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Small Cell Lung Cancer

Small cell lung cancer (SCLC) is so called because under the microscope the cancer cells look small; it is also called oat cell cancer. SCLC accounts for just under approximately a 6th of all lung cancers and is usually caused by smoking. Incidence has been declining in countries where there have been reductions in the number of people who smoke.

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Lung Cancer

Information Patients and the Public (7 links)

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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Li Y, Hu S, Xie J, et al.
Effects of surgery on survival of elderly patients with stage I small-cell lung cancer: analysis of the SEER database.
J Cancer Res Clin Oncol. 2019; 145(9):2397-2404 [PubMed] Related Publications
INTRODUCTION: Surgery improves survival of small-cell lung cancer (SCLC) patients in early stage. However, the role of surgery in the elderly stage I SCLC patients is not well established. We designed this retrospective study to explore the efficacy of surgery on survival of this subset population.
PATIENTS AND METHODS: Elderly patients aged ≥ 75 years with stage I SCLC diagnosed histologically from 1998 to 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Included patients were divided into surgery group (received surgery, accompanied by chemotherapy, radiotherapy, or both or neither), non-surgical group (only received radiotherapy, chemotherapy, or combination), and untreated group. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared among the three groups by the Kaplan-Meier analysis. Cox proportional hazards regression was used to identify factors associated with survival.
RESULTS: A total of 983 patients were included. Among all of the patients, 24.0% patients received surgery, 46.6% patients received non-surgical treatment, and 29.4% patients received no treatment. The 5-year OS rates of surgery, non-surgical and untreated groups were 31%, 12% and 6%, respectively (P < 0.0001). In multivariable analysis, surgery was an important factor that improved OS when compared with non-surgical treatment (HR 0.554; 95% CI 0.458-0.670 [P < 0.0001]). In subgroup analysis, surgery remained an independent factor for OS among patients aged 75-79 years (HR 0.506; 95% CI 0.391-0.655 [P < 0.0001]) and 80-84 years (HR 0.544; 95% CI 0.388-0.763 [P < 0.0001]), while did not reach statistical significance when compared to non-surgical treatment for patients age ≥ 85 years (HR 0.914; 95% CI 0.507-1.650; [P = 0.766]).
CONCLUSION: Surgical resection significantly improved OS in stage I SCLC patients aged 75-84 years in our study, but further exploration in larger prospective clinical trials is needed.

Lv P, Yang S, Wu F, et al.
Single-nucleotide polymorphisms (rs342275, rs342293, rs7694379, rs11789898, and rs17824620) showed significant association with lobaplatin-induced thrombocytopenia.
Gene. 2019; 713:143964 [PubMed] Related Publications
This study aimed to investigate single-nucleotide polymorphisms (SNPs) associated with lobaplatin-induced thrombocytopenia in patients with advanced lung cancer in China. Thirty-nine patients who received lobaplatin-based chemotherapy in the 307 Hospitals of Chinese People's Liberation Army from April 2017 to March 2018 were enrolled as study subjects. Peripheral blood DNA was extracted, and 79 candidate SNP positions were selected. A Sanger sequencing platform was employed to measure genotypes for locating the SNP positions associated with lobaplatin-induced thrombocytopenia. Of the 79 candidate genes, SNPs rs342275 and rs7694379 were significantly associated with lobaplatin-induced decrease in platelet (PLT) count (P < 0.05). SNPs rs342275, rs342293, rs11789898, and rs17824620 showed significant association with lobaplatin-induced lowest PLT counts (P < 0.05). SNPs rs342275, rs342293, rs11789898, rs17824620, and rs7694379 can be used as predictors of thrombocytopenia induced by lobaplatin-based chemotherapy in patients with advanced lung cancer in China.

Drąg-Zalesińska M, Saczko J, Choromańska A, et al.
Cisplatin and Vinorelbine -Mediated Electrochemotherapeutic Approach Against Multidrug Resistant Small Cell Lung Cancer (H69AR)
Anticancer Res. 2019; 39(7):3711-3718 [PubMed] Related Publications
BACKGROUND/AIM: Small cell lung cancer (SCLC) originates from neuroendocrine branchial cells (15-20%). It is regarded as distinct from other lung cancers due to its biological and clinical features. In most cases of SCLC, surgery or radiotherapy alone is not an effective cure. The aim of our study was to examine the cytotoxic effects of chemotherapy supported by electroporation (EP) on a resistant SCLC model, in vitro.
MATERIAL AND METHODS: The multidrug resistant small lung cell line H69AR was used to evaluate the cytotoxic effects of cisplatin (CPPD) and vinorelbine (Navirel®; NAV) at lower doses when used with EP. Cells were treated with different concentrations of CPPD and NAV, alone or in combination with the following EP parameters: 400-1200 V/cm, 8 pulses of 100 μs duration, at 1Hz. The cell viability was estimated by MTT assay after 24 and 48 h. Apoptotic cells were detected by neutral comet assay and immunofluorescence assay with PARP-6.
RESULTS: CPPD and NAV alone showed a dose-dependent effect on cell viability. Cytostatic drugs combined with EP revealed increased anticancer activity. Lower doses of CPPD or NAV delivered by EP were as effective as higher doses of these drugs without EP. The electrochemotherapeutic protocols increased the number of apoptotic cells and increased immunoreactivity of PARP-6. Our results indicated higher sensitivity of H69AR cells to NAV supported by EP.
CONCLUSION: In SCLC cells, an increased anticancer activity was potentiated by exposure of cells to high intensity electric pulses and low drug doses. It is suggested that this method could be effectively applied in the treatment of lung cancer.

Prabavathy D, Ramadoss N
Heterogeneity of Small Cell Lung Cancer Stem Cells.
Adv Exp Med Biol. 2019; 1139:41-57 [PubMed] Related Publications
Small cell lung cancer, a subtype of lung cancer is an extremely malignant disease due to its metastases and recurrence. Patients with SCLC develop resistance to chemotherapy and the disease relapses. This relapse and resistance are attributed to the heterogeneity of SCLC. Various factors such as recurrent mutations in key regulatory genes such as TP53, RB1, and myc, epigenetic changes, and cancer stem cells contribute to the observed heterogeneity. Cancer stem cell models predict neuroendocrine origin of SCLC. Though an unambiguous established CSC marker has not been assigned, markers CD133, CD44 have been found associated with SCLC. Genetically engineered mouse models (GEMMs) allow the validation of driver mutations and are necessary for design of targeted therapy. This chapter outlines the factors contributing to SCLC heterogeneity, detection methods, and the current therapy trials.

Yang MH, Chang KJ, Li B, Chen WS
Arsenic Trioxide Suppresses Tumor Growth through Antiangiogenesis via Notch Signaling Blockade in Small-Cell Lung Cancer.
Biomed Res Int. 2019; 2019:4647252 [PubMed] Free Access to Full Article Related Publications
Small-cell lung cancer (SCLC) is a highly malignant type of lung cancer with no effective second-line chemotherapy drugs. Arsenic trioxide (As

Liu X, Luo L, Qi P, et al.
A Comprehensive Preclinical Evaluation of Intravenous Etoposide Lipid Emulsion.
Pharm Res. 2019; 36(7):96 [PubMed] Related Publications
PURPOSE: Etoposide is one of the principal chemotherapeutic agents used for the treatment of small cell lung cancer (SCLC). There are some disadvantages of currently available etoposide injections (EI) such as low LD
METHODS: ELE was prepared through high-pressure homogenization method, and a series of evaluations such as encapsulation efficiency (EE%), in vitro release, stability studies, pharmacokinetics study, safety assessment and pharmacodynamic study were systematically performed.
RESULTS: ELE had high EE% and good stability. Pharmacokinetics study revealed ELE had a longer T
CONCLUSIONS: Unlike EI, ELE could further increase the dose, which endowed etoposide with a greater potential for cytotoxic agent. LE is a promising delivery system for etoposide.

Liu Y, Xi J, Zhou L, et al.
Clinical characteristics and long term follow-up of Lambert-Eaton myasthenia syndrome in patients with and without small cell lung cancer.
J Clin Neurosci. 2019; 65:41-45 [PubMed] Related Publications
In order to describe the clinical characteristics, treatment response and long-term follow up in Lambert-Eaton myasthenic syndrome (LEMS) patients with and without small cell lung cancer (SCLC) in East China, patients seen in Huashan Hospital from January 1997 to December 2017 were included. Clinical information was collected retrospectively and quantitative MG (QMG) score, manual muscle testing (MMT), activities of daily living (ADL) scale were evaluated when the patients were followed up. Of 50 patients, 23 (46%) were SCLC-LEMS and 20 (40%) were nontumor LEMS (NT-LEMS). The median onset age was 55.5 (18-86) years old and the gender ratio was about 1.8:1. It took less time to make the diagnosis (median time: 6 vs 22.5 months, p = 0.0003) and there were more patients with other paraneoplastic syndromes in SCLC-LEMS group than in NT-LEMS group (8/23 vs 0/20, p = 0.0042). Electrophysiologically, the peroneal compound motor action potential (CMAP) of rest showed difference between SCLC-LEMS and NT-LEMS (0.8 vs 1.6 mV, p = 0.0499). The median survival time of 19 SCLC-LEMS patients since the diagnosis of SCLC was 30 months. According to their survival time, SCLC patients with LEMS showed a more favorable prognosis than those without LEMS. In the time of follow-up, most NT-LEMS showed improvement or obtained status of CSR/PR/MM after immunosuppressive therapy and no significant difference in proportion of achieving CSR/PR/MM was found between SCLC-LEMS and NT-LEMS patients (0/5 vs 6/13, p = 0.114).

Carrera W, Tsamis KA, Shah R
A case of cancer-associated retinopathy with chorioretinitis and optic neuritis associated with occult small cell lung cancer.
BMC Ophthalmol. 2019; 19(1):101 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Cancer-associated retinopathy (CAR) is associated with various malignancies, including small cell lung cancer (SCLC). It is difficult to recognize, but prompt diagnosis is crucial for the patient, as retinopathy may be a herald sign that precedes systemic manifestations by months, thus allowing early treatment of the underlying malignancy.
CASE PRESENTATION: We present a rare case of CAR with chorioretinitis and optic neuritis in a patient with occult SCLC. The patient presented with rapidly progressive peripheral field loss and photopsias with "prism-like" visual disturbances. Her symptoms stabilized with intravenous methylprednisolone, and her cancer was treated with carboplatin, etoposide and radiotherapy.
CONCLUSIONS: This is the first reported case of SCLC-associated CAR to present with chorioretinitis. CAR can be a herald feature of SCLC, and early recognition of the disease should prompt a systemic evaluation for an occult malignancy, which may be critical for patient survival. Further understanding of CAR pathogenesis may offer potential avenues for treatment.

Xue P, Wang N, Mao Y, Zhu S
Anti-angiogenesis treatment in a patient with appendix metastasis of small cell lung cancer: A case report.
Medicine (Baltimore). 2019; 98(16):e15333 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Small-cell lung cancer (SCLC) is a common pathological type of lung cancer, but appendiceal metastasis of SCLC was rare. At present, clinical studies on the maintenance therapy of SCLC have not reached a significant conclusion.
PATIENT CONCERNS: We reported on a 52-year-old man who diagnosed as extensive stage SCLC with abdominal pain for 2 months, aggravated for 2 days.
DIAGNOSES: The patient was diagnosed with extensive-stage SCLC, relapsed with appendix metastasis after treatment by emergency abdominal surgery.
INTERVENTIONS: The patient received systemic treatments, including surgery, bevacizumab in combination with chemotherapy and bevacizumab alone was continued as maintenance therapy.
OUTCOMES: The patient had an overall survival would more than 23 months, and he gained another 8 months of progression-free survival after first-line radiochemotherapy.
LESSONS: Although SCLC appendix metastasis is rare, continuous anti-angiogenic therapy combined with bevacizumab maintenance therapy after surgical treatment can prolong survival.

Drapkin BJ, Farago AF
Unexpected Synergy Reveals New Therapeutic Strategy in SCLC.
Trends Pharmacol Sci. 2019; 40(5):295-297 [PubMed] Related Publications
DNA damage repair (DDR) inhibition and immune checkpoint blockade (ICB) have each individually shown modest clinical activity in small cell lung cancer (SCLC). Recently, Sen and colleagues (Cancer Discov. 2019;https://doi.org/10.1158/2159-8290.CD-18-1020) demonstrated that DDR inhibition can activate the stimulator of interferon genes (STING) innate immune pathway, providing strong rationale for combining DDR inhibition and ICB to treat SCLC.

Fu Y, Zhang P, Nan H, et al.
LncRNA CASC11 promotes TGF-β1, increases cancer cell stemness and predicts postoperative survival in small cell lung cancer.
Gene. 2019; 704:91-96 [PubMed] Related Publications
LncRNA CASC11 is a recently identified oncogenic lncRNA in colorectal cancer. This study aimed to investigate the role of lncRNA CASC11 in small cell lung cancer (SCLC). In the present study, expression levels of CASC11 and TGF-β1 were found to be positively and significantly correlated with the percentage of CDD133+ cells of SCLC cell lines. Plasma CASC11 and TGF-β1 were upregulated and positively correlated in SCLC patients, but not in healthy controls. Upregulation of plasma CASC11 and TGF-β1 predicted poor survival of SCLC patients. Overexpression of CASC11 and TGF-β1 also resulted in the increased percentage of CDD133+ cells of SCLC cell lines, while TGF-β inhibitor attenuated the effects of CASC11 overexpression. CASC11 overexpression mediated the upregulation of TGF-β1 in SCLC cells, while treatment with exogenous TGF-β1 showed no significant effect on CASC11. Therefore, lncRNA CASC11 promotes TGF-β1, increases cancer cell stemness and predicts postoperative survival in SCLC.

Winiarska A, Zareba L, Krolczyk G, et al.
Decreased Levels of Histidine-Rich Glycoprotein in Advanced Lung Cancer: Association with Prothrombotic Alterations.
Dis Markers. 2019; 2019:8170759 [PubMed] Free Access to Full Article Related Publications
Background: Histidine-rich glycoprotein (HRG) displays anticoagulant and antifibrinolytic properties in animal models, but its effects in humans are unclear. We investigated serum HRG levels and their associations with the disease stage and prothrombotic alterations in lung cancer (LC) patients.
Methods: In 148 patients with advanced LC prior to anticancer therapy (87 non-small-cell LC and 61 small-cell LC) versus 100 well-matched controls, we measured HRG levels in association with clot permeability (
Results: Compared to controls, LC patients had 45.9% lower HRG levels with no associations with demographics and comorbidities. Decreased HRG, defined as the 90
Conclusions: Our study is the first to show that decreased HRG levels occur in advanced LC and are associated with the disease stage and hypofibrinolysis.

Rudin CM, Poirier JT, Byers LA, et al.
Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data.
Nat Rev Cancer. 2019; 19(5):289-297 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
Small cell lung cancer (SCLC) is an exceptionally lethal malignancy for which more effective therapies are urgently needed. Several lines of evidence, from SCLC primary human tumours, patient-derived xenografts, cancer cell lines and genetically engineered mouse models, appear to be converging on a new model of SCLC subtypes defined by differential expression of four key transcription regulators: achaete-scute homologue 1 (ASCL1; also known as ASH1), neurogenic differentiation factor 1 (NeuroD1), yes-associated protein 1 (YAP1) and POU class 2 homeobox 3 (POU2F3). In this Perspectives article, we review and synthesize these recent lines of evidence and propose a working nomenclature for SCLC subtypes defined by relative expression of these four factors. Defining the unique therapeutic vulnerabilities of these subtypes of SCLC should help to focus and accelerate therapeutic research, leading to rationally targeted approaches that may ultimately improve clinical outcomes for patients with this disease.

Qiao R, Zhong R, Xu J, et al.
Prediction of lymph node status in completely resected IIIa/N2 small cell lung cancer: importance of subcarinal station metastases.
J Cardiothorac Surg. 2019; 14(1):63 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
BACKGROUND: The aim of this study was to determine the prognostic value of lymph node status in patients with pathologic N2 (pN2) stage IIIA small cell lung cancer (SCLC).
METHODS: A total of 163 consecutive pN2 stage IIIA SCLC patients who underwent pulmonary resections and systematic lymphadenectomies at Shanghai Chest Hospital between January 2006 and June 2014 were enrolled. We retrospectively analyzed the potential clinicopathologic factors that influenced survival, including the node levels (single or multiple-station) and the node-spreading patterns (skip N2 or non-skip N2). The prognostic significance was examined by Cox regression analysis.
RESULTS: The median overall survival (OS) was 23.7 months. Multiple-station lymph node metastasis indicated a poorer prognosis than single-station involvement (p = 0.003). Skip metastasis did not appear to influence survival (p = 0.099). With respect to the station of lymph node metastasis, the OS was only related to the involvement of the subcarinal node, regardless of tumor location (p < 0.05). Multivariate analysis showed two statistically significant risk factors for survival, including multiple-station lymph node and subcarinal node metastasis (hazard ratio [HR] = 1.76, 95% confidence interval [CI]:1.11-2.78, p = 0.015; HR = 1.61, 95% CI: 1.03-2.50, p = 0.036, respectively).
CONCLUSIONS: Multiple-station N2 metastasis and involvement of the subcarinal node predicted poor prognosis in pN2 stage IIIA SCLC patients, which may profoundly influence therapeutic decisions.

Wan Z, Zhang X, Yu X, Hou Y
Prognostic significance of serum soluble DR5 levels in small-cell lung cancer.
Int J Med Sci. 2019; 16(3):403-408 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
The death receptor 5 (DR5) is a member of the tumor necrosis factor receptor superfamily that can transduce the apoptosis signal in cells. This study assessed serum levels of soluble death receptor 5 (sDR5) in small-cell lung cancer (SCLC) patients compared with those in healthy controls. Clinicopathological features of patients, treatment responses, and overall survival of patients were also recorded and analyzed. The sDR5 levels were analyzed using ELISA in 50 healthy controls and 82 SCLC patients before and after first-line chemotherapy. The statistical data showed that pre-treatment levels of serum sDR5 in SCLC patients were higher than those of healthy controls (P<0.001). Pre-treatment levels of serum sDR5 were significantly associated with smoking history of patients, Veterans Administration Lung Study Group (VALSG) stage, tumor size, and lymph node (N) metastasis (P=0.028, 0.001, 0.028, and 0.01, respectively). After treatment with the first-line chemotherapy, the post-treatment levels of serum sDR5 were obviously decreased (P<0.001), and correlated with treatment responses (P<0.001), although there was no significant difference in their pretreatment sDR5 levels (P=0.62). Cox proportional hazard analysis demonstrated that the post-treatment levels of serum sDR5, VALSG stage, and PS status were all independent predictors for overall survival of patients. The results from the current study indicate that serum level of sDR5 could be further confirmed as a biomarker to predict treatment responses and survival of SCLC patients.

Chang H, Lee SJ, Lim J, et al.
Prognostic significance of metabolic parameters measured by
J Cancer Res Clin Oncol. 2019; 145(5):1361-1367 [PubMed] Related Publications
PURPOSE: Metabolic parameters measured by [
METHODS: This retrospective study included 30 LD-SCLC patients who underwent standard chemotherapy after radiotherapy with
RESULTS: For the median follow-up of 41.1 months, median overall survival (OS) was 75.0 months [95% confidence interval (CI) 20.9-129.1 months], and median progression-free survival (PFS) was 9.5 months (95% CI 6.8-12.1 months). Two-year OS was 78.6%, and PFS was 32.7%. OS analysis indicated that MTV and TLG were significant predictors of OS following standard treatment. High glucose-corrected SUV

Yang H, Liu L, Zhou C, et al.
The clinicopathologic of pulmonary adenocarcinoma transformation to small cell lung cancer.
Medicine (Baltimore). 2019; 98(12):e14893 [PubMed] Related Publications
Transformation to small cell lung cancer (SCLC) is one of the mechanisms of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it is uncertain how it works and there is no standard treatment after the transformation. In this study, 7 patients with transformation of SCLC from advanced lung adenocarcinoma (ADC) were analyzed retrospectively and the clinical pathology, imaging characteristics and treatment were analyzed.We identified 7 patients with primary lung ADC that showed transformation to SCLC on second biopsy during a 6-year period. Clinicopathologic information was analyzed and EGFR mutation results were performed in initial biopsy samples.Seven patients showed transformation from ADC to SCLC, of which 6 patients were 19 del EGFR mutation, only 1 patient is L858R mutations. The imaging forms did not have the typical imaging features of primary SCLC. All patients underwent etoposide and carboplatin (EC) regimen chemotherapy after pathological transformation. However, the response rate of EC was less than primary small cell lung cancer. One of the patients was receiving EC for 4 cycles. After chemotherapy the patients performed radiation therapy and finally with erlotinib maintains treatment, the progress free survival (PFS) was more than 12 months.NSCLC can acquire a neuroendocrine phenotype with EGFR-TKI treatment. The transmutation is more common in 19del mutation patients. A comprehensive treatment based on EC regimen chemotherapy and the maintenance with EGFR-TKI is likely to be the appropriate treatment for these patients.

Furuta M, Kikuchi H, Shoji T, et al.
DLL3 regulates the migration and invasion of small cell lung cancer by modulating Snail.
Cancer Sci. 2019; 110(5):1599-1608 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
Delta-like protein 3 (DLL3) is a ligand of Notch signaling, which mediates cell-fate decisions and is tumor-suppressive or oncogenic depending on the cellular context. Previous studies show that DLL3 is highly expressed in small cell lung cancer (SCLC) but not in normal lung tissue, suggesting that DLL3 might be associated with neuroendocrine tumorigenesis. However, its role in SCLC remains unclear. To investigate the role of DLL3 in tumorigenesis in SCLC, we performed loss-of-function and gain-of-function assays using SCLC cell lines. In vitro analysis of cell migration and invasion by transwell assay showed that DLL3 knockdown reduced migration and invasion of SCLC cells, whereas DLL3 overexpression increased these activities. In addition, DLL3 positively regulated SNAI1 expression and knockdown of SNAI1 attenuated the migration and invasion ability of SCLC cells. Moreover, upregulated DLL3 expression induced subcutaneous tumor growth in mouse models. These results indicate that DLL3 promoted tumor growth, migration and invasion in an SCLC model by modulating SNAI1/Snail.

Abbass K, Krug H
Granulomatosis with polyangiitis in a patient with biopsy-proven IgG4-related pulmonary disease and coincident small cell lung cancer.
BMJ Case Rep. 2019; 12(3) [PubMed] Article available free on PMC after 01/05/2020 Related Publications
Granulomatosis with polyangiitis (GPA) was diagnosed in a patient with a 16-month history of IgG4-related lung disease that spontaneously became asymptomatic. Cytoplasmic antineutrophil cytoplasmic antibody (ANCA) was positive at the time of diagnosis of IgG4-related disease (IgG4-RD), but there was no vasculitis or kidney disease. Sixteen months later he developed rapidly progressive glomerulonephritis that responded to cyclophosphamide treatment. While undergoing treatment for GPA, he was found to have a lung mass identified as small cell lung cancer. This mass was present at the time of the IgG4-RD diagnosis. GPA can be confused with IgG4-RD histologically and they rarely coexist. ANCA antibodies are primarily IgG4 subclass. IgG4-RD has been associated with cancer and may improve prognosis. We speculate that this patient may have had small cell lung cancer that incited an IgG4 predominant immune response with coexistent ANCA antibodies that eventually resulted in GPA. Immunosuppressive treatment of GPA likely accelerated the progression of the lung cancer.

Wang JJ, Wang YL, Ge XX, et al.
Prognostic Values of Platelet-Associated Indicators in Resectable Lung Cancers.
Technol Cancer Res Treat. 2019; 18:1533033819837261 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
BACKGROUND: Lung cancer is the leading cause of cancer death. Platelet-related indictors, including platelet count, plateletcrit, mean platelet volume, and platelet distribution width, not only associate with morphology and functions of platelet but also correlate with tumor development and metastasis. In the present study, we investigated the values of platelet-related indictors in the prognosis evaluation of resectable lung cancers.
METHODS: In total, 101 patients with resectable lung cancer were recruited in this study. Patients were divided into 2 groups according to the median pretreatment values. To evaluate the individual value changes after treatment, we introduced the concept of post-/pretreatment ratio (≤1 indicated value was not increased after treatment, while >1 suggested increased value).
RESULTS: The high pretreatment platelet count level was correlated with larger tumor size. High pretreatment plateletcrit level was associated with more lymph nodes metastasis. Patients with high pretreatment plateletcrit level had worse overall survival, whereas pretreatment platelet count, mean platelet volume, and platelet distribution width levels were not correlated with outcomes. Surgery had no impact on the values of platelet count, plateletcrit, mean platelet volume, or platelet distribution width. Adjuvant chemotherapy significantly decreased the values of platelet count and plateletcrit, whereas it had no effect on the values of mean platelet volume or platelet distribution width. Whole course of treatment (surgery combined with adjuvant chemotherapy) significantly decreased the values of platelet count and platelet distribution width, whereas it had no effect on the values of plateletcrit or mean platelet volume. Post-/pretreatment platelet count, plateletcrit, mean platelet volume, and platelet distribution width ratios were not correlated with outcomes. Univariate analyses demonstrated that American Joint Committee on Cancer stage and pretreatment plateletcrit level were significant risk factors for prognosis. Cox regression analysis revealed that no factor independently associated with worse survival.
CONCLUSION: Pretreatment plateletcrit level could be a potential prognostic factor in resectable lung cancers.

Wang GZ, Zhang L, Zhao XC, et al.
The Aryl hydrocarbon receptor mediates tobacco-induced PD-L1 expression and is associated with response to immunotherapy.
Nat Commun. 2019; 10(1):1125 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
Whether tobacco carcinogens enable exposed cells immune escape resulting in carcinogenesis, and why patients who smoke respond better to immunotherapies than non-smokers, remains poorly understood. Here we report that cigarette smoke and the carcinogen benzo(a)pyrene (BaP) induce PD-L1 expression on lung epithelial cells in vitro and in vivo, which is mediated by aryl hydrocarbon receptor (AhR). Anti-PD-L1 antibody or deficiency in AhR significantly suppresses BaP-induced lung cancer. In 37 patients treated with anti-PD-1 antibody pembrolizumab, 13/16 (81.3%) patients who achieve partial response or stable disease express high levels of AhR, whereas 12/16 (75%) patients with progression disease exhibit low levels of AhR in tumor tissues. AhR inhibitors exert significant antitumor activity and synergize with anti-PD-L1 antibody in lung cancer mouse models. These results demonstrate that tobacco smoke enables lung epithelial cells to escape from adaptive immunity to promote tumorigenesis, and AhR predicts the response to immunotherapy and represents an attractive therapeutic target.

Onishi H, Yamasaki A, Nakamura K, et al.
Liprin-α4 as a New Therapeutic Target for SCLC as an Upstream Mediator of HIF1α.
Anticancer Res. 2019; 39(3):1179-1184 [PubMed] Related Publications
BACKGROUND/AIM: Small-cell lung cancer (SCLC) remains one of deadliest types of cancers. Cis-diamminedichloroplatinum (CDDP) is a key chemotherapeutic agent for SCLC, however, its therapeutic effect is limited. Recently, hypoxia in the cancer microenvironment has been suggested to influence the effect of cancer therapy.
MATERIALS AND METHODS: Using small interfering RNA inhibition of leukocyte common antigen-related interacting protein alpha 4 (liprin-α4), and of hypoxia-inducible factor (HIF)-1α, proliferation, invasion, migration and chemosensitivity were investigated in SBC-5 SCLC cells, under normoxia and hypoxia.
RESULTS: Liprin-α4 was found to contribute to proliferation, but not migration and invasion of SBC-5 cells both under normoxia and hypoxia. Inhibition of liprin-α4 increased chemosensitivity of SBC-5 cells under hypoxia. Liprin-α4 signaling occurs through mitogen-activated protein kinase pathways via activation of HIF1α expression. Inhibition of HIF1α reduced proliferation and increased chemosensitivity of SBC-5 cells under hypoxia.
CONCLUSION: Liprin-α4 inhibition may enhance the effect of CDDP and liprin-α4 might be a novel therapeutic target in SCLC.

Gao F, Wu H, Wang R, et al.
MicroRNA-485-5p suppresses the proliferation, migration and invasion of small cell lung cancer cells by targeting flotillin-2.
Bioengineered. 2019; 10(1):1-12 [PubMed] Article available free on PMC after 05/03/2020 Related Publications
This study is aimed to elucidate the mechanisms underlying the role of miR-485-5p in small cell lung cancer (SCLC). The expression of miR-485-5p were quantified with real time quantitative PCR and it was found that the level of miR-485-5p was lower in SCLC tissues than normal tissues. In cultured SCLC cell lines, overexpression of miR-485-5p reduced cell proliferation, migration, and invasion in vitro, whereas knockdown of miR-485-5p performed contrary. FLOT2 expression was obviously upregulated and negatively correlated with miR-485-5p expression level in SCLC tissues. Overexpression of miR-485-5p significantly inhibited the protein expression of flotillin-2 (FLOT2) in cultured SCLC cells. Luciferase reporter assay confirmed that FLOT2 was a direct target of miR-485-5p in SCLC cells. It is concluded that miR-485-5p, as a tumor suppressor, inhibits the growth and metastasis in SCLC by targeting FLOT2. Upregulation of miR-485-5p expression may be an attractive strategy for SCLC therapy.

Han K, Yoon KW, Kim JH, Kim GM
Bronchial Artery Embolization for Hemoptysis in Primary Lung Cancer: A Retrospective Review of 84 Patients.
J Vasc Interv Radiol. 2019; 30(3):428-434 [PubMed] Related Publications
PURPOSE: To evaluate the safety and efficacy of bronchial artery embolization (BAE) in patients with primary lung cancer-related hemoptysis and to identify factors associated with hemoptysis-free survival.
METHODS: Data from 84 patients with primary lung cancer (non-small cell [n = 74] and small cell [n = 10]) who underwent BAE from 1997 to 2018 for the management of hemoptysis were retrospectively reviewed. Of these, 53 patients had stage IV lung cancer. The hemoptysis volume prior to initial BAE was trivial (blood-tinged sputum) in 21 patients, moderate (< 300 mL per 24 hours) in 34 patients, and massive (> 300 mL per 24 hours) in 29 patients.
RESULTS: Technical success, defined as the ability to selectively embolize the abnormal vessel, was achieved in 83 patients (98.8%), and clinical success was achieved in 69 (82.1%) patients. Polyvinyl alcohol particles were used to embolize in 51 patients, gelfoam in 15 patients, and gelfoam plus microcoils in 17 patients. Hemoptysis recurred in 20 patients (23.8%) during follow-up. The median hemoptysis-free survival and overall survival periods were both 61 days. In the clinical-success and clinical-failure groups, the median overall survival period was 99 and 9 days, respectively (P < .001). In multivariable analysis, massive hemoptysis (P = .012) and cavitary lung mass (P = .019) were predictive factors for shortened hemoptysis-free survival.
CONCLUSIONS: BAE is a safe and effective approach to control hemoptysis, although the prognosis in primary lung cancer patients presenting with hemoptysis is generally poor. Massive hemoptysis and cavitary lung mass are significant predictors of shortened hemoptysis-free survival.

Sugiyama K, Kogure Y, Torii A, et al.
Solvent-based paclitaxel or nab-paclitaxel for heavily treated relapsed/refractory small cell lung cancer: Retrospective single-institution observational study.
Medicine (Baltimore). 2019; 98(9):e14758 [PubMed] Related Publications
Treatment options for patients with relapsed/refractory small cell lung cancer (R/R SCLC) are limited, and the efficacy of salvage therapies for heavily treated patients should be assessed. Here, we evaluated the efficacy of paclitaxel (PTX) in R/R SCLC patients.A single-institute retrospective chart review was conducted. The primary endpoint was overall survival (OS), whereas the secondary endpoints were progression-free survival (PFS), overall response rate, disease control rate (DCR), and safety.Thirty-one patients (median age, 69 [range, 56-80] years) were analyzed. The median follow-up period was 122 (range, 28-1121) days. The median OS and PFS were 4.4 and 2.2 months, respectively. Adverse events of grade 3 or higher, other than hematological toxicity, were febrile neutropenia and neuropathy. Multivariate analyses identified the following independent predictors of poor OS: performance status and lactate dehydrogenase at the upper limit of normal.PTX monotherapy showed moderate efficacy with acceptable toxicity in heavily treated patients with R/R SCLC patients.

Shirasawa M, Fukui T, Kusuhara S, et al.
Efficacy and risk of cytotoxic chemotherapy in extensive disease-small cell lung cancer patients with interstitial pneumonia.
BMC Cancer. 2019; 19(1):163 [PubMed] Article available free on PMC after 05/03/2020 Related Publications
BACKGROUND: Small cell lung cancer (SCLC) is characterized by a high propensity for metastases and a poor prognosis irrespective of high sensitivity for initial chemotherapy. Although interstitial pneumonia (IP) is one of risk factors for lung cancer, efficacy of cytotoxic chemotherapy for patients with SCLC with IP remains unclear. Our study aims to evaluate the efficacy of systemic chemotherapy and assess risk of acute exacerbation (AE)-IP with cytotoxic drugs for extensive disease (ED)-SCLC patients with IP.
METHODS: We performed a retrospective study of 192 consecutive ED-SCLC patients with IP (n = 40) and without IP (n = 152) between 2008 and 2016.
RESULT: 31 of 40 ED-SCLC patients with IP and 130 of 152 patients without IP received systemic chemotherapy. The efficacy of chemotherapy in patients with IP was not inferior to that in patients without IP (overall survival [OS], 7.1 [95% confidence interval (CI): 0.2-14.0] vs. 10.0 [95% CI: 8.2-11.8] months, P = 0.57). Pretreatment serum levels of lactate dehydrogenase (LDH; 651.7 ± 481.0 vs. 301.4 ± 110.7 U/mL, P = 0.01) and C-reactive protein (CRP; 8.9 ± 9.6 vs. 1.8 ± 1.8 U/mL, P = 0.008) were correlated with developed AE-IP in the ED-SCLC patients with IP.
CONCLUSION: Systemic chemotherapy was effective even in ED-SCLC patients with IP. However, the risk of developed AE-IP that was high in patients with IP and should be evaluated using serum LDH and CRP levels before initial chemotherapy.

Debieuvre D, Locher C, Asselain B, et al.
Evidence of slight improvement in five-year survival in non-small-cell lung cancer over the last 10 years: Results of the French KBP-CPHG real-world studies.
Bull Cancer. 2019; 106(4):283-292 [PubMed] Related Publications
BACKGROUND: Although improved during the last decades, the prognosis of lung cancer is poor. In 2000, the French College of general hospital respiratory physicians, conducted KBP-2000-CPHG, a prospective multicenter epidemiological study including all volunteer adult patients diagnosed for primary lung cancer; with the five-year survival as primary endpoint. The primary objective of KBP-2010-CPHG was to compare overall five-year survival data with KBP-2000-CPHG ones.
MATERIAL AND METHODS: All consecutive patients≥18 years of age with primary lung cancer diagnosed between 1st January and 31st December 2010 were included. The KBP-2010-CPHG protocol was approved by the advisory committee on research information processing in the health field (CCTIRS) on November 19, 2009.
RESULTS: Respectively, 5667 and 7051 patients were included in KBP-2000-CPHG and KBP-2010-CPHG. Five-year survival was improved: 12.7% [11.9%-13.5%] in 2010 versus 10.0% [9.2%-10.9%] in 2000 (P<0.001). Non-small-cell lung cancer showed improvement (13.8% [13.0%-14.8%] in 2010 versus 11.4% [10.5%-12.4%] in 2000; P<0.001); but not small-cell lung cancer (5.7% [4.4%-7.4%] in 2010 versus 3.3% [2.3%-4.7%] in 2000; P=0.56). The KBP-2010-CPHG study showed an overall 6% reduction in risk of death (HR=0.94 [0.89-0.98]; P=0.004).
CONCLUSIONS: Survival of patients with lung cancer improved over a 10-year period. This improvement was slight and limited to non-small-cell lung cancer, possibly partly because of 2010 advances in diagnosis and targeted therapy.

Badzio A, Czapiewski P, Gorczyński A, et al.
Prognostic value of broad-spectrum keratin clones AE1/AE3 and CAM5.2 in small cell lung cancer patients undergoing pulmonary resection.
Acta Biochim Pol. 2019; 66(1):111-114 [PubMed] Related Publications
INTRODUCTION: Small cell lung carcinoma (SCLC) is an aggressive pulmonary neoplasm of neuroendocrine origin. Keratins form a large group of intermediate filaments, which are major structural proteins in epithelial cells and carcinomas. SCLC shows a wide spectrum of keratin expression, from very strong to completely negative. A prognostic role of keratin expression in SCLC is unknown.
MATERIAL AND METHODS: Tumor tissue microarray samples from a unique series of 82 SCLC patients who underwent pulmonary resection were stained with keratin specific antibodies AE1/AE3 and CAM5.2. The percentage o1f positively stained cells and their staining pattern (diffusely membranous, partially membranous and dot-like) were evaluated. The median expression value was used for the distinction between keratin-negative and -positive patients. Overall survival in respective groups was compared using the log-rank test. Multivariate Cox proportional hazards regression analysis was performed adjusting for age, gender, tumor site, tumor stage, and tumor histology.
RESULTS: edian expression of AE1/AE3 and CAM5.2 was 80% and 90%, respectively. Five cases were completely negative for AE1/AE3 and three for Cam5.2. Median overall survival for patients with stronger and weaker AE1/AE3 staining was 24.7 and 13.8 months, respectively (p=0.019). There was no difference in survival in relation to the CAM5.2 expression (p=0.44). In multivariate analysis adjusted for CAM5.2, T and N stage, gender and age at diagnosis, stronger AE1/AE3 expression was an independent predictor of increased survival (HR 0.50; 95% CI, 0.27-0.94; p=0.031).
CONCLUSION: High expression of AE1/AE3 is a favorable prognostic factor in surgically treated SCLC. The applicability of this finding to a typical patient population treated with non-surgical methods warrants further studies.

Wei Z, Cai X, Zhang J, et al.
High Sensitive Immunoelectrochemical Measurement of Lung Cancer Tumor Marker ProGRP Based on TiO₂-Au Nanocomposite.
Molecules. 2019; 24(4) [PubMed] Article available free on PMC after 05/03/2020 Related Publications
Progastrin-releasing peptide (ProGRP), which is known to be highly specific and sensitive to small cell lung cancer (SCLC), has been proven to be a valuable substitute for neuron-specific enolase in SCLC diagnostics and monitoring, especially in its early stages. The detection of ProGRP levels also facilitates a selection of therapeutic treatments. For the fabrication of our proposed biosensor, titanium (IV) oxide microparticles were first used, followed by dispersing gold nanoparticles into chitosan and immobilizing them onto a carbon paste electrode (CPE) surface. The developed immunosensor exhibits a much higher biosensing performance in comparison with current methods, when it comes to the detection of ProGRP. Therefore, the proposed CPE/TiO₂/(CS+AuNPs)/anti-ProGRP/BSA/ProGRP is excellent for the development of a compact diagnostics apparatus.

Atallah-Yunes SA, Clark J, Samanani S, Soe M
Small Cell Lung Cancer with Pituitary Metastasis Presenting as Secondary Adrenal Insufficiency: A Case Report and Literature Review.
Am J Case Rep. 2019; 20:207-211 [PubMed] Article available free on PMC after 05/03/2020 Related Publications
BACKGROUND Pituitary gland metastasis is rarely the initial presentation of metastatic cancer. Most cases of pituitary gland metastasis are asymptomatic with diabetes insipidus being the most common symptomatic presentation. It can rarely present with symptoms of hormone underproduction such as secondary adrenal insufficiency. Although pituitary gland metastasis is rare, it is underestimated, as it is commonly misdiagnosed with pituitary gland adenoma due to the lack of clear radiological criteria differentiating between both. CASE REPORT We present a case of a 62-year-old male who presented with weakness, blurry vision, and persistent hypoglycemia despite intravenous dextrose infusion and having discontinued taking his diabetes medications. Chest x-ray showed a left hilar mass, while computed tomography scan demonstrated a left superior hilar mass and hilar lymphadenopathy with bilateral adrenal nodules and a T6 vertebral lesion suspicious for metastasis. Further workup showed secondary adrenal insufficiency with a low adrenocorticotropic hormone (ACTH) level. Vertebral biopsy was performed and confirmed the diagnosis of small cell carcinoma of the lung. This was followed by a brain magnetic resonance imaging (MRI), which showed multiple metastatic lesions with an enhancing mass involving the right clivus, sella, and suprasellar cistern with mass effect on the optic chiasm and involvement of the cavernous sinus supporting the diagnosis of pituitary gland metastasis of small cell lung cancer. The patient received brain radiation, and repeated MRI showed regression of the previous MRI findings. CONCLUSIONS Secondary adrenal insufficiency is an unusual presentation of pituitary gland metastasis. Physicians should take into consideration both radiological findings and presentation to differentiate between pituitary gland metastasis and pituitary adenoma.

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