Primary Non-small Cell Lung Cancer Research Articles

Establishment and Validation of Patient-Derived Non-Small Cell Lung Cancer Organoids as In Vitro Lung Cancer Models

Background: Recent advances in the personalized treatment of non-small cell lung cancer (NSCLC) require representative in vitro model systems that reflect tumor heterogeneity and maintain the characteristic genetic aberrations. We therefore aimed to establish patient-derived NSCLC organoids that offer a reliable platform for further investigations. Methods: NSCLC organoids were cultured between May 2020 and February 2022 from surgically resected NSCLC tissue specimens. After histological and immunohistochemical validation, genetic validation was performed by targeted next-generation sequencing of tissue and organoid specimens using the Oncomine Focus Assay (ThermoFisher Scientific). Results: From 37 resected NSCLC samples, 18 primary organoid cultures were successfully established and expanded during early passages. Upon histomorphological validation, organoids showed complementary characteristics when compared to the resected parental tumor, including adenocarcinoma, squamous cell carcinoma, mucoepidermoid carcinoma, and lung carcinoid differentiation. Among nine parental tumors, traceable genetic alterations were detected, and three corresponding organoids lines retained this mutational profile, including a KRAS p.Gly12Val mutation, KRAS p.Gly12Cys mutation, and RET-fusion. Conclusions: The establishment of primary NSCLC organoids from surgically resected tissue is feasible. Histological, immunohistochemical, and genetic validation is essential to identify representative NSCLC organoids that maintain the characteristics of the parental tumor. Overall, low establishment rates remain a challenge for broad clinical applications.

Impact of perioperative high-protein nutritional support on the quality of life of patients with primary lung cancer: a Russian prospective multicenter comparative study (NUTRILUNC study)

BACKGROUND: Individuals over the age of 70 comprise over half of operable patients with stage 0–IIIA lung cancer. In the early postoperative period of this cohort, pain, fatigue, insomnia, and/or mood disturbances are the four most common symptoms, which can significantly diminish quality of life and functional status. Perioperative nutritional support in such patients, which enhances exercise tolerance, can have a positive impact on their quality of life and socialization. AIM: To assess the effect of perioperative nutritional support using high-protein oral nutrition supplements on the general health and quality of life of non-small cell lung cancer patients during the postoperative period. MATERIALS AND METHODS: Patients with primary non-small cell lung cancer (n=112, 69 males), aged 57.2±8.2, who were awaiting lung surgery and at risk of malnutrition (Nutritional Risk Screening Assessment 2002 score ≥3) were randomly assigned into two groups. Oral nutritional support (Nutridrink Compact Protein, Nutricia LLC) was administered to the study group (n=55) at a rate of 250 ml/d (36 g of protein, 612 kcal) for 14 days prior to and 14 days following the surgery, in addition to the standard diet. Control group patients (n=57) were provided a standard diet. The quality of life was assessed using the Quality of Life Questionnaire Core-30. Results are presented as mean ± standard deviation. Differences were considered significant at p ≤0.05. RESULTS: Throughout the entire observation period, the study group exhibited superior growth indicators in terms of general health status, physical, and role functioning than the control group (p 0.05). The study group patients exhibited a propensity toward improved emotional functioning, and by the end of the study, weakness and insomnia were less pronounced (p 0.05). Other indicators did not exhibit any significant variations. CONCLUSION: Нigh-protein perioperative oral nutrition supplements exert a positive impact on the quality of life of non-small cell lung cancer patients.

Prognostic Value of Sarcopenia in Elderly Patients with Metastatic Non-Small-Cell Lung Cancer Undergoing Radiotherapy

Background: Sarcopenia, a syndrome characterized by age-related loss of muscle mass and function, lacks universally accepted diagnostic criteria, particularly for its role as a prognostic factor in elderly patients with non-small-cell lung cancer (NSCLC). This study aimed to evaluate the prognostic significance of sarcopenia, assessed by psoas muscle size on baseline CT scans, in patients over 70 years of age with metastatic NSCLC. Methods: We retrospectively analyzed 85 elderly patients undergoing palliative radiation therapy between August 2022 and July 2024. Using morphometric analysis of psoas size, we investigated its correlation with overall survival (OS) and progression-free survival (PFS). Results: Our results showed that decreased psoas size was significantly associated with shorter OS and PFS, with median OS of 10 months and PFS of 4 months in sarcopenic patients compared to longer survival times in non-sarcopenic patients. Median survival of non-sarcopenic vs. sarcopenic patients was 21 ± 7 months (muscle area > median) versus 5 ± 2.3 months (muscle area < median). Multivariate analysis confirmed that psoas size, along with ECOG performance status and treatment of primary NSCLC, was a significant predictor of survival. Discussion: These findings suggest that psoas muscle size is a valuable prognostic marker for elderly NSCLC patients, potentially guiding treatment decisions and patient management. Further research is needed to validate these results and refine prognostic models for this population.

Recommendation for Clinical T Staging in Patients with Non-Small Cell Lung Cancer: Volumetric Measurement: A Retrospective Study from Turkey.

Currently, clinical T staging in non-small cell lung cancer (NSCLC) is based on the largest radiological diameter observed on computed tomography (CT). Under this system, tumors with varying shapes-such as spherical, amorphous, or spiculated tumors- can be assigned the same T stage even with different volumes. We aimed to propose a 3-dimensional (3D) volumetric staging system for NSCLC as an alternative to diameter-based T staging and to conduct comparative survival analyses between these methods. We retrospectively analyzed data from patients who underwent surgery for pT1-4N0M0 primary NSCLC between January 2018 and May 2022. Digital Imaging and Communications in Medicine data from patient CT scans were uploaded to 3D Slicer software for volumetric tumor measurement. Using the paired samples t-test or the Wilcoxon test, we compared the expected tumor volumes, calculated by tumor diameter, with the actual volumes measured by 3D Slicer. Receiver operating characteristic analysis was employed to determine the cut-off value for tumor volume. Kaplan-Meier analysis was utilized to assess overall survival, while the log-rank method was applied to compare survival differences between groups. The significance of changes in T stage was evaluated using the marginal homogeneity test. The study included 136 patients. Significant differences were observed between expected and actual tumor volumes (p=0.01), and associated changes in T stage were also significant (p=0.04). The survival analysis performed using tumor volume (p=0.009) yielded superior results compared to that based on diameter (p=0.04) in paients with early tumor stage. T-factor staging based on tumor volume could represent an alternative staging method for NSCLC.

Prise en charge des stades précoces des cancers bronchiques non à petites cellules : radiothérapie en conditions stéréotaxiques

Surgery remains the reference treatment for primary non-small cell lung cancer (NSCLC) T1-T2 N0. However, 20-30 % of patients present a surgical contraindication. For these patients who cannot be operated on, stereotactic radiotherapy (SBRT) has been validated as the alternative of choice by learned medical societies. These two treatments are aimed at different populations, with a recognized role for these tumours local control. Radiotherapy remains less risky for fragile patients, but maybe at the cost of a higher risk of lymph node recurrence. The role of systemic treatment in association with stereotactic radiotherapy remains to be determined, particularly for non-operable T3NO tumours.Several complex clinical situations can be identified depending on the location and size of the tumour, the patient’s history of irradiation and co-morbidities. The treatment of central tumours, re-irradiation, which is becoming increasingly frequent with advances in systemic treatments, and treatment of patients with pulmonary fibrosis represent a real technical challenge, requiring a specialized multi-disciplinary assessment to evaluate the benefit-risk ratio.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved

EP.07B.05 Comparison of Image-Guided Thermal Ablation or Stereotactic Body Radiation Therapy for Primary Non-Small Cell Lung Cancer

EP.07B.05 Comparison of Image-Guided Thermal Ablation or Stereotactic Body Radiation Therapy for Primary Non-Small Cell Lung Cancer

Association of area-level broadband and non-small cell lung cancer diagnosis and guideline-concordant care in the US.

96 Background: Access to broadband is a social determinant of health facilitating connections with healthcare services and other resources and alleviating burdens of travel distance, time, and cost. We used nationwide data to examine the association of zip code-level broadband usage and stage at diagnosis, as well as the receipt of quality care among individuals newly diagnosed with non-small cell lung cancer (NSCLC). Methods: Individuals ≥18 years newly diagnosed with first primary NSCLC between April - December of 2019-2021, were identified from the National Cancer Database (January - March were excluded to match the COVID-19 timeframe in 2020). Broadband usage percentage (the percentage of individuals per zip code with access to fixed broadband at speeds of 25 Mbps/3 Mbps in 2020) were combined with the cohort based on individual’s residential zip code. Multivariable logistic regression models examined associations between broadband usage quartiles and stage at diagnosis, as well as the receipt of guideline-concordant care based on National Comprehensive Cancer Network guidelines, including surgery and radiation, ≥10 lymph nodes sampling, chemotherapy, and neoadjuvant chemoradiation (NACR). Analyses were conducted overall and stratified by metropolitan status and year, adjusting for age group, sex, race and ethnicity, comorbidity, distance to facility, state, and zip code-level social deprivation index (SDI). Results: Cohort included 305,198 individuals newly diagnosed with NSCLC. Individuals living in areas with the highest broadband usage were more likely to be aged 65-74 years, female, non-Hispanic White, with Medicare coverage, living in metropolitan and low SDI areas. In adjusted models, individuals living in areas with the highest broadband usage were more likely to be diagnosed with stage I NSCLC (adjusted odds ratio [AOR] = 1.10, 95% confidence interval [95%CI] = 1.01-1.20) and to receive guideline-concordant NACR (AOR = 1.38, 95%CI = 1.09-1.73) compared with those living in areas with the lowest broadband usage in 2020. When stratified by metropolitan status, associations of broadband and diagnosis and receipt of NACR were only observed among individuals living in non-metropolitan areas with medium-low and medium-high broadband usage, respectively (AOR = 1.15, 95%CI = 1.01-1.32; AOR = 1.80, 95%CI = 1.25-2.58). No significant associations were identified for other care modalities or during 2019 and 2021. Conclusions: Increased access to broadband usage is associated with earlier stage NSCLC diagnosis and receiving guideline-concordant NACR in 2020. Our results suggest that increased broadband access, combined with the expansion of telehealth services during the COVID-19 pandemic, may have improved telehealth utilization throughout 2020, leading to enhanced quality of cancer care, particularly benefiting individuals residing in non-metropolitan areas.

Associations of Medicaid expansion with stage at diagnosis, timely initiation and receipt of guideline-concordant treatment, and survival among individuals newly diagnosed with non-small cell lung cancer.

47 Background: Medicaid expansion under the Patient Protection and Affordable Care Act improved health insurance coverage among patients with cancer. Individuals with non-small cell lung cancer (NSCLC) may benefit from Medicaid expansion throughout the cancer control continuum. This study examined the associations of Medicaid expansion with stage at disease diagnosis, timely initiation and receipt of guideline-concordant treatment, and five-year overall survival among individuals with NSCLC. Methods: We identified individuals newly diagnosed at age 18-64 with stages I-IV first primary NSCLC between January 1, 2008 and December 31, 2019 in 50 states and Washington, D.C. from the National Cancer Database (n=332,368). We examined the associations of Medicaid expansion with (1) diagnosis stage, which was categorized into early (I&II) and late (III&IV); (2) timely initiation of guideline-concordant treatment within 30 days after cancer diagnosis (yes/no); (3) receipt of guideline-concordant treatment (yes/no) derived from the National Comprehensive Cancer Network cancer treatment guidelines; and (4) five-year overall survival. We applied a difference-in-differences (DD) approach to examine the changes in study outcomes associated with Medicaid expansion, controlling for key sociodemographic and clinical factors. Results: The percentage of early-stage diagnoses increased from 23.1% pre-expansion to 31.9% post-expansion in expansion states and from 22.3% to 29.5% in non-expansion states, translating to greater increase of 1.7 (95% confidence interval (CI): 0.3-3.1) percentage points (ppt) in expansion states after adjustment (Table). Medicaid expansion was also associated with greater increases in timely initiation of guideline-concordant care (DD: 1.6 (95% CI: 0.1-3.1) ppt) and five-year overall survival (DD: 1.3 (95% CI: 0.7-1.9) ppt). Conclusions: Medicaid expansion may improve access to NSCLC care and outcomes across the cancer control continuum, from early-stage diagnosis, treatment initiation, and overall survival. Association of Medicaid expansion and study outcomes among NSCLC patients. Expansion States Non-expansion States Pre-ME Post-ME Difference Pre-ME Post-ME Difference DD Adjusted DD Early-stage diagnosis 23.1 31.9 8.7 (7.4 to 10.1) 22.3 29.5 7.2 (6.2 to 10.1) 1.5 (-0.1 to 3.2) 1.7 (0.3 to 3.1) Timely initiation of guideline-concordant care 31.3 27.5 -3.9 (-5.3 to -2.4) 33.4 27.8 -5.6 (-6.24 to -2.4) 1.7 (0.1 to 3.3) 1.6 (0.1 to 3.1) Receipt of guideline-concordant care 65.2 68.2 2.9 (1.8 to 4.0) 62.9 66.4 3.5 (2.7 to 4.0) -0.6 (-2.0 to 0.8) -0.2 (-1.7 to 1.3) Five-year survival 21.3 34.8 13.5 (13.1 to 13.9) 18.6 30.2 11.6 (11.1 to 12.2) 1.9 (1.2 to 2.5) 1.3 (0.7 to 1.9) Abbreviation: ME, Medicaid expansion.

Elevated origin recognition complex subunit 6 expression promotes non-small cell lung cancer cell growth

Exploring novel targets for non-small cell lung cancer (NSCLC) remains of utmost importance. This study focused on ORC6 (origin recognition complex subunit 6), investigating its expression and functional significance within NSCLC. Analysis of the TCGA-lung adenocarcinoma database revealed a notable increase in ORC6 expression in lung adenocarcinoma tissues, correlating with reduced overall survival, advanced disease stages, and other key clinical parameters. Additionally, in patients undergoing surgical resection of NSCLC at a local hospital, ORC6 mRNA and protein levels were elevated in NSCLC tissues while remaining low in adjacent normal tissues. Comprehensive bioinformatics analyses across various cancers suggested that ORC6 might play a significant role in crucial cellular processes, such as mitosis, DNA synthesis and repair, and cell cycle progression. Knocking down ORC6 using virus-delivered shRNA in different NSCLC cells, both primary and immortalized, resulted in a significant hindrance to cell proliferation, cell cycle progression, migration and invasion, accompanied by caspase-apoptosis activation. Similarly, employing CRISPR-sgRNA for ORC6 knockout (KO) exhibited significant anti-NSCLC cell activity. Conversely, increasing ORC6 levels using a viral construct augmented cell proliferation and migration. Silencing or knockout of ORC6 in primary NSCLC cells led to reduced expression of several key cyclins, including Cyclin A2, Cyclin B1, and Cyclin D1, whereas their levels increased in NSCLC cells overexpressing ORC6. In vivo experiments demonstrated that intratumoral injection of ORC6 shRNA adeno-associated virus markedly suppressed the growth of primary NSCLC cell xenografts. Reduced ORC6 levels, downregulated cyclins, and increased apoptosis were evident in ORC6-silenced NSCLC xenograft tissues. In summary, elevated ORC6 expression promotes NSCLC cell growth.

Sex-Based Differences in Lung Cancer Incidence: A Retrospective Analysis of Two Large US-Based Cancer Databases

Background/Objectives: Non-small cell lung cancer (NSCLC) has seen a relative rise in incidence among females versus males in recent years, although males still have a higher overall incidence. However, it is unclear whether this trend is consistent across all populations. Therefore, we retrospectively examined this relationship in two large high-risk clinical cohorts. Methods: First, we analyzed lung cancer incidence among individuals with a smoking history of over 40 pack-years in the National Lung Screening Trial (NLST). Then, we investigated the incidence of second primary NSCLC in patients who underwent lobectomy for previous stage I lung cancer using the Surveillance, Epidemiology, and End Results (SEER) database. We performed both univariate and multivariable time-to-event analyses to investigate the relationship between sex and lung cancer incidence. Results: In the NLST cohort (n = 37,627), females had a higher risk of developing primary NSCLC than males (HR = 1.11 [1.007–1.222], p = 0.035) after adjusting for age and pack-year history. In the SEER cohort (n = 19,327), females again exhibited an increased risk of developing a second primary lung cancer (HR = 1.138 [1.02–1.269], p = 0.021), after adjusting for age, race, grade, and histology. Conclusions: Our analysis reveals that females have a modestly higher lung cancer incidence than males in high-risk populations. These findings underscore the importance of further researching the underlying cellular processes that may cause sex-specific differences in lung cancer incidence.

FLAIR: A Phase II, Open Label, Randomized Study of Osimertinib Plus Bevacizumab Versus Osimertinib in Recurrent or Metastatic Treatment-Naïve NSCLC Patients Harboring EGFR 21L858R Mutation

IntroductionOsimertinib, the 3rd generation EGFR-TKI, has emerged as standard first-line treatment for patients with advanced EGFR mutated nonsmall cell lung cancer (NSCLC). Patients with exon 21 L858R mutation showed lower efficacy with EGFR-TKIs than those with 19Del mutation, even with osimertinib, it remains an unmet medical need to further improve the efficacy in L858R population. We present the rationale and design for FLAIR (NCT04988607), which will investigate the efficacy and safety of osimertinib plus bevacizumab versus osimertinib monotherapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation. Materials and MethodsFLAIR is a prospective, multicenter, randomized, open label study, which is initiated by Chinese Thoracic Oncology Group (CTONG2002). Patients age ≥18 years with primary recurrent or metastatic nonsquamous NSCLC who are treatment-naïve with documented EGFR exon 21 L858R mutation is eligible. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily plus bevacizumab 15mg/kg every 3 weeks or osimertinib monotherapy 80 mg once daily until progression or another discontinuation criterion is met. The primary endpoint is investigator-assessed progression free survival (PFS). Secondary endpoints include: overall survival rate at 24 months, time to treatment failure (TTF), overall response rate (ORR), disease control rate (DCR), duration of response (DoR), central nervous system (CNS) PFS, CNS ORR and safety. ResultsFLAIR has completed the enrollment, and results are expected in the fourth quarter of 2025 (depending on the actual event rate). ConclusionsThis study will offer better perspectives on the efficacy and safety of osimertinib plus bevacizumab combination therapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation, providing valuable guidance for clinical practice.

Circulating Interleukins as Biomarkers in Non-Small Cell Lung Cancer Patients: A Pilot Study Compared to Normal Individuals.

Identifying biomarkers in non-small cell lung cancer (NSCLC) can improve diagnosis and patient stratification. We evaluated plasmas and sera for interleukins (IL)-11, IL-6, IL-8, IL-17A, and IL-33 as biomarkers in primary NSCLC patients undergoing surgical treatment against normal volunteers. Exhaled-breath condensates (EBCs), a potential source without invasive procedures, were explored in normal individuals. Due to separate recruitment criteria and intrinsic cohort differences, the NSCLC and control cohorts were not well matched for age (median age: 65 vs. 40 years; p < 0.0001) and smoking status (p = 0.0058). Interleukins were first assessed through conventional ELISA. IL-11 was elevated in NSCLC plasma compared to controls (49.71 ± 16.90 vs. 27.67 ± 14.06 pg/mL, respectively, p < 0.0001) but undetectable in sera and EBCs by conventional ELISA. Therefore, high-sensitivity PCR-based IL-11 ELISA was repeated, albeit with concentration discrepancies. IL11 gene and protein upregulation by RT-qPCR and immunohistochemistry, respectively, were validated in NSCLC tumors. The lack of detection sensitivity across IL-6, IL-8, IL-17A, and IL-33 suggests the need for further, precise assays. Surprisingly, biomarker concentrations can be dissimilar across paired plasmas and sera. Our results identified a need to optimize detection limits for biomarker detection and caution against over-reliance on just one form of blood sample for biomarker assessment.

GABA(A) Receptor Activation Drives GABARAP-Nix Mediated Autophagy to Radiation-Sensitize Primary and Brain-Metastatic Lung Adenocarcinoma Tumors.

In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of both primary and brain-metastatic NSCLC cells. Employing a human-relevant ex vivo 'chip', AM-101 is as efficacious as docetaxel, a chemotherapeutic used with radiotherapy for advanced-stage NSCLC. In vivo, AM-101 potentiates radiation, including conferring a significant survival benefit to mice bearing NSCLC intracranial tumors generated using a patient-derived metastatic line. GABA(A) receptor activation stimulates a selective-autophagic response via the multimerization of GABA(A) receptor-associated protein, GABARAP, the stabilization of mitochondrial receptor Nix, and the utilization of ubiquitin-binding protein p62. A high-affinity peptide disrupting Nix binding to GABARAP inhibits AM-101 cytotoxicity. This supports a model of GABA(A) receptor activation driving a GABARAP-Nix multimerization axis that triggers autophagy. In patients receiving radiotherapy, GABA(A) receptor activation may improve tumor control while allowing radiation dose de-intensification to reduce toxicity.

The burden of tuberculosis among patients with non-small cell lung carcinoma in a tertiary care center

BackgroundLung cancer and tuberculosis share similar risk factors, clinical spectrum, radiological features and it is difficult to differentiate but it is important to diagnose both conditions for targeted therapy and better outcome. AimsOur primary objective was to estimate the proportion of TB in primary biopsy proven non-small cell lung carcinoma (NSCLC) cases. Material & methodsThis prospective observational study was conducted in the Departments of Medicine/Pulmonary Medicine/Medical Oncology and Microbiology at the All India Institute of Medical Sciences, New Delhi for a period of 2 years (January 2020–December 2021). Patients with biopsy proven, primary non-small cell lung cancer were recruited and sputum samples were subjected to microbiological investigations to confirm tuberculosis. Comparison was done in two groups of lung cancer patients with confirmed TB (Group A) and without confirmed tuberculosis (Group B). ResultsTotal 75 patients with biopsy proven, primary NSCLC were recruited and 16 % (12/75) were diagnosed with confirmed TB. Adenocarcinoma (36.48 %) and Squamous cell carcinoma (33.44 %) were the two predominant histopathological subtypes of NSCLC. About 57 (76 %) of them were found to be in stage IV of Lung cancer at initial presentation itself (75 % in group A & 74.6 % in group B; p value < 0.80). A majority of patients (11/12 cases; 91 %) of group A were males with a mean age of 59 ± 7.5 years. The upper lobes of the lung were involved in 65 % (49/75) of the cases and showing a mass lesion on imaging (75 % in group A & 65 % in group B; p value < 0.52). Kaplan Meier survival revealed a median survival time of 11 months in subjects with only NSCLC and a median survival time of 4 months in the group with concomitant TB and NSCLC (p value < 0.44).

Prognostic Implications of Selective Dissection of Left Lower Paratracheal Lymph Nodes in Patients with Left-Sided Non-Small Cell Lung Cancer.

This study aimed to examine the clinical implications of selective station 4L lymph node dissection (S4L-LND) on survival in non-small cell lung cancer (NSCLC) and to evaluate its potential advantages. We enrolled patients with primary left-sided NSCLC who underwent upfront video-assisted thoracoscopic surgery with R0 resection including lobectomy and segmentectomy, with or without S4L-LND, at our institution between January 2007 and December 2021. Following 1:1 propensity score matching (PSM), we compared overall survival (OS) and recurrence-free survival (RFS) between patients with and without S4L-LND. The study included 2,601 patients, of whom 1,126 underwent S4L-LND and 1,475 did not. PSM yielded 1,036 patient pairs. Among those who underwent S4L-LND, 87 (7.7%) exhibited S4L-LN involvement. Neither OS (p=0.12) nor RFS (p=0.24) differed significantly between matched patients with and without S4L-LND. In patients with S4L-LN involvement, metastases were more common in the left upper lobe (LUL) than in the left lower lobe (LLL) (3.6% vs. 2.0%, p=0.061). Metastasis became significantly more frequent with more advanced clinical N (cN) stage (cN0, 2.3%; cN1, 5.8%; cN2, 32.6%; p<0.001). Multivariate logistic regression analysis revealed that cN stage and tumor location were independently associated with S4L-LN involvement (p<0.001 for both). OS and RFS did not differ significantly between matched patients with and without S4L-LND. Among participants with S4L-LN involvement, metastases occurred more frequently in the LUL than the LLL, and their incidence increased significantly with more advanced cN stage. Thus, patients with LUL or advanced cN lung cancers may benefit from S4L-LND.

Patients with Pulmonary Artery Reconstruction or Double Sleeve Resection Show Inferior Survival than Patients with Bronchial Sleeve Resection for Non-small Cell Lung Cancer.

Sleeve lobectomy or resection with pulmonary artery reconstruction is a technique that allows for resection of locally advanced central lung carcinoma, preserving lung function, and is associated with lower morbidity and mortality than pneumonectomy. This survey aimed to assess the long-term survival comparing different types of sleeve lobectomy and identify risk factors affecting survival.All consecutive patients who underwent anatomical resection for primary non-small cell lung cancer with bronchial sleeve or pulmonary artery reconstruction in our department between September 2003 and September 2021 were included in this study. Cases with carinal sleeve pneumonectomy were excluded. Data were evaluated retrospectively.Bronchial sleeve resection was performed in 227 patients, double sleeve resection in 67 patients, and 45 cases underwent isolated lobectomy with pulmonary artery reconstruction. The mean follow-up was 33.5 months. The 5-year survival was 58.5% for patients after bronchial sleeve, 43.2% after double sleeve, and 36.8% after resection with vascular reconstruction. The difference in overall survival of these three groups was statistically significant (p=0.012). However, the UICC stage was higher in cases with double sleeve resection or resection with vascular reconstruction (p=0.016). Patients with lymph node metastases showed shorter overall survival (p=0.033). The 5-year survival rate was 60.1% for patients with N0 and 47% for patients with N1 and N2 status. Induction therapy, vascular sleeve resection, and double sleeve resection were independent adverse predictors for overall survival in multivariate analysis.Sleeve lobectomy and resection with vascular reconstruction are safe procedures with good long-term survival. However, double sleeve resection and vascular sleeve resection were adverse predictors of survival, possibly due to a higher UICC stage in these patients.

1224P Evaluation of safety and feasibility of adjuvant chemotherapy in elderly patients with primary non-small cell lung cancer

1224P Evaluation of safety and feasibility of adjuvant chemotherapy in elderly patients with primary non-small cell lung cancer

RILPL2 as a potential biomarker for predicting enhanced Tcell infiltration in non-small cell lung cancer.

Our previous bioinformatics analysis has revealed that Rab-interacting lysosomal protein-like 2 (RILPL2) is associated with tumor immune microenvironment in non-small cell lung cancer (NSCLC). In our study, we collected 140 patients with primary NSCLC to verify the RILPL2 expression and its prognostic value, the relationship between RILPL2 expression and CD4+, CD8+T cell infiltration. A total of 140 patients who had been diagnosed with primary NSCLC (including 66 lung adenocarcinomas and 74 lung squamous cell carcinomas) were enrolled in our study. Immunohistochemical (IHC) staining was performed to analyze the expression of RILPL2, CD4, and CD8 in these patients. Compared with peri-cancer tissues, the RILPL2 expression in NSCLC tissues was significantly lower (P < 0.0001). RILPL2 expression was significantly related to clinical stage (P = 0.019), and low RILPL2 expression indicated higher stage. Low RILPL2 expression predicted worse overall survival (OS) in NSCLC patients (P = 0.017). Correlational analyses revealed that RILPL2 expression was significantly positively correlated with CD4+T cell infiltration in NSCLC (R = 0.294, P < 0.001), LUAD subgroup (R = 0.256, P = 0.038), and LUSC subgroup (R = 0.333, P = 0.004); RILPL2 expression was also significantly positively correlated with CD8+ T cell infiltration in NSCLC (R = 0.263, P = 0.002), LUAD subgroup (R = 0.280, P = 0.023), and LUSC subgroup (R = 0.250, P = 0.031).In conclusion, RILPL2 expression was downregulated in NSCLC; low RILPL2 expression was significantly related to higher stage and worse prognosis; RILPL2 expression was significantly positively correlated with CD4+, CD8+T cell infiltration.

Evaluating predictors of kinase activity of STK11 variants identified in primary human non-small cell lung cancers.

Critical evaluation of computational tools for predicting variant effects is important considering their increased use in disease diagnosis and driving molecular discoveries. In the sixth edition of the Critical Assessment of Genome Interpretation (CAGI) challenge, a dataset of 28 STK11 rare variants (27 missense, 1 single amino acid deletion), identified in primary non-small cell lung cancer biopsies, was experimentally assayed to characterize computational methods from four participating teams and five publicly available tools. Predictors demonstrated a high level of performance on key evaluation metrics, measuring correlation with the assay outputs and separating loss-of-function (LoF) variants from wildtype-like (WT-like) variants. The best participant model, 3Cnet, performed competitively with well-known tools. Unique to this challenge was that the functional data was generated with both biological and technical replicates, thus allowing the assessors to realistically establish maximum predictive performance based on experimental variability. Three out of the five publicly available tools and 3Cnet approached the performance of the assay replicates in separating LoF variants from WT-like variants. Surprisingly, REVEL, an often-used model, achieved a comparable correlation with the real-valued assay output as that seen for the experimental replicates. Performing variant interpretation by combining the new functional evidence with computational and population data evidence led to 16 new variants receiving a clinically actionable classification of likely pathogenic (LP) or likely benign (LB). Overall, the STK11 challenge highlights the utility of variant effect predictors in biomedical sciences and provides encouraging results for driving research in the field of computational genome interpretation.

Preoperative respiratory assessment predicts post-operative survival in stage IA non-small cell lung cancer.

Respiratory impairment can lead to pulmonary complications after surgery; therefore, it should be considered when determining the choice of surgical procedure. Several studies have examined the relationship between preoperative respiratory function and postoperative mortality and morbidity after lung resection; however, there are no indicators for limited surgical procedure selection. The aim of this study was to examine the association between preoperative respiratory function and postoperative early and late complications, recurrence-free survival (RFS), and overall survival (OS) in patients undergoing pulmonary resection for stage I lung cancer. We performed a retrospective analysis of data from 192 patients undergoing pulmonary resection for primary pathological stage IA non-small cell lung cancer (NSCLC) at the Iwakuni Clinical Center in Japan between 2012 and 2015. We reviewed clinicopathological characteristics including preoperative pulmonary function and elucidated the relationship between them and postoperative survival. Obstructive ventilatory impairment was present in 55 patients (28.6%), and restrictive ventilatory impairment was present in 31 patients (16.1%). Seven patients (3.6%) had both ventilatory impairment. Obstructive ventilatory impairment did not affect the 5-year RFS (P=0.08) or OS (P=0.21). However, restrictive ventilatory impairment reduced the 5-year RFS (P=0.002) and OS (P=0.009). The rates of early and late complications were not significantly different based on the preoperative respiratory function. In patients with preoperative restrictive ventilatory impairment in whom lobectomy or segmentectomy cannot be performed, careful consideration is needed for surgical indications.