Overall Survival In Small Cell Lung Cancer Research Articles

Development and validation of prognostic models for small cell lung cancer patients with liver metastasis: a SEER population-based study

BackgroundThis study was to establish and validate prediction models to predict the cancer-specific survival (CSS) and overall survival (OS) of small-cell lung cancer (SCLC) patients with liver metastasis.MethodsIn the retrospective cohort study, SCLC patients with liver metastasis between 2010 and 2015 were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training group and testing group (3: 1 ratio). The Cox proportional hazards model was used to determine the predictive factors for CSS and OS in SCLC with liver metastasis. The prediction models were conducted based on the predictive factors. The performances of the prediction models were evaluated by concordance indexes (C-index), and calibration plots. The clinical value of the models was evaluated by decision curve analysis (DCA).ResultsIn total, 8,587 patients were included, with 154 patients experiencing CSS and 154 patients experiencing OS. The median follow-up was 3 months. Age, gender, marital status, N stage, lung metastases, multiple metastases surgery of metastatic site, chemotherapy, and radiotherapy were independent predictive factors for the CSS and OS of SCLC patients with liver metastasis. The prediction models presented good performances of CSS and OS among patients with liver metastasis, with the C-index for CSS being 0.724, whereas the C-index for OS was 0.732, in the training set. The calibration curve showed a high degree of consistency between the actual and predicted CSS and OS. DCA suggested that the prediction models provided greater net clinical benefit to these patients.ConclusionOur prediction models showed good predictive performance for the CSS and OS among SCLC patients with liver metastasis. Our developed nomograms may help clinicians predict CSS and OS in SCLC patients with liver metastasis.

Comparation between novel online models and the AJCC 8th TNM staging system in predicting cancer-specific and overall survival of small cell lung cancer.

Most of previous studies on predictive models for patients with small cell lung cancer (SCLC) were single institutional studies or showed relatively low Harrell concordance index (C-index) values. To build an optimal nomogram, we collected clinicopathological characteristics of SCLC patients from Surveillance, Epidemiology, and End Results (SEER) database. 24,055 samples with SCLC from 2010 to 2016 in the SEER database were analyzed. The samples were grouped into derivation cohort (n=20,075) and external validation cohort (n=3,980) based on America's different geographic regions. Cox regression analyses were used to construct nomograms predicting cancer-specific survival (CSS) and overall survival (OS) using derivation cohort. The nomograms were internally validated by bootstrapping technique and externally validated by calibration plots. C-index was computed to compare the accuracy and discrimination power of our nomograms with the 8th of version AJCC TNM staging system and nomograms built in previous studies. Decision curve analysis (DCA) was applied to explore whether the nomograms had better clinical efficiency than the 8th version of AJCC TNM staging system. Age, sex, race, marital status, primary site, differentiation, T classification, N classification, M classification, surgical type, lymph node ratio, radiotherapy, and chemotherapy were chosen as predictors of CSS and OS for SCLC by stepwise multivariable regression and were put into the nomograms. Internal and external validations confirmed the nomograms were accurate in prediction. C-indexes of the nomograms were relatively satisfactory in derivation cohort (CSS: 0.761, OS: 0.761) and external validation cohort (CSS: 0.764, OS: 0.764). The accuracy of the nomograms was superior to that of nomograms built in previous studies. DCA showed the nomograms conferred better clinical efficiency than 8th version of TNM staging system. We developed practical nomograms for CSS (https://guowei2020.shinyapps.io/DynNom-CSS-SCLC/) and OS (https://drboidedwater.shinyapps.io/DynNom-OS-SCLC/) prediction of SCLC patients which may facilitate clinicians in individualized therapeutics.

Low diffusion capacity predicts poor prognosis in extensive stage small cell lung cancer: a single-center analysis of 10 years

BackgroundPoor pulmonary function and chronic obstructive pulmonary disease (COPD) are associated with poorer overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. Few studies have investigated the association between pulmonary function and OS in small-cell lung cancer (SCLC) patients. We compared the clinical characteristics of extensive disease SCLC (ED-SCLC) with or without moderately impaired diffusion capacity for carbon monoxide (DLco) and investigated the factors associated with survival in ED-SCLC patients.MethodsThis retrospective single-center study was performed between January 2011 and December 2020. Of the 307 SCLC patients who received cancer therapy during the study, 142 with ED-SCLC were analyzed. The patients were divided into DLco < 60% group and DLco ≥ 60% groups. OS and predictors of poor OS were analyzed.ResultsThe median OS of the 142 ED-SCLC patients was 9.3 months and the median age was 68 years. In total, 129 (90.8%) patients had a history of smoking, and 60 (42.3%) had COPD. Thirty-five (24.6%) patients were assigned to the DLco < 60% group. Multivariate analysis revealed that DLco < 60% (odds ratio [OR], 1.609; 95% confidence interval [CI], 1.062–2.437; P = 0.025), number of metastases (OR, 1.488; 95% CI, 1.262–1.756; P < 0.001), and < 4 cycles of first-line chemotherapy (OR, 3.793; 95% CI, 2.530–5.686; P < 0.001) were associated with poor OS. Forty (28.2%) patients received < 4 cycles of first-line chemotherapy; the most common reason for this was death (n = 22, 55%) from grade 4 febrile neutropenia (n = 15), infection (n = 5), or massive hemoptysis (n = 2). The DLco < 60% group had a shorter median OS than the DLco ≥ 60% group (10.6 ± 0.8 vs. 4.9 ± 0.9 months, P = 0.003).ConclusionsIn this study, approximately one quarter of the ED-SCLC patients had DLco < 60%. Low DLco (but not forced expiratory volume in 1 s or forced vital capacity), a large number of metastases, and < 4 cycles of first-line chemotherapy were independent risk factors for poor survival outcomes in patients with ED-SCLC.

Clinical characteristics and outcomes of extrapulmonary small cell cancer: A retrospective analysis of the SEER database.

e20616 Background: Extrapulmonary small cell cancer (EPSCC) accounts for only 5-10% of small cell carcinoma, with the rest consisting of small cell lung cancer (SCLC). The incidence of this entity has been rising due to better diagnosis, however it is not well described and data is limited. We performed a Surveillance, Epidemiology and End Results (SEER) database analysis to further characterize the biology and clinical aspects of this entity, in comparison to SCLC. Methods: The Surveillance, Epidemiology and End Results (SEER) 18 database was used to obtain data on age, gender, ethnicity, survival, and tumor characteristics of n = 9,712 US patients diagnosed with EPSCC between 2000-2018 and these were compared to n = 118,514 patients with SCLC diagnosed during the same period. Results: Among the EPSCC cohort 58.1 % were males while in the SCLC cohort 50.3% were males. Median age of diagnosis was 65.50 years for EPSCC and 66.81years for SCLC. Among the EPSCC patients, 75.9 % were Caucasians, 9.2 % were African-Americans, and 8.8% were Hispanics. Amongst SCLC patients, Caucasians made up 83.1% of the patients, while African-Americans made up 8.6% and Hispanics made up 4.5 % of the patients. Most common sites for EPSCC were urinary bladder (20.2%), prostate (7%), cervix uteri (6.2%), pancreas (4.5%), rectum (3%), and ovaries (2.6%). Median OS for EPSCC was 8 months (95% CI: 8 - 8), while median overall survival for SCLC was 7 month (95% CI: 7 - 7). Hazard ratio for death for EPSCC: 0.77 (95% CI: 0.75 - 0.79), p &lt; 0.001. The survival at 12 months, 24 months and 60 months was 36%, 22%, and 13 % for EPSCC and 29%, 13%, and 5% for SCLC. There were no significant gender or racial differences in overall survival (OS). Conclusions: EPSCC has better overall and 5-year survival as compared to SCLC. There are no significant differences in survival outcomes in EPSCC patients based on location of primary, gender or race.

Prognostic Significance of the Systemic Immune-Inflammation Index (SII) in Patients With Small Cell Lung Cancer: A Meta-Analysis

BackgroundPrevious studies have investigated the prognostic value of the systemic immune-inflammation index (SII) in small cell lung cancer (SCLC). However, the results have been inconsistent. The study aimed to investigate the prognostic and clinicopathological significance of SII in SCLC through a meta-analysis.MethodsThe PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were thoroughly searched. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the prognostic value of the SII for survival outcomes. The combined odds ratios (ORs) and 95% CIs were used to evaluate the correlation between SII and clinicopathological features.ResultsEight studies comprising 2,267 patients were included in the meta-analysis. Pooled analyses indicated that a high SII was significantly associated with worse overall survival (OS) (HR=1.52, 95% CI=1.15–2.00, p=0.003) but not progression-free survival (HR=1.38, 95% CI=0.81–2.35, p=0.238) in patients with SCLC. Moreover, a high SII was associated with extensive-stage SCLC (OR=2.43, 95% CI=1.86–3.17, p<0.001). However, there was a non-significant correlation between SII and age, sex, smoking history, Karnofsky Performance Status score, or initial therapeutic response.ConclusionOur meta-analysis demonstrated that a high SII could be an efficient prognostic indicator of OS in SCLC. We recommend adopting SII to predict OS in patients with SCLC, and SII in combination with other parameters or biomarkers may aid in addressing the clinical strategy and choosing the best treatment for an individual patient.

Inflammation scores as prognostic biomarkers in small cell lung cancer: a systematic review and meta-analysis

BackgroundInflammation scores based on general inflammation markers as leucocyte count or C-reactive protein have been evaluated as prognostic markers of inferior survival in several cancers. In small cell lung cancer (SCLC), however, inflammation scores are less studied. In the present study, we set out to perform a systematic review and meta-analysis investigating reported associations between inflammation scores and overall survival (OS) in SCLC.MethodsA literature search was performed in PubMed, Embase, Scopus, and Web of Science following the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) guidelines. Of the identified publications, only studies in English containing original data evaluating inflammation scores as a prognostic factor in SCLC patients were included. Hazard ratios (HRs) for OS were pooled in a random-effects model.ResultsIn total, 33 articles were included evaluating eight different inflammation scores in 7762 SCLC patients. Seven of the identified scores were based on leucocyte count. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) ratio were the most frequently evaluated scores (NLR: n = 23; PLR: n = 22). For NLR, a meta-analysis including 16 studies demonstrated that patients with a high NLR had a significantly shorter OS compared to patients with a low NLR (pooled HR = 1.39 (95% CI, 1.23–1.56)). For PLR, an association with survival could not be confirmed in a meta-analysis performed based on eight studies (pooled HR = 1.20 (95% CI, 0.96–1.51)).ConclusionsThis review identifies that inflammation scores based on general inflammation markers have some potential as prognostic biomarkers in SCLC. The meta-analyses indicated that NLR is associated with inferior OS, whereas an association between PLR and OS could not be confirmed. Thus, NLR could be a useful biomarker of OS in SCLC patients.Systematic review registrationThe protocol for the study was submitted to the PROSPERO database (registration number CRD42020188553).

Assessment of the Clinical Utility of Circulating Tumor Cells at Different Time Points in Predicting Prognosis of Patients With Small Cell Lung Cancer: A Meta-Analysis.

ObjectivesNumerous studies have elucidated that circulating tumor cells (CTCs) have significant prognostic value in various solid tumors. However, the prognostic value of CTCs in small cell lung cancer (SCLC) remains controversial. The current study was performed to investigate the prognostic significance of different time points of CTCs in SCLC.MethodsPubMed, EMBASE, Web of Science, and Cochrane Library databases were retrieved for eligible studies. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the association between CTCs level and overall survival (OS) and progression-free survival (PFS) in SCLC. Furthermore, subgroup analyses, sensitivity analysis, Begg’s and Egger’s tests were also conducted.ResultsSixteen cohort studies with 1103 participants were eligible for this meta-analysis. Our results revealed that higher pretreatment CTCs level was significantly correlated with worse OS in SCLC no matter CellSearch (HR, 2.95; 95%CI, 1.56-5.58; P = .001) or other methods (HR, 2.37; 95%CI, 1.13-4.99; P = .023) was used to detect CTCs. Higher pretreatment CTCs status detected by CellSearch was associated with shorter PFS (HR, 3.75; 95%CI, 2.52-5.57; P < .001), while there was no significant association when other methods were adopted to CTC detection (HR, 2.04; 95%CI, .73-5.68; P = .172). Likewise, we observed that higher post-therapy CTCs level detected by both CellSearch (HR, 2.99; 95%CI, 1.51-5.93; P = .002) and other methods (HR, 4.79; 95%CI, 2.03-11.32; P < .001) was significantly correlated with decreased OS in SCLC. However, higher post-therapy CTCs count detected by CellSearch was not correlated with worse PFS (HR, 1.80; 95%CI, .83-3.90; P = .135). Sensitivity analysis demonstrated that the pooled data were still stable after eliminating studies one by one. However, significant publication bias was observed between pretreatment CTCs level detected by CellSearch and OS of SCLC.ConclusionDynamic monitoring of CTCs level could be a non-invasive and effective tool to predict the disease progression and prognosis in patients with SCLC.

The prognostic value of pretreatment prognostic nutritional index in patients with small cell lung cancer and it's influencing factors: a meta-analysis of observational studies.

BackgroundNumerous studies identified that pretreatment prognostic nutritional index (PNI) was significantly associated with the prognosis in various kinds of malignant tumors. However, the prognostic value of PNI in small cell lung cancer (SCLC) remains controversial. We performed the present meta-analysis to estimate the prognostic value of PNI in SCLC and to explore the relationship between PNI and clinical characteristics.MethodsWe systematically and comprehensively searched PubMed, EMBASE, and Web of Science for available studies until April 17, 2020. Pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to evaluate the correlation between PNI and overall survival (OS) and progression-free survival (PFS) in SCLC. Odds ratios (ORs) and 95% CIs were applied to evaluate the relationship between clinical features and PNI in SCLC.ResultsA total of nine studies with 4,164 SCLC patients were included in the meta-analysis. The pooled data elucidated that lower PNI status was an independent risk factor for worse OS in SCLC (HR =1.43; 95% CI: 1.24–1.64; P<0.001), while there was no significant correlation between PNI status and PFS (HR =1.44; 95% CI: 0.89–2.31; P=0.134). We also found that Eastern Cooperative Oncology Group (ECOG) performance status ≥2 (OR =2.72; 95% CI: 1.63–4.53; P<0.001) and extensive-stage (ES) disease (OR =1.93; 95% CI: 1.62–2.30; P<0.001) were risk factors for low PNI, while prophylactic cranial irradiation (PCI) (OR =0.53; 95% CI: 0.40–0.69; P<0.001) was a protective factor for low PNI.ConclusionsOur findings suggested that low PNI status was closely correlated with the decreased OS in SCLC. Surveillance on PNI, amelioration of nutritional and immune status, and timely initiation of PCI may improve the prognosis of SCLC.

A Retrospective Cohort Study on Pretreated Neutrophil-to-Lymphocyte Ratio and Prognosis of Small Cell Lung Cancer: Evidence of Effect Modification by Chemotherapy Regimen.

PurposeNeutrophil-to-lymphocyte ratio (NLR) has been suggested as an independent risk factor for progression-free survival (PFS) and overall survival (OS) in small cell lung cancer (SCLC). However, it is still unknown whether there is a linear relationship between the NLR and the risk of death in SCLC. The objective of this study is to provide further results.Patients and MethodsA retrospective cohort study was performed among a total of 251 participants with SCLC. Smooth curve fitting and piecewise Cox regression model were used to determine the linear relationship between NLR and mortality risk. A multivariable Cox regression model was used to estimate the effects of NLR on OS. Interaction and stratified analyses were conducted according to covariates.ResultsThe analysis indicated no significant nonlinear relationship or threshold effect between NLR and hazard of death. Multivariate analysis revealed that every unit increase in NLR was associated with a 10% increase in mortality risk. High NLR (>3.5) at baseline was associated with poor OS (hazard ratio [HR]=1.97, P=0.009). The difference in median OS duration between the high and low NLR groups was statistically significant (9.1 months vs 14.6 months, P=0.0067). Furthermore, interaction analysis identified the chemotherapy regimen to play an interactive role in the association between NLR and hazard of death.ConclusionNLR was identified as an independent risk factor for OS in SCLC and the linear correlation was observed between them. Administration of etoposide plus cisplatin (EP) regimen in patients with low NLR resulted in better long-term outcome than that of etoposide plus carboplatin (EC) regimen, while administration of the EC regimen conferred longer OS than that of the EP regimen in patients with high NLR.

The clinicopathological and prognostic value of the pretreatment neutrophil-to-lymphocyte ratio in small cell lung cancer: A meta-analysis.

Although many scholars have recently studied the relationships between the pretreatment neutrophil-to-lymphocyte ratio (NLR) and prognosis in patients with small cell lung cancer (SCLC), the conclusions have been inconsistent. Accordingly, in this meta-analysis, we attempted to assess the clinicopathological and prognostic value of the pretreatment NLR in SCLC. Related literature was searched using PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature, China National Knowledge Infrastructure (CNKI), and Wanfang databases. Each eligible study was extracted, and a meta-analysis was performed using hazard ratios (HRs) and 95% confidence intervals (95% CIs) to assess the prognostic value of NLR. Evaluation of the clinicopathological significance of NLR in SCLC used odds ratios (ORs) and 95% confidence intervals (95% CIs). We included a total of 20 studies with 21 outcomes (5141 patients) in this meta-analysis. The results showed that high pretreatment NLR was closely related to poorer progression free survival (PFS) and overall survival (OS) (PFS, HR = 1.55, 95% CI = 1.27–1.88, P < 0.0001; I2 = 0%; OS, HR = 1.40, 95% CI = 1.26–1.55, P < 0.00001; I2 = 64%). In addition, pretreatment NLR was significantly associated with clinical stage of SCLC (OR = 2.14, 95% CI = 1.35–3.39, P = 0.001). Our meta-analysis showed that high levels of pretreatment NLR were significantly associated with a more serious clinical stage and poorer PFS and OS in SCLC.

Analysis of systemic inflammatory biomarkers in neuroendocrine carcinomas of the lung: prognostic and predictive significance of NLR, LDH, ALI, and LIPI score.

Background:Lung neuroendocrine carcinoma (NEC) is characterized by aggressive clinical behavior and lack of treatment advances. We evaluate the prognostic and the predictive roles of systemic inflammatory biomarkers in patient circulating blood: neutrophil–lymphocyte ratio (NLR), lactate dehydrogenase (LDH), advanced lung cancer inflammation index (ALI), and the Lung Immune Prognostic Index (LIPI) score.Methods:A total of 120 patients with small-cell lung cancer (SCLC) (n = 110) and large cell neuroendocrine carcinoma (LCNEC) (n = 10) were enrolled. Overall survival (OS) was evaluated by Kaplan–Meier estimator and univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic factors associated with OS while χ2 test was used for categorical data.Results:NLR cutoff value was 1.93. NLR was measured before and after first-line chemotherapy; 25 (21%) patients had higher NLR (delta NLR >1), whereas NLR was lower in 37 (31%). At the univariate analysis, median OS was 12 months: OS for SCLC and LCNEC were 11 months and 14 months, respectively. OS had a prognostic positive value in patients with pre-treatment NLR <1.93 (p = 0.0002), LDH <600 U/L (p = 0,03) and ALI ⩾34 (p = 0,0065). At the multivariate analysis, Eastern Cooperative Oncology Group performance status, LDH levels and response after first-line chemotherapy were independently associated with OS. Median OS for good, intermediate, and poor LIPI was 15 months, 11 months, and 9 months, respectively(p = 0.091). Patients with higher NLR (>1.93) had an increased probability of tumor progression (p = 0.045, χ2 test).Conclusion:This study demonstrated that systemic inflammatory biomarkers could facilitate the understanding of survival differences in the clinical management of lung NEC patients, underlying the need for prospective biomarker-driven studies in the immune checkpoint inhibitors setting.

P1.03-33 Analysis of Lipid Metabolism Genes in Advanced Small Cell Lung Cancer

Lung cancer is the leading cause of cancer death worldwide. Although most of the knowledge about metabolic dysregulation in cancer focuses on carbohydrates, the importance of alterations related to lipid metabolism is starting to be recognized. There is increasing data on lipid metabolism and non-small lung cancer, but much less is known about this in small cell lung cancer (SCLC). In order to improve our knowledge of these alterations we evaluated a genetic profile related to lipid metabolism and studied clinical outcomes We performed a retrospective analysis of 22 genes related to lipid metabolism in 37 tumoral tissue samples of SCLC patients and evaluated clinical features and outcomes. Advanced SCLC patients enrolled from November 1, 2008 through December 31, 2015 were included in this analysis. Clinical data were collected from medical records at the time of enrollment. The study was approved by an Ethics Committee and all patients signed an Informed Consent form. We used formalin-fixed, paraffin- embedded tumor tissue. Samples were deparaffinated and total RNA was extracted. A Taq-Man Low Density Array (Applied Biosystems) was specifically designed and gene-expression assays were performed in a HT-7900 Fast Real time PCR. RT-StatMiner software was used to detect and determine the quality control and differential expression analyses of data. We included 37 patients, 73 % males and 27 % women, with a median age of 62. 29 patients (78%) had stage IV tumor and nearly all of them (92%) were treated with platinum- based chemotherapy. 11 % (4/37) received thoracic radiotherapy and 5% (2/37) received whole brain radiotherapy. 6 patients (16%) were on chronic treatment with metformin and 15 (40%) on statins. We performed a multivariable analysis and found that overexpression of two metabolic genes (a mitochondrial enzyme and a lipid metabolism regulator) led to longer overall survival. (HR 0.13 (0.04-0.42), p 0.0019, padjusted 0.04 and HR 0.11 (0.03-0.35) p 0.0006, padjusted 0.01, respectively). These genes contribute to normal functioning and regulation of lipid metabolism and could be considered as potential prognostic biomarkers. There is no previous evidence of association between levels of expression of these genes and overall survival in SCLC. Validation in a larger series of patients is ongoing.

The Effect of Thoracic Radiation Therapy on Overall Survival in SCLC: Findings from the National Cancer Database

This study aimed to report the effect of thoracic radiation therapy (TRT) on overall survival (OS) and examine whether the OS effect varies with the timing of TRT regarding systemic therapy in small cell lung cancer (SCLC). Patients with SCLC from the national cancer database (NCDB) 2005-2014 formed the base of the study population. TRT, dose and time effects were analyzed individually in patients treated with systemic therapy. Exploratory analysis on TRT survival effect was also performed for patients received immunotherapy. The primary endpoint was OS. Kaplan-Meier test was used for the OS analysis; Log rank was used for significant testing. A total of 169,397 patients were eligible. Median survival time (MST) was 8.5 months (mo). Younger age, female gender, non-African American, lower Charlson Comorbidity Index, and any TRT were all significantly associated with favorable OS in all stages (all Ps < 0.001). In 53,926 patients received TRT, the median survival was 14.9 mo vs 5.5 mo in 99,649 patients without TRT (P<0.0001). In 53,375 patients receiving non-immune systemic therapy, TRT significantly improved OS (MST 15.0 for TRT group vs 5.4 mo for non-TRT group, P < 0.0001). Compared to those receiving TRT before non-immune systemic therapy (n = 16,076, MST = 12.2 mo), patients with concurrent TRT (within 30 days of systemic therapy) had significantly better OS (n = 31,068, MST = 16.2 mo, P < 0.001), also significantly better than that of patients receiving TRT after systemic therapy (n = 1,036, MST = 15.7 mo, P <0.0001). Concurrent TRT has better survival than sequential systemic therapy followed by TRT in patients with stage I-III disease; while chemotherapy followed by TRT had better survival than concurrent TRT in stage IV disease (P<0.0001). In 338 patients treated with any immunotherapy, the median survival was 15.5 and 9.6 mo for TRT (n=104) and non-TRT group (n=234). In 94 patients treated with immunotherapy and TRT with treatment time available for analysis, the median survival was 20 mo (n = 21), 15.3 mo (n=42), and 15.9 months (n=31) for TRT followed by immunotherapy, concurrent TRT and immunotherapy followed by TRT (P = 0.656), respectively. This US national database validated the significant effect of TRT on OS in all stages of SCLC treated with systemic therapy. TRT with any systemic therapy followed by immunotherapy seemed to be associated with best survival.

Expression of delta-like protein 3 is reproducibly present in a subset of small cell lung carcinomas and pulmonary carcinoid tumors

ObjectivesDelta-like protein 3 (DLL3), an inhibitory Notch ligand, is the target for rovalpituzumab tesirine in development for the treatment of small cell lung cancer (SCLC). We studied the expression of DLL3, its reproducibility and prognostic role in pulmonary neuroendocrine tumors. Materials and MethodsInstitutional pathology files were searched for resected pulmonary neuroendocrine tumors (1995–2017). Expression of DLL3 (clone SP347) was categorized as high (≥50% of tumor cells) or low (<50%). Interobserver agreement among 5 thoracic pathologists was measured by Krippendorff’s α coefficient. Staging (N = 148) was performed according to the 8th AJCC. ResultsOur study included 157 patients with a median age of 62.2 years (range 23.2–88.1) including 59 men (37.6%). Tumors included 44 (28.0%) SCLC, 46 (29.3%) atypical and 67 (42.7%) typical carcinoid tumors at stages I (N = 83, 56.1%), II (N = 28, 18.9%), and III/IV (N = 37, 25.0%). Interobserver agreement for high vs low DLL3 expression (N = 70) was 82.9% (α = 0.79, substantial). High DLL3 expression was observed in 35 (79.5%) SCLC, 17 (37.0%) atypical and 22 (32.8%) typical carcinoid tumors. High DLL3 was associated with SCLC morphology (p < 0.0001). During a median follow-up of 4.2 years (range, 2 days–20.3 years), 70 patients died; 19 died from disease. High DLL3 expression was associated with better overall survival in SCLC (p = 0.049) but not after adjusting for age, tumor size and stage. ConclusionsDLL3 expression is reliably quantifiable by pathologists and is highly expressed in the majority of SCLC and a subset of carcinoid tumors, making it an attractive target for anti-DLL3 treatment.

Analysis of lipid metabolism genes in advanced small cell lung cancer.

e14737 Background: Lung cancer is the leading cause of cancer death worldwide. Although most of the knowledge about metabolic dysregulation in cancer focuses on carbohydrates, the importance of alterations related to lipid metabolism is starting to be recognized. There is increasing data on lipid metabolism and non-small lung cancer, but much less is known about this in small cell lung cancer (SCLC). In order to improve our knowledge of these alterations we evaluated a genetic profile related to lipid metabolism and studied clinical outcomes. Methods: We performed a retrospective analysis of 22 genes related to lipid metabolism in 37 tumoral tissue samples of SCLC patients and evaluated clinical features and outcomes. Advanced SCLC patients enrolled from November 1, 2008 through December 31, 2015 were included in this analysis. Clinical data were collected from medical records at the time of enrollment. The study was approved by an Ethics Comittee and all patients signed an Informed Consent form. We used formalin-fixed, paraffin- embedded tumor tissue. Samples were deparaffinated and total RNA was extracted. A Taq-Man Low Density Array (Applied Biosystems) was specifically designed and gene-expression assays were performed in a HT-7900 Fast Real time PCR. RT-StatMiner software was used to detect and determine the quality control and differential expression analyses of data. Results: We included 37 patients, 73 % males and 27 % women, with a median age of 62. 29 patients (78%) had stage IV tumor and nearly all of them (92%) were treated with platinum- based chemotherapy. 11 % (4/37) received thoracic radiotherapy and 5% (2/37) received whole brain radiotherapy. 6 patients (16%) were on chronic treatment with metformin and 15 (40%) on statins. We performed a multivariable analysis and found that overexpression of two metabolic genes (a mitochondrial enzyme and a lipid metabolism regulator) led to longer overall survival. (HR 0.13 (0.04-0.42), p 0.0019, padjusted 0.04 and HR 0.11 (0.03-0.35) p 0.0006, padjusted 0.01, respectively). Conclusions: These genes contribute to normal functioning and regulation of lipid metabolism and could be considered as potential prognostic biomarkers. There is no previous evidence of association between levels of expression of these genes and overall survival in SCLC. Validation in a larger series of patients is ongoing.

Prognostic value of metabolic tumour volume and total lesion glycolysis measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography in small cell lung cancer: A systematic review and meta-analysis.

The aim of this study was to evaluate the prognostic value of metabolic tumour volume (MTV) and total lesion glycolysis (TLG) for small cell lung cancer (SCLC). MEDLINE, EMBASE and Cochrane Library databases were systematically searched. The pooled hazard ratio (HR) was used to measure the influence of MTV and TLG on survival. The subgroup analysis according to VALSG stage and the measured extent of MTV was performed. Patients with high MTV values experienced a significantly poorer prognosis with a HR of 2.42 (95% CI 1.46-4.03) for overall survival (OS) and a HR of 2.78 (95% CI 1.39-5.53) for progression-free survival (PFS) from the random effect model, and the pooled HR from the fixed effect model was 2.10 (95% CI 1.77-2.50) for OS and 2.27 (95% CI 1.83-2.81) for PFS. Patients with high TLG experienced a poorer prognosis with a HR of 1.61 (95% CI: 1.24-2.07) for OS from the random effect model, and the pooled HR from the fixed effect model was 1.64 (95% CI 1.37-1.96). Heterogeneity among studies was high for MTV in both OS and PFS meta-analyses (I2 =87% and 88% respectively). After removing one outlier study the heterogeneity was substantially reduced (I2 =0%) and the pooled HR for the effect of MTV on OS was 1.80 (1.51-2.16, P<0.00001), and on PFS it was 1.86 (1.49-2.33, P<0.00001), using either the fixed or random effects model. High MTV is associated with a significantly poorer prognosis OS and PFS, and high TLG is associated with a significantly poorer prognosis regarding OS for SCLC.

Clinical value of carcinoembryonic antigen for predicting the incidence of brain metastases and survival in small cell lung cancer patients treated with prophylactic cranial irradiation.

BackgroundAlthough the role of prophylactic cranial irradiation (PCI) in the treatment of small cell lung cancer (SCLC) has been confirmed, the occurrence of brain metastases (BM) in patients remains a major problem. We designed this study to evaluate the clinical value of carcinoembryonic antigen (CEA) for predicting the incidence of BM and survival in SCLC patients who received PCI.Materials and methodsThe records of 128 consecutive SCLC patients, who underwent PCI in our institute between 2005 and 2015, were analyzed. The collected data included clinicopathological features and the levels of CEA, neuron-specific enolase (NSE), cytokeratin 19 fragments (CYFRA21-1), and albumin. Kaplan–Meier and Cox regression analyses were used to determine the factors that affect BM and survival in SCLC patients after PCI.ResultsIn total, 128 patients were identified, with a median (range) age of 62 (30–83) years. Thirty-two patients developed BM at some time during follow-up. The median levels of CEA, NSE, CYFRA21-1, and albumin were 7.6 ng/mL, 44 ng/mL, 4.6 ng/mL, and 42.1 g/L, respectively. In the multivariate analysis, CEA level (HR: 2.479, 95% CI: 1.101–5.581; P=0.028), advanced clinical stage (HR: 2.929, 95% CI: 1.338–6.413; P=0.007), and NSE level (HR: 3.021, 95% CI: 1.226–7.442; P=0.016) were significantly correlated with BM. CEA (HR: 1.903, 95% CI: 1.133–3.195; P=0.015) and advanced clinical stage (HR: 2.002, 95% CI: 1.227–3.267; P=0.005) were independently associated with worse overall survival in SCLC patients.ConclusionCEA is an independent predictive factor for the incidence of BM after PCI in SCLC and can be used as a predictor of BM in SCLC. In addition, a high level of CEA indicates a poor prognosis in SCLC patients after PCI. Prospective randomized clinical studies are required to confirm these findings.

Premorbid BMI as a prognostic factor in small-cell lung cancer-a single institute experience.

Numerous evidence has indicated that excess weight is associated with an increased risk of mortality in patients in several cancer types including breast, colorectal, pancreatic, endometrial, and prostate cancer However, with respect to non-small cell lung cancer and upper aero-digestive cancer, evidence suggests that low body mass index (BMI) may increase the risk of mortality of these cancers, but a definitive link between premorbid BMI and overall survival in small cell lung cancer patients has yet to be fully explored. To investigate this possibility, we conducted a retro-spective of 173 small-cell lung cancer patients. Multivariate Cox analysis indicated that pretreatment overweight (BM I ≥ 23) was an independent prognostic factor for overall survival (OS) (Hazard ratio, = 0.58, 95% CI = 0.39–0.87, p = 0.008). In addition, meta-regression revealed that per-formance status (≤ 2) marginally interacted with increased BMI (p = 0.068). However, subgroup analysis showed that patients with a BMI ≥ 23 and performance status ≤ 2 had the best OS (Hazard ratio: 0.31, 95% CI: 0.16–0.61, p = 0.001). Premorbid BMI and performance status level are easy to measure and may provide physicians an additional measurement to predict a small-cell lung cancer patient’s survival. The data from the present study indicates that a, further large scale prospective study is warranted to better assess the association of pretreatment BMI and OS in small-cell lung cancer.

Overexpression of Programmed Cell Death-Ligand 1 in Small-Cell Lung Cancer and Survival Analysis

Purpose: Programmed cell death-ligand-1 (PD-L1) has identified overexpression in many solid carcinomas. However, the expression in small cell lung cancer (SCLC) remains unclear and the association between the PD-L1 expression and prognosis is not well investigated. Methods: The expression of PD-L1 was evaluated in 136 specimens of SCLC by immunohistochemistry in Huai’an First People’s Hospital. PD-L1 expression was defined as tumors staining in over 5% of tumor cells. Survival analysis was evaluated using the Kaplan-Meier method. Multivariate regression was performed with the Cox proportional hazards model. Results: One hundred and thirty-six patients were enrolled in present study,including 78 of extensive and 58 with limited stage. PD-L1 expression was detected in 54.4% of all the patients (53.8% in extensive and 55.2% in limited stage). Patients with PD-L1 positive expression showed better overall survival (OS) than PD-L1 negative patients regardless of extensive or limited small cell lung cancer (P value were 0.002 and 0.016, respectively). One hundred and twenty-one patients were with recurrence or metastasis. Median progression free survival of first-line chemotherapy in PD-L1 positive patients was 5.30 and 3.50 months in PD-L1 negative patients (P=0.030). PD-L1 remained as significant prognostic factor for better survival with multivariate analyses (HR=0.76; P=0.041). Conclusion: Our results that PD-L1 is overexpressed in 54.4% of SCLC patients. Expression of PD-L1 is correlated with a favorable PFS and OS in SCLC.

Abstract C11: The effect of payer status on small cell lung cancer survival

Abstract Background: The overall survival for small cell lung cancer (SCLC) patients at 5 years is only about 5% to 10% and improvements in treatment have proved to be unsatisfactory in prolonging SCLC survival. One of the challenges in improving cancer survival beyond treatment is identifying disparities in health care access. In this study, we determined how disparities in payer status affected SCLC patient survival by analyzing data from the National Cancer Data Base (NCDB) between 1998 and 2011. Materials and Methods: We evaluated a cohort of 71,724 patients ages 18-65 diagnosed with stage III or IV SCLC who had not undergone surgery or hormonal therapy registered in the NCDB. Overall survival (OS) was the outcome variable, and payer status was the primary predictor variable. Other variables adjusted for included sex, age, race, Charlson Comorbidity Index, income, education, distance travelled, type of cancer program, diagnosing/treating facility, stage, chemotherapy and radiation therapy. Multivariate Cox regression was used to investigate the effect of payer status on OS in SCLC while adjusting for other factors. Results: The majority of patients diagnosed at stage III-IV had private insurance (57.93 %), while 17.75%, 14.69% and 9.64% of patients had Medicare, Medicaid or were uninsured, respectively. The overall mean age in the study population was 56.3 and the mean age for privately insured, uninsured, Medicaid and Medicare patients was 56.3, 55, 54.6, and 58.2 years, respectively. Privately insured patients, which had a median OS of 10.71 months, lived longer in comparison to uninsured, Medicare, and Medicaid patients (median OS of 8.02, 8.25, and 8.67 months for uninsured, Medicare, and Medicaid patients, respectively). Multivariate Cox regression analysis revealed a statistically significant relationship between payer status and overall survival when controlling for other variables. Uninsured, Medicaid, and Medicare patients were found to have a 25% higher risk of death (HR=1.25) from SCLC compared to privately insured patients. Female patients (HR=0.83) had a reduced risk of dying by 17% compared to male patients. Asian (HR=0.82) and black patients (HR=0.95) were found to have an 18% and 5% lesser risk of death, respectively, compared to white patients. For patients receiving radiation therapy, the addition of chemotherapy (HR=0.45) reduced mortality by 55% compared to patients not receiving chemotherapy. For patients not receiving radiation therapy, the addition of chemotherapy (HR=0.50) reduced mortality only by 50% compared to patients not receiving chemotherapy. Conclusion: In the multivariate analysis, payer status proved to be a statistically significant predictor of overall survival for SCLC, which remained true after adjusting for all other factors. Payer status presented as a disparity since uninsured, Medicaid, and Medicare patients had higher mortality compared to privately insured patients. The study also revealed that patients receiving a combination of chemotherapy and radiation therapy had a reduced risk of death in comparison to patients only receiving chemotherapy. Further study is needed to investigate the mechanism of payer status on survival of SCLC. Citation Format: Runhua Shi, Hong Liu, Ruth Bishop, Glenn Mills. The effect of payer status on small cell lung cancer survival. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C11.