Non-metastatic Non-small Cell Lung Cancer Research Articles

Non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) is one of the most frequent cancer types and is responsible for the majority of cancer-related deaths worldwide. The management of NSCLC has improved considerably, especially in the past 10 years. The systematic screening of populations at risk with low-dose CT, the implementation of novel surgical and radiotherapeutic techniques and a deeper biological understanding of NSCLC that has led to innovative systemic treatment options have improved the prognosis of patients with NSCLC. In non-metastatic NSCLC, the combination of various perioperative strategies and adjuvant immunotherapy in locally advanced disease seem to enhance cure rates. In metastatic NSCLC, the implementation of novel drugs might prolong disease control together with preserving quality of life. The further development of predictive clinical and genetic markers will be essential for the next steps in individualized treatment concepts.

The diagnostic value of serum exosomal SNORD116 and SNORA21 for NSCLC patients.

Non-small cell lung cancer (NSCLC) is a widespread and serious global malignancy. This study aimed to examine the clinical relevance of serum exosomal SNORD116 and SNORA21 as novel diagnostic biomarkers for NSCLC. Serum exosomes from 226 healthy controls and 305 NSCLC patients were isolated by ultracentrifugation. Characterization of exosomes was conducted by qNano, transmission electron microscopy (TEM) and Western immunoblotting. RT-PCR revealed snoRNAs that were differentially expressed. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance. In NSCLC patients, the levels of serum exosomal SNORD116 and SNORA21 were significantly reduced compared to those in healthy controls (P < 0.0001 for both). ROC curves showed AUC values of 0.738 and 0.761. By combining SNORD116 and SNORA21 with traditional blood biomarkers CYFRA21-1 and carcinoembryonic antigen (CEA), the AUC increased to 0.917. Moreover, these two exosomal snoRNAs distinguished between patients with metastatic NSCLC (n = 132) and those with non-metastatic NSCLC (n = 173) significantly (P < 0.0001 for both). The ROC curves gave AUC values of 0.743 and 0.694, respectively. The combined analysis raised the AUC to 0.751. The diagnostic power of these two exosomal snoRNAs combined with CYFRA21-1 and CEA increased to 0.784. This study demonstrated that serum exosomal SNORD116 and SNORA21 can be used as potential promising non-invasive diagnostic biomarkers for NSCLC.

Targeting AKR1B10 by Drug Repurposing with Epalrestat Overcomes Chemoresistance in Non-Small Cell Lung Cancer Patient-Derived Tumor Organoids.

Systemic treatments given to patients with non-small cell lung cancer (NSCLC) are often ineffective due to drug resistance. In the present study, we investigated patient-derived tumor organoids (PDTO) and matched tumor tissues from surgically treated patients with NSCLC to identify drug repurposing targets to overcome resistance toward standard-of-care platinum-based doublet chemotherapy. PDTOs were established from 10 prospectively enrolled patients with non-metastatic NSCLC from resected tumors. PDTOs were compared with matched tumor tissues by histopathology/immunohistochemistry, whole exome sequencing, and transcriptome sequencing. PDTO growths and drug responses were determined by measuring 3D tumoroid volumes, cell viability, and proliferation/apoptosis. Differential gene expression analysis identified drug-repurposing targets. Validations were performed with internal/external data sets of patients with NSCLC. NSCLC cell lines were used for aldo-keto reductase 1B10 (AKR1B10) knockdown studies and xenograft models to determine the intratumoral bioavailability of epalrestat. PDTOs retained histomorphology and pathological biomarker expression, mutational/transcriptomic signatures, and cellular heterogeneity of the matched tumor tissues. Five (50%) PDTOs were chemoresistant toward carboplatin/paclitaxel. Chemoresistant PDTOs and matched tumor tissues demonstrated overexpression of AKR1B10. Epalrestat, an orally available AKR1B10 inhibitor in clinical use for diabetic polyneuropathy, was repurposed to overcome chemoresistance of PDTOs. In vivo efficacy of epalrestat to overcome drug resistance corresponded to intratumoral epalrestat levels. PDTOs are efficient preclinical models recapitulating the tumor characteristics and are suitable for drug testing. AKR1B10 can be targeted by repurposing epalrestat to overcome chemoresistance in NSCLC. Epalrestat has the potential to advance to clinical trials in patients with drug-resistant NSCLC due to favorable toxicity, pharmacological profile, and bioavailability.

PPD01.09 Cardiac Events following Concurrent Chemotherapy and Radiation with Durvalumab Consolidation for Unresectable Non-metastatic Non-Small Cell Lung Cancer

PPD01.09 Cardiac Events following Concurrent Chemotherapy and Radiation with Durvalumab Consolidation for Unresectable Non-metastatic Non-Small Cell Lung Cancer

Algorithms to identify radiotherapy intent in unresected non-metastatic non-small-cell lung cancer: an I-O Optimise analysis.

This study aimed to develop and evaluate the performance of algorithms for identifying radiotherapy (RT) treatment intent in real-world data from patients with non-metastatic non-small-cell lung cancer (NSCLC). Using data from IPO-Porto hospital (Portugal) and the REAL-Oncology database (England), three algorithms were developed based on available RT information (#1: RT duration, #2: RT duration and type, #3: RT dose) and tested versus reference datasets. Study results showed that all three algorithms had good overall accuracy (91-100%) for patients receiving RT plus systemic anticancer therapy (SACT) and algorithms #2 and #3 also had good accuracy (>99%) for patients receiving RT alone. These algorithms could help classify treatment intent in patients with NSCLC receiving RT with or without SACT in real-world settings where intent information is missing/incomplete.

RWD89 Healthcare Resource Utilization and Health-Related Quality of Life in Patients With Resectable Non-Metastatic Non-Small Cell Lung Cancer Treated With Neoadjuvant Chemotherapy in China: A Real-World Survey

RWD89 Healthcare Resource Utilization and Health-Related Quality of Life in Patients With Resectable Non-Metastatic Non-Small Cell Lung Cancer Treated With Neoadjuvant Chemotherapy in China: A Real-World Survey

Predictive factors for cardiac events following concurrent chemotherapy and radiation with durvalumab consolidation for unresectable non-metastatic non-small cell lung cancer.

Predictive factors for cardiac events following concurrent chemotherapy and radiation with durvalumab consolidation for unresectable non-metastatic non-small cell lung cancer.

Preoperative CT-based radiomic prognostic index to predict the benefit of postoperative radiotherapy in patients with non-small cell lung cancer: a multicenter study

BackgroundThe value of postoperative radiotherapy (PORT) for patients with non-small cell lung cancer (NSCLC) remains controversial. A subset of patients may benefit from PORT. We aimed to identify patients with NSCLC who could benefit from PORT.MethodsPatients from cohorts 1 and 2 with pathological Tany N2 M0 NSCLC were included, as well as patients with non-metastatic NSCLC from cohorts 3 to 6. The radiomic prognostic index (RPI) was developed using radiomic texture features extracted from the primary lung nodule in preoperative chest CT scans in cohort 1 and validated in other cohorts. We employed a least absolute shrinkage and selection operator-Cox regularisation model for data dimension reduction, feature selection, and the construction of the RPI. We created a lymph-radiomic prognostic index (LRPI) by combining RPI and positive lymph node number (PLN). We compared the outcomes of patients who received PORT against those who did not in the subgroups determined by the LRPI.ResultsIn total, 228, 1003, 144, 422, 19, and 21 patients were eligible in cohorts 1–6. RPI predicted overall survival (OS) in all six cohorts: cohort 1 (HR = 2.31, 95% CI: 1.18–4.52), cohort 2 (HR = 1.64, 95% CI: 1.26–2.14), cohort 3 (HR = 2.53, 95% CI: 1.45–4.3), cohort 4 (HR = 1.24, 95% CI: 1.01–1.52), cohort 5 (HR = 2.56, 95% CI: 0.73–9.02), cohort 6 (HR = 2.30, 95% CI: 0.53–10.03). LRPI predicted OS (C-index: 0.68, 95% CI: 0.60–0.75) better than the pT stage (C-index: 0.57, 95% CI: 0.50–0.63), pT + PLN (C-index: 0.58, 95% CI: 0.46–0.70), and RPI (C-index: 0.65, 95% CI: 0.54–0.75). The LRPI was used to categorize individuals into three risk groups; patients in the moderate-risk group benefited from PORT (HR = 0.60, 95% CI: 0.40–0.91; p = 0.02), while patients in the low-risk and high-risk groups did not.ConclusionsWe developed preoperative CT-based radiomic and lymph-radiomic prognostic indexes capable of predicting OS and the benefits of PORT for patients with NSCLC.

LKB1 Loss Correlates with STING Loss and, in Cooperation with β-Catenin Membranous Loss, Indicates Poor Prognosis in Patients with Operable Non-Small Cell Lung Cancer.

To investigate the incidence and prognostically significant correlations and cooperations of LKB1 loss of expression in non-small cell lung cancer (NSCLC), surgical specimens from 188 metastatic and 60 non-metastatic operable stage I-IIIA NSCLC patients were analyzed to evaluate their expression of LKB1 and pAMPK proteins in relation to various processes. The investigated factors included antitumor immunity response regulators STING and PD-L1; pro-angiogenic, EMT and cell cycle targets, as well as metastasis-related (VEGFC, PDGFRα, PDGFRβ, p53, p16, Cyclin D1, ZEB1, CD24) targets; and cell adhesion (β-catenin) molecules. The protein expression levels were evaluated via immunohistochemistry; the RNA levels of LKB1 and NEDD9 were evaluated via PCR, while KRAS exon 2 and BRAFV600E mutations were evaluated by Sanger sequencing. Overall, loss of LKB1 protein expression was observed in 21% (51/248) patients and correlated significantly with histotype (p < 0.001), KRAS mutations (p < 0.001), KC status (concomitant KRAS mutation and p16 downregulation) (p < 0.001), STING loss (p < 0.001), and high CD24 expression (p < 0.001). STING loss also correlated significantly with loss of LKB1 expression in the metastatic setting both overall (p = 0.014) and in lung adenocarcinomas (LUACs) (p = 0.005). Additionally, LKB1 loss correlated significantly with a lack of or low β-catenin membranous expression exclusively in LUACs, both independently of the metastatic status (p = 0.019) and in the metastatic setting (p = 0.007). Patients with tumors yielding LKB1 loss and concomitant nonexistent or low β-catenin membrane expression experienced significantly inferior median overall survival of 20.50 vs. 52.99 months; p < 0.001 as well as significantly greater risk of death (HR: 3.32, 95% c.i.: 1.71-6.43; p <0.001). Our findings underscore the impact of the synergy of LKB1 with STING and β-catenin in NSCLC, in prognosis.

Real-World Treatment Patterns and Survival Outcomes for Patients with Non-Metastatic Non-Small-Cell Lung Cancer in Sweden: A Nationwide Registry Analysis from the I-O Optimise Initiative.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, with ~40-50% of patients diagnosed with non-metastatic disease (stages IA-IIIC). The treatment landscape is evolving rapidly as immunotherapies and targeted therapy are introduced in the non-metastatic setting, creating a need to assess patient outcomes prior to their introduction. This real-world study using Swedish National Lung Cancer Registry data examined outcomes (overall survival (OS) and time to next treatment or death (TTNTD)) and treatment patterns for adults diagnosed with non-metastatic NSCLC. Baseline characteristics and OS from diagnosis were described for all patients; OS, treatment patterns, and TTNTD from treatment start were described for the treatment subgroup (patients diagnosed from 2014 onwards), stratified by disease stage and initial treatment. OS and TTNTD were described using the Kaplan-Meier estimator. The overall population (2008-2019) included 17,433 patients; the treatment subgroup included 5147 patients. Median OS (interquartile range) overall ranged from 83.3 (31.6-165.3) months (stage I patients) to 10.4 (4.3-24.2) months (stage IIIB patients). Among the treatment subgroup, median OS and TTNTD were longest among patients receiving surgery versus other anticancer treatments. These findings provide a baseline upon which to evaluate the epidemiology of non-metastatic NSCLC as newer treatments are introduced.

Clinical Perspectives on the Evolution of Non-small Cell Lung Cancer Treatment With Immuno-oncology and ROS1 Tyrosine Kinase Inhibitors

The non-small cell lung cancer (NSCLC) treatment landscape has rapidly evolved over the last two decades. The addition of immuno-oncology (I-O) and targeted agents has improved treatment options for patients with non-metastatic and metastatic NSCLC; however, there remains significant unmet need. In this symposium, Jürgen Wolf, University Hospital Cologne, Germany; Tina Cascone, MD Anderson Cancer Center, Houston, Texas, USA; and Jose Luis Campo-Cañaveral de la Cruz, Puerta de Hierro Majadahonda University Hospital, Madrid, Spain, discussed the increasingly complex NSCLC treatment landscape, and how the latest data may impact treatment selection. This symposium focused on I-O monotherapy and I-O combinations in treatment-naïve metastatic NSCLC, as well as the application of I-O in non-metastatic or resectable NSCLC in the neoadjuvant, peri-operative, and adjuvant settings. In addition, the latest data regarding treatment options for patients with targetable alterations, such as ROS1, were discussed, with a focus on next generation tyrosine kinase inhibitors (TKI), and how these may impact treatment selection in the future. The role of the surgeon as part of the multidisciplinary team was also discussed, with particular attention to assessment and definition of surgical complexity, as well as the importance of close collaboration and communication between the multidisciplinary team (MDT) and the patient, to ensure they are receiving the optimal treatment at the right time to improve outcomes.

EP08.02-04 Real-World Disease-Free Survival (DFS) in Non-metastatic Non-small Cell Lung Cancer (NSCLC): A German I-O Optimise Analysis

EP08.02-04 Real-World Disease-Free Survival (DFS) in Non-metastatic Non-small Cell Lung Cancer (NSCLC): A German I-O Optimise Analysis

P1.25-05 Real-World Outcomes in Non-metastatic Non-small Cell Lung Cancer (NSCLC): An I-O Optimise Multi-Country Analysis

P1.25-05 Real-World Outcomes in Non-metastatic Non-small Cell Lung Cancer (NSCLC): An I-O Optimise Multi-Country Analysis

Real-world treatment patterns and survival outcomes for patients with stage III non-small cell lung cancer in Spain: a nationwide cohort study.

The burden of non-small cell lung cancer (NSCLC) remains high in Spain, with lung cancer accounting for 20% of cancer-related deaths annually. Programs such as the Spanish Thoracic Tumour Registry (TTR) and the global I-O Optimise initiative have been developed to observe patients in clinical practice with the aim of improving outcomes. This analysis examined treatment patterns and survival in patients with stage III NSCLC from the TTR. These patients represent a heterogenous group with complex treatment pathways. The TTR is an ongoing, observational, prospective, and retrospective cohort multicentre study (NCT02941458) that follows patients with thoracic cancer in Spain. Adults aged ≥18 years with stage IIIA/IIIB NSCLC enrolled in the TTR between 01 Jan 2010 and 31 Oct 2019 were included in this analysis. Initial treatment received was described by cancer stage and histology (squamous and non-squamous NSCLC). Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were calculated over a 5-year period. A total of 1,838 patients were included in the cohort, including 1,082 with stage IIIA (58.9%) and 756 with stage IIIB (41.1%). Median follow-up was 18.3 months. The median age of patients was 66 years, and most had non-squamous NSCLC (54.0%), were male (81.2%), and were active or former smokers (93.4%). Overall, 26.3% of patients received surgical resection (37.0% for stage IIIA and 11.1% for stage IIIB). The most frequent initial treatment received was concurrent chemoradiotherapy for stage IIIA (30.2%) and stage IIIB (37.0%) patients. Median OS was lower in patients with stage IIIB than stage IIIA (28 vs. 37 months) disease and was lower for patients with squamous than non-squamous histology (19 vs. 26 months). Median PFS and OS varied when patients were stratified by initial treatment. This TTR analysis describes the clinical reality surrounding the initial management and survival outcomes for stage III NSCLC in Spain and presents survival outcomes comparable with other real-world evidence. It provides insights into the diverse approaches used before the availability of immunotherapies and targeted treatments in the non-metastatic NSCLC setting.

Impact of pathological nodal staging and tumour differentiation on survival and postoperative radiotherapy in completely resected stage IIIA Non-small-cell lung cancer

BackgroundTumour differentiation is an important index for adjuvant therapy in many cancers; however, non-small cell lung cancer (NSCLC) is an exception. Furthermore, postoperative radiotherapy (PORT) is controversial in patients with NSCLC with N0-1 and N2 disease. We aimed to evaluate the impact of tumour-related factors on overall survival (OS), cancer-specific survival (CSS), and distant control (DC) in patients with completely resected stage IIIA NSCLC. Materials and MethodsPatients with stage IIIA non-metastatic NSCLC who underwent complete resection and adjuvant chemotherapy were identified from the Taiwan Cancer Registry (January 2007–December 2017). Logistic regression analysis was performed to determine the factors associated with PORT. Survival and relapse outcomes were compared using log-rank tests and Cox regression analysis. Sensitivity analysis was performed using propensity score-matched pairs. ResultsIn total, 1,897 patients were included and stratified according to PORT use (PORT vs. non-PORT). After adjusting for covariates, PORT was not found to be associated with improved survival outcomes. In patients with poorly differentiated tumours and N2 disease, absolute benefits for OS (adjusted hazard ratio [aHR] 0.76), CSS (aHR 0.80), and DC (aHR 0.74) were observed. Multivariable hazard models of propensity score-matched pN2 disease and poorly differentiated tumour subgroups also showed significant survival benefit with PORT treatment. ConclusionsPatients with poorly differentiated tumours and receiving PORT for pN2 disease showed a lower risk of distant recurrence and more favourable survival outcomes in stage IIIA NSCLC with R0 resection.

Body Composition as Prognostic Markers for Survival of Patients with Non-Metastatic Non-Small-Cell Lung Cancer

Objective: Lung cancer is the leading cause of cancer-related deaths. Although, previous research have shown that patients with non-small-cell lung cancer (NSCLC), with a higher body mass index (BMI), have a lower risk of death, only a few studies have examined the effects of body composition. Hence, this study examined the prognostic value of skeletal muscle mass and fat mass in patients with non-metastatic NSCLC. Material and Methods: This was a retrospective cohort study; from 2008 to 2012. Eighty-eight of 130 non-metastatic NSCLC patients underwent computed tomography to assess paravertebral skeletal muscle, subcutaneous adipose tissue (SAT), and visceral adipose-tissue (VAT) at the 3rd lumbar vertebral level. Spearman correlation analysis was used to analyze body-composition correlations. Cox regression analysis was used to determine prognostic markers. Results: Higher SAT and VAT indices were associated with a higher-survival probability (HR, 0.79; p-value=0.001 and, HR 0.88; p-value=0.016, respectively). In contrast, higher SAT density and VAT/SAT ratio were associated with a lower survival probability (HR 1.16, p-value=0.012; HR 1.28, p-value=0.006, respectively). Lower performance status and TNM stage 3 were associated with lower-survival probability (HR 2.60; p-value=0.004, HR 1.92; p-value=0.035, respectively).Conclusion: The VAT index predicts a better prognosis for patients with non-metastatic lung cancer; however, visceral-fat distribution, as measured by a high VAT/SAT ratio, is associated with a worse prognosis.

Is Sarcomatoid Lung Cancer Associated With Inferior Overall Survival? A National Cancer Database Analysis

IntroductionSarcomatoid lung cancer has mainly been described in case series and single institution reviews. Although often associated with a poor prognosis, the overall survival compared to other forms of nonsmall cell lung cancer (NSCLC) is unknown. We hypothesize that sarcomatoid lung cancers have worse overall survival relative to other forms of NSCLC. Materials and methodsIn this retrospective cohort study, we identified adult patients with nonmetastatic NSCLC from 2004 to 2018 in the National Cancer Database. Patients were categorized by histology as sarcomatoid, adenocarcinoma, or squamous cell carcinoma. We compared clinical and demographic characteristics between the groups. The primary outcome of overall survival was analyzed using Kaplan-Meier analysis. Multivariable Cox analysis was used to analyze factors associated with overall survival in sarcomatoid patients undergoing surgery. ResultsAmong 1,259,109 patients with lung cancer, there were 5223 (0.4%) sarcomatoid cancers. Sarcomatoid patients were more likely to be male, of Hispanic ethnicity, have fewer comorbidities, and receive treatment at an academic program. Despite higher cT- and M-stages, patients with sarcomatoid cancer were more likely to undergo surgical resection in multivariate analysis (odds ratio = 1.8 [confidence interval 1.60-2.11]; P < 0.001). Among nonmetastatic patients, overall survival was lower for sarcomatoid cancer relative to other histologies in Kaplan-Meier analysis (median survival sarcomatoid 17.6 mo versus nonsarcomatoid 31.5 mo, P < 0.001). ConclusionsThis National Cancer Database study confirms the findings of smaller studies that sarcomatoid cancer is associated with inferior overall survival compared to other NSCLCs. Given the inferior prognosis, further studies regarding optimal staging practices are appropriate.

Correlation analysis of lung mucosa-colonizing bacteria with clinical features reveals metastasis-associated bacterial community structure in non-small cell lung cancer patients

BackgroundMicrobes colonizing lower airways can regulate the host immune profile and consequently participate in lung disease. Increasing evidence indicate that individual microbes promote lung cancer progression and are involved in metastasis incidence. To date, however, no study has revealed the community structure of lung bacteria in metastatic non-small cell lung cancer (NSCLC) patients.MethodsWe prospectively enrolled 50 healthy subjects and 57 NSCLC patients. All healthy subjects and NSCLC patients underwent bronchoscope procedures for brush specimen collection. The 16 S ribosomal RNA gene was sequenced to characterize the community structure of lung mucosa-colonizing bacteria. The peripheral blood of NSCLC patients was also measured for leukocytes and cancer markers.ResultsThe lung bacteria of healthy subjects and NSCLC patients were divided into four communities. All community 2 members showed increased abundance in NSCLC patients compared with healthy subjects, and most community 2 members showed increased abundance in the metastatic NSCLC patients compared with the non-metastatic group. These bacteria were significantly and positively correlated with eosinophils, neutrophils and monocytes in the metastatic NSCLC group. In addition, the correlation between lung bacteria and cancer markers differed between the metastatic and non-metastatic NSCLC patients. Furthermore, bronchoalveolar lavage fluid from lung adenocarcinoma patients directly promoted NSCLC cell migration.ConclusionsThe community structure of lung mucosa-colonizing bacteria was relatively stable, but changed from the healthy population to NSCLC patients, especially the metastatic group. This distinct community structure and specific correlation with immune cells and cancer markers could help to distinguish NSCLC patients with or without metastasis.

18F-FDG primary tumor uptake to improve N status prediction in cT1 non-metastatic non-small cell lung cancer: development and validation of a positron emission tomography model.

Occult lymph node involvement is a major issue in the management of non-small cell lung carcinoma (NSCLC), with an estimated prevalence of approximately 2.9-21.6% in 18F-FDG PET/CT series. The aim of the study is to construct a PET model to improve lymph node assessment. Patients with a non-metastatic cT1 NSCLC were retrospectively included from two centers, one used to constitute the training set, the other for the validation set. The best multivariate model based on Akaike's information criterion was selected, considering age, sex, visual assessment of lymph node (cN0 status), lymph node SUVmax, primary tumor location, tumor size, and tumoral SUVmax (T_SUVmax). A threshold minimizing false pN0 prediction was chosen. This model was then applied to the validation set. In total, 162 patients were included (training set: 44, validation set: 118). A model combining cN0 status and T_SUVmax was selected (AUC 0.907, specificity at threshold: 88.2%). In the validation cohort, this model resulted in an AUC of 0.832 and a specificity of 92.3% versus 65.4% for visual interpretation alone (p = 0.02). A total of two false N0 predictions were noted (1 pN1 and 1 pN2). Primary tumor SUVmax improves N status prediction and could allow a better selection of patients who are candidates for minimally invasive approaches.

96P Characteristics of patients with resectable non-metastatic non-small cell lung cancer treated with or without neoadjuvant therapy in Europe and Canada: A real-world survey

96P Characteristics of patients with resectable non-metastatic non-small cell lung cancer treated with or without neoadjuvant therapy in Europe and Canada: A real-world survey