Treatment Of Lung Cancer Patients Research Articles

A Retrospective Review of the Management of Lung Cancer Patients Referred into the Regional Neuro-Oncology Pathway in Merseyside, United Kingdom

Abstract AIMS Brain metastases (BMs) are common in lung cancer and carry adverse prognostic significance. Such occurrences should be reviewed through a regional specialist neuro-oncology MDT. Our aim is to highlight which aspects of the pathway could be contributing to delays in the treatment of lung cancer patients with BMs. METHOD All lung cancer patients discussed at the Neuro-Oncology MDT in 2020 were identified. Details of the patient journey through the pathway from diagnosis to death were obtained from the Orion System, regional PACS system, regional neuro-oncology MDT notes and electronic case notes from Clatterbridge. RESULTS Full datasets were available for 100 patients discussed at the Neuro-Oncology MDT. 49 of these were patients presenting with BMs and lung cancer synchronously. Only 5 out of 13 (38%) of synchronous patients recommended for SRS received this treatment. 7 of 13 patients received a suboptimal treatment (best supportive care or whole-brain radiotherapy). Length of time from neuro-oncology MDT discussion to receiving SRS in the synchronous cohort was 47 versus 20.3 days in the asynchronous group. A review of all 13 cases found that 4 of the 7 cases of CNS-specific deterioration were potentially preventable. Further analysis of these cases revealed common themes of lengthy delays in histological sampling (9), delayed referral or discussion in the appropriate MDT (8) and not jointly referring to neuro-oncology and respiratory oncology (7). CONCLUSION Lung cancer patients with synchronous BMs receive SRS after full staging and biopsy. There is potential evidence of suboptimal outcomes due to inflexible MDT systems and delays for histology.

From COPD to Lung Cancer: Mechanisms Linking, Diagnosis, Treatment, and Prognosis.

Many studies have proved that the pathogenesis of the chronic obstructive pulmonary disease (COPD) and lung cancer is related, and may cause and affect each other to a certain extent. In fact, the change of chronic airway obstruction will continue to have an impact on the screening, treatment, and prognosis of lung cancer.In this comprehensive review, we outlined the links and heterogeneity between COPD and lung cancer and finds that factors such as gene expression and genetic susceptibility, epigenetics, smoking, epithelial mesenchymal transformation (EMT), chronic inflammation, and oxidative stress injury may all play a role in the process. Although the relationship between these two diseases have been largely determined, the methods to prevent lung cancer in COPD patients are still limited. Early diagnosis is still the key to a better prognosis. Thus, it is necessary to establish more intuitive screening evaluation criteria and find suitable biomarkers for lung cancer screening in high-risk populations with COPD. Some studies have indicated that COPD may change the efficacy of anti-tumor therapy by affecting the response of lung cancer patients to immune checkpoint inhibitors (ICIs). And for lung cancer patients with COPD, the standardized management of COPD can improve the prognosis. The treatment of lung cancer patients with COPD is an individualized, comprehensive, and precise process. The development of new targets and new strategies of molecular targeted therapy may be the breakthrough for disease treatment in the future.

Infections virales chroniques (hépatites, VIH) et impact sur le choix thérapeutique

Hepatitis B (HBV) and C (HCV) viral infections, and human immunodeficiency virus (HIV) infection are still largely under-screened in routine before the beginning of systemic treatment in lung cancer patients. These infections can however have several therapeutic implications, with notably the risk of viral reactivation and hepatitis flare (HBV, HCV), and the necessity of a specific anti(retro)viral treatment in many patients. Data from literature are scarce, but suggest an equivalent efficacy and toxicity profile of chemotherapy and immune checkpoint inhibitors compared to global population. A systematic screening of HBV, HCV and HIV infections is needed in all patients before any systemic treatment. Recommendations have been published for chronic HBV and HCV infections management in cancer patients. The cases of HIV patients with lung cancer should be discussed in the national board ONCOVIH. Inclusions in dedicated clinical trials are encouraged.1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Changes in the Number of Newly Diagnosed Lung Cancer Patients Before and During the COVID-19 Pandemic: A Single-Center Experience.

OBJECTIVE:The coronavirus disease-2019 pandemic has affected the entire health system and patients other than coronavirus-infected patients. Hospital admissions of cancer patients decreased during the closure periods due to the pandemic. This study was conducted to determine whether there was an effect on the hospital admissions of newly diagnosed lung cancer patients in Turkey during the coronavirus disease-2019 pandemic.MATERIAL AND METHODS:In this retrospective study, newly diagnosed lung cancer patients were recorded from the Hospital Information Management System between January 1, 2017, and December 31, 2020, at our tertiary hospital. The number of newly diagnosed lung cancer patients diagnosed in 2020 was compared with each year from 2017 to 2019.Results:Between 2017 and 2020, 15 150 newly diagnosed lung cancer cases were analyzed. According to Global Cancer Observatory data, in 2018, 34 703 newly diagnosed lung cancer cases, and in 2020, 41 264 newly diagnosed lung cancer cases were observed in Turkey. Although a decrease was not observed in the number of patients according to Global Cancer Observatory data, both the total number of patients admitted to our hospital and the number of newly diagnosed lung cancer patients decreased in 2020. The number of newly diagnosed lung cancer patients by year was 4030 patients in 2017, 4004 patients in 2018, 4391 patients in 2019, and 2725 in 2020, respectively. In 2020, newly diagnosed lung cancer patients decreased by 38%, 32%, and 32% compared to 2019, 2018, and 2017, respectively. Also, a significant decrease was seen in the number of newly diagnosed lung cancer patients in the months with closure due to the pandemic compared to the months without closure.Conclusion:There was a significant decrease in hospital admissions of newly diagnosed lung cancer cases in the coronavirus disease-2019 pandemic in our referral hospital. Precautions should be considered to diagnose and treat lung cancer patients in specialized centers during a pandemic due to epidemic diseases such as coronavirus disease-2019.

EP04.01-011 Diagnostic Approach and Treatment of Lung Cancer Patients in Portugal: Portuguese Lung Cancer Study Group Survey

In Portugal, in 2020, 5415 new lung cancer patients were diagnosed and 4797 deaths were caused by lung cancer. Lung cancer ranks third in terms of cancer incidence and is the leading cause of cancer mortality. Early diagnosis, complete and fast patient assessment and staging, multidisciplinary approach, access to personalized medicine, new treatment options and research are essential to improve survival and quality of life. Access to clinical trials is critical for this improvement.The aim of this study is to assess the techniques available to the diagnostic work-up, treatments, the waiting time and the needs perceived by physicians.

EP06.01-013 Differences of Oncology Treatment for Lung Cancer Patients in Pandemic COVID-19 Year: Our Clinical Experience

IntroductionIt is estimated that in North Macedonia delays in diagnosis due to COVID-19 pandemic, could result in significant reductions in the number of potentially curative stages in lung cancer patients.MethodsThe aim of this study was to evaluate patient characteristics and treatment strategy of lung cancer patients treated at the University Clinic of Radiotherapy and Oncology (UCRO), during the pre-pandemic year (from 1 of March 2019 to the end of February 2020) compared to pandemic year (from 1 of March 2020 to the end of February 2021). We analyzed eligible patients in the course of these two years according to the patient characteristics and treatment strategies.ResultsWe have record increasing in number of undefined lung cancer patients without any pathological or histological conformation (11% pandemic year compared to 7 % in the previous year), and increased number of stage III and IV NSCLC patients in pandemic year 449 (87%) patients of NSCLC, in comparison to the pre-pandemic year 403 (74%). We have found decreasing number of stage II NSCLC patients in pandemic year 82 (13%) compared to 141 (26%) patients in pre-pandemic year and reporting decreasing number of operated patients with NSCLC from 218 to the 123 in the pandemic group. But we have to report increasing number of early stage IA and stage IB patients total 16, treated only by surgery.ConclusionsThe strict screening and admittance criteria instilled by hospitals during the pandemic might have improved oncology treatment course of the lung cancer patients.KeywordsCOVID-19, lung cancer, pandemic year IntroductionIt is estimated that in North Macedonia delays in diagnosis due to COVID-19 pandemic, could result in significant reductions in the number of potentially curative stages in lung cancer patients. It is estimated that in North Macedonia delays in diagnosis due to COVID-19 pandemic, could result in significant reductions in the number of potentially curative stages in lung cancer patients. MethodsThe aim of this study was to evaluate patient characteristics and treatment strategy of lung cancer patients treated at the University Clinic of Radiotherapy and Oncology (UCRO), during the pre-pandemic year (from 1 of March 2019 to the end of February 2020) compared to pandemic year (from 1 of March 2020 to the end of February 2021). We analyzed eligible patients in the course of these two years according to the patient characteristics and treatment strategies. The aim of this study was to evaluate patient characteristics and treatment strategy of lung cancer patients treated at the University Clinic of Radiotherapy and Oncology (UCRO), during the pre-pandemic year (from 1 of March 2019 to the end of February 2020) compared to pandemic year (from 1 of March 2020 to the end of February 2021). We analyzed eligible patients in the course of these two years according to the patient characteristics and treatment strategies. ResultsWe have record increasing in number of undefined lung cancer patients without any pathological or histological conformation (11% pandemic year compared to 7 % in the previous year), and increased number of stage III and IV NSCLC patients in pandemic year 449 (87%) patients of NSCLC, in comparison to the pre-pandemic year 403 (74%). We have found decreasing number of stage II NSCLC patients in pandemic year 82 (13%) compared to 141 (26%) patients in pre-pandemic year and reporting decreasing number of operated patients with NSCLC from 218 to the 123 in the pandemic group. But we have to report increasing number of early stage IA and stage IB patients total 16, treated only by surgery. We have record increasing in number of undefined lung cancer patients without any pathological or histological conformation (11% pandemic year compared to 7 % in the previous year), and increased number of stage III and IV NSCLC patients in pandemic year 449 (87%) patients of NSCLC, in comparison to the pre-pandemic year 403 (74%). We have found decreasing number of stage II NSCLC patients in pandemic year 82 (13%) compared to 141 (26%) patients in pre-pandemic year and reporting decreasing number of operated patients with NSCLC from 218 to the 123 in the pandemic group. But we have to report increasing number of early stage IA and stage IB patients total 16, treated only by surgery. ConclusionsThe strict screening and admittance criteria instilled by hospitals during the pandemic might have improved oncology treatment course of the lung cancer patients. The strict screening and admittance criteria instilled by hospitals during the pandemic might have improved oncology treatment course of the lung cancer patients.

EP08.05-003 Evaluation of Dose Changes in Different Periods after 125I Seed Implantation in Lung Cancer

125I seed brachytherapy has the characteristics of sustainable, low dose rate and low damage to peripheral organs in the treatment of non-small cell lung cancer, and it is a better choice for local treatment of lung cancer patients. According to the location and size of the target volume, the preoperative plan simulates the seed implantation situation that achieves the optimal dose, and the postoperative verification plan evaluates the quality of the seed implantation. The number of seeds, the angle of needle insertion and the distribution of seeds in the monolayer implant surface are all determinants of dose.

EP05.01-028 Thoracic Radiotherapy of Baseline Severe Pulmonary Dysfunction NSCLC Patients and Predictive Analysis for Acute Radiation Pneumonitis

Currently, there is no standard treatment for lung cancer patients with deteriorated pulmonary function. In this study, we aimed to assess the efficacy of thoracic radiotherapy for unresectable non-small cell lung cancer (NSCLC) with baseline severe pulmonary dysfunction and severe acute radiation pneumonitis (SARP).

The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing

A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer (NSCLC) patients. Single-cell RNA sequencing (scRNA-seq) techniques have prompted the opportunity to dissect the distinct immune signatures between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC. Here, we performed scRNA-seq on 72,475 immune cells from 40 samples of tumor and matched adjacent normal tissues spanning 19 NSCLC patients, and drew a systematic immune cell transcriptome atlas. Joint analyses of the distinct cellular compositions, differentially expressed genes (DEGs), cell–cell interactions, pseudotime trajectory, transcriptomic factors and prognostic factors based on The Cancer Genome Atlas (TCGA), revealed the central roles of cytotoxic and effector T and NK cells and the distinct functional macrophages (Mφ) subtypes in the immune microenvironment heterogeneity between LUAD and LUSC. The dominant subtype of Mφ was FABP4-Mφ in LUAD and SPP1-Mφ in LUSC. Importantly, we identified a novel lymphocyte-related Mφ cluster, which we named SELENOP-Mφ, and further established its antitumor role in both types, especially in LUAD. Our comprehensive depiction of the immune heterogeneity and definition of Mφ clusters could help design personalized treatment for lung cancer patients in clinical practice.

AC099850.3/NCAPG Axis Predicts Poor Prognosis and is Associated with Resistance to EGFR Tyrosine-Kinase Inhibitors in Lung Adenocarcinoma.

BackgroundTKI-acquired resistance markedly interferes with treatment of lung cancer patients with EGFR mutant features. Long non-coding RNAs (lncRNAs) modify EGFR-TKI resistance during tumor progression. Non-structural maintenance of chromosomes condensin I complex subunit G (NCAPG) is a mitosis-related protein that is involved in tumorigenesis. We investigated the potential regulatory lncRNAs of NCAPG in lung adenocarcinoma (LUAD) and assessed their roles in EGFR-TKI resistance.MethodsData for 1678 lung cancer patients were retrieved from TCGA and GEO databases and used to evaluate NCAPG and lncRNAs expressions, as well as their prognostic significance in LUAD. Protein levels of NCAPG in LUAD were validated by immuno-histochemistry. To assess the relationship between NCAPG levels and EGFR-TKIs sensitivity, a cohort of 57 LUAD patients administered with EGFR-TKIs was used.ResultsBoth NCAPG and lncRNA AC099850.3 were over-expressed in LUAD tissues, and correlated with tumor progression and poor prognosis in LUAD. LncRNA AC099850.3 was identified as a potential regulator of NCAPG expressions. The AC099850.3/NCAGP axis was markedly correlated with EGFR mutations and IC50 of EGFR-TKIs. Besides, elevated NCAPG levels were associated with EGFR-TKIs resistance in 57 LUAD patients undergoing TKIs treatment. Gene set enrichment analysis revealed that both AC099850.3 and NCAGP were abundant in the cell cycle and the p53 signaling pathway.ConclusionThe AC099850.3/NCAPG axis is a potential prognostic predictor and therapeutic biomarker for EGFR-TKIs in LUAD.

Prognostic value of computed tomography derived skeletal muscle mass index in lung cancer: A meta-analysis.

BACKGROUNDThe prognostic role of the skeletal muscle mass index (SMI) derived from computed tomography (CT) imaging been well verified in several types of cancers. However, whether the SMI could serve as a reliable and valuable predictor of long-term survival in lung cancer patients remains unclear.AIMTo identify the prognostic value of the CT-derived SMI in lung cancer patients.METHODSThe PubMed, Web of Science, and Embase electronic databases were searched up to November 5, 2021 for relevant studies. The Reference Citation Analysis databases were used during the literature searching and selection. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association of the SMI with the overall survival (OS) of lung cancer patients. All statistical analyses were performed with STATA 12.0 software.RESULTSA total of 12 studies involving 3002 patients were included. The pooled results demonstrated that a lower SMI was significantly related to poorer OS (HR = 1.23, 95%CI: 1.11-1.37, P < 0.001). In addition, the subgroup analyses stratified by treatment (nonsurgery vs surgery), tumor stage (advanced stage vs early stage), and tumor type (non-small cell lung cancer vs lung cancer) showed similar results.CONCLUSIONThe CT-derived SMI is a novel and valuable prognostic indicator in lung cancer and might contribute to the clinical management and treatment of lung cancer patients.

FGFR1 promotes tumor immune evasion via YAP-mediated PD-L1 expression upregulation in lung squamous cell carcinoma

BackgroundVariations in FGFR1 are common driver mutations of LSQCC. And immune checkpoint inhibitors targeting PD-1 and PD-L1 are powerful anticancer weapons. Activation of FGFR1 leads to tumorigenesis through multiple downstream molecules, including YAP, but whether and how FGFR1 regulates tumor immune evasion remain largely unclear. MethodsLSQCC cells were modified to increase or decrease the expression of FGFR1, YAP and PD-L1, as assessed by molecular assays. After FGFR1 knockdown, cancer cells were assessed after cocultured with Jurkat T cells in vitro, and the tumor microenvironment were analyzed in C57BL/6 mice. The effect of the combination of FGFR1 knockdown and PD-1 blockade was also explored. ResultsIn human LSQCC, activation of FGFR1 was positively correlated with transcription of PD-L1. In H520 and HCC95 cells, FGFR1 upregulated PD-L1 expression via YAP, and YAP initiated the transcription of PD-L1 after binding to its promoter region. FGFR1 knockdown decreased tumor growth, reduced immune escape and induced reactivation of CD8+ T cells. The combination of FGFR1 knockdown and PD-1 blockade synergistically exerted antitumor effects. ConclusionsThe FGFR1/YAP/PD-L1 regulatory axis mediates tumor-associated immune suppression in lung squamous cell carcinoma, and FGFR1 knockdown reactivates T cells in the tumor microenvironment. Synergistic inhibition of both FGFR1 and PD-1/PD-L1 pathways may be a possible treatment for lung cancer patients.

Effect of Thymosin on Inflammatory Factor Levels, Immune Function, and Quality of Life in Lung Cancer Patients Undergoing Radical Thoracoscopic Surgery.

Purpose To explore the effect of thymosin on inflammatory factor levels, immune function, and quality of life in patients undergoing radical thoracoscopic lung cancer surgery. Methods One hundred and twenty patients admitted to the Surgical Oncology Department of the First Hospital of Jiaxing from January 2018 to January 2019 were randomized into the study group and the control group using the random number table method, with 60 cases in each group. The control group was treated with radical thoracoscopic lung cancer surgery, and the study group was treated with radical thoracoscopic lung cancer surgery combined with thymosin. The clinical efficiency, inflammatory factors, immune function, and quality of life between the two groups of patients were compared. Results There was no significant difference between the two groups in terms of pathological stage, tissue type, maximum tumor diameter, and perioperative indicators such as operative time, intraoperative bleeding, pleural drainage, hospital stay, and the number of intraoperative lymph nodes removed. The levels of CD4 (+%), CD8 (+%), CD4+/CD8+, and natural killer cell (NK) (%) were significantly decreased in both groups after treatment, with significantly higher results in the study group than in the control group. The study group had significantly lower serum interleukin-6 (IL-6) levels and higher interleukin-10 (IL-10) levels than the control group. After treatment, patients in the study group had better postoperative physiological status and overall score than the control group. There was no significant difference in postoperative survival and adverse reactions between the two groups. Conclusion The use of thymosin treatment in lung cancer patients undergoing radical thoracoscopic surgery significantly improves immune function, mitigates inflammatory response, and enhances the quality of life, which is worthy of clinical application.

Gilteritinib Enhances Anti-Tumor Efficacy of CDK4/6 Inhibitor, Abemaciclib in Lung Cancer Cells.

Abemaciclib is a cyclin-dependent kinases 4/6 (CDK4/6) inhibitor approved for the treatment of metastatic breast cancer. Preclinical studies suggest that abemaciclib has the potential for lung cancer treatment. However, several clinical trials demonstrate that monotherapy with abemaciclib has no obvious superiority than erlotinib to treat lung cancer patients, limiting its therapeutic options for lung cancer treatment. Here, we show that the US Food and Drug Administration (FDA)-approved drug, gilteritinib, enhances the cytotoxicity of abemaciclib through inducing apoptosis and senescence in lung cancer cells. Interestingly, abemaciclib in combination with gilteritinib leads to excessive accumulation of vacuoles in lung cancer cells. Mechanistically, combined abemaciclib and gilteritinib induces complete inactivation of AKT and retinoblastoma (Rb) pathways in lung cancer cells. In addition, RNA-sequencing data demonstrate that combination of abemaciclib and gilteritinib treatment induces G2 phase cell-cycle arrest, inhibits DNA replication, and leads to reduction in homologous recombination associated gene expressions. Of note, abemaciclib-resistant lung cancer cells are more sensitive to gilteritinib treatment. In a mouse xenograft model, combined abemaciclib and gilteritinib is more effective than either drug alone in suppressing tumor growth and appears to be well tolerated. Together, our findings support the combination of abemaciclib with gilteritinib as an effective strategy for the treatment of lung cancer, suggesting further evaluation of their efficacy is needed in a clinical trial.

Serum immunoinflammatory-related protein complexes as personalized biomarkers for monitoring disease progression and response to treatment in lung cancer patients

BackgroundAlthough routine surveillance to detect lung cancer recurrence with clinical imaging is recommended, early detection of disease progression has a major role in avoiding over-treatment. MethodsHere, serum immunoinflammatory-related protein complexes (IIRPCs) of a series of 1331 serum samples collected from 119 patients during the follow-up period were isolated using native-PAGE and then their levels were quantified. The associations of representative IIRPCs levels at their beginning, maximum, and minimum and the ratios of the maximum or minimum to the beginning IIRPCs levels with clinical characteristics were statistically analyzed. ResultsThe statistical results indicate that patients with these ratios below the first quantiles of the minimum ratios had shorter progressive-free survival (PFS) and the follow-up time points for 108 of 113 patients with over 1.5-fold change in IIRPCs level relative to the beginning level as the beginning time point of humoral immune response has a median lead time of 61.9 weeks (IQR, 30.9–105.3) relative to progressive disease(PD) detected using clinical imaging. ConclusionsThese findings suggest that changes in IIRPCs levels may be early-warning signals of disease progression and response to treatment for lung cancer patients.

Abstract 937: Novel role of deubiquitylase USP13 in lineage plasticity and drug resistance of non-small cell lung cancer

Abstract Lineage plasticity, the ability of cells to transition from one defined cell type to another, has been proposed as a source of intertumoral heterogeneity and therapeutic resistance.However, molecular drivers and underlying mechanisms of lineage plasticity remain largely unknown. Here, we found a novel role of deubiquitylase USP13 in lineage transition of lung adenocarcinoma (ADC) to squamous cell carcinoma (SCC) using mouse model: Usp13-overexpressing (Usp13OE) ADC loses its characteristics while gaining SCC features are enhanced. Transcriptomic analysis showed that Usp13OE lung cancers were heterogeneous and epithelial-mesenchymal transition (EMT), hypoxia, and PI3K-Akt-mTOR signaling pathway were enriched. Furthermore, development disease pathways including neurological and gastrointestinal diseases were overrepresented in Usp13OE tumors. Notably, Usp13OE primary tumor cell lines showed higher drug resistance against first-line therapy. Collectively, our findings demonstrate the novel role of USP13 in lineage transition of lung cancer and suggest that targeting USP13 is a promising strategy for the further treatment of lung cancer patients. Citation Format: Juntae Kwon, Cecil Han. Novel role of deubiquitylase USP13 in lineage plasticity and drug resistance of non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 937.

Abstract 1088: Therapeutic targeting of sphingosine kinase 2 in tyrosine kinase inhibitor resistance and non-small cell lung cancer tumorigenicity

Abstract It is anticipated that there will be 235,760 cases and 131,880 deaths due to lung cancer in the US in 2021. Tyrosine Kinase Inhibitors (TKIs) such as Erlotinib (ER) and Osimertinib (OR) are currently being used to treat lung cancer patients with EGFR mutations; however, patients develop resistance to these drugs within 10-18 months. Sphingosine kinase 2 (SK2), which is upregulated in Non-Small Cell Lung Cancer (NSCLC), phosphorylates sphingosine to sphingosine-1-phosphate (S1P), promoting cancer cell proliferation. The sphingolipid rheostat controls the cell fate by maintaining a balance between pro-survival and pro-apoptotic sphingolipids, which is regulated by SK2. However, the role of SK2 in TKI resistance is not established. To determine if SK2 causes TKI resistance, we have studied its role in NSCLC and TKI resistance. We hypothesize that SK2 may be involved in inducing TKI- resistance in NSCLC cells and is positively correlated with tumor progression. We studied SK2 in both drug resistant (OR and ER) and drug sensitive (parental) H358, H2170, H3255 and PC9 NSCLC cell lines. Our study investigated SK2 expression in drug resistant cells versus parental cells using qPCR and Western Blotting. The effects of SK2 inhibitor, Opaganib, on NSCLC cell proliferation was studied through an MTT assay. We have also studied its expression in early- and late-stage tumors using Immunohistochemistry (IHC). In drug resistant cells, qPCR studies showed that SK2 was upregulated in H2170 by 1.30-fold (ER) and 1.5-fold (OR); in H358 by 1.36-fold (ER) and 1.17-fold (OR); in PC9 by 3.3-fold (ER) and 1.8-fold (OR) and in H3255 by 4.3-fold (OR) compared to parental cells. A western blotting experiment demonstrated that SK2 was upregulated significantly by 1.7-fold and 1.5-fold in H358OR and H2170OR cells, respectively, compared to parental cells. These results suggest that SK2 may play a role in TKI resistance, as displayed by SK2 upregulation in TKI-resistant cells. MTT assay data showed 71% inhibition of cell growth by Osimertinib and SK2 inhibitor in H2170OR. The inhibition due to the combination of the drug and inhibitor was more than additive by 9% compared to the drug and inhibitor individually. This indicates SK2s potential to overcome TKI- Resistance. To analyze SK2 expression in cancer progression, IHC experiments were performed on 63 early and 48 late stage lung cancer patient sections. We observed upregulation of SK2 in late- stage lung cancer (p&amp;lt;0.05), indicating its role in cancer progression. In conclusion, SK2 may be a key biomarker in combating TKI-resistance and play a role in cancer progression in NSCLC. Thus, SK2 may be a promising candidate for molecular targeted therapy against NSCLC. Citation Format: Namrata Umeshchandra Dube, Katie Lam, Neelu Puri. Therapeutic targeting of sphingosine kinase 2 in tyrosine kinase inhibitor resistance and non-small cell lung cancer tumorigenicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1088.

Bone-targeting agent utilization among lung cancer patients with bone metastasis in Taiwan.

e24111 Background: Bone is a common metastatic site among patients with advanced lung cancer. With new treatments available to improve survival of lung cancer and in all likelihood to change the natural history of disease, the diagnosis and management of bone metastasis (BM) may be of increasing clinical relevance. This study aimed to describe the management of BM using bone targeting agents (BTA) among lung cancer patients in Taiwan. Methods: A retrospective cohort of lung cancer patients with BM from 2004 through 2016 was identified using Taiwan National Health Insurance (NHI) data and Taiwan Cancer Registry. Diagnosis codes of International Classification of Disease 9th revision (ICD-9: 198.5) and ICD-10 (C79.51 and C78.03) were used to define BM. Patients were followed from the time of BM diagnosis till death or the end of study period (2017/12/31). We ascertained demographic information and BTA use among these patients. Two classes of BTAs were included: bisphosphonates (zoledronic acid (ZA), pamidronate, and clodronate) and denosumab. Results: A total of 44,800 patients with lung cancer and incident BM diagnosis were identified during the study period. Median age at the time of BM diagnosis was 67 years (25th and 75th percentile: 57-76), with 58.2% male (n = 26,058). The annual number of lung cancer patients with incident BM increased from 2,814 in 2004 to 3,829 in 2016, while the proportion of these patients receiving any BTA during the follow-up ranged from 25.2% to 34.8% annually. Clodronate and pamidronate were the common BTA prescriptions, whereas denosumab became the most frequently prescribed BTA after reimbursement by NHI since 2015. Among patients who initiated BTA after BM diagnosis (n = 10,879), the median time from BM diagnosis to BTA initiation ranged from 31 to 152 days by initial BTA type. More than half of them received more than one dose (56.3%, n = 6,126), with median numbers of doses received as 3, 4, 6 and 6 for ZA, pamidronate, clodronate and denosumab, respectively. Conclusions: A large population of patients with lung cancer were diagnosed with BM every year. However, overall, we observed only a small proportion of eligible patients receiving a BTA and a delayed initiation of BTA, indicating suboptimal treatment for lung cancer patients with BM in Taiwan.[Table: see text]

Stereotactic Body Radiotherapy for Stage I Lung Cancer With a New Real-time Tumor Tracking System.

Suppression of respiratory movement is crucial for safe and effective stereotactic body radiotherapy (SBRT). SyncTraX FX4 is a novel device for synchronous respiratory irradiation. The purpose of this study was to evaluate the efficacy and toxicity of SBRT using SyncTraX FX4 for patients with lung cancer. Patients treated with SBRT using SyncTraX FX4 between November 2017 and August 2020 were included. In all cases, fiducial markers were inserted into the lung, and the total dose administered was 55 or 60 Gy, depending on the distance from the central region of the lung. Acute and late toxicities were reported, and local control, progression-free survival, cancer-specific survival, and overall survival were analyzed. We evaluated 16 patients and 17 sites. The median follow-up period was 14.4 months. In both the acute and late phases, one patient experienced grade 3 radiation pneumonitis; however, grade 4 or higher toxicities were not observed. There was no local recurrence during the observation period, and the overall survival, cancer-specific survival, and progression-free survival at 2 years were 54.6%, 85.1%, and 33.7%, respectively. SBRT with SyncTraX FX4 can provide safe and effective treatment for lung cancer patients in poor condition.

Role of SWI/SNF chromatin remodeling genes in lung cancer development.

SWI/SNF family of chromatin remodeling complexes uses the energy of ATP to change the structure of DNA, playing key roles in DNA regulation and repair. It is estimated that up to 25% of all human cancers contain alterations in SWI/SNF, although the precise molecular mechanisms for their involvement in tumor progression are largely unknown. Despite the improvements achieved in the last decades on our knowledge of lung cancer molecular biology, it remains the major cause of cancer-related deaths worldwide and it is in urgent need for new therapeutic alternatives. We and others have described recurrent alterations in different SWI/SNF genes in nearly 20% of lung cancer patients, some of them with a significant association with worse prognosis, indicating an important role of SWI/SNF in this fatal disease. These alterations might be therapeutically exploited, as it has been shown in cellular and animal models with the use of EGFR inhibitors, DNA-damaging agents and several immunotherapy approaches. Therefore, a better knowledge of the molecular mechanisms regulated by SWI/SNF alterations in lung cancer might be translated into a therapeutic improvement of this frequently lethal disease. In this review, we summarize all the evidence of SWI/SNF alterations in lung cancer, the current knowledge about the potential mechanisms involved in their tumorigenic role, as well as the results that support a potential exploitation of these alterations to improve the treatment of lung cancer patients.