Stage Lung Cancer Research Articles

Inaccurate Clinical Stage Is Common and Associated With Poor Survival in Patients With Lung Cancer

IntroductionClinical staging in lung cancer has implications for treatment planning and prognosis. We sought to determine the rate of inaccurate clinical stage (relative to pathologic), identify risk factors for inaccuracy, and evaluate the association of inaccuracy on survival. We hypothesized that inaccurate staging was associated with poor survival. MethodsIn this retrospective cohort study, adult patients who received surgical resection without neoadjuvant treatment for nonsmall cell lung cancer from 2004 to 2020 in the National Cancer Database were categorized by accuracy of clinical stage (relative to pathologic stage). Multivariate models were used to determine risk factors for inaccuracy. The association between inaccuracy and overall survival was also analyzed. ResultsWe identified 255,598 patients with lung cancer, including 84,543 patients (33.1%) who were inaccurately staged. Stage inaccuracy was associated with higher tumor, node, metastasis stage (T-category 3: odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.15-1.28; N-category 2: OR = 2.6, 95% CI 2.47-2.79), greater quantity of lymph nodes evaluated, and more extensive resection (extended lobectomy/bilobectomy: OR = 1.3, 95% CI 1.20-1.37; pneumonectomy: OR = 1.6, 95% CI 1.54-1.74). Patients undergoing robotic surgery were less likely to be inaccurately staged (OR = 0.89, 95% CI 0.852-0.939). Inaccurate staging was associated with worse overall survival (5-y 67.5% accurate versus 55.4% inaccurate, P < 0.001). Inaccurate staging was also associated with worse survival in a multivariate Cox model (hazard ratio [HR] = 1.3, 95% CI 1.29-1.33). Both “understaging” (path > clinical) and “overstaging” (clinical > path) were associated with inferior survival. ConclusionsInaccurate clinical stage (relative to pathologic) occurs in one-third of patients receiving surgery for lung cancer. Inaccuracy is associated with poor survival. Quality improvement initiatives should focus on improving clinical staging accuracy.

Using quality indicators to assess performance of endobronchial ultrasound in the staging and diagnosis of lung cancer: a pre/post study at a New Zealand centre.

There are no data on the performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the staging and diagnosis of lung cancer in New Zealand. We aimed to assess the performance of EBUS-TBNA for lung cancer staging and diagnosis at our institution before and after the commencement of regular performance monitoring with comparison to published EBUS quality indicators. The performance of EBUS-TBNA in the staging and diagnosis of lung cancer was assessed in two phases. Phase 1 consisted of a retrospective review of all lung cancer EBUS performed over a 2-year period. Published quality indicators were determined from the literature with relevant indicators being extracted and used to determine EBUS performance. Local reporting and education were undertaken and prospective data collection was commenced. Phase 2 consisted of prospective assessment of all lung cancer EBUS over the subsequent year. Performance of EBUS was then compared between phases 1 and 2 in order to determine the effect of performance monitoring and identify areas for service improvement. A total of 115 staging EBUS and 117 diagnostic EBUS were performed during the study period. Staging EBUS demonstrated good performance across phases 1 and 2 with high sensitivity and negative predictive values (NPV) for the detection of N2/3 disease, meeting published quality standards. During phase 2 there was evidence of a transition towards more guideline-concordant practice evidenced by more detailed nodal sampling during staging EBUS; however, this did not affect overall sensitivity or NPV. Diagnostic EBUS resulted in high rates of pathological confirmation meeting published quality standards across both phases. Pathway times were similar between phases 1 and 2, with reporting of molecular profiling being the predominant factor in delayed pathway times. Monitoring and reporting of local performance allows critical assessment of practice and can identify areas for quality improvement. This review demonstrated good overall performance but prompted a move towards more guideline-concordant practice with increased mediastinal nodal sampling during staging procedures. Consideration should be given to the adoption of routine EBUS performance monitoring within local and/or regional networks, which could be incorporated alongside the newly proposed Lung Cancer Clinical Quality Registry.

A novel anti-CD47 protein antibody and toll-like receptor agonist complex detects tumor surface CD-47 changes in early stage lung cancer by in vivo imaging

CD47, a cell surface protein known for inhibiting phagocytosis, plays a critical role in the tumor microenvironment (TME) and is a potential biomarker for cancer. However, directly applying αCD47, a hydrophilic macromolecular antibody that targets CD47, in vivo for cancer detection can have adverse effects on normal cells, cause systemic toxicities, and lead to resistance against anti-cancer therapies. In this study, we developed a novel complex incorporating aluminum-based metal-organic frameworks (Al-MOF) loaded with indocyanine green (ICG), αCD47, and resiquimod (R848), a hydrophobic small molecule Toll-like receptor 7/8 (TLR7/8) agonist. Upon activation with an infrared 808 nm laser, the nanocomposites exhibited photothermal effects that triggered the release of the loaded reagents, induced ROS production, and induced changes in the TME. This led to the polarization of immune-suppressive M2 macrophages towards an immune-stimulatory M1 phenotype, promoted dendritic cell (DC) maturation, and enabled mature DCs to facilitate antigen presentation, T-cell activation, and critical roles in tumor immunity. Furthermore, in vivo imaging successfully detected the specific binding of αCD47 with CD47 on tumor cells. Overall, the complex composed of αCD47 antibody and toll-like receptor agonist showed promising efficacy in both tumor diagnosis and therapy, providing a potential strategy for detecting early lung cancer and modulating the tumor microenvironment for improved treatment outcomes.

Effectiveness Analysis of the Combined Detection of CEA, SCC, CYFRA21-1, NSE and ProGRP for Early Diagnosis of Lung Cancer

Objective To explore the diagnostic value and application effect of the combined detection of CEA (carcinoembryonic antigen), SCC (squamous cell carcinoma antigen), CYFRA21-1 (soluble fragment of cytokeratin 19), NSE (neuron specific enolase) and proGRP (gastrin releasing peptide precursor) in early lung cancer. Method 66 patients who admitted to the hospital from April 2019 to February 2024 were selected as the early stage lung cancer group and the other 159 patients were selected as the benign lung group, in which all subjects were tested for NSE, CEA, ProGRP, CYFRA21-1, and SCC levels and were confirmed by histopathological analysis. In ROC analysis, the cut-off point, AUC, accuracy, sensitivity and specificity between single and combined detection indicators are analyzed. Result The size of cut-off point, AUC, accuracy, sensitivity, specificity, positive and negative detection rate and accuracy rate is 0.3072, 0.790, 89.33%, 0.894, 0.893, 89.40% (59/66), 89.31% (142/159) and 89.33% ((142+59)/225) respectively and it is obviously superior to those of single detection method. Meanwhile, indicator of SCC showed the worst performance by single detection. Conclusion The combined detection indicators have high diagnostic value in early diagnosis of lung cancer, and the sensitivity, positive detection rate, AUC value and accuracy have been significantly improved.

Tumor promoting effect of PDLIM2 downregulation involves mitochondrial ROS, oncometabolite accumulations and HIF-1α activation

BackgroundCancer is characterized by dysregulated cellular metabolism. Thus, understanding the mechanisms underlying these metabolic alterations is important for developing targeted therapies. In this study, we investigated the pro-tumoral effect of PDZ and LIM domain 2 (PDLIM2) downregulation in lung cancer growth and its association with the accumulation of mitochondrial ROS, oncometabolites and the activation of hypoxia-inducible factor-1 (HIF-1) α in the process.MethodsDatabases and human cancer tissue samples were analyzed to investigate the roles of PDLIM2 and HIF-1α in cancer growth. DNA microarray and gene ontology enrichment analyses were performed to determine the cellular functions of PDLIM2. Seahorse assay, flow cytometric analysis, and confocal microscopic analysis were employed to study mitochondrial functions. Oncometabolites were analyzed using liquid chromatography–mass spectrometry (LC–MS). A Lewis lung carcinoma (LLC) mouse model was established to assess the in vivo function of PDLIM2 and HIF-1α.ResultsThe expression of PDLIM2 was downregulated in lung cancer, and this downregulation correlated with poor prognosis in patients. PDLIM2 highly regulated genes associated with mitochondrial functions. Mechanistically, PDLIM2 downregulation resulted in NF-κB activation, impaired expression of tricarboxylic acid (TCA) cycle genes particularly the succinate dehydrogenase (SDH) genes, and mitochondrial dysfunction. This disturbance contributed to the accumulation of succinate and other oncometabolites, as well as the buildup of mitochondrial reactive oxygen species (mtROS), leading to the activation of hypoxia-inducible factor 1α (HIF-1α). Furthermore, the expression of HIF-1α was increased in all stages of lung cancer. The expression of PDLIM2 and HIF-1α was reversely correlated in lung cancer patients. In the animal study, the orally administered HIF-1α inhibitor, PX-478, significantly reduces PDLIM2 knockdown-promoted tumor growth.ConclusionThese findings shed light on the complex action of PDLIM2 on mitochondria and HIF-1α activities in lung cancer, emphasizing the role of HIF-1α in the tumor-promoting effect of PDLIM2 downregulation. Additionally, they provide new insights into a strategy for precise targeted treatment by suggesting that HIF-1α inhibitors may serve as therapy for lung cancer patients with PDLIM2 downregulation.

Transbronchial cryoablation in peripheral lung parenchyma with a novel thin cryoprobe and initial clinical testing

BackgroundTransbronchial cryoablation shows potential as a local therapy for inoperable peripheral lung cancer. However, its clinical application for peripheral pulmonary lesions has not been reported yet.MethodsAn improved cryoprobe with an...

Franseen needle in endobronchial ultrasound-guided transbronchial needle aspiration: a phase II prospective study.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been used to diagnose and stage lung cancer. Acquire™ Pulmonary and Expect™ Pulmonary dedicated EBUS-TBNA needles were introduced as the Franseen and Lancet needles, respectively. It is still unclear whether the Franseen or Lancet needles yield a higher quality specimen especially focusing on next-generation sequencing-based molecular testing. A single-center, prospective study performed at the Chiba University Hospital randomly assigned patients to two groups: Group A, wherein the first and second EBUS-TBNA were performed using Lancet and Franseen needles, respectively, and Group B, wherein the first and second EBUS-TBNA were performed using Franseen and Lancet needles, respectively. Each specimen was compared and analyzed pathologically. The primary outcome was the histological tissue area except blood clot and the cellularity of each sample. We also examined the success rate of molecular testing. Twelve patients who underwent EBUS-TBNA between November 2022 and February 2023 were enrolled in this study. The tissue area of the specimens obtained by the Franseen and Lancet needles was 13.3±6.4mm2 and 10.6±6.3mm2, respectively (P=.355). The tumor cellularity in the specimens obtained using the Franseen and Lancet needles was 54.0±30.3 and 46.2±36.3%, respectively (P=.608). The success rate of molecular testing using the single-pass sample by Franseen needle was 85.7 and 57.1% by Lancet needle. No serious complications were reported. The Franseen needle tended to show a greater amount of specimen with higher tumor cellularity than the Lancet needle which may contribute higher success rate of molecular testing. Further studies must be conducted to validate the results of this study. What is known and what is new? What is the implication, and what should change now?

Impact of annual trend volume of low-dose computed tomography for lung cancer screening on overdiagnosis, overmanagement, and gender disparities

BackgroundWith the increasing prevalence of nonsmoking-related lung cancer in Asia, Asian countries have increasingly adopted low-dose computed tomography (LDCT) for lung cancer screening, particularly in private screening programs. This study examined how annual LDCT volume affects lung cancer stage distribution, overdiagnosis, and gender disparities using a hospital-based lung cancer database.MethodsThis study analyzed the annual utilized LDCT volume, clinical characteristics of lung cancer, stage shift distribution, and potential overdiagnosis. At the individual level, this study also investigated the relationship between stage 0 lung cancer (potential strict definition regarding overdiagnosis) and the clinical characteristics of lung cancer.ResultsThis study reviewed the annual trend of 4971 confirmed lung cancer cases from 2008 to 2021 and conducted a link analysis with an LDCT imaging examination database over these years. As the volume of lung cancer screenings has increased over the years, the number and proportion of stage 0 lung cancers have increased proportionally.Our study revealed that the incidence of stage 0 lung cancer increased with increasing LDCT scan volume, particularly during the peak growth period from 2017 to 2020. Conversely, stage 4 lung cancer cases remained consistent across different time intervals. Furthermore, the increase in the lung cancer screening volume had a more pronounced effect on the increase in stage 0 lung cancer cases among females than it had among males. The estimated potential for overdiagnosis brought about by the screening process, compared to non-participating individuals, ranged from an odds ratio of 7.617 to one of 17.114. Both strict and lenient definitions of overdiagnosis (evaluating cases of stage 0 lung cancer and stages 0 to 1 lung cancer) were employed.ConclusionsThese results provide population-level evidence of potential lung cancer overdiagnosis in the Taiwanese population due to the growing use of LDCT screening, particularly concerning the strict definition of stage 0 lung cancer. The impact was greater in the female population than in the male population, especially among females younger than 40 years.To improve lung cancer screening in Asian populations, creating risk-based prediction models for smokers and nonsmokers, along with gender-specific strategies, is vital for ensuring survival benefits and minimizing overdiagnosis.

Impact of lung cancer screening on stage migration and mortality among the national Veterans Health Administration population with lung cancer.

Despite randomized trials demonstrating a mortality benefit to low-dose computed tomography screening to detect lung cancer, uptake of lung cancer screening (LCS) has been slow, and the benefits of screening remain unclear in clinical practice. This study aimed to assess the impact of screening among patients in the Veterans Health Administration (VA) health care system diagnosed with lung cancer between 2011 and 2018. Lung cancer stage at diagnosis, lung cancer-specific survival, and overall survival between patients with cancer who did and did not receive screening before diagnosis were evaluated. We used Cox regression modeling and inverse propensity weighting analyses with lead time bias adjustment to correlate LCS exposure with patient outcomes. Of 57,919 individuals diagnosed with lung cancer in the VA system between 2011 and 2018, 2167 (3.9%) underwent screening before diagnosis. Patients with screening had higher rates of stage I diagnoses (52% vs. 27%; p ≤ .0001) compared to those who had no screening. Screened patients had improved 5-year overall survival rates (50.2% vs. 27.9%) and 5-year lung cancer-specific survival (59.0% vs. 29.7%) compared to unscreened patients. Among screening-eligible patients who underwent National Comprehensive Cancer Network guideline-concordant treatment, screening resulted in substantial reductions in all-cause mortality (adjusted hazard ratio [aHR], 0.79; 95% confidence interval [CI], 0.67-0.92; p=.003) and lung-specific mortality (aHR, 0.61; 95% CI, 0.50-0.74; p<.001). While LCS uptake remains limited, screening was associated with earlier stage diagnoses and improved survival. This large national study corroborates the value of LCS in clinical practice; efforts to widely adopt this vital intervention are needed.

Further knowledge and developments in resistance mechanisms to immune checkpoint inhibitors.

The past decade has witnessed a revolution in cancer treatment, shifting from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular immune-checkpoint inhibitors (ICIs). These immunotherapies release the host's immune system against the tumor and have shown unprecedented durable remission for patients with cancers that were thought incurable, such as metastatic melanoma, metastatic renal cell carcinoma (RCC), microsatellite instability (MSI) high colorectal cancer and late stages of non-small cell lung cancer (NSCLC). However, about 80% of the patients fail to respond to these immunotherapies and are therefore left with other less effective and potentially toxic treatments. Identifying and understanding the mechanisms that enable cancerous cells to adapt to and eventually overcome therapy can help circumvent resistance and improve treatment. In this review, we describe the recent discoveries on the onco-immunological processes which govern the tumor microenvironment and their impact on the resistance to PD-1/PD-L1 checkpoint blockade.

Predicting radiation-induced immune suppression in lung cancer patients treated with stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) is known to modulate the immune system and contribute to the generation of anti-tumor T cells and stimulate T cell infiltration into tumors. Radiation-induced immune suppression (RIIS) is a side effect of radiation therapy that can decrease immunological function by killing naive T cells as well as SBRT-induced newly created effector T cells, suppressing the immune response to tumors and increasing susceptibility to infections. RIIS varies substantially among patients and it is currently unclear what drives this variability. Models that can accurately predict RIIS in near real time based on treatment plan characteristics would allow treatment planners to maintain current protocol specific dosimetric criteria while minimizing immune suppression. In this paper, we present an algorithm to predict RIIS based on a model of circulating blood using early stage lung cancer patients treated with SBRT. This Python-based algorithm uses DICOM data for radiation therapy treatment plans, dose maps, patient CT data sets, and organ delineations to stochastically simulate blood flow and predict the doses absorbed by circulating lymphocytes. These absorbed doses are used to predict the fraction of lymphocytes killed by a given treatment plan. Finally, the time dependence of absolute lymphocyte count (ALC) following SBRT is modeled using longitudinal blood data up to a year after treatment. This model was developed and evaluated on a cohort of 64 patients with 10-fold cross validation. Our algorithm predicted post-treatment ALC with an average error of cells/L with 89% of the patients having a prediction error below 0.5×109 cells/L. The accuracy was consistent across a wide range of clinical and treatment variables. Our model is able to predict post-treatment ALC<0.8 (grade 2 lymphopenia), with a sensitivity of 81% and a specificity of 98%. This model has a ∼38-s end-to-end prediction time of post treatment ALC. Our model performed well in predicting RIIS in patients treated using lung SBRT. With near-real time model prediction time, it has the capability to be interfaced with treatment planning systems to prospectively reduce immune cell toxicity while maintaining national SBRT conformity and plan quality criteria.

The role of leptin, resistin, and irisin levels as prognostic indicators of lung cancer in Iraqi patients

ABSTRACT Lung cancer is the most lethal malignancy and is often associated with a poor prognosis because of a lack of prognostic markers. Thus, this study aimed to determine whether irisin, resistin, and leptin could be useful biomarkers for lung cancer prognosis. The study is designed on 100 lung cancer patients, (66) patients with non-small cell lung cancer (NSCLC) and (34) patients with small cell lung cancer (SCLC). For the purpose of comparison, (66) samples as control group. Using the ELISA technique to estimate leptin, resistin, and irisin levels in patients and controls. The results indicate a significant increase in mean leptin in NSCLC and SCLC groups (10.71 ± 0.30 and 10.13 ± 0.51) ng/ml, respectively, in contrast to the control (8.26 ± 0.47) ng/ml. The mean of irisin and resistin had been significantly increased in SCLC group (5.86 ± 0.13 pg/ml and 7.25 ± 0.38 ng/ml, respectively) and NSCLC group (5.08 ± 0.09 pg/ml and 6.35 ± 0.13 ng/ml, respectively) in contrast to the control (4.13 ± 0.09 pg/ml and 3.96 ± 0.17 ng/ml, respectively). The higher levels of leptin in NSCLC patients could serve as a prognostic marker for NSCLC. The variations in Resistin and Irisin levels across different stages of lung cancer suggest that they might be useful in predicting the prognosis of lung cancer.

Does clinical T1N0 GGN really require checking for distant metastasis during initial staging for lung cancer?

BackgroundAccurate clinical staging is crucial for selection of optimal oncological treatment strategies in non-small cell lung cancer (NSCLC). Although brain MRI, bone scintigraphy and whole-body PET/CT play important roles in detecting distant metastases, there is a lack of evidence regarding the indication for metastatic staging in early NSCLCs, especially ground-grass nodules (GGNs). Our aim was to determine whether checking for distant metastasis is required in cases of clinical T1N0 GGN.MethodsThis was a retrospective study of initial staging using imaging tests in patients who had undergone complete surgical R0 resection for clinical T1N0 Stage IA NSCLC.ResultsA total of 273 patients with cT1N0 GGNs (n = 183) or cT1N0 solid tumors (STs, n = 90) were deemed eligible. No cases of distant metastasis were detected on initial routine imaging evaluations. Among all cT1N0M0 cases, there were 191 incidental findings on various modalities (128 in the GGN). Most frequently detected on brain MRI was cerebral leukoaraiosis, which was found in 98/273 (35.9%) patients, while cerebral infarction was detected in 12/273 (4.4%) patients. Treatable neoplasms, including brain meningioma and thyroid, gastric, renal and colon cancers were also detected on PET/CT (and/or MRI). Among those, 19 patients were diagnosed with a treatable disease, including other-site cancers curable with surgery.ConclusionsExtensive staging (MRI, scintigraphy, PET/CT etc.) for distant metastasis is not required for patients diagnosed with clinical T1N0 GGNs, though various imaging modalities revealed the presence of adventitious diseases with the potential to increase surgical risks, lead to separate management, and worsen patient outcomes, especially in elderly patients. If clinically feasible, it could be considered to complement staging with whole-body procedures including PET/CT.

Correlation between chest DW-MRI and 18F-FDG PET/CT in newly diagnosed non-small cell lung cancer (NSCLC)

BackgroundPET/CT is currently the gold standard for lung cancer staging, and it is also used to identify distant and nodal metastases. High-resolution MRI can also be used to diagnose and provide morphological details about lung cancer. Standardized uptake value ‘SUV’ calculated from PET/CT gives information about tumor behavior where the SUV reflects metabolic tumor activity. Apparent diffusion coefficient ‘ADC’ calculated from DW-MRI is a quantitative imaging marker aiming to assess tumor cellularity which reflects tumor behavior. The study aimed to correlate ADC assessed by DW-MRI and metabolic activity determined by SUV max in PET/CT in local and nodal staging of newly diagnosed NSCLC.ResultsOur study involved twenty-one patients who were pathologically proven to be NSCLC, 19 males (90.5%) and 2 females (9.5%), with a median age of 61 years (ranging from 37 to 84 years). Among all NSCLC primary mass lesions, we observed a statistically significant inverse correlation between SUV max achieved from PET/CT and ADC max, ADC mean, and ADC min calculated from DW-MR (r = − 0.509 and p = 0.019, r = − 0.472 and p = 0.031 and r = − 0.434 and p = 0.049 for correlation between SUV max of PET/CT and ADC max, ADC mean and ADC min of DW-MR, respectively). Additionally, we observed another statistically significant inverse correlation between SUV max achieved from PET/CT and ADC max, ADC mean, and ADC min calculated from DW-MR in NSCLC mediastinal lymph nodes (r = − 0.699 and p = 0.011, r = − 0.58 and p = 0.048 and r = − 0.629 and p = 0.028 for correlation between SUV max of PET/CT and ADC max, ADC mean and ADC min of DW-MR, respectively).ConclusionsADC values calculated from DW-MRI might act as a new prognostic tool owing to its significant inverse correlation with SUV max achieved from PET/CT in NSCLC primary mass lesions as well as mediastinal lymph nodes.

PLWH and lung cancer: A single cancer center experience in Philadelphia, PA.

e20502 Background: Lung cancer has been identified as the leading cause of cancer-related deaths in people living with HIV (PLWH), and disproportionately affects this population independently of smoking status and CD4 count. At the Sidney Kimmel Cancer Center (SKCC) at Jefferson Health, we serve a uniquely underserved patient population of PLWH. As PLWH were categorically excluded from most lung cancer clinical trials, we aim to study the clinical course of our patients with HIV and lung cancer. Methods: A retrospective review of 36 patients within SKCC at Jefferson Health in Philadelphia, PA from 2016 to 2023 were obtained utilizing ICD codes for lung cancer and HIV. Patients who were found to have HIV after their lung cancer diagnosis were excluded. Patient demographics, viral status, antiviral therapy, lung cancer stage, histology, molecular and fusion status, PD-L1 status, form of cancer-directed therapy, date of progression, last date of treatment, and date of death were recorded. Results: Of our 36 patients, 24 (66.7%) were male, and 20 (55.6%) racially identified as Black. 27 patients had NSCLC (20 with adenocarcinoma, 7 with squamous cell carcinoma), and 3 had SCLC. 24 (66.7%) patients had an undetectable viral load at the time of diagnosis and 35 (97.2%) were on antiviral therapy. 32 of 36 patients (88.9%) had advanced stage at the time of diagnosis; 11 had stage III disease (30.6%), and 21 (58.3%) had stage IV disease. Only 4 patients (11.1%) were diagnosed with stage I disease. The mean age of patients at diagnosis was 61.6 years (+/- 8.7 years). Of 18 patients with molecular testing performed, 4 had a KRAS mutation (22.2%) and 1 (5.6%) had a targetable EGFR mutation. Of 16 patients with PD-L1 testing, 7 (43.8%) had 0% expression, 8 (50%) had 1-49% expression, and 1 patient (6.2%) had PD-L1 expression &gt; 50%. The OS among this cohort was 1.3 years (95% CI: 0.8-3.8 years). Conclusions: Our cohort of patients demonstrated more advanced disease at presentation, a younger mean age at diagnosis and poor OS. These trends exist despite the majority of these patients having an undetectable HIV viral load at the time of diagnosis in the setting of ongoing antiviral therapy, indicating a potential relationship between even well-controlled HIV and aggressive lung cancer that warrants further exploration.

Assessing secular trends in lung cancer stage in the United States community oncology setting from 2013 to 2023.

11178 Background: Detecting disease at an early stage is critical to improving lung cancer (LC) survival, as reflected in guidelines recommending screening with low dose computed tomography for individuals at high risk by clinical societies including the NCCN (2011) and US Preventive Services Task Force (2013, updated 2021). Presenting stage distribution may also be impacted by healthcare utilization changes following the COVID-19 pandemic. Real-world data (RWD)-based investigations are important complements to national cancer registries to provide insight into this potentially changing diagnostic landscape, especially given utilization, practice and referral patterns unique to community settings. We thus assessed LC stage from 2013-23 in a large, nationally representative sample of community oncology practices leveraging RWD. Methods: This is a retrospective observational cohort study of patients within The US Oncology Network and non-Network practices, which include a nationally representative network of over 3,700 providers and more than 1 million patients seen annually in community-based oncology practices. All adult (≥18 years) patients diagnosed with non-small cell LC (NSCLC) or small-cell LC (SCLC) who had a first observed stage available in the community oncology setting within 2013 to 2023 were included. Demographics and medical history data were sourced from structured data fields in iKnowMed, an oncology-specific electronic health record system. Time trends of patient diagnosis and characteristics were descriptively evaluated. Results: The analysis included 98,806 patients with LC (84,023 [85.0%] NSCLC and 14,783 [15.0%] SCLC). Approximately half were female (49.7% and 50.3% in each disease), three-fourths were White (72.7% and 77.0%, respectively), and mean ages at diagnosis were 69.9 and 68.1 years. From 2013 to 2023, there was an increase in the total number of patients observed in the database with a documented stage, from 7,159 to 9,115 (27.3% increase) for NSCLC and from 1,162 to 1,595 (37.3% increase) for SCLC. This was largely driven by an absolute increase in advanced stage diagnoses. The proportion of patients diagnosed with Stage IV NSCLC increased from 43.3% in 2013 to 49.3% in 2023, while the proportions of Stage 0/I and II diagnoses decreased. A similar trend was observed for SCLC, with 60.3% of patients diagnosed with Stage IV in 2013 compared to 68.2% in 2023. The proportion of Stage IV NSCLC cancers increased in the pandemic period, from 48.0% in 2019 to 51.6% in 2020 and 50.6% in 2021. Conclusions: Over the last decade, the proportion of advanced stage LC cases has increased, possibly reflecting changes in referral patterns and utilization specific to the community setting, including those related to the COVID-19 pandemic. The burden of advanced disease highlights the need for continuous investment in advanced-stage treatments as well as early detection efforts.

Immune checkpoint inhibitors (ICI): From cancer killers to electrolyte disruptors.

e24146 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Cancer patients, especially lung cancer (LCa), are at an increased risk of developing electrolyte imbalance due to several etiologies such as poor nutrition, paraneoplastic syndromes, etc. It is vital to address electrolyte disturbances with the use of ICIs. Objective: The study aims to understand the relationship between ICIs and electrolyte disturbance in LCa patients. Methods: TrinetX, a global federated research network, provides a dataset of electronic medical records from different healthcare organizations (HCOs), was utilized. Initial query was made to isolate patients with LCa stages 2-4. The 2 groups were based on the presence or absence of IO (atezolizumab, durvalumab, pembrolizumab, nivolumab, ipilimumab). Further, propensity score matching (PSM) was carried out to match age, sex, race, chronic kidney disease, diarrhea. Compare outcome analytic function was utilized to map the co-relation with electrolyte imbalance. Results: 41,818 patients were identified, out of which 12.37% (n = 5172) patients received immunotherapy at some point in their cancer treatment. There was no statistical difference in age (65.9 ± 10.3 vs 65.9 ± 11.3, p = 0.8608) as well as gender in both groups. Caucasians (69% vs 66% for Causians (p &lt; 0.0001)) were the predominant race in both groups and were more likely to receive immunotherapy compared to African Americans (12% vs 14% in AA (p = 0.0004)). Diarrhea (30% vs 9%, p &lt; 0.0001) and Chronic kidney disease (CKD) (18% vs 8%, p &lt; 0.0001) were predominantly seen in IO group. Prior to matching, hypomagnesemia (HypoMg) (10.47% vs 5.85%, p &lt; 0.0001), hypocalcemia(HypoCa) (3.36% vs 2.03%, p &lt; 0.0001), hypokalemia (HypoK) (16.91% vs 11.02%, p &lt; 0.0001), hyperkalemia (HyperK) (7.69% vs 4.88%, p &lt; 0.0001), hyponatremia (HypoNa) (16.82% vs 10.66%, p &lt; 0.0001) and hypercalcemia (HyperCa) (5.26% vs 3.05%, p &lt; 0.0001) were seen higher in IO group while hypermagnesemia (HyperMg) (2.04% vs 2.62%, p = 0.0150) was more seen in the non IO group, with no significant difference in hypernatremia (HyperNa) (2.34% vs 1.95%, p = 0.0634). After PSM, HypoMg (10.48% vs 7.01%, p &lt; 0.0001), HypoK (16.92% vs 12.64%, p &lt; 0.0001), HyperK (7.69% vs 6.26%, p = 0.0060), HypoNa (16.80% vs 11.56%, p &lt; 0.0001) and HyperCa (5.26% vs 3.06%, p &lt; 0.0001) were seen more in IO group, while HyperMg (2.04% vs 2.67%, p = 0.0399) was higher in non IO and there was no significant difference for HypoCa (3.36% vs 2.77, p = 0.0829) and HyperNa (2.34% vs 1.89%, p = 0.1135). Conclusions: Our study demonstrated that there is correlation between ICI use and electrolyte imbalance. Providers should be vigilant about the potential electrolyte abnormalities when treating patients with ICI therapy.

With eyes on the future: Prospective evaluation of immune-related adverse events in patients with lung cancer.

e23177 Background: Immune checkpoint inhibitors (ICIs) bear unique, time-dependent immune-related adverse events (irAEs). However, limited data exist regarding tolerability in real-world populations. We report interim, non-sex stratified results of the first study prospectively evaluating ICI tolerability in patients with lung cancer (LC) in a real-world setting. Methods: Recruitment began in July 2023 and is ongoing. The electronic Patient-Reported Outcomes version of the Common Terminology Criteria (PRO-CTCAE) was utilized to assess patients’ irAEs. Patients (pts) complete up to 6 questionnaires throughout their treatment plus an end of treatment evaluation. Inclusion criteria includes pts ≥18 years, with LC stage I to IV, receiving single-agent ICI at Dana-Farber Cancer Institute. Descriptive statistics summarized patients' demographics, clinical characteristics, and symptoms. Results: 36 pts were enrolled in the study as of January 23, 2024. 35 pts have completed their first PRO-CTCAE questionnaire; the median number of completed questionnaires was 2 (range: 1-6). Due to the current sample size, results reported reference pts’ first PRO-CTCAE assessment. 53% of pts identified as female, 92% identified as White, and 6% as Black (Table 1). 56% of pts (19/34) reported having shortness of breath (SOB), most of whom (63%; 12/19) reported having moderate to severe SOB that often (somewhat to very much; 42%; 8/19) interfered with daily activities; 21% of them (4/19) stated that the SOB had worsened since starting ICIs. Similarly, of the 54% (19/35) with a cough, 42% (8/19) reported a moderate to very severe cough and 16% (3/19) reported its worsening since ICI initiation. 14 pts reported anorexia secondary to treatment, with most of them (57%; 8/14) reporting that it interfered with daily activities. Most pts (79%; 27/34) noted some degree of lack of energy. Rates of skin toxicity were low, with only 6% (2/35) experiencing a rash after beginning ICIs. Many pts did not experience nausea, abdominal pain, or unexpected sweating (80%; 28/35, 83%; 29/35, 77%; 27/35). However, of the pts reporting nausea and abdominal pain, high severity of these symptoms was noted (43%; 3/7, 50%; 3/6). Other low frequency irAEs included diarrhea, dry mouth, and dysgeusia. Conclusions: SOB and cough were the most common symptoms experienced with high severity in this ongoing prospective evaluation of irAEs in pts with LC. Though nausea and abdominal pain were less common, when present, these symptoms were reported with high severity. Future data from this study will elucidate patient experiences with irAEs throughout their treatment course. [Table: see text]

Dissecting racial/ethnic disparities in non-small cell lung cancer staging at diagnosis: Intra-ethnic and geographic differences.

1575 Background: Lung cancer outcomes significantly rely on accurate and early detection. This population-based study aims to identify factors contributing to disparities in the stage of non-small cell lung cancer (NSCLC) diagnoses, focusing on Hispanic ethnic subgroups. Methods: Incident cases diagnosed from 2005–2018 were extracted from the Florida State Cancer Registry. Stage was categorized as resectable (Stage I-IIIA) or nonresectable (Stage IIIB/IIIC/IV) NSCLC. Multivariable logistic regression models were used to assess the association between race/ethnicity and stage at diagnosis, adjusted for socioeconomic, smoking status, and clinical factors. Regional stratification involved separate analyses for heavily Hispanic South Florida and the rest of Florida. Results: Among 157,034 NSCLC patients, with a racial distribution of 81.0% White, 8.3% Black, and 9.2% Hispanic, 43.2% were diagnosed at a resectable stage. Age-adjusted models showed Black patients had 22% higher odds (odds ratio [OR]=1.22; 95% CI: 1.21-1.23) and Hispanic patients had 11% higher odds (OR=1.11; 95% CI: 1.10-1.12) of non-resectable stage across all subgroups diagnoses compared to White patients. However, after further adjustment, higher odds were significant only for NHB (ORadj=1.12; 95% CI: 1.11-1.14) and Central American Hispanics (ORadj=1.41; 95% CI: 1.35-1.47). Regional differences were significant, with Hispanic patients in South Florida showing more favorable staging outcomes than Whites (ORadj=0.95; 95% CI: 0.94-0.97), while in the rest of Florida, Hispanic patients were at a disadvantage (ORadj=1.09; 95% CI: 1.07-1.10). Conclusions: Pronounced NSCLC staging disparities are manifest in Black and Hispanic populations, coupled with striking regional variations among Florida's Hispanic groups which underscores the necessity for targeted research to dissect and address the underlying causes of these inequities in the cancer care continuum.

Outcome analysis of the traditional therapeutic approach in patients with bronchopulmonary cancer and advanced anesthetic-surgical risk

Background. Lung cancer exhibits high global incidence and mortality rates. Surgical resection remains crucial to diagnosis, staging, and treatment of non-small cell lung cancer (NSCLC). However, advanced stages often require multimodal approaches. Prehabilitation, innovative perioperative techniques, and the exploration of immunotherapy hold promise for improving outcomes. Materials and methods. This two-phase observational cohort study included a retrospective arm (100 patients, traditional treatment) and a prospective arm (100 patients, innovative perioperative management, and risk stratification). Descriptive and inferential statistics were used to evaluate data, identify risk factors, and compare the 2-year survival between treatment groups. Results. Despite advances, lung cancer prognosis remains poor, with limited cure rates. Mean survival in the traditional approach was 1.3 years with a 5-year survival of only 1%. While prehabilitation and innovative techniques showed potential, no statistically significant differences in survival times were observed between the treatment groups. Patients with stage III (Charlson score 0-4) and stage I-II (Charlson score 5-12) demonstrated comparable outcomes, highlighting the importance of comorbidity burden. Conclusions. Targeted screening protocols are of paramount importance for early detection and intervention. Populationwide smoking cessation programs, environmental protection measures, and the promotion of healthy lifestyles are vital for prevention and reducing incidence. Standard chemotherapy and radiotherapy offer limited therapeutic benefits in advanced lung cancer. This highlights a pressing need for breakthroughs in basic research to develop novel treatment paradigms that significantly improve outcomes. While this study did not reveal statistically significant survival differences between traditional and innovative perioperative approaches, prehabilitation and optimization techniques hold promise and deserve further research. The development of anti-tumor immunotherapy offers a significant potential in non-surgical lung cancer treatment, especially given the limitations in advanced-stage disease management. Harnessing the immune system to fight cancer represents a promising new frontier.