Diagnosis Of Small Cell Lung Cancer Research Articles

New electrocatalyst of Ni6MnO8@AB/PtNPs with efficient synergistic enhancement in electrochemical aptasensor for sensitive detection of neuron specific enolase

As one of the specific markers for small cell lung cancer (SCLC), the clinical value for serum neuron-specific enolase (NSE) detection in diagnosis, monitoring and therapy of SCLC is considerable. Herein, a sensitive amperometric aptasensor was developed for the detection of NSE based on nickel-manganese oxide@acetylene black/platinum nanoparticles (Ni6MnO8@AB/PtNPs) composite as signal amplifier. The combination of Ni6MnO8, AB and PtNPs not only showed synergistically catalytic activity to hydrogen peroxide (H2O2), but also possessed lots of binding sites for loading the thiol-terminated signal probes (TSPs) through Pt-S bonds. Additionally, nitrogen-doped carbon nanotubes/poly (diallyldimethylammonium chloride)/ZnO microflowers (N-CNTs/P/ZnO MFs) exhibited outstanding electric conductivity and was used as substrate material to load more biotin-terminated capture probes (BCPs). In the presence of the NSE, the TSPs and BCPs specifically recognized the NSE to form a sandwich-type electrochemical aptasensor, which exhibited a broad linear response range from 0.00001 ∼ 100 ng mL−1 and a low detection limit of 2.86 fg mL−1 (S/N = 3). In addition, the electrochemical aptasensor obtained favorable detection results in diluted human serum, indicating that it had potential application in clinical NSE detection.

A Population-Based Analysis of Brain Metastasis Burden and Management in 8705 Small Cell Lung Cancer Patients

INTRODUCTION: Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for intracranial metastatic disease (IMD), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. These patients traditionally receive whole brain radiation therapy (WBRT) for IMD, however, a recent systematic review has indicated that OS following stereotactic radiosurgery (SRS) may be non-inferior compared with WBRT. METHODS: We included all patients diagnosed with SCLC between April 2007 and March 2018 identified through a provincial health administrative database. Information on patient and treatment characteristics, incidence and time to IMD, and OS from time of SCLC diagnosis were collected and analyzed using R. RESULTS: A total of 8705 patients were included. Median age was 68 years (range 18-103). Most patients presented with extensive disease (n = 5625) and were diagnosed after 2011 (n = 5768). Patients who received chemotherapy (n = 5563) had significantly longer OS than those who did not (median 10.64 vs 1.58 mo, HR 0.36, 95% CI 0.34-0.37). 6662 patients received brain imaging at the time of primary diagnosis (CT: 5126, MRI: 1536), and 88% of patients surviving longer than 6 mo received more than one follow-up brain scan. 31% developed IMD (synchronous: 1175, asynchronous: 1511) with median intracranial progression-free survival of 5.65 mo. Median OS of patients with IMD was 9.76 mo, 29 and 1300 received SRS and WBRT as first treatment for their IMD, respectively. OS was in favour of SRS over WBRT (median 20.47 vs 8.74 mo, HR 0.57, 95% CI 0.39-0.84), which remained significant in multivariate analysis (p < 0.001). CONCLUSIONS: OS for patients with SCLC remains poor and many patients present with IMD. Some patients with SCLC may benefit from SRS treatment.

Novel electrochemical platform based on C3N4-graphene composite for the detection of neuron-specific enolase as a biomarker for lung cancer

Lung cancer remains the leading cause of cancer mortality worldwide. Small cell lung cancer (SCLC) accounts for 10–15% of cases and has an overall 5-years survival rate of only 15%. Neuron-specific enolase (NSE) has been identified as a useful biomarker for early SCLC diagnosis and therapeutic monitoring. This work reports an electrochemical immunosensing platform based on a graphene-graphitic carbon nitride (g-C3N4) nanocomposite for ultrasensitive NSE detection. The g-C3N4 nanosheets and graphene nanosheets were synthesized via liquid exfoliation and integrated through self-assembly to form the nanocomposite. This nanocomposite was used to modify screen-printed carbon electrodes followed by covalent immobilization of anti-NSE antibodies. The unique properties of the graphene-g-C3N4 composite facilitated efficient antibody loading while also enhancing electron transfer efficiency and electrochemical response. Systematic optimization of experimental parameters was performed. The immunosensor exhibited a wide linear detection range of 10 pg/mL to 100 ng/mL and low limit of detection of 3 pg/mL for NSE along with excellent selectivity against interferences. Real serum matrix analysis validated the applicability of the developed platform for sensitive and accurate NSE quantifica-tion at clinically relevant levels. This novel graphene-g-C3N4 nanocomposite based electro-chemical immunoassay demonstrates great promise for early diagnosis of SCLC.

Synchronous double primary small cell lung cancer and invasive ductal breast carcinoma: a case report

BackgroundAlthough lung and breast cancers are common malignancies, the occurrence of primary synchronous neoplasms involving these organs has been rarely reported in literature.Case presentationA 75-year-old female patient presented at a local hospital with a ten-day history of dizziness and slurred speech. A CT contrast-enhanced scan revealed a 4.2 cm mass in the lower lobe of the right lung and a 3.8 cm space-occupying lesion in the right breast. Subsequent breast ultrasound identified a hypoechoic lesion measuring5.41 × 4.75 × 3.06 cm in the right breast, and an ultrasound-guided biopsy confirmed the presence of infiltrating ductal carcinoma of the right breast. The immunohistochemistry analysis of the breast mass revealed positive staining for ER, PR, HER-2, AR and Ki67 in the tumor cells, while negative staining was observed for P63, Calponin, CK5/6 and CK14. MR imaging of the head detected abnormal signals in the right frontal lobe (3.6 cm×2.9 cm in size), left cerebellar hemisphere, and punctate enhancement in the left temporal lobe, indicating potential metastasis. Pathological examination of a lung biopsy specimen confirmed the presence of small cell lung cancer (SCLC). Furthermore, immunohistochemistry analysis of the lung lesions demonstrated positive staining for TTF-1, CK-Pan, Syn, CgA, CD56, P53 (90%) and Ki67 (70%), and negative staining for NapsinA and P40 in the tumor cells. The patient’s diagnosis of SCLC with stage cT2bN0M1c IVB and brain metastases (BM), as well as invasive ductal breast carcinoma (IDC), was confirmed based on the aforementioned results. Whereupon we proposed a treatment plan consisting of whole-brain radiation (40 Gy/20fractions), focal radiotherapy (60 Gy/20fractions), and adjuvant concurrent chemotherapy with oral etoposide (50 mg on days 1 to 20).ConclusionsTo the best of our knowledge, the present case is the first of its kind to describe the synchronous double cancer, consisting of primary SCLC and IDC.

Lurbinectedin in small cell lung cancer: real-world experience of a multicentre national early access programme.

Lurbinectedin is a novel oncogenic transcription inhibitor active in several cancers, including small cell lung cancer (SCLC). We aimed to describe the first Australian experience of the clinical efficacy and tolerability of lurbinectedin for the treatment of SCLC after progression on platinum-containing therapy. Multicentre real-world study of individuals with SCLC initiating lurbinectedin monotherapy (3.2 mg/m2 three-weekly) on an early access programme between May 2020 and December 2021. Key outcomes were clinical utilisation, efficacy and tolerability. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Outcome data were collected within the AUstralian Registry and biObank of thoRacic cAncers (AURORA). Data were analysed for 46 individuals across seven sites. Lurbinectedin was given as second- (83%, 38/46) or subsequent- (17%, 8/46) line therapy, mostly with prior chemoimmunotherapy (87%, 40/46). We report dose modifications (17%, 8/46), interruptions/delays (24%, 11/46), high-grade toxicities (28%, 13/46) and hospitalisations (54%, 25/46) during active treatment. The overall response rate was 33% and the disease control rate was 50%. Six-month OS was 44% (95% confidence interval (CI): 29.0-57.1). Twelve-month OS was 15% (95% CI: 6.5-26.8). From lurbinectedin first dose, the median PFS was 2.5 months (95% CI: 1.8-2.9) and OS was 4.5 months (95% CI: 3.5-7.2). From SCLC diagnosis, the median OS was 12.9 months (95% CI: 11.0-17.2). Individuals with a longer chemotherapy-free interval prior to lurbinectedin had longer PFS and OS. This real-world national experience of lurbinectedin post-platinum chemotherapy and immunotherapy for individuals with SCLC was similar to that reported in clinical trials.

Evaluating CD133 as a Radiotheranostic Target in Small-Cell Lung Cancer.

Despite decades of work, small-cell lung cancer (SCLC) remains a frustratingly recalcitrant disease. Both diagnosis and treatment are challenges: low-dose computed tomography (the approved method used for lung cancer screening) is unable to reliably detect early SCLC, and the malignancy's 5 year survival rate stands at a paltry 7%. Clearly, the development of novel diagnostic and therapeutic tools for SCLC is an urgent, unmet need. CD133 is a transmembrane protein that is expressed at low levels in normal tissue but is overexpressed by a variety of tumors, including SCLC. We previously explored CD133 as a biomarker for a novel autoantibody-to-immunopositron emission tomography (PET) strategy for the diagnosis of SCLC, work that first suggested the promise of the antigen as a radiotheranostic target in the disease. Herein, we report the in vivo validation of a pair of CD133-targeted radioimmunoconjugates for the PET imaging and radioimmunotherapy of SCLC. To this end, [89Zr]Zr-DFO-αCD133 was first interrogated in a trio of advanced murine models of SCLC─i.e., orthotopic, metastatic, and patient-derived xenografts─with the PET probe consistently producing high activity concentrations (>%ID/g) in tumor lesions combined with low uptake in healthy tissues. Subsequently, a variant of αCD133 labeled with the β-emitting radiometal 177Lu─[177Lu]Lu-DTPA-A″-CHX-αCD133─was synthesized and evaluated in a longitudinal therapy study in a subcutaneous xenograft model of SCLC, ultimately revealing that treatment with a dose of 9.6 MBq of the radioimmunoconjugate produced a significant increase in median survival compared to a control cohort. Taken together, these data establish CD133 as a viable target for the nuclear imaging and radiopharmaceutical therapy of SCLC.

The Significance of Insulinoma-Associated Protein 1 in the Pathological Diagnosis of Small-Cell Lung Cancer in Biopsy Specimens.

Objective: Our purpose was to investigate the clinicopathological diagnostic value of immunohistochemical antibody for insulinoma-associated protein 1 (INSM1) in biopsy specimens of SCLC. Methods: Biopsy specimens of SCLC diagnosed at the pathology department of Tangshan Gongren Hospital from January 2022 to June 2023 were selected. INSM1 expression was detected and compared with conventional neuroendocrine markers synaptophysin (SYP), chromogranin A (CHGA), and CD56 regarding expression sensitivity and specificity. Results: The sensitivity of INSM1 expression was significantly higher than that of CHGA (95% vs 50%, P = .000), but there was no statistically significant difference in the specificity of INSM1, SYP, CHGA, and CD56 expression (100% vs 94% vs 98% vs 92%, respectively, P = .241, 1.000, .126). Conclusions: INSM1 antibody shows high sensitivity and specificity in the expression of SCLC and serves as a reliable immunohistochemical marker in the clinicopathological diagnosis of SCLC in biopsy specimens.

Molecular and Pathologic Characterization of YAP1-Expressing Small Cell Lung Cancer Cell Lines Leads to Reclassification as SMARCA4-Deficient Malignancies.

The classification of small cell lung cancer (SCLC) into distinct molecular subtypes defined by ASCL1, NEUROD1, POU2F3, or YAP1 (SCLC-A, -N, -P, or -Y) expression, paves the way for a personalized treatment approach. However, the existence of a distinct YAP1-expressing SCLC subtype remains controversial. To better understand YAP1-expressing SCLC, the mutational landscape of human SCLC cell lines was interrogated to identify pathogenic alterations unique to SCLC-Y. Xenograft tumors, generated from cell lines representing the four SCLC molecular subtypes, were evaluated by a panel of pathologists who routinely diagnose thoracic malignancies. Diagnoses were complemented by transcriptomic analysis of primary tumors and human cell line datasets. Protein expression profiles were validated in patient tumor tissue. Unexpectedly, pathogenic mutations in SMARCA4 were identified in six of eight SCLC-Y cell lines and correlated with reduced SMARCA4 mRNA and protein expression. Pathologist evaluations revealed that SMARCA4-deficient SCLC-Y tumors exhibited features consistent with thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT). Similarly, the transcriptional profile SMARCA4-mutant SCLC-Y lines more closely resembled primary SMARCA4-UT, or SMARCA4-deficient non-small cell carcinoma, than SCLC. Furthermore, SMARCA4-UT patient samples were associated with a YAP1 transcriptional signature and exhibited strong YAP1 protein expression. Together, we found little evidence to support a diagnosis of SCLC for any of the YAP1-expressing cell lines originally used to define the SCLC-Y subtype. SMARCA4-mutant SCLC-Y cell lines exhibit characteristics consistent with SMARCA4-deficient malignancies rather than SCLC. Our findings suggest that, unlike ASCL1, NEUROD1, and POU2F3, YAP1 is not a subtype defining transcription factor in SCLC.

Proteomic Profiling of Small-Cell Lung Cancer: A Systematic Review.

The accurate diagnosis of small-cell lung cancer (SCLC) is crucial, as treatment strategies differ from those of other lung cancers. This systematic review aims to identify proteins differentially expressed in SCLC compared to normal lung tissue, evaluating their potential utility in diagnosing and prognosing the disease. Additionally, the study identifies proteins differentially expressed between SCLC and large cell neuroendocrine carcinoma (LCNEC), aiming to discover biomarkers distinguishing between these two subtypes of neuroendocrine lung cancers. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted across PubMed/MEDLINE, Scopus, Embase, and Web of Science databases. Studies reporting proteomics information and confirming SCLC and/or LCNEC through histopathological and/or cytopathological examination were included, while review articles, non-original articles, and studies based on animal samples or cell lines were excluded. The initial search yielded 1705 articles, and after deduplication and screening, 16 articles were deemed eligible. These studies revealed 117 unique proteins significantly differentially expressed in SCLC compared to normal lung tissue, along with 37 unique proteins differentially expressed between SCLC and LCNEC. In conclusion, this review highlights the potential of proteomics technology in identifying novel biomarkers for diagnosing SCLC, predicting its prognosis, and distinguishing it from LCNEC.

A plasma miRNA-based classifier for small cell lung cancer diagnosis.

Small cell lung cancer (SCLC) is characterized by poor prognosis and challenging diagnosis. Screening in high-risk smokers results in a reduction in lung cancer mortality, however, screening efforts are primarily focused on non-small cell lung cancer (NSCLC). SCLC diagnosis and surveillance remain significant challenges. The aberrant expression of circulating microRNAs (miRNAs/miRs) is reported in many tumors and can provide insights into the pathogenesis of tumor development and progression. Here, we conducted a comprehensive assessment of circulating miRNAs in SCLC with a goal of developing a miRNA-based classifier to assist in SCLC diagnoses. We profiled deregulated circulating cell-free miRNAs in the plasma of SCLC patients. We tested selected miRNAs on a training cohort and created a classifier by integrating miRNA expression and patients' clinical data. Finally, we applied the classifier on a validation dataset. We determined that miR-375-3p can discriminate between SCLC and NSCLC patients, and between SCLC and Squamous Cell Carcinoma patients. Moreover, we found that a model comprising miR-375-3p, miR-320b, and miR-144-3p can be integrated with race and age to distinguish metastatic SCLC from a control group. This study proposes a miRNA-based biomarker classifier for SCLC that considers clinical demographics with specific cut offs to inform SCLC diagnosis.

Construction of a Diagnostic Model for Small Cell Lung Cancer Combining Metabolomics and Integrated Machine Learning.

To date, no study has systematically explored the potential role of serum metabolites and lipids in the diagnosis of small cell lung cancer (SCLC). Therefore, we aimed to conduct a case-cohort study that included 191 cases of SCLC, 91 patients with lung adenocarcinoma, 82 patients with squamous cell carcinoma, and 97 healthy controls. Metabolomics and lipidomics were applied to analyze different metabolites and lipids in the serum of these patients. The SCLC diagnosis model (d-model) was constructed using an integrated machine learning technology and a training cohort (n = 323) and was validated in a testing cohort (n=138). Eight metabolites, including 1-mristoyl-sn-glycero-3-phosphocholine, 16b-hydroxyestradiol, 3-phosphoserine, cholesteryl sulfate, D-lyxose, dioctyl phthalate, DL-lactate and Leu-Phe, were successfully selected to distinguish SCLC from controls. The d-model was constructed based on these 8 metabolites and showed improved diagnostic performance for SCLC, with the area under curve (AUC) of 0.933 in the training cohort and 0.922 in the testing cohort. Importantly, the d-model still had an excellent diagnostic performance after adjusting the stage and related clinical variables and, combined with the progastrin-releasing peptide (ProGRP), showed the best diagnostic performance with 0.975 of AUC for limited-stage patients. This study is the first to analyze the difference between metabolomics and lipidomics and to construct a d-model to detect SCLC using integrated machine learning. This study may be of great significance for the screening and early diagnosis of SCLC patients.

Machine Learning Model-based Detection of Potential Genetic Markers Associated with the Diagnosis of Small-cell Lung Cancer

Background: Small-cell lung cancer (SCLC), which is in the category of intractable cancers, has a low survival rate. It is essential to understand the pathophysiological pathways underlying its development to create powerful treatment alternatives for the disease. Objectives: This study aimed to classify gene expression data from SCLC and normal lung tissue and identify the key genes responsible for SCLC. Methods: This study used microarray expression data obtained from SCLC tissue and normal lung tissue (adjacent tissue) from 18 patients. An Extreme Gradient Boosting (XGBoost) model was established for the classification by five-fold cross-validation. Accuracy (AC), balanced accuracy (BAC), sensitivity (Sens), specificity (Spec), positive predictive value (PPV), negative predictive value (NPV), and F1 scores were utilized for performance assessment. Results: AC, BAC, Sens, Spec, PPV, NPV, and F1 scores from the XGBoost model were 90%, 90%, 80%, 100%, 100%, 83.3%, and 88.9%, respectively. Based on variable importance values from the XGBoost, the HIST1H1E, C12orf56, DSTNP2, ADAMDEC1, and HMGB2 genes can be considered potential biomarkers for SCLC. Conclusion: A machine learning-based prediction method discovered genes that potentially serve as biomarkers for SCLC. After clinical confirmation of the acquired genes in the following medical study, their therapeutic use can be established in clinical practice.

Small Cell Lung Carcinoma: Current Diagnosis, Biomarkers, and Treatment Options with Future Perspectives.

Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid proliferation, early dissemination, acquired therapy resistance, and poor prognosis. Early diagnosis of SCLC is crucial since most patients present with advanced/metastatic disease, limiting the potential for curative treatment. While SCLC exhibits initial responsiveness to chemotherapy and radiotherapy, treatment resistance commonly emerges, leading to a five-year overall survival rate of up to 10%. New effective biomarkers, early detection, and advancements in therapeutic strategies are crucial for improving survival rates and reducing the impact of this devastating disease. This review aims to comprehensively summarize current knowledge on diagnostic options, well-known and emerging biomarkers, and SCLC treatment strategies and discuss future perspectives on this aggressive malignancy.

Outcomes with bevacizumab for radiation induced-brain necrosis.

e14006 Background: Radiation necrosis (RN) is post-radiation complication that leads to increased permeability and disruption of the blood brain barrier (BBB). This in turn leads to a pro-inflammatory state and an increased production of vascular-endothelial growth factor (VEGF). Bevacizumab is a monoclonal antibody against VEGF and is a potential treatment for RN. The objective of the study is to assess effectiveness of bevacizumab (BEV) for the treatment of brain RN in adults. Methods: Retrospective chart review of 22 patients with various solid malignancies including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), metastatic melanoma and breast cancer with clinical or radiographic diagnosis of RN seen at Memorial Cancer Institute (MCI) in a 3-year period, from January 1st, 2019 to January 1st, 2023. Radiation doses ranged from 18-24 Gy (single fraction) or 24-27 Gy (3-fraction) for radiosurgery and 30-37.5 Gy for whole brain radiotherapy. Patients were identified that developed RN and VEGF inhibitors were subsequently given to assess effectiveness in the treatment of the condition. We evaluated the dose, frequency, number of treatments received, adverse effects and therapeutic benefits of BEV. Therapeutic benefit was defined as patients that received bevacizumab had a radiological and clinical improvement of the RN (clinical benefit). Brain imaging with MRI or PET/CT scan was completed both pre and post treatment to evaluate efficacy of treatment. Patients were initially given 4 cycles with a subsequent 4 more cycles if it was beneficial and tolerated treatment. Results: 22 patients were included in the study, 9 were males (41%) and median age 66 (range 31-81). 91% (20/22) had a diagnosis of lung cancer. 1 patient had a diagnosis of SCLC, while 19 were diagnosed with NSCLC. The study had a good representation of different races including Non-Hispanic Whites 7 (32%), Hispanics 10 (45%), Blacks 13% (3) and Asians 10% (2). Over 95% (21/22) of patients achieved a clinical benefit, while one patient did not (5%). Patients experienced improvement in cognitive function, headaches, dizziness, weakness, and other symptoms with BEV. MRIs showed improvement in edema and a reduction/stabilization of brain lesions. The most frequent dosing regimen used was BEV 10 mg/kg every two weeks. The median number of cycles given was 4 cycles (1-12). The most common adverse events were hypertension, minor nose bleeding, an occasional protein found in urine. There were no severe AEs or discontinuation of therapy with bevacizumab. Conclusions: This study demonstrated treatment with BEV 10 mg/kg every two weeks for a total of 12 cycles is well tolerated and has potential clinical benefit in RN in lung cancer patients with CNS metastasis. The therapeutic effects of VEGF inhibitors were seen in our small population study but warrants further investigation in a larger population study.

A phase III study of lurbinectedin alone or in combination with irinotecan vs investigator's choice (topotecan or irinotecan) in patients with relapsed small cell lung cancer (SCLC; LAGOON trial).

TPS8613 Background: Lurbinectedin is a novel synthetic chemical entity that acts as an inhibitor of oncogenic transcription and is active in tumors addicted to transcription. A phase II Basket trial (NCT02454972) in patients with small cell lung cancer (SCLC) treated with lurbinectedin in the second-line setting showed overall response rate (ORR) of 35.2% and median duration of response (DoR) of 5.3 months, with durable responses (43.0% ≥ 6 months). Based on these results, lurbinectedin was granted accelerated approval by the US FDA. An ongoing phase I/II trial (NCT02611024) is evaluating the lurbinectedin/irinotecan combination. Preliminary results showed ORR of 62% and median DoR of 5.7 months (2020 World Conference on Lung Cancer) warranting expansion to 100 patients. These results have supported the conduction of a phase III trial (LAGOON - NCT05153239). Methods: LAGOON is a randomized phase III clinical trial evaluating two experimental arms (lurbinectedin alone, 3.2 mg/m2 D1 q3wk, or lurbinectedin 2 mg/m2 D1 plus irinotecan D1, D8 q3wk) versus Investigator’s Choice (topotecan D1-5 q3wk or irinotecan D1 q3wk according to label) as control arm in relapsed SCLC patients. Approximately 705 patients will be enrolled. Central randomization will be implemented (1:1:1 ratio). Stratification will be done according to chemotherapy-free interval (CTFI) after first line (sensitive vs. resistant); prior anti-PD-(L)1; baseline central nervous system (CNS) involvement; lactate dehydrogenase value, and Investigator’s preference for the Control Arm. Main inclusion criteria include age ≥ 18 years, confirmed SCLC diagnosis, one prior line of platinum-containing chemotherapy with/without anti-PD-(L)1, and CTFI ≥ 30 days. Patients with CNS metastases can participate if pretreated and radiologically stable for at least 4 weeks. Main exclusion criteria include platinum-naïve patients, patients pretreated with more than one prior chemotherapy regimen (including platinum re-challenge), and prior treatment with lurbinectedin, trabectedin, PM14, or topoisomerase I inhibitors. An Independent Data Monitoring Committee will oversee the conduct of the study. An Independent Review Committee will provide the patient’s response at each tumor assessment endpoint to determine the best patient’s response and the date of objective response or progression/censoring according to RECIST v.1.1. Clinical trial information: NCT05153239 .

The effect of various social determinants of health on overall survival in the SCLC population.

8588 Background: Small cell lung cancer (SCLC) comprises 10-15% of all lung cancers yet little is known about the impact of social determinants of health (SDOH) on outcomes in patients with SCLC. This study aims to assess the impact of various SDOH on overall survival (OS) in patients diagnosed with SCLC at a single institution. Methods: We have established a large clinical/pathologic/genomic database of all patients diagnosed and treated for SCLC between 1998-2022 at our institution for retrospective study. Demographic data including sex, race, age, stage, address, and smoking status were collected. Poverty index was assessed by percent of school-aged children in poverty at the school district level based off 2021 census using the SAIPE tool and stratified as low (poverty index <=15.1) and high (poverty index >15.1). Water/Air carcinogens were obtained by zip code through EPA TRI Explorer database at year of SCLC diagnosis. Food desert designation was acquired through USDA low income and low access atlas at 0.5 miles for urban residences and 10 miles for rural residences respectively. Violent crime rates were obtained from the FBI Crime Data Explorer by year of diagnosis and police department jurisdiction. OS was computed from date of diagnosis to death or last known follow up date, and univariate Cox proportional hazards (PH) regression analysis was performed. Factors that were significant at significance level of 0.25 in univariate analysis were further evaluated using multivariable Cox PH model. Results: A total of 982 patients with SCLC were included. Univariate PH analysis demonstrated statistically significant improvement in OS with younger age (HR = 1.03, 95% CI 1.02-1.03, p <0.0001), female sex (HR = 0.8, 95% CI 0.7-0.92, p 0.001), low poverty index (HR = 1.12, 95% CI 0.98-1.12, p = 0.097), limited stage disease (HR = 3.12, 95% CI 2.66-3.66, p = <0.0001), and lack of air pollution exposure (HR = 1.09, 95% CI 0.95-1.24, p = 0.227). Multivariable PH analysis showed statistically significant OS improvement for those from lower poverty areas (HR = 1.22, 95% CI: 1.07- 1.4, p = 0.004) as well as in those without air pollution exposure (HR = 1.21, 95% CI: 1.05- 1.39, p = 0.008), controlling for age, sex, stage and smoking. Exposure to water pollution, violent crime rate, food desert designation and pack years smoked were not found to be independent predictors of OS. Conclusions: In this large detailed cohort of 982 patients with SCLC, there was a significantly lower OS for patients living in high poverty areas and for patients exposed to air pollutants. This effect was durable even after for controlling for age, sex, stage, and smoking status, demonstrating that these are independent risk factors associated with poorer OS. Our next research steps will be to examine the biologic basis for these disparities through genomic and transcriptomic analysis.

Brain metastasis burden and management in small cell lung cancer: An analysis of 8705 patients.

8596 Background: Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for intracranial metastatic disease (IMD), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. These patients traditionally receive whole brain radiation therapy (WBRT) for IMD, however, a recent systematic review has indicated that OS following stereotactic radiosurgery (SRS) may be non-inferior compared with WBRT. We aim to describe the clinical characteristics and outcomes of patients with SCLC and IMD in Ontario, Canada. Methods: We included all patients diagnosed with SCLC between April 2007 and March 2018 identified through a provincial health administrative database. Information on patient and treatment characteristics, incidence and time to IMD, and OS from time of SCLC diagnosis were collected and analyzed using R. Results: A total of 8705 patients were included. Median age was 68 years (range 18-103). Most patients presented with extensive disease (n = 5625) and were diagnosed after 2011 (n = 5768). Patients who received chemotherapy (n = 5563) had significantly longer OS than those who did not (median 10.64 vs 1.58 months (mo), hazard ratio (HR) 0.36, 95% confidence interval (CI) 0.34-0.37). 6662 patients received brain imaging at the time of primary diagnosis (CT: 5126, MRI: 1536), and 88% of patients surviving longer than 6 mo received more than one follow-up brain scan. 31% developed IMD (synchronous: 1175, asynchronous: 1511) with median intracranial progression-free survival of 5.65 mo. Median OS of patients with IMD was 9.76 mo, 29 and 1300 received SRS and WBRT as first treatment for their IMD, respectively. OS was in favour of SRS over WBRT (median 20.47 vs 8.74 mo, HR 0.57, 95% CI 0.39-0.84), which remained significant in multivariate analysis (p < 0.001). Conclusions: OS for patients with SCLC remains poor, and many patients present with IMD. With careful selection, patients with SCLC may benefit from SRS treatment.

Phase 2 small cell lung cancer (SCLC) cohort of a phase 1b/2 trial of a liposomal formulation of eribulin in combination with nivolumab.

8593 Background: E7389-LF is a liposomal formulation of the microtubule dynamics inhibitor eribulin. Combining E7389-LF with an immune checkpoint inhibitor (ICI; eg, nivolumab) may improve antitumor response via vascular remodeling. The phase 1b part of the open-label Study 120 evaluated the dosing and safety of E7389-LF in combination with nivolumab in patients (pts) with solid tumors. The phase 2 part assessed efficacy and safety in disease cohorts; herein, we report results from the SCLC cohort. Methods: Pts with unresectable and measurable SCLC who had progression during or after 1st-line (1L) platinum-based chemotherapy with/without an ICI were enrolled to the SCLC cohort of the phase 2 part of Study 120. Pts received E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg IV Q3W. The primary objective of the phase 2 part was to assess the objective response rate (ORR). Secondary objectives included assessments of safety and progression-free survival (PFS); exploratory objectives included the disease control rate (DCR), overall survival (OS), and biomarker analysis. Tumor response was assessed by investigators per RECIST v1.1 Q6W. All adverse events (AEs) were monitored and recorded. Results: In the SCLC cohort, 34 pts were enrolled; the median age was 66.0 years (range 46–81). At data cutoff (May 31, 2022), 5 pts (14.7%) were undergoing treatment. Discontinuations occurred in 29 pts (85.3%)—26 (76.5%) primarily due to disease progression, 3 (8.8%) due to an AE. Efficacy analyses included 33 pts, as 1 pt had their diagnosis of SCLC changed to a different cancer type after being enrolled. Of the 33 evaluable pts, 27 (81.8%) had an ICI as part of their prior 1L therapy. The ORR of E7389-LF in combination with nivolumab was 24.2% (95% CI 11.1–42.3) in the evaluable population; the DCR was 75.8% (95% CI 57.7–88.9). Median PFS was 3.98 mos (95% CI 2.63–4.40); the 6-mo PFS rate was 27.7% (95% CI 13.0–44.6). At a median follow-up period of 10.6 mos, median OS was not reached (95% CI not estimable); the 6-mo OS rate was 90.9% (95% CI 74.4–97.0). Treatment-related, treatment-emergent (TE)AEs of any grade and of grade ≥3 severity occurred in 97.1% (n = 33) and 82.4% (n = 28) of the 34 enrolled pts, respectively; the most common treatment-related TEAE was neutropenia (any grade: 58.8% [n = 20]; grade ≥3: 52.9% [n = 18]). The neutrophil count nadir occurred around cycle 1 day 8. TEAEs led to dose reduction of E7389-LF in 19 pts (55.9%). Withdrawal of E7389-LF or nivolumab occurred in 5 pts (14.7%): acute kidney injury, cough, myocarditis, pneumonitis, and radiation pneumonitis (n = 1 each). Changes in vascular and immune-related plasma markers were observed. Conclusions: E7389-LF in combination with nivolumab showed notable antitumor activity as 2L therapy in pts with SCLC, as evidenced by the notable ORR of 24.2%. No new safety signals were observed for this combination. Clinical trial information: NCT04078295 .

Characteristics and outcomes of patients with small cell lung cancer (SCLC) detected with CT screening at a single health system.

8581 Background: At diagnosis, the majority of SCLC patients have extensive-stage disease, and their median survival is only 13 months, even with the addition of checkpoint inhibitors. Previous CT screening trials did not reveal reduction in mortality for SCLC patients. The aim of our study was to analyze the baseline characteristics and clinical outcomes of SCLC patients diagnosed with low-dose CT scan as a part of lung cancer screening program. Methods: A retrospective chart review-based study of SCLC patients diagnosed clinically or by lung cancer screening between January 2018 and June 2022 at the Henry Ford Health System was conducted. Baseline characteristics, details of SCLC diagnosis and treatment, and outcome were recorded. Statistical analysis was performed using Chi-squared test, T-test and log-rank test. Results: Of the 258 patients who met eligibility criteria, 34 were diagnosed by lung cancer screening. Patients diagnosed with screening tended to be older (mean age- 70.5 years vs. 67.3 years, p=0.010). There were no differences in gender distribution, race and smoking status. Mean smoking history was 43 pack-years in both groups. Among screen-detected patients, 73.5% had limited-stage disease compared to 36.6% among clinically detected patients (p<0.001). No significant difference in the presence of brain metastases at diagnosis was observed. Among screen-detected patients, 97.1% received any therapy compared to 85.3% among the clinically detected patients (p=0.105). Overall survival (OS) was significantly better in screen-detected patients, with a 3-year survival rate of 45.5% vs. 17% (p=0.00027). By multivariable analysis, OS was better in screen-detected patients (HR=0.37, 95% CI 0.20-0.68; p=0.001) (Table). There was no significant difference in progression-free survival between the groups. Conclusions: Our results demonstrate that SCLC patients diagnosed through the lung cancer screening program have better overall survival rates than those diagnosed clinically. These results suggest that developing appropriate screening measures may impact SCLC-related mortality. [Table: see text]

Evaluating the diagnostic and prognostic value of serum TuM2-PK, NSE, and ProGRP in small cell lung cancer.

The aim of this study was to explore the diagnostic and prognostic value of serum tumor M2-pyruvate kinase (TuM2-PK), neuron-specific enolase (NSE), and progastrin-releasing peptide (ProGRP) levels in patients with small cell lung cancer (SCLC). The levels of serum TuM2-PK, NSE, and ProGRP in 102 patients with SCLC, 60 patients with benign lung disease (BLD), and 90 healthy controls were detected. The serum TuM2-PK, NSE, and ProGRP levels in the SCLC group were higher than those in BLD group (p < 0.05) and healthy control group (p < 0.05). The sensitivity of TuM2-PK, NSE, and ProGRP detection in SCLC was 82.35%, 60.78%, and 77.45% respectively, and specificity was 91.11%, 81.11%, and 86.67%, respectively. The area under the curve (AUC) of SCLC resulting from TuM2-PK was significantly better than that of NSE and ProGRP. The application of TuM2-PK combined with NSE and ProGRP improved the diagnostic yield of SCLC patients and had better diagnostic value than TuM2-PK alone. Univariate and multivariate analysis indicated that an elevated TuM2-PK level was an independent prognostic factor for shorter survival in SCLC. These results suggest that TuM2-PK levels in the serum could be an effective biomarker for the diagnosis and prognosis of SCLC.