Outcomes In Small Cell Lung Cancer Research Articles

A retrospective study on the impact of radiotherapy on the survival outcomes of small cell lung cancer patients based on the SEER database

Small cell lung cancer (SCLC) patients exhibit significant heterogeneity in tumor burden, physical condition, and responses to initial treatment. This diversity in treatment responses can result in varying treatment outcomes. The primary objective of this study was to explore the patient demographics associated with improved survival outcomes through radiotherapy. Based on the SEER database, we identified 42,824 SCLC patients enrolled between 2004 and 2015. These patients were stratified into radiotherapy (n = 20,360) and non-radiotherapy groups (n = 22,464). We controlled for confounding factors using propensity score matching (PSM) analysis. Subsequently, Kaplan–Meier (KM) analysis was employed to evaluate the impact of radiotherapy on patients’ overall survival (OS) and cancer-specific survival (CSS). Cancer-specific mortality was further analyzed using competitive risk models. Cox analysis was also conducted to examine additional variables potentially affecting the survival of SCLC patients. We identified a total of 42,824 eligible patients, and following PSM, 13,329 patients were successfully matched in both the radiotherapy and non-radiotherapy groups. The KM analysis showed that the median OS was 9 months in the radiotherapy group and 6 months in the non-radiotherapy group. The median CSS was 10 months in the radiotherapy group and 7 months in the non-radiotherapy group. The 5-year OS and 10-year OS rates were 6.2% versus 1.6% in the radiotherapy group and 2.6% versus 0.8% in the non-radiotherapy group (P < 0.001). Competitive risk analysis showed that cancer-specific mortality was significantly higher in the non-radiotherapy group than in the radiotherapy group (P < 0.001). Multivariate Cox analysis showed that the radiotherapy group (relative non-radiotherapy group) showed a significant positive effect on survival outcomes (OS: HR 0.658 95% CI [0.642, 0.675] P < 0.001; CSS: HR 0.662 95% CI [0.645, 0.679], P < 0.001). In addition, age, gender, race, primary tumor site, T stage, N stage, M stage, chemotherapy, and surgery were also considered as important predictors of SCLC outcome. The results of the subgroup analysis showed that the radiotherapy group showed a significant survival advantage regardless of age, sex, race, primary tumor site, M stage, chemotherapy, and surgery (P < 0.001). Radiotherapy may improve both OS and CSS in SCLC patients. Patients with SCLC may benefit from radiotherapy regardless of age, sex, race, primary tumor site, M stage, chemotherapy, and surgery.

Comprehensive analysis of transcription factor-based molecular subtypes and their correlation to clinical outcomes in small-cell lung cancer

Recent studies have reported the predictive and prognostic value of novel transcriptional factor-based molecular subtypes in small-cell lung cancer (SCLC). We conducted an in-depth analysis pairing multi-omics data with immunohistochemistry (IHC) to elucidate the underlying characteristics associated with differences in clinical outcomes between subtypes. IHC (n=252), target exome sequencing (n=422), and whole transcriptome sequencing (WTS, n=189) data generated from 427 patients (86.4% males, 13.6% females) with SCLC were comprehensively analysed. The differences in the mutation profile, gene expression profile, and inflammed signatures were analysed according to the IHC-based molecular subtype. IHC-based molecular subtyping, comprised of 90 limited-disease (35.7%) and 162 extensive-disease (64.3%), revealed a high incidence of ASCL1 subtype (IHC-A, 56.3%) followed by ASCL1/NEUROD1 co-expressed (IHC-AN, 17.9%), NEUROD1 (IHC-N, 12.3%), POU2F3 (IHC-P, 9.1%), triple-negative (IHC-TN, 4.4%) subtypes. IHC-based subtype showing high concordance with WTS-based subtyping and non-negative matrix factorization (NMF) clusterization method. IHC-AN subtype resembled IHC-A (rather than IHC-N) in terms of both gene expression profiles and clinical outcomes. Favourable median overall survival was observed in IHC-A (15.2 months) compared to IHC-N (8.0 months, adjusted HR 2.3, 95% CI 1.4-3.9, p=0.002) and IHC-P (8.3 months, adjusted HR 1.7, 95% CI 0.9-3.2, p=0.076). Inflamed tumours made up 25% of cases (including 53% of IHC-P, 26% of IHC-A, 17% of IHC-AN, but only 11% of IHC-N). Consistent with recent findings, inflamed tumours were more likely to benefit from first-line immunotherapy treatment than non-inflamed phenotype (p=0.002). This study provides fundamental data, including the incidence and basic demographics of molecular subtypes of SCLC using both IHC and WTS from a comparably large, real-world Asian/non-Western patient cohort, showing high concordance with the previous NMF-based SCLC model. In addition, we revealed underlying biological pathway activities, immunogenicity, and treatment outcomes based on molecular subtype, possibly related to the difference in clinical outcomes, including immunotherapy response. This work was supported by AstraZeneca, Future Medicine 2030 Project of the Samsung Medical Center [grant number SMX1240011], the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) [grant number 2020R1C1C1010626] and the 7th AstraZeneca-KHIDI (Korea Health Industry Development Institute) oncology research program.

The changing landscape of small cell lung cancer.

Small-cell lung cancer (SCLC) is characterized by rapid proliferation and early dissemination. The objective of this study was to examine the demographic trends and outcomes in SCLC. The authors queried the National Cancer Institute's Surveillance, Epidemiology, and End Results database to assess the trends in incidence, demographics, staging, and survival for SCLC from 1975 to 2019. Trends were determined using joinpoint analysis according to the year of diagnosis. Among the 530,198 patients with lung cancer, there were 73,362 (13.8%) with SCLC. The incidence per 100,000 population peaked at 15.3 in 1986 followed by a decline to 6.5 in 2019. The percentage of SCLC among all lung tumors increased from 13.3% in 1975 to a peak of 17.5% in 1986, declining to 11.1% by 2019. There was an increased median age at diagnosis from 63 to 69 years and an increased percentage of women from 31.4% to 51.2%. The percentage of stage IV increased from 58.6% in 1988 to 70.8% in 2010, without further increase. The most common sites of metastasis at diagnosis were mediastinal lymph nodes (75.3%) liver (31.6%), bone (23.7%), and brain (16.4%). The 1-year and 5-year overall survival rate increased from 23% and 3.6%, respectively, in 1975-1979 to 30.8% and 6.8%, respectively, in 2010-2019. The incidence of SCLC peaked in 1988 followed by a gradual decline. Other notable changes include increased median age at diagnosis, the percentage of women, and the percentage of stage IV at diagnosis. The improvement in 5-year overall survival has been statistically significant but clinically modest.

Genetic overlap and causal inferences between diet-derived antioxidants and small-cell lung cancer.

Several studies have reported that antioxidants exert both preventive and inhibitory effects against tumors. However, their causal effects on small-cell lung cancer (SCLC) remain controversial. Herein, we explored the causal effects of 6 antioxidants on SCLC by combining a genome-wide association study database and the Mendelian randomization (MR) approach. We obtained antioxidant genetic variance data for 6 exposure factors: carotene, vitamin A (retinol), selenium, zinc, vitamin C, and vitamin E, from the genome-wide association study database. The instrumental variables for exposure factors and SCLC outcomes were integrated by screening instrumental variables and merging data. Two-sample MR was used to analyze the causal relationship between exposure and outcomes. Finally, we examined the heterogeneity and horizontal pleiotropy of the MR analysis by performing multiple sensitivity analyses. We found a causal relationship between carotene and SCLC using two-sample MR analysis and sensitivity analysis (P = .02; odds ratio = 0.73; 95% confidence interval: 0.55-0.95). In contrast, there was no causal relationship between other examined antioxidants and SCLC. We found that diet-derived circulating antioxidants could afford protection against SCLC, and carotene is the causal protective factor against SCLC.

Aspartate Transaminase-to-Albumin Ratio (ATAR), a Novel Prognostic Index, Predicts Outcomes in Patients with Small-Cell Lung Cancer.

Small cell lung cancer (SCLC) is characterized by high invasion rates, rapid progression, and poor prognoses. Thus, identifying SCLC patients at high risk of progression and death is critical to improve long-term survival. In this study, the aspartate transaminase-to-albumin ratio (ATAR) was examined as a prognostic factor for SCLC patients. We screened 196 SCLC patients from December 2013 to September 2022 at the Sichuan Cancer Hospital. The data was collected from patients' medical information as well as from their blood results during diagnosis. Using the Youden index as a cutoff value, patients were divided into high-risk（> 0.54) and low-risk (≤ 0.54) ATAR groups. We analyzed the prognostic factors for overall survival (OS) using the Kaplan-Meier method, univariate and multivariate analyses, Cox regression, and the C-index. There were 109 (55.6%) smokers among the patients, and the median OS was 17.55 months. The Kaplan-Meier analysis indicated that patients with high-risk ATAR had significantly lower OS (p < 0.0001). A multivariate analysis demonstrated that elevated ATAR is an independent adverse predictor of OS (p < 0.001, HR = 1.907). Our study found that ATAR is an independent predictor of survival outcomes in SCLC, which was superior to ALB, PNI, and SII in predicting outcomes in low-risk and high-risk groups (all p < 0.05). Models combining ATAR with ALB, PNI, and SII showed more powerful prognostic value than their corresponding original models. Moreover, the prognostic indicator ATAR can significantly stratify stage I - II and III - IV SCLC patients (p ＜ 0.05). Peripheral blood ATAR prognostic index can be used as an independent predictor of SCLC patients before treatment.

Tumor microenvironment-mediated immune profiles and efficacy of anti-PD-L1 antibody plus chemotherapy stratified by DLL3 expression in small-cell lung cancer.

Delta-like ligand 3 (DLL3) is a therapeutic target in small-cell lung cancer (SCLC). However, how DLL3 expression status affects the tumor microenvironment (TME) and clinical outcomes in SCLC remains unclear. This retrospective study included patients with postoperative limited-stage (LS)-SCLC and extensive-stage (ES)-SCLC treated with platinum and etoposide (PE) plus anti-programmed cell death ligand 1 (PD-L1) antibody. We investigated the relationship of DLL3 expression with TME, mutation status, tumor neoantigens, and immunochemotherapy. In the LS-SCLC cohort (n = 59), whole-exome sequencing revealed that DLL3High cases had significantly more neoantigens (P = 0.004) and a significantly higher rate of the signature SBS4 associated with smoking (P = 0.02) than DLL3Low cases. Transcriptome analysis in the LS-SCLC cohort revealed that DLL3High cases had significantly suppressed immune-related pathways and dendritic cell (DC) function. SCLC with DLL3High had significantly lower proportions of T cells, macrophages, and DCs than those with DLL3Low. In the ES-SCLC cohort (n = 30), the progression-free survival associated with PE plus anti-PD-L1 antibody was significantly worse in DLL3High cases than in DLL3Low cases (4.7 vs. 7.4 months, P = 0.01). Although SCLC with DLL3High had a higher neoantigen load, these tumors were resistant to immunochemotherapy due to suppressed tumor immunity by inhibiting antigen-presenting functions.

Abstract 4546: Comprehensive analysis using transcriptional factor based molecular subtypes and correlation to clinical outcomes in small-cell lung cancer

Abstract Background: Several studies have reported the predictive and prognostic value of novel transcriptional factor-based molecular subtypes in small-cell lung cancer (SCLC). We conducted an in-depth analysis using multi-omics data to elucidate the underlying characteristics that lead to differences in clinical outcomes between subtypes. Patients and Methods: Immunohistochemistry (IHC, n=252), target exome sequencing (n=422), and whole transcriptome sequencing (WTS, n=189) data generated from 427 patients with SCLC patients were comprehensively analyzed. The differences in the mutation profile, gene expression profile were analyzed according to the IHC-based molecular subtype. Clinical implication was evaluated based on treatment outcomes of individual patients. Results: IHC based molecular subtyping revealed a high incidence of ASCL1 subtype (SCLC-A, 56.3%) followed by ASCL1/NEUROD1 co-expressed (SCLC-trans, 17.9%), NEUROD1 (SCLC-N, 12.3%), POU2F3 (SCLC-P, 9.1%), triple-negative (SCLC-TN, 4.4%) subtypes showing high concordance with WTS-based subtyping. We delineated the SCLC-trans subtype resembling SCLC-A rather than SCLC-N in terms of both gene expression profiles and clinical outcomes. SCLC-TN type was defined as non-significant expression of A, N, P. Favorable overall survival (OS) was observed in SCLC-A compared to SCLC-N (adjusted HR 2.4, 95% CI 1.5-3.9, p &amp;lt; 0.001) and SCLC-P (adjusted HR 1.7, 95% CI 0.9-2.9, p = 0.087). SCLC-TN showed a similar OS with SCLC-A (adjusted HR 1.2, 95% CI 0.6 -2.7, p = 0598). The clinical outcome based on inflamed phenotype, clustered by effector cell gene expression profile which are only found in 5% of SCLC-N but 60% of SCLC-P, was more likely to benefit from first-line immunotherapy treatment than non-inflamed phenotype (p = 0.013). Inflammed phenotype demonstrated longer progression-free survival to the first line immunotherapy compared to the non-inflammed phenotype. (10.5 vs 4.3, p = 0.013) Conclusions: This study provides fundamental data, including the incidence and basic demographics of molecular subtypes of SCLC using both IHC and WTS from a comparably large cohort including potential differences in the distribution of subtypes based on ethnicity. Additionally, our results reveal differences in the underlying biological pathway activities and immunogenicity based on molecular subtype, possibly related to the difference in clinical outcomes, including immunotherapy response. Citation Format: Sehhoon Park, Tae Hee Hong, Soohyun Hwang, Hyun-Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Jong Ho Cho, Yong Soo Choi, Jhingook Kim, Young Mog Shim, Hong Kwan Kim, Yoon-La Choi, Se-hoon Lee, Keunchil Park. Comprehensive analysis using transcriptional factor based molecular subtypes and correlation to clinical outcomes in small-cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4546.

Peripheral T-cell receptor repertoire dynamics in small cell lung cancer.

Identifying a circulating biomarker predictive of immune checkpoint inhibitor (ICI) benefit in patients with small cell lung cancer (SCLC) remains an unmet need. Characteristics of peripheral and intratumoral T-cell receptor (TCR) repertoires have been shown to predict clinical outcomes in non-small cell lung cancer (NSCLC). Recognizing a knowledge gap, we sought to characterize circulating TCR repertoires and their relationship with clinical outcomes in SCLC. SCLC patients with limited (n=4) and extensive (n=10) stage disease were prospectively enrolled for blood collection and chart review. Targeted next-generation sequencing of TCR beta and alpha chains of peripheral blood samples was performed. Unique TCR clonotypes were defined by identical CDR3, V gene, and J gene nucleotide sequences of the beta chain and subsequently used to calculate TCR diversity indices. Patients with stable versus progressive and limited versus extensive stage disease did not demonstrate significant differences in V gene usage. Kaplan-Meier curve and log-rank analysis did not identify a statistical difference in progression-free survival (PFS) (P=0.900) or overall survival (OS) (P=0.200) between high and low on-treatment TCR diversity groups, although the high diversity group exhibited a trend toward increased OS. We report the second study investigating peripheral TCR repertoire diversity in SCLC. With a limited sample size, no statistically significant associations between peripheral TCR diversity and clinical outcomes were observed, though further study is warranted.

The maximum tumor growth rate predicts clinical outcomes of patients with small-cell lung cancer undergoing first-line chemotherapy plus immune-checkpoint inhibitor therapy.

Currently, no biomarkers can accurately predict survival outcomes in patients with SCLC undergoing treatment. Tumor growth rate (TGR; percent size change per month [%/m]) is suggested as an imaging predictor of response to anti-cancer treatment. We aimed to evaluate the predictive role of the maximum TGR (TGRmax) for outcomes of small-cell lung cancer (SCLC) patients undergoing first-line chemotherapy plus immune-checkpoint inhibitor (ICI) treatment. Patients with SCLC receiving first-line chemotherapy plus immunotherapy were analyzed within this retrospective study. The X-tile program was used to identify the cut-off value of TGRmax based on maximum progression-free survival (PFS) stratification. The Kaplan-Meier methods and Cox regression models were used to evaluate the effect of the presence of TGRmax on PFS and overall survival (OS). In total, 104 patients were evaluated. Median (range) TGRmax was -33.9 (-65.2 to 21.6) %/m and the optimal cut-off value of TGRmax was -34.3%/m. Multivariate Cox regression analysis revealed that patients with TGRmax > -34.3%/m was associated with shorter PFS (hazard ratio [HR], 2.81; 95% CI, 1.71-4.63; p < 0.001) and OS (HR, 3.17; 95% CI, 1.41-7.08; p=0.005). In patients who received partial response (PR), Kaplan-Meier survival analyses showed that superior PFS and OS (p=0.005 and p=0.009, respectively) benefit was observed when TGRmax ≤-34.3%/m. SCLC patients with TGRmax > -34.3%/m had worse PFS and OS in first-line ICI plus platin-based chemotherapy. TGRmax could independently serve as an early biomarker to predict the benefit from chemoimmunotherapy.

Organoids as a Systems Platform for SCLC Brain Metastasis.

Small Cell Lung Cancer (SCLC) is a highly aggressive, neuroendocrine tumor. Traditional reductionist approaches have proven ineffective to ameliorate the uniformly dismal outcomes for SCLC – survival at 5 years remains less than 5%. A major obstacle to improving treatment is that SCLC tumor cells disseminate early, with a strong propensity for metastasizing to the brain. Accumulating evidence indicates that, contrary to previous textbook knowledge, virtually every SCLC tumor is comprised of multiple subtypes. Important questions persist regarding the role that this intra-tumor subtype heterogeneity may play in supporting the invasive properties of SCLC. A recurrent hypothesis in the field is that subtype interactions and/or transition dynamics are major determinants of SCLC metastatic seeding and progression. Here, we review the advantages of cerebral organoids as an experimentally accessible platform for SCLC brain metastasis, amenable to genetic manipulations, drug perturbations, and assessment of subtype interactions when coupled, e.g., to temporal longitudinal monitoring by high-content imaging or high-throughput omics data generation. We then consider systems approaches that can produce mathematical and computational models useful to generalize lessons learned from ex vivo organoid cultures, and integrate them with in vivo observations. In summary, systems approaches combined with ex vivo SCLC cultures in brain organoids may effectively capture both tumor-tumor and host-tumor interactions that underlie general principles of brain metastasis.

Heterogeneity of neuroendocrine transcriptional states in metastatic small cell lung cancers and patient-derived models

Molecular subtypes of small cell lung cancer (SCLC) defined by the expression of key transcription regulators have recently been proposed in cell lines and limited number of primary tumors. The clinical and biological implications of neuroendocrine (NE) subtypes in metastatic SCLC, and the extent to which they vary within and between patient tumors and in patient-derived models is not known. We integrate histology, transcriptome, exome, and treatment outcomes of SCLC from a range of metastatic sites, revealing complex intra- and intertumoral heterogeneity of NE differentiation. Transcriptomic analysis confirms previously described subtypes based on ASCL1, NEUROD1, POU2F3, YAP1, and ATOH1 expression, and reveal a clinical subtype with hybrid NE and non-NE phenotypes, marked by chemotherapy-resistance and exceedingly poor outcomes. NE tumors are more likely to have RB1, NOTCH, and chromatin modifier gene mutations, upregulation of DNA damage response genes, and are more likely to respond to replication stress targeted therapies. In contrast, patients preferentially benefited from immunotherapy if their tumors were non-NE. Transcriptional phenotypes strongly skew towards the NE state in patient-derived model systems, an observation that was confirmed in paired patient-matched tumors and xenografts. We provide a framework that unifies transcriptomic and genomic dimensions of metastatic SCLC. The marked differences in transcriptional diversity between patient tumors and model systems are likely to have implications in development of novel therapeutic agents.

Real-world treatment patterns and outcomes in small-cell lung cancer: a systematic literature review.

BackgroundSmall-cell lung cancer (SCLC) accounts for 12–15% of lung cancers and is associated with poor survival outcomes and high symptom burden. This study employed a broad, systematic search strategy and timeframe to identify evidence on real-world treatment patterns and outcomes for SCLC outside the USA, including understanding sub-populations such as extensive-stage (ES) or limited-stage (LS) disease.MethodsDatabases (MEDLINE, Embase, and EBM reviews) were searched for journal articles published in the English language between 1 January 2000–1 March 2020 and supplemented by hand searching of conference abstracts and posters presented at conferences between 1 January 2016–1 March 2020 reporting real-world treatment outcomes in patients with SCLC. A targeted clinical guideline review was also completed.ResultsOne-hundred studies provided quantitative data; 57 were available as full-text articles, whilst the remaining 43 were presented as abstracts or posters. The majority (80 studies, 80%) of included studies reported treatment in the first-line setting, where platinum-based chemotherapy and chemoradiotherapy was the most commonly used treatment strategy, in line with current treatment guidelines in SCLC. First-line treatments were found to have a high response rate; however, most patients relapsed early. No studies reported treatment or outcomes with immune-oncology therapies. Second-line treatment options were very limited, and primarily consisted of either re-treatment with first-line regimen or topotecan, but the prognosis for these patients remained poor. Outcomes were particularly poor amongst those with ES or relapsed disease vs. LS disease.ConclusionsSCLC treatment patterns and short survival outcomes have remained constant over the previous 20 years. Due to the search timeframe, none of the studies identified reported on the impact of recently approved immune-oncology therapies in SCLC. Further data is needed on the impact of immunotherapies on treatment patterns and real-world outcomes in SCLC.

The clinical efficacy of olaparib monotherapy or combination with ceralasertib (AZD6738) in relapsed small cell lung cancer.

8562 Background: The molecular profiling of small cell lung cancer (SCLC) has demonstrated a high incidence of genomic alterations in cell cycle-related genes and DNA damage and response (DDR) pathways, which correlates with devastating clinical outcomes of SCLC. Using two small molecules targeting the DNA repair pathway, olaparib (PARP inhibitor) and ceralasertib (ATR inhibitor), we evaluated their clinical efficacy in monotherapy or in combination, in relapsed SCLC. Methods: As part of the phase II biomarker-driven umbrella study in SCLC (SUKSES), patients who failed prior platinum-based regimen were enrolled and allocated based on their genomic alterations. Patients with mutations harboring HR pathway gene mutation not limited to BRCA 1 or 2, ATM deficiency or MRE11A mutations were allocated to the olaparib monotherapy (SUKSES-B, NCT03009682). As an biomarker non-matched arm, biomarker unselected patients were also allowed to receive olaparib and ceralasertib arm (SUKSES-N2, NCT0328607). The primary endpoint was objective response rate (ORR), and two-stage Simon’s design was used. Results: Based on pre-defined protocol criteria, both arms terminated at stage 1. In the olaparib monotherapy arm (SUKSES-B, n = 15), ORR was 6.7%, and disease control rate (DCR) was 26.7%, 1 partial response (PR), and 3 stable diseases (SD). Median progression-free survival (PFS) was 1.25 months (95% confidential interval [CI] 1.18–NA), and median overall survival (OS) was 8.56 months (95% CI, 6.62–NA). Adverse events that led to treatment discontinuation (n = 2 total, 13.3%) were drug related grade 3 renal impairment, thrombocytopenia, and grade 2 anemia. A patient with confirmed PR showed a tumor volume decrease of 37% compared to the baseline, and a splicing site mutation in BRCA2 was identified from deep target sequencing. In the olaparib and ceralasertib treatment arm (SUKSES-N2, n = 26), ORR was 3.8% (n = 1) and DCR was 42.3% (n = 11). Median PFS was 2.75 months (95% CI 1.77–5.44), and OS was 7.18 months (95% CI 5.97-10.79). Three patients discontinued treatment due to drug related grade 5 pneumonia, grade 3 drug-induced pneumonitis and grade 2 anemia. The most common adverse events for the combination were anemia (n = 11, 42.3%), followed by thrombocytopenia (n = 6, 23.1%). A patient with confirmed PR with a 43% decreases in tumor volume compared with baseline had a mutation in TP53. Conclusions: Targeting the DDR pathways with olaparib as single agent or in combination with ceralasertib demonstrated early signal of efficacy in relapsed SCLC patients with a tolerable safety profile. Clinical trial information: NCT03009682, NCT0328607.

Impact of socioeconomic disparities on diagnosis and overall survival in small cell lung cancer: A National Cancer Database analysis.

8515 Background: Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer diagnoses in the United States. The demographics of this disease have evolved over time; in the 1970s 28% of patients with SCLC were female, while in the early 2000s, 50% were female. Remarkable differences in incidence, mortality rates, and trends by race and geographic location have also been noted. There has been a paucity of data regarding changes in epidemiology and patient demographics in SCLC since the early 2000s. Given recent treatment advances, the impact these factors have on patient outcomes for SCLC requires further evaluation. Methods: We identified all patients with SCLC in the NCDB from 2004 to 2016. Differences in demographic, disease, and treatment characteristics were assessed by year of diagnosis using Chi-square test. The effect of age, race, insurance status, income, distance to treatment center, and education level on overall survival (OS) was assessed by log-rank test. Results: There were 137,253 cases of SCLC diagnosed in the NCDB between 2004-2010 and 124,796 cases between 2011-2016. Patients diagnosed after 2010 were significantly older, had more comorbidities, had more stage IV disease, were more frequently treated at academic centers, more commonly had government primary payer insurance, and lived significantly further away from their treatment center. There were significant differences in gender, race/ethnicity groups, education level, and residence area, with more females, more African Americans, more patients without a high school diploma, and more rural patients diagnosed after 2010. OS in general improved between the two time periods, with median OS of 8.41 months (95% CI: 8.34-8.48%) and 5-year OS rate of 6.8% (95% CI: 6.6-6.9%) in patients diagnosed between 2004-2010 and median OS of 8.61 months (95% CI: 8.54-8.67%) and 5-year OS rate of 8.7% (95% CI: 8.5-8.9%) in patients diagnosed after 2010, despite an increase in stage IV disease in the latter group. Some of the differences in demographics were associated with changes in OS. Older patients, male patients, Caucasian patients, patients with stage IV disease, patients with government primary payer insurance, and rural patients all had significantly worse OS. Patients without comorbidities and patients treated at an academic center had significantly better OS. OS was found to significantly increase as both income and education level increase. Conclusions: SCLC continues to be a frequent cancer diagnosis. Despite improvement in overall survival during the time frame studied, there were significant disparities noted in key demographics that negatively affect access to healthcare resources, including rural communities, distance to an academic center, income, insurer, and education level. Collective efforts to impact these disparities will likely lead to improved outcomes for patients with SCLC.

Metabolic Health Together with a Lipid Genetic Risk Score Predicts Survival of Small Cell Lung Cancer Patients.

Simple SummaryDespite the progress in surgery and therapies, small cell lung cancer (SCLC) is still one of the most lethal types of cancer. The disease control remains heterogeneous and consequently, the ability to predict patient survival would be of great clinical value. Here, we propose for the first time, a metabolic precision approach for SCLC patients. We found that a healthy metabolic status contributes to increasing SCLC survival. Moreover, we discovered that two lipid metabolism-related genes, racemase and perilipin 1, and a genetic risk score of both genes, predict better SCLC survival. Our results show that a metabolic scenario characterized by metabolic health, lipid gene expression and environmental factors, is crucial for increase SCLC survival.Small cell lung cancer (SCLC) prognosis is the poorest of all types of lung cancer. Its clinical management remains heterogeneous and therefore, the capability to predict survival would be of great clinical value. Metabolic health (MH) status and lipid metabolism are two relevant factors in cancer prevention and prognosis. Nevertheless, their contributions in SCLC outcome have not yet been analyzed. We analyzed MH status and a transcriptomic panel of lipid metabolism genes in SCLC patients, and we developed a predictive genetic risk score (GRS). MH and two lipid metabolism genes, racemase and perilipin 1, are biomarkers of SCLC survival (HR = 1.99 (CI95%: 1.11–3.61) p = 0.02, HR = 0.36 (CI95%: 0.19–0.67), p = 0.03 and HR = 0.21 (CI95%: 0.09–0.47), respectively). Importantly, a lipid GRS of these genes predict better survival (c-index = 0.691). Finally, in a Cox multivariate regression model, MH, lipid GRS and smoking history are the main predictors of SCLC survival (c-index = 0.702). Our results indicate that the control of MH, lipid gene expression and environmental factors associated with lifestyle is crucial for increased SCLC survival. Here, we propose for the first time, a metabolic precision approach for SCLC patients.

P50.01 A Year Experience With Atezolizumab Plus Chemotherapy For Small Cell Lung Cancer In Alberta, Canada

The authors assessed the real-world effectiveness of newly approved regimen, atezolizumab plus carboplatin-etoposide (Atezo-CaE) for extensive stage (ES) small cell lung cancer (SCLC) in Alberta, Canada. Atezo-CaE is yet to be provincially funded for ES treatment but can be accessed through special access programs. Included in this study were confirmed ES patients treated with first-line Atezo-CaE at the tertiary and community cancer care centres in Alberta, Canada post FDA/ Health Canada approval (2019) up to the data cut-off date (September 1, 2020). Demographic and clinical data were extracted from the institutional Glans-Look Research Database. Any with active multiple malignancies and/or prior curative-intent treatment were excluded. Outcomes including overall response rate (ORR, RECIST v1.1), adverse events (CTCAE criteria v5), progression-free and overall survival were estimated using descriptive and Kaplan-Meier survival (Log-Rank) statistics. A priori statistical significance was p < 0.05. Analyses were performed using SPSS statistical software (version 25). There were 34 patients seen at the community care centres (18%) or academic tertiary institutions (82%). 53% were male, 24% had ECOG performance status ≥2 and the median age was 65 years. The median number of days from diagnosis to Atezo-CaE receipt was 40 (range: 14-128) days. 21% had no maintenance atezolizumab. In addition, 65% had radiotherapy treatment. 21% were still having ongoing atezolizumab treatment. The median duration of atezolizumab was 4.2 (range: 0.1-13.5) months. ORR was 62% with a median of 84 (range: 47-210) days time to best response. 18% have an ongoing response to atezolizumab. Disease progression was the commonest reason for 1L discontinuation while also accounting for the 2nd most common reason for no maintenance atezolizumab only after adverse events. Overall, progressive disease rate was 76%. The median duration of response was 98 (range: 35-635) days. 24% continued atezolizumab for ≥ 1 month past disease progression. 2L rate was 26%. The median progression-free and overall survival for all patients were 6 (95% CI: 4-8) and 11 (95% CI: 9-11) months while in those who received maintenance atezolizumab were 8 (p=0.01) and 13 (p<0.01) months respectively. Within a year of Atezo-CaE treatment for ES, there was 18% ongoing response to Atezo-CaE. The ORR (62 vs 60%), median treatment duration (4.2 vs 4.7 months) and overall survival outcomes (12.7 vs 12.3 months) appeared consistent in real-world versus clinical trial patients1. Future study to identify factors predicting Atezo-CaE treatment response and survival outcomes in SCLC is very much needed.

Effect of Hospitalization During First Chemotherapy and Performance Status on Small-cell Lung Cancer Outcomes

IntroductionSmall-cell lung cancer (SCLC) is highly responsive to chemotherapy (CT) and one of the few malignancies treated in hospitalized patients with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS). Because of the little current information available on the outcomes experienced by hospitalized patients with SCLC receiving CT, we explored the outcomes for these patients to improve the evidence base for practice. Materials and MethodsWe conducted a retrospective cohort study to evaluate patients with a diagnosis of SCLC and treated with CT during a 10-year period. Progression-free survival (PFS) and overall survival (OS) were evaluated according to site of first CT (inpatient vs. outpatient) and PS. Multivariable analysis was completed to assess for independent survival predictors. ResultsA total of 530 patients with SCLC were treated, with 82 (15%) receiving their first CT in hospital. Inpatients had a greater burden of disease and poorer PS. Neutropenia, thrombocytopenia, nephrotoxicity, and fatigue were all experienced less often by the inpatient cohort (P < .001, P < .001, P < .001, and P = .007, respectively). For inpatients and outpatients, the OS rate at 12, 24, and 60 months was 22%, 9%, and 7% and 43%, 20%, and 9%, respectively (P < .001 for all). The median PFS and OS were longer for outpatients and highly functional patients. On multivariable analysis, ECOG PS was an independent predictor of the outcome and the site of first CT was not (P = .04 and P = .49, respectively). ConclusionPatients with SCLC initially treated as inpatients and those with poor functional status had shorter PFS and OS; however, some experienced long-term survival, including 5-year survival of 7% for the inpatient cohort and 5% for the ECOG PS 3-4 cohort. CT toxicities were less common in the inpatient cohort, validating that administration of CT in hospital should be considered for these patients because they could experience a meaningful long-term response to therapy.

Survival of Patients with Small Cell Lung Cancer in King Abdulaziz University Hospital, Jeddah, Saudi Arabia.

BackgroundLung cancer is estimated to be 12% of all new cases of cancer. It is one of the most common cancers in men and women, and it is the main cause of cancer-related death in the United States of America. More than 90% of small cell lung cancer (SCLC) patients are elderly, with a current or past history of smoking. In Saudi Arabia, lung cancer incidence is low as compared to the global incidence. In 2013, the age-standardized ratio (ASR) was 1.8 per 100,000 for females and 5.5 per 100,000 for males. In our study, we aimed to assess the outcomes of SCLC at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia.MethodsThis retrospective cohort study included all patients aged 14 years and older with a diagnosis of SCLC from 2007 to 2017 using electronic medical records at KAUH.Data analysis was performed using Stata SE, version 15.0 (StataCorp LLC, TX). The primary outcome of this study was the survival of patients diagnosed with SCLC. Survival was defined as the time the patient lived in months from the date of pathological diagnosis to the date of the last follow-up or death. We included all variables in a univariate and multivariate analysis to determine the hazard ratio for each variable.ResultsIn our study, we initially collected 193 lung cancer cases diagnosed during the period of 2007 to 2017 at KAUH, which was then narrowed to 22 after the selection of only SCLC cases.Data obtained showed 20 males (90.91%) and two females (9.09%), the median age of diagnosis was 64 years, and 45% of patients are active smokers, 9% are ex-smokers, and the smoking status of 41% of patients is unknown. Our data showed an overall median survival of 6.4 months (interval=11).ConclusionWe observed that more than half of our patients who received chemotherapy showed improvement and a higher survival rate than those who didn't. In addition, 19% who received radiation therapy showed improvement and a higher survival rate than those who didn't. Future efforts to address the major issues that surround SCLC survivors, and to formulate a comprehensive survivorship care plan are required to develop better outcomes in survival and to improve the overall quality of life to pretreatment levels.

Clinicopathological characteristics and treatment outcome in small cell lung cancer: A single institutional experience from India.

Background and Objectives:Small cell lung cancer (SCLC) constitutes 14%–20% of all lung cancers. Clinical data on SCLC are scarce in literature. To report clinical features and treatment outcome of SCLC treated at our center.Materials and Methods:This is a single institutional data review of SCLC patients treated between June 2011 and December 2018. Patients were staged as either localized or extensive disease after appropriate staging work-up. Patients with localized disease were treated with concurrent chemoradiation with platinum-based chemotherapy. Those with extensive disease were treated with platinum based palliative chemotherapy. Clinicopathological characteristics, treatment details, and outcome were recorded in this study. Patients who received at least one cycle of chemotherapy were included for survival analysis as intent-to-treat analysis.Results:A total of 181 were patients registered with a median age of 62 years (range: 35–86 years) and male: female ratio of 166:15. Eighty-seven percent (n = 157) of patients had smoking history and 15% (n = 28) of patients had symptom of superior vena cava obstruction at baseline. Twenty-seven (15%) patients had localized disease at presentation. One hundred and twenty (66%) patients took systemic chemotherapy. Chemotherapy regimen was carboplatin only in 9 (7%), etoposide-carboplatin in 54 (45%), and cisplatin-etoposide in 57 (48%). Patients received median cycle number of 6 (range: 1–6). Of the evaluable 87 (73%) patients, initial response was complete response in 4, partial response in 57, stable disease in 20, and progressive disease in 6. Twenty patients received second-line chemotherapy at time of disease progression. After a median follow-up of 8.8 months (range: 0.3–46.1), median progression-free survival (PFS) of the whole population was 9.3 months.Conclusions:Small cell carcinoma in our series had a high incidence of advanced stage (85%) and 13% of patients were nonsmoker. Only 66% of patients received palliative chemotherapy and achieved high disease control rate (>75%) in the evaluable patients with median PFS of 9.3 months.

Characterization of PD-L1 protein expression and CD8+ tumor-infiltrating lymphocyte density, and their associations with clinical outcome in small-cell lung cancer.

This study aimed to characterize programmed death ligand-1 (PD-L1) expression and CD8+ tumor-infiltrating lymphocytes (TILs) density, and their impact on survival in patients with surgically resected small-cell lung cancer (SCLC). Fifty-six patients with surgically resected SCLC were included. PD-L1 protein expression and CD8+ TILs were tested by immunohistochemistry. A meta-analysis of 15 articles with 1,505 patients that investigated the prevalence and prognostic significance of PD-L1 expression in SCLC was conducted. Twenty-two (39.3%) patients had positive PD-L1 protein expression and 42 (75.0%) had high CD8+ TILs density. PD-L1 expression level was not associated with CD8+ TILs density (P=0.528). No any association between clinicopathological features and PD-L1 expression level or CD8+ TILs density was observed. Positive PD-L1 expression [hazard ratio (HR) =0.374, P=0.002] and high CD8+ TILs density (HR =0.429, P=0.008) were independently associated with significantly longer overall survival (OS), which remain the statistical significance in multivariate analyses (P=0.007, P=0.002; respectively). Meta-analysis showed that the prevalence of positive PD-L1 expression was 0.35 [95% confidence interval (CI), 0.22-0.48] and positive PD-L1 expression was correlated with markedly longer OS (HR =0.61; 95% CI, 0.31-0.91) in patients with SCLC. The prevalence of PD-L1 expression in surgically resected SCLC is lower than that published for NSCLC. There was no association between PD-L1 expression or CD8+ TILs density and clinicopathological parameters. PD-L1 expression and CD8+ TILs density was independently correlated with better outcome in patients with SCLC.