Primary Non-small Cell Lung Cancer Research Articles

Genetic profiles of oligometastatic non-small cell lung cancer and corresponding brain metastases.

In patients with oligometastatic non-small cell lung cancer, systemic therapy in combination with local ablative treatment of the primary tumor and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary non-small cell lung cancer and corresponding brain metastases. We retrospectively identified patients with oligometastatic non-small cell lung cancer and synchronous (<3 months) or metachronous (>3 months) brain metastases who underwent surgical resection of both primary tumor and brain metastases. Mutation profiling of formalin-fixed paraffin-embedded tumor cell blocks was performed by targeted next generation sequencing using the oncomine focus assay panel. Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumors (67.4%) and 40 brain metastases (86.9%). The alteration of the primary tumors was preserved in the corresponding brain metastases in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumors and brain metastases was a KRAS mutation (n = 21). In 16 patients (34.8%), the brain metastasis harbored additional oncogenic alterations. The presence of a private genetic alteration in the brain metastasis was an independent predictor of shorter overall survival. In oligometastatic non-small cell lung cancer, brain metastases retain the main genetic alterations of the primary tumors. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the brain metastases are dismal.

Prognostic and predictive value of interstitial lung abnormalities and EGFR mutation status in patients with non-small cell lung cancer

BackgroundTo determine the predictive value of interstitial lung abnormalities (ILA) for epidermal growth factor receptor (EGFR) mutation status and assess the prognostic significance of EGFR and ILA in patients with non-small cell lung cancer (NSCLC).MethodsWe reviewed 797 consecutive patients with a histologically proven diagnosis of primary NSCLC from January 2013 to October 2018. Of these, 109 patients with NSCLC were found to have concomitant ILA. Multivariate logistic regression analysis was used to identify the significant clinical and computed tomography (CT) findings in predicting EGFR mutations. Cox proportional hazard models were used to identify significant prognostic factors.ResultsEGFR mutations were identified in 22 of 109 tumors (20.2%). Multivariate analysis showed that the models incorporating clinical, tumor CT and ILA CT features yielded areas under the receiver operating characteristic curve (AUC) values of 0.749, 0.838, and 0.849, respectively. When combining the three models, the independent predictive factors for EGFR mutations were non-fibrotic ILA, female sex, and small tumor size, with an AUC value of 0.920 (95% confidence interval[CI]: 0.861–0.978, p < 0.001). In the multivariate Cox model, EGFR mutations (hazard ratio = 0.169, 95% CI = 0.042–0.675, p = 0.012; 692 days vs. 301 days) were independently associated with extended overall survival compared to the wild-type.ConclusionNon-fibrotic ILA independently predicts the presence of EGFR mutations, and the presence of EGFR mutations rather than non-fibrotic ILA serves as an independent good prognostic factor for patients with NSCLC.

Impact of perioperative high-protein nutritional support on postoperative outcomes in the treatment of primary lung cancer: Russian prospective multicenter comparative study (NUTRILUNC-study)

BACKGROUND: Up to 60% of lung cancer pts experience weight loss. Prevalence of sarcopenia in patients (pts) with non-small cell lung cancer (NSCLC) is about 43% and is an independent predictor of worse overall survival. It was shown that nutritional support improves outcomes in pts with cancer. AIM: To evaluate impact of perioperative nutritional support on surgical treatment outcomes of patients with NSCLC. MATERIALS AND METHODS: Patients with primary NSCLC (n=112, 69 males), aged 57,2±8,2, awaiting lung surgery and being at risk of malnutrition (Nutritional Risk Screening Assessment 2002 score ≥3) were randomized into 2 groups. Study group (n=55) received oral nutritional support (Nutridrink Compact Protein, Nutricia LLC), 250 ml/d (36 g of protein, 612 kcal) for 14 d before and 14 d after surgery in addition to standard diet. Control group (n=57) had a standard diet. The number of respiratory complications after surgery, length of hospitalization, anthropometric, functional, laboratory parameters, quality of life (according to Quality of Life Questionnaire Core-30) were assessed. Results were presented as mean ± standard deviation. Differences were considered significant at p ≤0.05. RESULTS: In the study group there were fewer respiratory complications (p 0.01), and a shorter length of hospitalization (p=0.03). Body weight in the study group did not change significantly, while in the control group it decreased (0.15±3.7 kg versus loss of 3.47±3.6 kg). Results of six-minute walk test and hand grip dynamometry were higher in the study group then in the control group (411.8±56.0 m versus 383.2±52.1 m; 33.5±8.4 kg versus 27.1±6.8 kg). Quality of life was better in the study group, p 0.05. The total protein and albumin levels were higher in the study group (70.9±5.6 g/l versus 63.1±4.0 g/l; 38.5±5.8 g/l versus 33.2±3.0 g/l). One patient in study group experienced 1st grade diarrhea. CONCLUSION: In patients with NSCLC at risk of malnutrition perioperative nutritional support with high protein oral nutritional support has a positive effect on surgical treatment outcomes.

Development of crizotinib-associated renal cyst in a non-small cell lung cancer patient with ALK fusion: a case report and review of the literature

BackgroundCrizotinib, an oral first-generation tyrosine kinase inhibitor (TKI), is superior to systemic chemotherapy for the treatment of non-small cell lung cancer (NSCLC) with positive rearrangement of anaplastic lymphoma kinase (ALK). However, an increased incidence of renal and hepatic cysts has been reported in the patients on crizotinib treatment.Case presentationHere, we describe a case of a 71-year-old Chinese women developed multiple cystic lesions in kidney and liver during crizotinib treatment for the primary and metastatic NSCLC. The renal and hepatic cysts were noted by CT scan 3 months after crizotinib treatment, which were spontaneously and significantly regressed after stopping crizotinib.ConclusionsBased on literature review and our experience in this case report, we concluded that crizotinib-associated renal cyst (CARCs) has features of malignancy and abscess in radiographic imaging, and thus, pathological confirmation is necessary to avoid inappropriate treatment decision. In addition, to benefit the patients with progress-free survival (PFS), switching from crizotinib to alectinib is recommended for the treatment of NSCLC patients who developed CARCs.

Cancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome.

Cancer-associated fibroblasts (CAFs) are a dominant cell type in the stroma of non-small cell lung cancer (NSCLC). Fibroblast heterogeneity reflects subpopulations of CAFs, which can influence prognosis and treatment efficacy. We describe the subtypes of CAFs in NSCLC. Primary human NSCLC resections were assessed by flow cytometry and multiplex immunofluorescence for markers of fibroblast activation which allowed identification of CAF subsets. Survival data were analysed for our NSCLC cohort consisting of 163 patients to understand prognostic significance of CAF subsets. We identified five CAF populations, termed CAF S1-S5. CAF-S5 represents a previously undescribed population, and express FAP and PDPN but lack the myofibroblast marker αSMA, whereas CAF-S1 populations express all three. CAF-S5 are spatially further from tumour regions then CAF-S1 and scRNA data demonstrate an inflammatory phenotype. The presence of CAF-S1 or CAF-S5 is correlated to worse survival outcome in NSCLC, despite curative resection, highlighting the prognostic importance of CAF subtypes in NSCLC. TCGA data suggest the predominance of CAF-S5 has a poor prognosis across several cancer types. This study describes the fibroblast heterogeneity in NSCLC and the prognostic importance of the novel CAF-S5 subset where its presence correlates to worse survival outcome.

Abstract 703: GABA(A) receptor activation drives GABARAP-Nix mediated autophagy to radiosensitize primary and metastatic lung adenocarcinoma tumors

Abstract In non-small cell lung cancer (NSCLC) treatment, targeted therapies help a subset of patients, and radiotherapy responses are not durable and toxicity limits therapy. Most advanced-stage NSCLC patients have brain metastases that render an abysmal prognosis. Standard-of-care radiation therapy for NSCLC brain metastasis includes stereotactic radiosurgery (SRS) if the number of lesions is less than ten, otherwise whole brain radiation therapy (WBRT) is administered. Challenges in applying radiotherapy include overcoming radiation resistance and reducing significant associated co-morbidities. Cancer neuroscience is an evolving area, and the purpose of this study is to determine if activation of GABA(A) receptors intrinsic to NSCLC cells can improve radiation efficacy in primary NSCLC and its brain metastasis. We find that a GABA(A) receptor activator, AM-101, impairs the viability and clonogenicity of NSCLC primary and brain metastatic 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 multimerization of GABA(A) Receptor-Associated Protein (GABARAP), stabilization of mitochondrial receptor Nix, utilization of ubiquitin-binding protein p62, and upregulation of Beclin-1. A high-affinity peptide disrupting Nix binding to GABARAP inhibits the cytotoxicity of AM-101. This supports a model of GABA(A) receptor activation driving a GABARAP-Nix multimerization axis that triggers autophagy. In NSCLC brain metastases patients, GABA(A) receptor activation may improve radiation efficacy and tumor control while allowing radiation dose de-intensification to reduce toxicity. Citation Format: Debanjan Bhattacharya, Riccardo Barrile, Donatien Kamdem Toukam, Vaibhavkumar S. Gawali, Laura Kallay, Taukir Ahmed, Hawley Brown, Sepideh Rezvanian, Aniruddha Karve, Pankaj B. Desai, Mario Medvedovic, Kyle Wang, Dan Ionascu, Nusrat Harun, Chenran Wang, Andrew M. Baschnagel, Joshua A. Kritzer, James Cook, Daniel A. Pomeranz Krummel, Soma Sengupta. GABA(A) receptor activation drives GABARAP-Nix mediated autophagy to radiosensitize primary and metastatic lung adenocarcinoma tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 703.

Abstract 6496: Assessment of tyrosine kinase inhibitor bypass mechanisms in lung cancer using single cell multiomics, patient derived organoids and rationally designed drug screens

Abstract Lung cancer (LC) is the leading cause of cancer-induced mortality, with 350 patients in the US dying from LC daily, the majority from non-small cell lung cancer (NSCLC). Molecular-targeted therapy such as tyrosine kinase inhibitors (TKI) are effective in first and subsequent lines of therapy against oncogenic drivers (KRAS, EGFR, or ALK fusions, others); however, nearly all treated patients progress eventually and run out of therapeutic options. Key reasons are the lack of predictive biomarkers and LC models that reflect the underlying heterogeneity and different phenotypic cell states among subclones within and between patients. Here, we developed a novel platform for refining the resolution of molecular interrogation to the single cell level, using single cell spatial multiomic (scSpMO), coupled with rational designed drug screens in patient-derived organoids (PDOs) from LC biopsies obtained upon progression. By deriving LC PDOs in epithelial and tumor microenvironment (TME) conditions to faithfully maintain the histological and genetic features of their respective LC tissues, we identified enrichment conditions for LC PDOs guided by tumor mutation variants and activated pathways. PDOs are maintained under the same treatment condition in the clinic (e.g., Lorlatinib) and drug testing is tailored to identify next lines of combined therapy. With six patients enrolled and others in ongoing studies, single cell PDOs (at &amp;gt;80% establishment rate) were used to determine key molecular bypass mechanism for resistance to TKI, including on-target variants, driver bypass, lineage plasticity and acquired resistance. Functional assays for acquired resistance such as PI3K/AKT signaling, Src kinase, BRAF fusion and MET hyperactivity allow the identification of potential novel combined lines of therapy for each patient through the compassionate care program and/or trial participation. Our platform when empowered with datasets of bulk, scRNA-seq and scSpMO signatures of primary human NSCLC, together with PDOs offer the ability to perform analysis of LC phenotypes such as lineage transformation in high-content assays, predict and/or act on resistance to therapy and provides a path for precision medicine-guided immediate impact on patient care. Citation Format: Liqiong Liu, Ann Strange, Schuyler Lee, Bifeng Gao, Daniel Merrick, Tejas Patil, James DeGregori, D Ross Camidge, Sharon R. Pine, Hatim E. Sabaawy. Assessment of tyrosine kinase inhibitor bypass mechanisms in lung cancer using single cell multiomics, patient derived organoids and rationally designed drug screens [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6496.

Abstract 6158: Tumor genomic heterogeneity in non-small cell lung cancer (NSCLC) patients from Latin America

Abstract Motivation: Life prospects of non-small cell lung cancer (NSCLC) patients have greatly improved over the last decades with the adoption of tumor genomic profiling. A better understanding of the mutational landscape has allowed for a more precise molecular characterization and the development of more effective treatment alternatives. However, tumors present a widespread heterogeneity, and many challenges remain to fully comprehend the influencing factors. Of particular importance is the Latin America population which i) is commonly underrepresented in clinical trials and large-scale epidemiological studies, ii) presents higher incidence and mortality rates in comparison to the developed world, and iii) is constituted by a genetically admixed population. Our research attempts to close this gap by investigating the interplay between sociodemographic, clinical, and lifestyle factors, and the effect these exert on the mutational profiles of Latin-American NSCLC patients. Methodology: The study population is derived from the NIRVANA study, a cross-sectional multicenter observational study aiming to characterize and validate molecular diagnostic technologies for NSCLC patients in Chile, Brazil, and Peru. Between July 2015 to October 2018, 5030 NSCLC patients were recruited from 37 centers, meeting inclusion criteria of age ≥18, histologically or cytological proven NSCLC diagnostic, and naïve treatment. Exclusion criteria included prior chemotherapy treatment and refusal to give informed consent. Primary or metastatic NSCLC samples were collected during standard of care biopsy and processed for the DNA and RNA isolation. Next Generation Sequencing (NSG) genomics profiles were obtained using the Oncomine Focus Assay (OFA). Covariates of interest, including sociodemographic, clinical, and lifestyle factors, were assessed at enrollment. QC-approved genomic profiles were obtained for 1864 participants. Results and Conclusions: The prevalence of mutations and fusions in the eight most relevant NSCLC genes (EGFR, KRAS, ALK, MET, RET, BRAF, ROS1 and ERBB2) varies based on sociodemographic, clinical and lifestyle characteristics. Clear distinctions emerged in the prevalence of EGFR, KRAS and ERBB2 mutations among the three countries (EGFR: 20.9%, 17.6%, 35.3%; KRAS: 21.8%, 15.6%, 10.3%; ERBB2: 2.8%, 3.3%, 4.4% for Brazil, Chile, and Peru, respectively). Furthermore, distinct association patterns were identified between the prevalence of genetic alterations and the studied factors, with attributes such as sex, tobacco use and ethnicity mostly influencing the occurrence of EGFR, ALK and ROS1 alterations. These findings provide novel insights into NSCLC studies among Latin-American patients, potentially serving as guidelines for more tailored strategies in the overall management of this underrepresented population. Citation Format: Javiera Garrido, Evelin González, Gonzalo Sepúlveda-Hermosilla, Matias Freire, Alejandro Blanco, Solange Rivas, Katherine Marcelain, Gareth I. Owen, Carolina Ibañez, Alejandro Corvalan, Marcelo Garrido, Rodrigo Assar, Rodrigo Lizana, Javier Cáceres-Molina, Diego Ampuero, Liliana Ramos, Paola Pérez, Osvaldo Aren, Sara Chernilo, Cristina Fernández, María Loreto Spencer, Jacqueline Flores, Giuliano Bernal, Mónica Ahumada, Germán Rasse, Carolina Sánchez, Maria Galli de Amorim, Gabriela Branco, Diana Noronha Nunes, Emmanuel Dias-Neto, Helano C. Freitas, NIRVANA team, Ricardo Armisén. Tumor genomic heterogeneity in non-small cell lung cancer (NSCLC) patients from Latin America [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6158.

Abstract 1419: Locoregional delivery with engineered stem cells modulates immunosuppressive tumor microenvironment in brain leptomeningeal metastasis

Abstract Leptomeningeal metastasis (LM) is one of the severe disease conditions in brain metastasis (BM) and results in poor prognosis and reduction of quality of life. Immunotherapies such as anti-Programmed cell Death (PD)-1 antibodies have shown improved overall survival against non-small cell lung cancer (NSCLC).. However, the clinical benefit of patients with NSCLC derived LM is still limited due to poor penetration of therapeutic agents into the brain and cerebrospinal fluid (CSF) and lack of understanding of the tumor microenvironment in LM. In this study, we first developed immune-competent mouse models of LM which show significantly decreased immune cells and increased PD-1+ T cells in the tumor microenvironment as compared to primary NSCLC tumors, thus mimicking primary and LM NSCL in patients. Next, we explored the use of oncolytic herpes simplex virus (oHSV) that selectively replicate in tumor cells and illicit an antitumor effect via oncolysis and production of neoantigens for targeting LM NSCLC. Given that virus neutralization, and inefficient extravasation are the major barriers to the effective systemic delivery of oHSV to target metastatic tumor lesions in the brain, we utilized mesenchymal stem cells (SC) and created two population of mesenchymal SC types: one for loading oncolytic herpes simplex virus (oHSV) and another one, engineered with knockout of Nectin-1 receptor by CRISPR/Cas9 technique to be resistant to oHSV, for secreting single-chain variable fragment (scFv) anti-PD-1. We show that locoregional treatment improved therapeutic outcomes by inducing oHSV-mediated immunogenic cell death, and activation of anti-tumor T cell signaling in mouse NSCLC LM tumors. Our novel SCs based immunotherapeutic strategy provides a roadmap towards treatment of lung to brain leptomeningeal metastatic patients. Citation Format: Nobuhiko Kanaya, Waleed Seddiq, Kok-Siong Chen, Yoshinori Kajiwara, Lucia Moreno Lama, Shinji Kuroda, Toshiyoshi Fujiwara, Hiroaki Wakimoto, Khalid Shah. Locoregional delivery with engineered stem cells modulates immunosuppressive tumor microenvironment in brain leptomeningeal metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1419.

Effects of mindful breathing training combined with diary-based rehabilitation guidance in lung cancer patients undergoing surgery: A randomized controlled trial

Background and purposeLung cancer surgery patients experience severe physical and mental symptoms, which seriously affect their quality of life and prognosis. Mindful breathing training is a promising strategy to improve their symptoms, but its effectiveness is affected by training compliance, and diary-based rehabilitation instruction has been shown to help improve training compliance. Therefore, the aim of this study was to evaluate the effects of mindful breathing training combined with diary-based rehabilitation guidance on improving perioperative outcomes in lung cancer surgery patients. Materials and methodsThis single-center, assessor-blinded, prospective, three-arm randomized controlled trial was conducted from November 1, 2021 to November 1, 2022. Patients diagnosed with primary non-small cell lung cancer and scheduled for thoracoscopic surgery were randomly allocated to the combined intervention group, the mindful breathing group or the control group, with 34 patients in each group. The control group received routine care, while the mindful breathing group received mindful breathing training and routine care. The combined intervention group received both mindful breathing training and diary-based rehabilitation guidance, along with routine care. ResultsThe per-protocol analysis revealed that patients in the mindful breathing group experienced statistically significant improvements in dyspnea, fatigue and anxiety. Patients in the combined intervention group had statistically significant improvements in dyspnea, fatigue, anxiety, depression, exercise self-efficacy and training compliance. ConclusionThis study provides evidence that mindful breathing training combined with diary-based rehabilitation guidance can be effective in improving perioperative outcomes in lung cancer patients. It can be applied in clinical practice in the future.

Improved Prediction of Epidermal Growth Factor Receptor Status by Combined Radiomics of Primary Nonsmall-Cell Lung Cancer and Distant Metastasis.

This study aimed to investigate radiomics based on primary nonsmall-cell lung cancer (NSCLC) and distant metastases to predict epidermal growth factor receptor (EGFR) mutation status. A total of 290 patients (mean age, 58.21 ± 9.28) diagnosed with brain (BM, n = 150) or spinal bone metastasis (SM, n = 140) from primary NSCLC were enrolled as a primary cohort. An external validation cohort, consisting of 69 patients (mean age, 59.87 ± 7.23; BM, n = 36; SM, n = 33), was enrolled from another center. Thoracic computed tomography-based features were extracted from the primary tumor and peritumoral area and selected using the least absolute shrinkage and selection operator regression to build a radiomic signature (RS-primary). Contrast-enhanced magnetic resonance imaging-based features were calculated and selected from the BM and SM to build RS-BM and RS-SM, respectively. The RS-BM-Com and RS-SM-Com were developed by integrating the most important features from the primary tumor, BM, and SM. Six computed tomography-based features showed high association with EGFR mutation status: 3 from intratumoral and 3 from peritumoral areas. By combination of features from primary tumor and metastases, the developed RS-BM-Com and RS-SM-Com performed well with areas under curve in the training (RS-BM-Com vs RS-BM, 0.936 vs 0.885, P = 0.177; RS-SM-Com vs RS-SM, 0.929 vs 0.843, P = 0.003), internal validation (RS-BM-Com vs RS-BM, 0.920 vs 0.858, P = 0.492; RS-SM-Com vs RS-SM, 0.896 vs 0.859, P = 0.379), and external validation (RS-BM-Com vs RS-BM, 0.882 vs 0.805, P = 0.263; RS-SM-Com vs RS-SM, 0.865 vs 0.816, P = 0.312) cohorts. This study indicates that the accuracy of detecting EGFR mutations significantly enhanced in the presence of metastases in primary NSCLC. The established radiomic signatures from this approach may be useful as new predictors for patients with distant metastases.

Risk Factors Analysis of AKI in Patients with Primary Non-small Cell Lung Cancer Treated with PD-1/PD-L1 Inhibitor.

To investigate the risk factors of Programmed Cell Death Protein 1 (PD-1), Programmed Cell Death Ligand 1(PD-L1) inhibitor associated acute kidney injury (AKI) in patients with primary non-small cell lung cancer (NSCLC) and construct a predictive model. 120 NSCLC patients were selected as the research subjects and their clinical data were collected. Patients were divided into AKI and Non-AKI (N-AKI) group based on the development of AKI. Exploring the risk factors of PD-1P/D-L1 inhibitor related AKI in NSCLC patients using multivariate logistic regression analysis and visualized the logistic regression analysis to obtain a nomogram model. Meanwhile, evaluate the predictive value of the model. The results of multivariate analysis showed that the presence of extrarenal immune related adverse reactions (irAEs) is a risk factor for PD-1/PD-L1 inhibitor related AKI in NSCLC patients; At the same time, the risk of developing PD-1/PD-L1 inhibitor related AKI in NSCLC patients increases with increasing serum creatinine (SCr) and C-reactive protein (CRP) levels, decreasing baseline estimated glomerular filtration rate (eGFR) levels (P < .05). The analysis results of receiver operator characteristic curve (ROC), calibration curve, and decision curve show that the model has good discrimination and accuracy, and can achieve a high clinical benefit rate. Primary NSCLC patients with extrarenal irAEs, high levels of SCr and CRP, and low levels of eGFR have a higher risk of AKI after PD-1/PD-L1 inhibitor treatment. Establishing a predictive model with high accuracy is more conducive to early detection of high-risk patients. DOI: 10.52547/ijkd.7964.

Factors affecting accuracy of clinical staging in resectable non-small cell lung cancer in a real-world study.

The clinical staging of non-small cell lung cancer (NSCLC) is well known to be related to their prognosis. However, there is usually a discrepancy between clinical staging and pathological staging. There are few analyses of clinical staging accuracy in patients with NSCLC. We compared the concordance rate between clinical and pathological staging of NSCLC and evaluated factors affecting the accuracy in real-world data. Altogether, 811 patients with primary NSCLC who had undergone curative lung resection surgery in Severance Hospital from January 2019 to December 2020 were retrospectively reviewed. We used the eighth edition of the American Joint Committee on Cancer TNM staging. Among 811 patients, endobronchial ultrasound (EBUS) and positron emission tomography (PET-CT) were performed in 31.6% and 96.7%, respectively. The concordance rates between clinical and pathological TNM staging, T factor, and N factor, were 68.7%, 77.7%, and 85.8%, respectively. With multivariable logistic regression analysis, current smokers (OR 0.49; 95% CI: 0.32-0.76, p = 0.001) and a higher clinical stage (p < 0.001) contributed to the clinical staging inaccuracy. Additionally, the presence of a bronchoscopy specialist was significantly associated with clinical staging accuracy (OR 1.53; 95% CI: 1.10-2.13, p = 0.011). Clinical staging accuracy in NSCLC improved compared to before the widespread use of PET-CT and EBUS in clinical staging work-up. Smoking history and absence of expert bronchoscopy specialists showed a meaningful correlation with the inaccuracy of clinical staging. Thus, training more bronchoscopy experts would improve the staging accuracy of NSCLC, which could positively affect the prognosis of NSCLC.

Disparities in Stage at Presentation Among Hispanic and Latinx Patients With Non-Small-Cell Lung Cancer in the United States.

Hispanic and Latinx people in the United States are the fastest-growing ethnic group. However, previous studies in non-small-cell lung cancer (NSCLC) often analyze these diverse communities in aggregate. We aimed to identify differences in NSCLC stage at diagnosis in the US population, focusing on disaggregated Hispanic/Latinx individuals. Data from the National Cancer Database from 2004 to 2018 identified patients with primary NSCLC. Individuals were disaggregated by racial and ethnic subgroup and Hispanic country of origin. Ordinal logistic regression adjusting for age, facility type, income, educational attainment, comorbidity index, insurance, and year of diagnosis was used to create adjusted odds ratios (aORs), with higher odds representing diagnosis at later-stage NSCLC. Of 1,565,159 patients with NSCLC, 46,616 were Hispanic/Latinx (3.0%). When analyzed in the setting of race and ethnicity, Hispanic patients were more likely to be diagnosed with metastatic disease compared with non-Hispanic White (NHW) patients: 47.0% for Hispanic Black, 46.0% Hispanic White, and 44.3% of Hispanic other patients versus 39.1% of non-Hispanic White patients (P < .001 for all). By country of origin, 51.4% of Mexican, 41.7% of Puerto Rican, 44.6% of Cuban, 50.8% of South or Central American, 48.4% of Dominican, and 45.6% of other Hispanic patients were diagnosed with metastatic disease, compared with 39.1% of NHWs. Conversely, 20.2% of Mexican, 26.9% of Puerto Rican, 24.2% of Cuban, 22.5% of South or Central American, 23.7% of Dominican, and 24.5% of other Hispanic patients were diagnosed with stage I disease, compared with 30.0% of NHWs. All Hispanic groups were more likely to present with later-stage NSCLC than NHW patients (greatest odds for Mexican patients, aOR, 1.44; P < .001). Hispanic/Latinx patients with non-small-cell lung cancer were more likely to be diagnosed with advanced disease compared with NHWs. Disparities persisted upon disaggregation by both race and country of origin, with over half of Mexican patients with metastatic disease at diagnosis. Disparities among Hispanic/Latinx groups by race and by country of origin highlight the shortcomings of treating these groups as a monolith and underscore the need for disaggregated research and targeted interventions.

Effectiveness of Roy Adaptation Model-Based Cognitive Stimulation Therapy in Elderly Patients with Non-Small Cell Lung Cancer Undergoing Curative Resection.

This study aimed to investigate the effects of a Roy adaptation model (RAM)-based cognitive stimulation therapy (CST) intervention on elderly patients diagnosed with primary non-small cell lung cancer (NSCLC) undergoing curative resection. A total of 280 patients diagnosed with primary NSCLC were randomized into RAM-based CST group and control group. Outcomes were assessed at three intervals: pre-surgery, discharge, and one-month post-discharge. Cognitive function was evaluated using Mini-Cognitive test. Postoperative delirium prevalence was determined within 48 hours post-surgery using Nursing Delirium Screening Scale. The Hospital Anxiety and Depression Scale evaluated anxiety and depression symptoms, while Quality of Life (QoL) was assessed via Short Form-36 (SF36) Health Survey. The RAM-based CST group demonstrated significantly higher Mini-Cog test scores than the control group upon discharge and post-intervention. Patients with RAM-based CST exhibited a decrease in postoperative delirium compared to the control group. The RAM-based CST intervention yielded an improvement in anxiety and depression at discharge and 1-month post-discharge compared to preoperative levels. Additionally, the RAM-based CST group exhibited substantial enhancements in SF36 subcategory scores at 1-month post-discharge compared to pre-surgery. At post-intervention, the RAM-based CST group demonstrated significantly higher scores than the control group across various health-related domains, including role limitations due to emotional problems, mental health, general health perception, bodily pain, and role limitations due to physical problems. The RAM-based CST intervention in elderly NSCLC patients undergoing curative resection yielded significant enhancements in cognitive function, reduced delirium incidence, improved emotional well-being, and better QoL postoperatively.

Sublobar resection for metachronous stage I second primary non-small cell lung cancer: A single-centre experience.

More patients are developing second primary lung cancer (SPLC). This study aimed to evaluate the impact of the extent of SPLC resection on outcomes. We retrospectively investigated 1,895 patients with lung cancer who underwent pulmonary resection from 2011 to 2018. SPLC was diagnosed using the criteria of Martini and Melamed. Patients with pathological stage I SPLC who underwent lobectomy for first primary lung cancer (FPLC) were included in the study. Outcomes and clinical factors that could affect survival were evaluated. Fifty-four patients were eligible for the study. Lobectomy, segmentectomy, or wedge resection was performed for 10, 32, and 12 patients, respectively. Neither overall nor relapse-free survival was significantly different based on the extent of resection for stage I SPLC. Multivariate analysis revealed that interval between FPLC and SPLC of less than 5 years was an independent risk factors for worse relapse-free survival after SPLC resection (interval: hazard ratio, 0.28; P = 0.048). The median interval from prior resection to secondary resection was 68 months. Sublobar resection might be a realistic option for stage I SPLC. To realize early detection of SPLC that can undergo radical sublobar resection, the surveillance period after prior resection of FPLC is worth reconsidering.

Study on prognostic index for survival m-LCPI in patients with primary non-small cell lung cancer

Background: Lung cancer is a common cancer with a high mortality rate. The identification of prognostic factors in lung cancer patients in Vietnam is still limited and inconsistent in clinical practice. Objectives: To describe the clinical, paraclinical characteristics and m-LCPI index in patients with primary non-small cell lung cancer and evaluate the factors affecting overall survival in patients with primary non-small cell lung cancer. Methods: Prospective study of 210 cases of non-small cell lung cancer diagnosed with primary non-small cell lung cancer at the Oncology Department of Hue University of Medicine and Pharmacy Hospital and Hue Central Hospital from February 2020 to February 2023. Results: The majority of hospitalizations were at late stages, from stage IIIA (89%), group 3 and 4 in m-LCPI grading scale constituted the majority (80%). Average overall survival at 3 years was 20.0 ± 14 months, and gradually decreased to 54.8%, 40%, and 38.6% after 1 year, 2 years and 3 years, respectively. Regression analysis of COX model between m-LCPI and OS showed statistical significance with m-LCPI 4 (HR = 3.9, 95%CI = 1.57 - 9.69, p = 0.003), while m-LCPI 3 (HR = 2.44, 95% CI 0.97 - 6.13), p = 0.058) had a weak correlation. Conclusion: Our study shows that 38.6% of patients were still alive after 3 years of diagnosis. m-LCPI index is a good predictor of the patients’ overall survival. Key words: non-small cell lung cancer, overall survival, prognostic index, mLCPI.

Abstract LB_A04: Quantitative digital spatial protein profiling of non-small cell lung cancer brain metastasis

Abstract Metastatic brain tumor is the most common form of adult central nervous system (CNS) tumor, and the majority of the cerebral metastasis originate from lung cancer. Along with recent combination strategies applying immune checkpoint inhibitor, evaluating tumor microenvironment of the brain metastasis (BM) needs to be unveiled. In this study, we tried to disclose immune context information of BM of non-small cell lung cancer (NSCLC) by using highly multiplex NanoString digital spatial profiling (DSP) method. Seven cases of NSCLC and metastatic brain tumor were evaluated. To detect proteins at quantitative and high multiplex with spatial resolution, NanoString optical barcoding technology was used to digitally profile protein expression in FFPE samples. Immuno-oncology protein targets, including immune cell markers and checkpoint proteins are included. DSP identified differentially expressed proteins between primary NSCLC and BM. Proteins associated with immune regulation, evasion, and adaptive immunity, such as IDO-1, PD1, PDL1, STAT3, PTEN, and CD44 revealed decreased expression in patients with BM (P&amp;lt;0.01). The expression of pS6 was significantly increased in BM (P&amp;lt;0.01), which is associated with activation induced T-cell death. This study demonstrated differentially expressed proteins in BM associated with immune regulation and evasion via NanoString DSP platform. This study highlighted the localized expression of immune-related proteins of BM in patients with NSCLC. Moreover, our results presented the possibility of using digitally quantified and spatially allocated novel method in BM eliminating the subjectivity and variability associated with the immunohistochemistry techniques. Citation Format: Tae Jung Kim. Quantitative digital spatial protein profiling of non-small cell lung cancer brain metastasis [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_A04.

Effect of examining lymph nodes count on mortality risk in resected T1 non-small-cell lung cancer.

This study aims to estimate the effect of the examined lymph node count (ELNC) on the cancer-related mortality risk and non-cancer-related mortality risk in patients with resected T1 non-small-cell lung cancer (NSCLC). Patients diagnosed as primary T1 NSCLC between 2000 and 2017 were extracted from the Surveillance, Epidemiology and End Results database. Patients were divided into 2 groups according to the ELNC cutoff value, which was calculated based on overall survival outcomes. Propensity score matching was used to equalize the differences in baseline characteristics between groups. A total of 38242 resected T1 NSCLC patients were extracted from the database with the ELNC cutoff value of 8. After propensity score matching, 27676 patients were included in this study. Examining ≥8 ELNC was associated with a more accurate assessment of lymph node (LN) metastasis and significantly improving the prognosis. These trends remained consistent in subgroup analysis by histology type. In competing risk mode, examining ≥8 LNs could significantly reduce the risk of death from lung cancer, risk of death from chronic obstructive pulmonary disease, and risk of death from cardiac diseases. In the subgroup analysis, these trends were consistent. Given the mortality risk associated with lung cancer, chronic obstructive pulmonary disease, and cardiac diseases, at least 8 LNs should be examined in surgery for T1 NSCLC.

Effects of lung resection on heart structure and function: A tissue Doppler ultrasound survey of 43cases.

Changes in heart structure and function after lung resection in patients with lung cancer are challenging to manage. Therefore, a non-invasive and reliable measurement tool to gauge such changes is critical. The purpose of the present study was to compare cardiological changes before and after lung resection using tissue Doppler imaging (TDI). A total of 43 patients (19 men and 24 women) with primary non-small cell lung cancer (n=37) and metastatic cancer in the lungs (n=6) were enrolled in the study.nTDI was used to determine the thickness of the ascending aorta, the open size of the ascending valve, the anterior-oposterior diameters of the left atrium and left ventricle, and the thickness of the ventricular septum and right ventricle before and after lung resection. Left ventricular (LV) ejection fraction (EF), pulmonary valve flow rate, tricuspid annular or mitral leaflet tip early (E) peak/late (A) diastolic blood flow velocities, tricuspid regurgitation flow, the lateral mitral annulus early (e') diastolic velocity and mitral E/e' ratio were used to determine LV filling pressure. Results revealed no significant differences between male and female patients in terms of the open size of the ascending valve, the anterior-posterior diameter of the left ventricle and the mitral E/e' ratio. Significant differences were found in the width of the ascending aorta, anterior-posterior diameter of the left atrium, width of the LV septum and right ventricular (RV) diameter before and after lung resection. Finally, there were significantchanges in EF and tricuspid pressure. The results indicated that TDI was useful as a non-invasive method for assessing left and right heart function following lung resection. The LV and RV dimensions were affected, but LV filling pressure was preserved after lobectomy.