Late-stage Lung Cancer Research Articles

Abstract 987: Seamless statistical analysis of adverse event data for clinical association

Abstract Purpose: Adverse event (AE) is a critical element in clinical trial to evaluate patient safety profile of the drug for benefit-risk assessment. AE is also shown to have clinical association. However, due to its complexity, utilization of AE data has been suboptimal. This study takes a unique approach to utilize AE parameters and to derive a set of innovative AE metrics which could have the potential as a predictive biomarker of treatment response and survival outcomes. Methods: The AE-derived biomarkers integrated toxicity severity level (grade) and treatment relatedness, with further tune-up by AE occurrence, frequency, and duration. Implementation of AE-derived biomarkers was performed in a comprehensive strategy starting from overall AE, toxicity category, down to individual AE. Landmark analysis at day 30 from initial treatment date was used to define early AE biomarkers. Two study cohorts (Cohort A and B) from two immunotherapy trials in late-stage non-small cell lung cancer were used to evaluate the potential of AE-derived biomarkers. Clinical outcomes for statistical analysis included progression-free survival, overall survival, disease control, and duration of treatment. Results: Both cohorts showed that early AEs were associated with clinical outcomes. Patients experienced with low-grade AEs (including treatment related AEs) at early time point had improved PFS, OS, and were associated with disease control. The significant early AEs included treatment related low-grade AE in overall AE, endocrine disorders, hypothyroidism (immune-related adverse event (irAE)), and platelet count decreased for Cohort A and low-grade AE in overall AE, gastrointestinal disorders, and nausea for Cohort B. In contrast, patients with early development of higher-grade AEs tended to have poorer PFS, OS, and correlated with PD. The associated early AEs included treatment related high-grade AE in overall AE, gastrointestinal disorders with two members, diarrhea and vomiting, for Cohort A and high-grade AE in overall AE, 3 toxicity categories, and 5 related individual AEs for Cohort B. One treatment related low-grade AE, alanine aminotransferase increased, was irAE and correlated with worse OS in Cohort A. Conclusions: The study demonstrated evidence of AE utility in predicting positive and negative clinical outcomes. It could be treatment related AEs or combination of treatment related and not related AEs. Grade level played a key role in determining direction of clinical outcomes with low-grade leaning to positive effect and high-grade to negative impact. Significant AEs covering overall AEs, toxicity category AEs, to individual AEs provided relatively comprehensive view of AE results for clinical relevance. Citation Format: Dung-Tsa Chen, Jhanelle Gray, Andreas Saltos, Trevor A Rose, Alberto Chiappori, Zachary Thompson, Ram Thapa. Seamless statistical analysis of adverse event data for clinical association [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 987.

The efficacy of earth cultivation and gold generation method in the treatment of middle and late stage lung cancer

Lung cancer is the number one malignant tumor disease in China in terms of death rate, and early stage patients can choose surgery for better prognosis. However, most patients usually lose the chance of surgery when they are diagnosed in the middle and late stages of the disease, with poor prognosis and poor quality of life. Based on the theory of five elements in Chinese medicine, nourishing the spleen and stomach can effectively enhance the physiological state of lung, which is the method of cultivating earth and generating gold. In the late stage of lung cancer, together with other treatments such as radiotherapy, targeted therapy and immunotherapy, it can relieve clinical symptoms, improve the quality of life and prolong the survival period.

ENHANCING RESILIENCE IN OLDER ADULTS WITH ADVANCED LUNG CANCER

Abstract For older adults with advanced cancer, the negative impacts on their emotional and physical health are prevalent, often jeopardizing their capacity to effectively cope and exhibit resilience. Research on multidisciplinary interventions that promote resilience in older adults facing advanced lung cancer has received limited attention. To enhance how healthcare systems/teams may improve oncogeriatric care, we present study findings from a theory-driven behavioral intervention pilot (Self-System Therapy; SST) designed to target patient self-regulation (e.g., behavioral activation, promotion-focused goal setting) to enhance psychological and physical resilience. A total of 15 older adults with late-stage lung cancer completed 6–8-weeks of SST all delivered via videoconference. Self-report, accelerometry, and exit interview data will be presented along with prior pilot data of 30 older adults (total N = 45). Preliminary findings suggest that participants found the use of videoconference feasible and acceptable; with a 95% adherence rate, 7% attrition rate, and 95% satisfaction with SST.

Combination of Paclitaxel and PXR Antagonist SPA70 Reverses Paclitaxel-Resistant Non-Small Cell Lung Cancer.

Paclitaxel (PTX) is one of the most efficient drugs for late-stage non-small cell lung cancer (NSCLC) patients. However, most patients gradually develop resistance to PTX with long-term treatments. The identification of new strategies to reverse PTX resistance in NSCLC is crucially important for the treatment. PTX is an agonist for the pregnane X receptor (PXR) which regulates PTX metabolism. Antagonizing PXR, therefore, may render the NSCLC more sensitive to the PTX treatment. In this study, we investigated the PXR antagonist SPA70 and its role in PTX treatment of NSCLC. In vitro, SPA70 and PTX synergistically inhibited cell growth, migration and invasion in both paclitaxel-sensitive and paclitaxel-resistant A549 and H460 lung cancer cells. Mechanistically, we found PTX and SPA70 cotreatment disassociated PXR from ABCB1 (MDR1, P-gp) promoter, thus inhibiting P-gp expression. Furthermore, the combination regimen synergistically enhanced the interaction between PXR and Tip60, which abrogated Tip60-mediated α-tubulin acetylation, leading to mitosis defect, S-phase arrest and necroptosis/apoptosis. Combination of PXT and SPA70 dramatically inhibited tumor growth in a paclitaxel-resistant A549/TR xenograft tumor model. Taken together, we showed that SPA70 reduced the paclitaxel resistance of NSCLC. The combination regimen of PTX and SPA70 could be potential novel candidates for the treatment of taxane-resistant lung cancer.

2MO Tracking immunoediting from early to late-stage lung cancer

2MO Tracking immunoediting from early to late-stage lung cancer

Evaluating treatment strategies for non-small cell lung cancer during COVID-19: A propensity score matching analysis.

We employed pandemic treatment strategies that we developed at the beginning of the coronavirus disease 2019 (COVID-19) pandemic, and it was not clear whether any adverse results were associated with our strategies. Therefore, we carried out a retrospective study to compare our pandemic treatment strategies with prepandemic protocols to determine whether the strategies used during the high-risk period of COVID-19 were appropriate. The observation period was September 2019 to February 2020. Patients hospitalized from December 2019 to February 2020 were included as an experimental group, and individuals hospitalized from September 2019 to November 2019 were included as a control group. All non–small cell lung cancer patients hospitalized during the observation period were included except for pediatric and obstetric patients, patients younger than 18 years old, and patients admitted only for routine follow-up examinations. Treatment strategies were evaluated based on the prognosis of the different treatment methods, including surgical and nonsurgical treatments and discontinuation of therapy. Survival curves were analyzed using the Kaplan–Meier method. Cox regression analysis was used for multivariate analysis of risk factors for progress-free survival. Propensity score matching was used for clinical characteristics to adjust for selection bias. Therapy discontinuation in the experimental group was significantly higher than in the control group (P < .001). The differences in cancer progression and the number of deaths between the 2 groups were not significant (P = .38 and .13, respectively). For late-stage patients, there were significant differences in nonsurgical treatment and discontinued therapy (P < .001 and < .001, respectively) between the 2 groups, while the cancer progression and death toll differences were not significant (P = .20 and .20, respectively). For early-stage patients, the differences in surgical treatment, discontinued therapy, cancer progression, and death toll were not significant (P = .24, 0.24, 0.61, and 0.49, respectively) between the 2 groups. Multivariate analysis revealed that temporary discontinuation of therapy did not predict poor progress-free survival independently (hazard ratio = 1.007, 95% confidence interval: 0.653–1.552, P = .98). For patients in geographical regions with a high risk for COVID-19 infections, temporarily suspending treatment for late-stage non–small cell lung cancer patients is not likely to significantly impact their prognosis if they can return to treatment within 3 months of discontinuation.

Impact of U.S. Preventive Services Task Force lung cancer screening update on drivers of disparities in screening eligibility.

In 2021, the U.S. Preventive Services Task Force (USPSTF) updated its recommendation to expand lung cancer screening (LCS) eligibility and mitigate disparities. Although this increased the number of non-White individuals who are eligible for LCS, the update's impact on drivers of disparities is less clear. This analysis focuses on racial disparities among Black individuals because members of this group disproportionately share late-stage lung cancer diagnoses, despite typically having a lower intensity smoking history compared to non-Hispanic White individuals. We used data from the National Health Interview Survey to examine the impact of the 2021 eligibility criteria on racial disparities by factors such as education, poverty, employment history, and insurance status. We also examined preventive care use and reasons for delaying medical care. When comparing Black individuals and non-Hispanic White individuals, our analyses show significant differences in who would be eligible for LCS: Those who do not have a high school diploma (28.7% vs. 17.0%, p=0.002), are in poverty (26.2% vs. 14.9%, p < 0.001), and have not worked in the past 12 months (66.5% vs. 53.9%, p=0.009). Further, our analyses also show that more Black individuals delayed medical care due to not having transportation (11.1% vs. 3.6%, p < 0.001) compared to non-Hispanic White individuals. Our results suggest that despite increasing the number of Black individuals who are eligible for LCS, the 2021 USPSTF recommendation highlights ongoing socioeconomic disparities that need to be addressed to ensure equitable access.

In situ self-assembled peptide enables effective cancer immunotherapy by blockage of CD47

Treatment of late-stage lung cancer has witnessed limited advances. In contrast to the tremendous efforts toward improving adaptive immunity, approaches to modulating innate immunity are relatively immature. As important innate immune cells, tumor-associated macrophages (TAMs) account for a substantial fraction of tumor-infiltrating lymphocytes, which not only reverses the immune-suppressive tumor microenvironment but also facilitates an adaptive immune response. In this study, we developed a tumor-specific MMP-2-responsive CD47 blockage (TMCB) strategy to enable effective cancer immunotherapy. Briefly, the matrix metalloproteinase-2 (MMP-2)-responsive self-assembly peptide specifically recognizes CD47, which is highly expressed in lung tumor cells. Second, the MMP-2-responsive self-assembly peptide is efficiently cleaved by MMP-2, which is overexpressed in the tumor microenvironment. Finally, the generated residual peptide naturally self-assembles into peptide-based nanofibers. The in situ constructed nanofibers inhibit the canonical CD47 “Do not eat me” signal expressed on tumor cells to promote phagocytosis of tumor cells by macrophages, which further induces effective antigen presentation and initiates T cell-mediated adaptive immune responses to inhibit tumor growth. Thus, we described a peptide-based TMCB strategy that induces both innate and adaptive immune systems to inhibit tumor growth.

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.

Abstract 468: Quantitative assessment of IHC using computational pathology allows superior patient selection for biomarker-informed patients

Abstract Many targeted cancer therapies rely on biomarkers, which are assessed by standard pathologist scoring of immunohistochemically stained tissue. However, this process is subjective, semi-quantitative and does not assess expression heterogeneity. A quantitative method to measure IHC markers might therefore significantly improve patient selection particularly of proteins expressed at low levels. To address these challenges, we have developed the Quantitative Continuous Scoring (QCS) that deploys the power of fully supervised Deep Learning (DL) algorithms to provide objective and continuous data of biomarkers in digitized IHC whole slide images (WSI). The two DL-based algorithms, developed using pathologist input as the ground truth, identify areas of invasive tumor and segment each individual tumor cell across the WSI into pixels that represent cell nuclei, cytoplasm and/or membrane. This allows to compute biomarker expression as mean Optical Density (OD) in each of these subcellular compartments based on the Hue-Saturation-Density (HSD) model. Of note, this also allows computation of the spatial distribution of tumor cells across the WSI. The measured OD for each cell is aggregated as a histogram to quantitative continuous readouts for each patient sample. The method’s ability to accurately detect low expression range facilitates selection of antibody clones for IHC assays, has been successfully used to delineate mode of action and PK/PD mechanisms, has provided surrogate markers of spatial expression heterogeneity to predict potential bystander activity and has facilitated marker co-expression analysis to inform rational combination therapies. In retrospective clinical trials analysis, QCS showed superior performance in identifying a patient population gaining maximum treatment benefit. QCS-based quantification of PD-L1 membrane expression was able to stratify anti-PD-L1 treated late-stage non-small cell lung cancer (NSCLC) patients [NCT01693562] with a higher prevalence and more significant log rank p-value (64%, p=0.0001) for OS compared to pathologist TPS (59%, p=0.01). In summary, we describe a computational pathology-based approach for precise biomarker quantification and superior patient selection with broad applicability and the potential to transform pathology, thus addressing one of the key challenges of precision oncology. Citation Format: Hadassah Sade, Ansh Kapil, Philipp Wortmann, Andreas Spitzmueller, Nicolas Triltsch, Lina Meinecke, Susanne Haneder, Anatoliy Shumilov, Jan Lesniak, Valeria Bertani, Tze-Heng Tan, Ana Hidalgo-Sastre, Simon Christ, Andrea Storti, Regina Alleze, Dasa Medrikova, Jessica Chan, Simon Lanzmich, Markus Schick, Guenter Schmidt, J. Carl Barrett. Quantitative assessment of IHC using computational pathology allows superior patient selection for biomarker-informed patients [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 468.

Tiragolumab Results Cast Shadow on TIGIT Pipeline.

Genentech's TIGIT-targeted antibody tiragolumab missed its endpoints in two late-stage lung cancer trials, raising doubts about one of the most widely studied next-generation checkpoint targets in immuno-oncology. But numerical signs of benefit among certain patients with metastatic non-small cell lung cancer suggest that TIGIT blockade still has potential-if drug developers can successfully identify the best indications, drug combinations, or patient populations.

Not just biology: Comparing social determinants of health in patients diagnosed with late-stage lung, breast, and colon cancer.

e18582 Background: Lung, colorectal, and breast cancer account for the majority of cancer deaths in the U.S. Patients with late stage lung cancer have the shortest survival of the three, and lung cancer patients are more likely to be diagnosed at later stages. We undertook this study to compare social determinants of health in patients diagnosed with late stages of lung, breast, and colon cancer to assess the impact they have on health and mortality. Methods: Data from the National Cancer Database was used for this study. We compared factors including insurance, income, and residency among late stage cancer patients (Stage III and IV). We also compared baseline health status measured by comorbidity index. Descriptive statistics were used to compare patient characteristics. Statistical significance was determined on the basis of a two-sided p value &lt; 0.05. All statistical analysis was performed using SAS, version 9.4. Results: Between 2004 - 2016, 3,005,513 patients were diagnosed with lung (1,004,999), breast (1,309,796), and colon (690,718) cancer. The racial make-up of the groups was similar. 72.5% of lung cancer patients were diagnosed at late stage compared to 48.8% of colon and 13.8% of breast cancer patients. Patients with late stage lung cancer were more likely to have income &lt; $38,000, reside in rural locations, and less likely to have private insurance. Late stage lung cancer patients were 2 and 4 times more likely to have at least 2 comorbidities than patients with colon and breast cancer respectively. Conclusions: Patients with lung cancer are disproportionately affected by several negative social determinants of health. The association between smoking and lung cancer may help explain this because the highest smoking rates in the U.S. occur in populations with lower income, low education status, less insurance coverage, and significantly more comorbidities (e.g. COPD, Heart Disease). These patients are dealing with the complex interplay of negative social determinants of health and worse baseline health status causing delays in diagnosis and treatment when compared to other cancers. Recognizing this may allow systems to better support this disadvantaged population and improve access to screening, clinical trial inclusion, and personalized treatment options while working longitudinally to reverse the systemic factors affecting disproportionate tobacco use and lack of healthcare access in for this underserved population.

Natural killer cell activity as a biomarker for the diagnosis of lung cancer in high-risk patients

ObjectiveNatural killer (NK) cells play an essential role in the immune response against cancer. However, immune escape mechanisms may cause inferior NK cell activity (NKA) in patients with cancer. This prospective study examined the relationship between NKA and lung cancer in a high-risk cohort.MethodsIn a cohort study, 250 participants referred by their general practitioner for suspicion of lung cancer were included. Before clinical investigation, blood was collected into NK Vue tubes, and the level of interferon gamma after 24 hours served as a surrogate marker for NKA.ResultsAmong 250 patients, 79 were diagnosed with lung cancer. No difference in NKA was found between patients with lung cancer and control participants in which lung cancer was ruled out (median 226 pg/mL vs. 450 pg/mL). However, there was a significant difference in NKA between patients with late-stage lung cancer and controls (median 161 pg/mL vs. 450 pg/mL). A linear regression model showed that NKA was not influenced by age, sex or smoking status.ConclusionsThe significantly lower NKA in patients with late-stage lung cancer warrants further investigation combining NKA with other biomarkers and examining the potential role of NKA as a marker of disseminated disease.

The association of social and demographic factors on the time interval between a suspected diagnosis of cancer, diagnosis, treatment, and outcomes in a lung cancer patient population.

e18598 Background: Delays in lung cancer (LC) diagnosis and treatment adversely affect patient outcomes. Prior studies report mixed results on the association between delays in diagnosis and various demographic factors. Methods: A retrospective cohort analysis was conducted utilizing a randomly selected subset of LC patients treated at the IU Simon Comprehensive Cancer Center between 1/1/18 and 12/31/20. Chart search identified the dates of first suspected cancer finding (SCF; imaging or high-risk presentation), diagnosis, first treating physician contact, and treatment initiation. Patient characteristics (sex, age, race, marital status, insurance status/type, employment status, smoking status, LC stage, LC type) and healthcare utilization (setting of SCF, modality used to discover SCF) were also collected. Asymptomatic patients with SCF at routine screening were excluded. Multivariable Cox proportional hazards and logistic regression models were utilized with significance defined as p &lt; 0.05. Results: Patient characteristics (n = 203): white 86.7%; ever smokers 86.0%; Medicare 61.3%; NSCLC 87.7%; stage IV 44.3%. SCF was primarily identified in an ambulatory setting (57.4%) by CT imaging (62.1%). Median time from SCF to diagnosis, treating physician contact, and treatment were 24d (IQR: 8-67), 24.5d (IQR: 9-54), and 57d (IQR: 28-98), respectively. Median time from diagnosis to treatment was 22d (IQR: 7-41). Time from SCF to LC care was significantly associated with cancer type (median times - diagnosis: NSCLC = 27d, SCLC = 9d, p = 0.001; treating physician contact: NSCLC = 27d, SCLC = 6d, p = 0.002; treatment: NSCLC = 66.5d, SCLC = 23d, p &lt; 0.001), stage (median times - diagnosis: stage I = 52d, stage IV = 9d, p &lt; 0.001; treating physician contact: stage I = 32.5d, stage IV = 13.5d, p = 0.008; treatment: stage I = 97d, stage IV = 23d, p &lt; 0.001), and setting of SCF (median times - diagnosis: ambulatory = 30d, emergency = 7d, p &lt; 0.001; treating physician contact: ambulatory = 31d, emergency = 9d, p &lt; 0.001; treatment: ambulatory = 74.5d, emergency = 28d, p &lt; 0.001). Risk of delays were highest among those with Stage I NSCLC and when SCF occurred in the ambulatory setting. Adjusted by cancer types and modality, patients presenting to the ER were 2.15 times more likely to be diagnosed with stage IV disease than those presenting in the ambulatory setting (p &lt; 0.001). Conclusions: Streamlined transitions of care are needed in the ambulatory setting to reduce delays in LC diagnosis and treatment to optimize patient outcomes. The extended delays experienced by early vs late-stage LC patients may be explained by access to care. However, no demographic factors (insurance, age, race) were significantly associated with delays in this dataset. Further studies are needed to assess the timeliness of cancer diagnosis and treatment in large, diverse populations.

Pituitary gland metastasis from breast cancer: case report

Cancer metastasis to the pituitary gland is rare, but in most cases, it originates from a late-stage breast tumor or lung cancer. The most common symptoms of metastasis to the pituitary gland are diabetes insipidus and visual disturbance. The common site of metastasis is the posterior portion of the pituitary gland because it is highly vascularized. Metastases to this site represent 1% of all tumors [1]. Metastasis to the pituitary gland is difficult to diagnose by hormonal analysis and magnetic resonance imaging of the brain and requires biopsy for confirmation [2]. The recent increase in survival of cancer patients and the advancement in diagnostic techniques have resulted in a more frequent diagnosis of breast and lung cancer metastasis to the pituitary gland, which has a poor prognosis [3,4].

Expression of CD91 in extracellular vesicles: A potential biomarker for the diagnosis of non-small cell lung cancer

Lung cancer is the leading cause of death; by the time it is diagnosed, the patient is usually in late-stage grade IV. Late-stage lung cancer is mainly associated with metastasis in the liver, brain, and lymphoid tissues; as a result, a localized lung cancer treatment remains meaningless. Early diagnosis of non-small cell lung cancer (NSCLC) may be curable or will improve the survival rate. Although with advanced developments to screen high-risk patients by LDCT scan, false-positive rates and limited resolution necessitated the development of advanced diagnostic techniques for NSCLC. Extracellular vesicles (EVs) released from cells freely circulate in the blood and contain various transmembrane proteins, and they may be a non-invasive biomarker for cancer diagnosis and prognosis. Current studies predict that the CD91 marker in EVs may be a potential biomarker of NSCLC; however, the expression of CD91 in lung cancer tissues is not fully known. Here, this study determines the differential expression of CD91 in lung cancer cells and in circulating EVs in blood as a potential biomarker of NSCLC patients. Our results confirmed the expression of CD91 in NCI–H1975 cultured cells and NSCLC lung biopsy tissues. Furthermore, biophysical characterization of EVs from lung cancer cells determines the substantial expression of CD91, which the Transmission Electron Microscope confirms. Thus, this study suggests EVs containing CD91 could be an asset to studying the development of diagnostic and prognostic biomarkers in NSCLC disease.

A Multilevel Approach to Investigate Relationships Between Healthcare Resources and Lung Cancer.

Screening for lung cancer is an evidence-based but underutilized measure to reduce the burden of lung cancer mortality. Lack of adequate data on geographic availability of lung cancer screening inhibits the ability of healthcare providers to help patients with decision-making and impedes equity-focused implementation of screening-supportive services. This analysis used data from the 2012-2016 Surveillance, Epidemiology, and End Results (SEER) Program, the Behavioral Risk Factor Surveillance System, and the county health ranking to examine (a) which cancer resources and county-level factors are associated with late-stage lung cancer at diagnosis and (b) associations between county rurality and lung cancer incidence/mortality rates. Using the New York state SEER data, we identified 68,990 lung cancer patients aged 20-112 years; 48.3% had late-stage lung cancers, and the average lung cancer incidence and mortality rates were 70.7 and 46.2 per 100,000, respectively. There were 144 American College of Radiology-designated lung cancer screening centers and 376 Federally Qualified Health Centers identified in New York state. County rurality was associated with a higher proportion of late-stage lung cancers and higher lung cancer mortality rates. Visual geomapping showed the scarcity of rural counties' healthcare resources. County rurality is a significant factor in differences in lung cancer screening resources and patient outcomes. Use of publicly available data with geospatial methods provides ways to identify areas for improvement, populations at risk, and additional infrastructure needs.

The efficacy and safety of selumetinib as secondary therapy for late-stage and metastatic non-small cell lung cancer: results from a systematic review and meta-analysis.

BackgroundNon-small cell lung cancer (NSCLC) is the most common subtype of all lung cancers, and KRAS is the most common mutation in this population. Unfortunately, this subgroup remains “undruggable” with the lack of an approved targeted therapy. Selumetinib has been investigated as a secondary therapy in several trials and compared to various drug regimens. Therefore, we conducted this systematic review and network meta-analysis to determine the comparative effectiveness of this drug as compared to others in patients with late-stage and malignant NSCLC.MethodsUp to July 1, 2020, 9 databases (PubMed, Scopus, Web of Science, mRCT, ICTRP, clinicaltrials.gov, VHL, SIGLE, and Google Scholar) were searched for studies following the PICOS framework: randomized trials reporting the efficacy (rate of disease progression/lack of response) of selumetinib compared to other therapies in patients with late-stage/metastatic NSCLC. The quality of retrieved studies were assessed with the revised Cochrane risk-of-bias tool. Frequentist network meta-analysis was conducted to estimate the efficacy of selumetinib as compared to other therapies and/or placebo.ResultsOut of the 163 articles yielded from the primary search, 9 studies (1,195 patients) were finally included in our systematic review. The majority of clinical cases had a performance status (PS) of 0–2, and the mean age was 62 years. The overall efficacy of selumetinib was 71.77% (95% CI: 63.24–81.45%), with selumetinib administered alone having better efficacy compared to combined therapy (65.20% vs. 74.08%). In the network analysis, selumetinib had higher efficacy compared to chemo- or immune therapy, but not significantly so. The overall SAE rate of selumetinib was 42.96% (95% CI: 34.74–53.13%), with selumetinib having a significantly better safety profile compared to combined therapy (10.49% vs. 47.38%). In the network analysis, the placebo had the best safety profile followed by selumetinib and chemo- and immune therapy. Five studies had high risk of bias, 2 had some concerns, and 2 had low risk of bias.DiscussionThe efficacy of selumetinib is not superior compared to combined therapy for treating NSCLC but does have a better safety profile. Current evidence is still limited, and more robust trials are still required.

The Clinically Actionable Molecular Profile of Early versus Late-Stage Non-Small Cell Lung Cancer, an Individual Age and Sex Propensity-Matched Pair Analysis.

Background: Despite meticulous surgery for non-small cell lung cancer (NSCLC), relapse is as high as 70% at 5 years. Many institutions do not conduct reflexive molecular testing on early stage specimens, although targeted gene therapy may extend life by years in the event of recurrence. This ultimately delays definitive treatment with additional biopsy risking suboptimal tissue acquisition and quality for molecular testing. Objective: To compare molecular profiles of genetic alterations in early and late NSCLC to provide evidence that reflexive molecular testing provides clinically valuable information. Methods: A single-center propensity matched retrospective analysis was conducted using prospectively collected data. Adults with early and late-stage NSCLC had tissue subject to targeted panel-based NGS. Frequencies of putative drivers were compared, with 1:3 matching on the propensity score; p < 0.05 deemed statistically significant. Results: In total, 635 NSCLC patients underwent NGS (59 early, 576 late); 276 (43.5%) females; age 70.9 (±10.2) years; never smokers 140 (22.0%); 527 (83.0%) adenocarcinomas. Unadjusted frequencies of EGFR mutations were higher in the early cohort (30% vs. 18%). Following adjustment for sex and smoking status, similar frequencies for both early and late NSCLC were observed for variants in EGFR, KRAS, ALK, MET, and ROS1. Conclusion: The frequency of clinically actionable variants in early and late-stage NSCLC was found to be similar, providing evidence that molecular profiling should be performed on surgical specimens. This pre-determined profile is essential to avoid treatment delay for patients who will derive clinical benefit from targeted systemic therapy, in the high likelihood of subsequent relapse.

Association of Personal Characteristics and Effectiveness of Immunotherapy in Late-Stage Non-Small Cell Lung Cancer: A Systematic Review.

BackgroundAlthough immunotherapy can increase survival in non-small cell lung cancer (NSCLC), response rates are low. It is unclear which characteristics contribute to variability in immunotherapy efficacy and survival. Research is needed to identify reasons for heterogeneity in response rates to better tailor treatments.MethodsWeb of Science, Ovid EMBASE, and MEDLINE were queried from 2013 to January 2021, and all studies reporting overall or progression-free survival for patients treated with immunotherapy for NSCLC of at least stage IIIB were screened.ResultsIncluded were 18 randomized controlled trials (RCTs; 6534 immunotherapy RCTs; 11 192 nonimmunotherapy RCTs) and 16 observational studies (n = 9073 immunotherapy patients). Among RCTs, there was improved survival with the addition of immunotherapy in patients aged younger than 65 years in 10 of 17 studies; smokers in 8 of 15 studies; and males in 10 of 17 studies and 6 of 17 females. Only 5 studies reported outcomes by race. Among observational studies, younger patients (aged younger than 60, younger than 65, or younger than 70 years in most studies) had better survival than older patients (aged 60 years and older, 65 years and older, or 70 years and older) in 4 of 13 studies, ever-smokers in 7 of 13, and females in 2 of 14. Three studies reported race with mixed results.ConclusionAlthough evidence is mixed, younger patients, smokers, and males may derive more benefit from immunotherapy. Evidence on racial differences is limited. Physicians should be mindful of personal characteristics when formulating treatment plans. Further research is needed to understand underlying mechanisms and to identify the best immunotherapy candidates and alternative treatments for those unlikely to benefit.