemotherapy and chemoradiotherapy in the treatment of limited-disease small cell lung cancer with ipsilateral pleural effusion

Objective:The aim of the study was to explore the effects and side effects of induction chemotherapy followed by chemoradiotherapy for limited-disease small cell lung cancer (LD-SCLC) patients with ipsilateral pleural effusion.Methods:From January 2005 to May 2009,52 LD-SCLC patients with ipsilateral pleural effusion were treated with induction chemotherapy first.The regimen was taken as follows:etoposide 100 mg iv,d1-d5,cisplatin 25 mg/m2 iv,d1-d3 or CBP AUC 4 iv,d1.Three-week therapy was a cycle.According to pleural effusion status after 2-4 cycles induction chemotherapy,patients got disappearance of pleural effusion after chemotherapy were underwent thoracic radiotherapy (TRT;50 Gy/25 fraction) or same chemotherapy regimen;patients without disappearance or with increasing of pleural effusion after chemotherapy were given same chemotherapy regimen.Therapeutic effect was evaluated every two cycles according to RECIST 1.0 and side-effects were evaluated every cycle according to NCI-CTC AE Grades.All patients were followed up,and the median follow-up time was 26 months.Results:The response rate of patients was 80.7% (42/52) after induction chemotherapy and 34 patients got disappearance of pleural effusion.The median survival time,1-and 2-year survival rates were 15.4 months,76.9% (40 /52) and 38.5% (20 /52) respectively.The median survival time,1-and 2-year survival rates of patients with pleural effusion remission received chest radiotherapy (A group,n=20),patients with pleural effusion remission received chemotherapy (B group,n=14) and patients without pleural effusion remission received chemotherapy (C group,n=18) were 21.5 months,14.4 months,12.5 months,80.0%,64.3%,55.6% and 35%,21.4%,11.1%,respectively.Main side effects were grades 1-2,including myelosuppression,fatigue,nausea and vomiting.No therapeutic related death was occurred.Conclusion:Induction chemotherapy plus chemoradiotherapy has shown better effect in prolonging survival of small cell lung cancer (SCLC) patients with ipsilateral pleural effusion than chemotherapy alone.The patients with decreased ipsilateral pleural effusion may receive benefit from subsequent TRT.

Progress in diagnosis and treatment of small cell lung cancer with integrated traditional Chinese and Western medicine

Lung cancer is one of the most common major diseases that seriously threaten human health,lung cancer includes small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC).Although patients with SCLC account for about 20%of the total number of patients with lung cancer,the mortality rate is much higher than that of patients with NSCLC.Integrated traditional Chinese and Western medicine has obvious advantages in the treatment of patients with SCLC.According to the relevant literature reports on the treatment of SCLC in recent years,this article will summarize the research progress of integrated traditional Chinese and western medicine in the treatmentof SCLC from the aspects of traditional Chinese medicine(TCM)combined with surgery,chemotherapy,radiotherapy,and molecular targeted therapy.

Treatment of etoposide capsule combined with cisplatin or carboplatin in elderly patients with small cell lung cancer

We aimed to explore the efficacy and safety of etoposide capsule combined with cisplatin or carboplatin in the treatment of elderly patients with small cell lung cancer （SCLC）. Methods： From October 2011 to November 2013, 32 elderly patients （71-79 years old） with histopathologically confirmed SCLC in General Hospital of Shenyang Military Region （China） were enrolled in the research. The patients were administrated with lastet capsule 150-175 mg, dl-5, combined with cisplatin 20 mg/m^2 dl-3 or carbopiatin AUC = 5, applied over 2 days. Twenty-one days were 1 treatment cycle. Results：After treatments, 2 cases acquired complete response （CR）, 19 cases acquired partial response （PR）, 8 cases acquired stable disease （SD）, and 3 cases had progression of disease （PD）. The objective response rate was 65.6% （21/32）, disease control rate was 90.6% （29/32）. The median time of progression-free survival （PFS） was 6.9 months, the median survival time was 14.0 months, and 1 year survival rate was 62.4%. The main adverse reactions of 1/11 leukopenia and gastrointestinal reaction were observed. Conclusion： Etoposide capsule combined with cisplatin or carboplatin therapy have curative effect and good tolerance in elderly patients with SCLC.