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Due to the recent advances in the systemic treatment of non-small cell lung cancer, the management of locoregional recurrences, especially after initial radiotherapy (with or without concurrent chemotherapy), is of increasing significance. The potential alternatives in this setting include: a salvage local strategy (based on surgery, radiotherapy or thermoablative treatment), promising approach, but sometimes difficult to implement in often frail patients, and whose modalities remain under-researched; or alternatively, the initiation of systemic treatment, where the prognosis aligns with that of de novo metastatic patients. This comprehensive literature review focused on salvage radiotherapy treatment of recurrent non-small cell lung carcinomas, after initial radiotherapy, with or without associated systemic treatment. It aims to present the main findings on this area, from patient selection and preparation, to key characteristics, including dosimetric aspects, and the main limitations and uncertainties associated with this therapeutic modality. [ABSTRACT FROM AUTHOR]

Small-cell lung cancer is the most aggressive form of lung neoplasia, treated in recent decades with chemoradiotherapy in case of limited stage and chemotherapy alone at the metastatic stage. In the last few years, the advent of immunotherapy has changed the landscape in the treatment of non-small-cell lung cancer, and to a lesser degree in small-cell lung cancer. Despite the recent advances in research, small-cell lung cancer is still considered an aggressive and lethal disease characterized by high recurrence or metastatic potential. As stereotactic radiotherapy has established itself as the standard of care in the early stage of inoperable non-small-cell lung cancer and in metastatic disease to treat brain and extracranial metastases, these same issues now arise in the management of small-cell lung cancer. This article aims to review the current knowledge and the potential of stereotactic radiotherapy in small-cell lung cancer. [ABSTRACT FROM AUTHOR]

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This research addresses a significant gap in lung cancer prediction, focusing on the critical need for highly accurate models to improve early detection and treatment outcomes. Despite advances in machine learning, achieving higher accuracy in classification models for lung cancer remains a persistent challenge. This study aims to fill this gap by developing advanced machine-learning models specifically designed to enhance the prediction of lung cancer outcomes. The research employs a rigorous methodology that involves the systematic exploration of various machine learning algorithms applied to a comprehensive lung cancer dataset. Through meticulous phases of model development, training, validation, and testing, this study evaluates the performance and accuracy of the proposed models. The findings underscore the effectiveness of these models in addressing the challenge of early lung cancer detection, offering more precise and reliable classification outcomes than existing approaches. The novelty of this research lies in the extensive experimental work, which demonstrates the superiority of the selected algorithm for lung cancer data classification. This not only highlights the potential of the algorithm for clinical application but also provides a concrete solution to the ongoing issue of achieving higher accuracy in lung cancer prediction models. By bridging this research gap, the study offers promising new avenues for early-stage lung cancer prognosis and treatment strategies, with the potential to significantly impact clinical practices. [ABSTRACT FROM AUTHOR]

Background Body mass index (BMI) has been shown to be an independent predictor of survival following lung resection surgery. This study aimed to quantify the short- to midterm impact of abnormal BMI on postoperative outcomes. Methods Lung resections at a single institution were examined between 2012 and 2021. Patients were divided into low BMI (<18.5), normal/high BMI (18.5–29.9), and obese BMI (>30). Postoperative complications, length of stay, and 30- and 90-day mortality were examined. Results A total of 2,424 patients were identified. Of these patients, 2.6% (n = 62) had a low BMI, 67.4% (n = 1,634) had a normal/high BMI, and 30.0% (n = 728) had an obese BMI. Overall postoperative complications were higher in the low BMI group (43.5%) when compared with normal/high (30.9%) and obese BMI group (24.3%) (p = 0.0002). Median length of stay was significantly higher in the low BMI group (8.3 days) compared with 5.2 days in the normal/high and obese BMI groups (p < 0.0001). Ninety-day mortality was higher in the low (16.1%) compared with the normal/high (4.5%) and obese BMI groups (3.7%) (p = 0.0006). Subgroup analysis of the obese cohort did not elucidate any statistically significant differences in overall complications in the morbidly obese. Multivariate analysis determined that BMI is an independent predictor of reduced postoperative complications (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.94–0.97; p < 0.0001) and 90-day mortality (OR, 0.96; 95% CI, 0.92–0.99; p = 0.02). Conclusion Low BMI is associated with significantly worse postoperative outcomes and an approximate fourfold increase in mortality. In our cohort, obesity is associated with reduced morbidity and mortality following lung resection surgery, confirming the existence of the obesity paradox. [ABSTRACT FROM AUTHOR]

Non-Small Cell Lung Cancer (NSCLC) is a prevalent and deadly form of lung cancer worldwide with a low 5-year survival rate. Current treatments have limitations, particularly for advanced-stage patients. P21, a protein that inhibits the CCND1-CDK4 complex, plays a crucial role in cell proliferation. Computer-Aided Drug Design (CADD) based on pharmacophores can screen and design PPI inhibitors targeting the CCND1-CDK4 complex. By analyzing known inhibitors, key pharmacophores are identified, and computational methods are used to screen potential PPI inhibitors. Molecular docking, pharmacophore matching, and structure-activity relationship studies optimize the inhibitors. This approach accelerates the discovery of CCND1-CDK4 PPI inhibitors for NSCLC treatment. Molecular dynamics simulations of CCND1-CDK4-P21 and CCND1-CDK4 complexes showed stable behavior, comprehensive sampling, and P21's impact on complex stability and hydrogen bond formation. A pharmacophore model facilitated virtual screening, identifying compounds with favorable binding affinities. Further simulations confirmed the stability and interactions of selected compounds, including 513457. This study demonstrates the potential of CADD in optimizing PPI inhibitors targeting the CCND1-CDK4 complex for NSCLC treatment. Extended simulations and experimental validations are necessary to assess their efficacy and safety. [ABSTRACT FROM AUTHOR]

Context • SCLC has had few drugs for treatment and a high malignancy rate. About two-thirds of SCLC patients have distant metastasis by the time they receive a diagnosis, and once it occurs, patient’s survival time is short. Immunotherapy treatments can block immunosuppression and increase the body’s antitumor ability. PD-1 is the main immune checkpoint of tumors’ immune response, and PD-L1 is one of the ligands of PD-1. Objective • The study intended to analyze the therapeutic effects of inhibitors of programmed death-1 (PD-1)/ programmed cell death 1 ligand 1 (PD-L1) combined with chemotherapy for patients with advanced small cell lung cancer (SCLC), evaluate the safety of that treatment, and compare it with chemotherapy alone. Design • The research team performed a retrospective randomized controlled study. Setting •The study took place at Cangzhou Central Hospital. Participants • Participants were 72 patients with advanced SCLC who received treatment at the hospital between December 2021 and December 2022. Intervention • The research team divided participants into two groups, each with 36 participants, using the random number method: (1) the control group, which received platinum-etoposide chemotherapy, and (2) the intervention group, which received a PD-1/PD-L1 inhibitor combined with the same chemotherapy that the control group received. Outcome Measures • The research team examined: (1) short-term efficacy; (2) long-term efficacy; (3) tumor-marker levels—neuron-specific enolase (NSE), progastrin releasing peptide (ProGRP), cytokeratin-19-fragment (CYFRA21-1), and squamous cell carcinoma antigen (SCCA); (4) T lymphocyte-subset levels—cluster of differentiation 3+ (CD3+ ), CD4+, and CD8+ ; (5) adverse reactions, and (6) Karnofsky performance status (KPS) scores. Results • Compared with the control group, the intervention group’s: (1) overall response rate (ORR), with P = .002, and disease control rate (DCR), with P = .041, were significantly higher; (2) median survival time was significantly longer (P = .035); (3) levels of NSE, ProGRP, CYFRA21-1, and SCCA were significantly lower (all P < .001); (4) levels of CD3+ (P = .043) and CD4+ (P < .001) levels were significantly higher; and (5) Karnofsky performance status (KPS) scores were significantly higher than those of the control group (P = .018). No difference existed in the number of adverse reactions between the groups (P > .05). Conclusions • The PD-1/PD-L1 inhibitor combined with chemotherapy can benefit advanced SCLC patients, controlling patients’ conditions and improving their quality of life, with good safety. [ABSTRACT FROM AUTHOR]

Objective • To explore the risk factors and predictive effects of visceral pleural invasion in lung adenocarcinoma patients with mGGN type, in order to identify high-risk groups of visceral pleural invasion early, and to provide more references for targeted intervention and individualized treatment adjustment of high-risk groups based on the analysis of risk factors. Methods • The clinical data of 135 patients with mGGN-type lung adenocarcinoma who received surgical treatment in our hospital from January 2018 to December 2022 were selected from our hospital’s medical record database for retrospective analysis. The patient information was entered by a two-person summary and analyzed after verification.The patients were divided into invasion group (60 cases) and non-invasion group (75 cases) according to the invasion of pleural viscera, which was helpful to analyze the difference of clinical features between the two groups. The independent risk factors for visceral pleural invasion in patients with mGGN lung adenocarcinoma were evaluated using univariate and multivariate factor methods, and receiver operating characteristic (ROC) curves were drawn to evaluate the clinical efficacy of these risk factors above alone and in combination in predicting of visceral pleural invasion risk. The larger the area under ROC curve, the higher the corresponding sensitivity and specificity, and the greater the predictive value for the risk of visceral pleural invasion in mGGN lung adenocarcinoma patients. Results • Univariate analysis showed that gender, family history of hypertension, location of focus, maximum diameter of solid component, proportion of solid component, pleural indentation, burr sign, bronchial and nodular route may be related to visceral pleural invasion in lung adenocarcinoma patients with mGGN type (P < .05). Multivariate Logistic regression analysis showed that pleural indentation (OR=2.49, 95%CI:1.17~4.58, P < .001) and abnormal broncho-nodular travel (OR=3.06, 95%CI: 1.35~7.02, P = .01) were the independent risk factors for visceral pleural invasion in lung adenocarcinoma patients with mGGN type (P < .05). ROC curve analysis results showed that pleural indentation (AUC=0.70, 95%CI: 0.65~0.79, P = .02), abnormal bronchial and nodular running relationship (AUC=0.74, 95%CI: 0.69~0.81, P = .01) could both be used to predict the visceral pleural invasion risk in lung adenocarcinoma patients with mGGN type, and combined prediction efficacy of both indexes (AUC=0.90, 95%CI: 0.85~0.97, P < .001) was better than single index. Conclusion • The occurrence of visceral pleural infiltration in patients with mGGN lung adenocarcinoma is related to the relationship between pleural indentation and bronchus and nodules. Combined with the above indicators, the risk of visceral pleural infiltration in patients can be effectively predicted, and early intervention and treatment can be performed on high-risk patients accordingly to effectively prevent and treat visceral pleural infiltration. [ABSTRACT FROM AUTHOR]

Objective: This study aims to identify activating mutations in the epidermal growth factor receptor (EGFR) gene in patients with non-small cell lung cancer (NSCLC) and to evaluate their correlation with responses to EGFRtyrosine kinase inhibitors (TKI) treatment. This study aims to identify activating mutations in the epidermal growth factor receptor (EGFR) gene in patients with non-small cell lung cancer (NSCLC) and to evaluate their correlation with responses to EGFR-tyrosine kinase inhibitors (TKI) treatment. We conducted a comparative analysis of Real-Time PCR and immunohistochemistry to detect EGFR mutation status in non-small cell lung cancer patients, focusing on the sensitivity, specificity, and predictive values of immunohistochemistry. Material and Method: We evaluated 788 non-small cell lung cancer samples which were analyzed for EGFR mutation status by RT-PCR. We detected 126 EGFR mutated cases among these patients. We evaluated mutationspecific EGFR immunohistochemistry directed towards the exon 19 deletions (15 bp E746-A750) and exon 21point mutation (L858R) to the 47 EGFR mutated patients histologic material and cell blocks of cytologic specimens. Results: 32 of the 47 cases (68%) had exon 19 deletion, 14 of them (30%) had point mutation in exon 21, and one of them (2%) showed exon 18 mutation. EGFR exon 19 (15 bp E746-A750 deletion) antibody showed a sensitivity of 100%, specificity of 40%, negative predictive value of 100%, and positive predictive value of 78%. The sensitivity of the exon 21 (L858R point mutation) antibody was 93%, specificity was 91%, negative predictive value was 97% and positive predictive value was 82%. Conclusion: Our investigation indicates that mutation-specific EGFR immunohistochemistry has demonstrated a notable sensitivity and specificity for exon 21. However, while sensitive, the exon 19 (15 bp E746-A750 deletion) antibody lacked specificity. While positive immunohistochemical staining may suggest the presence of an EGFR mutation, making the patient potentially eligible for TKI treatment, it should not be the sole determinant. If immunohistochemistry results are negative, it is essential to resort to molecular tests to ensure accurate diagnosis and appropriate therapeutic guidance. With evolving diagnostic landscapes, it is crucial to harness both IHC and molecular techniques judiciously for optimal patient care. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer is the most common type of cancer, causing worldwide mortality. Therefore, this study is necessary for continuing research into new effective and safe treatments. Recently, herbal medicines have been used for the treatment of various diseases such as cancer. This study aimed to investigate the potential anti-proliferative activity and investigate the mechanisms of hesperidin extract on the non-small lung cancer cells A549 and H460 vs. cisplatin via targeting the miR 34a/PD-L1/NF-κB signalling pathway. Material and methods: To determine the cytotoxic effects of the hesperidin extract on non-small lung cancer cells, sulphorhdamine B assay was performed. To show the inhibition of migration by hesperidin extract, wound healing assay was conducted. A quantitative polymerase chain reaction test was used to quantify the expressions of miR-34a, programmed cell death ligand-1 (PDL-1), epidermal growth factor receptor (EGFR), and P53 genes, which are involved in apoptosis pathway. Also, cell cycle assay was performed by using a flow cytometer. Results: The hesperidin extract could significantly inhibit proliferation of non-small lung cancer cells A549 and H460. Western blot assay demonstrated that hesperidin induced suppression of nuclear factor κB signalling pathway. The messenger RNA expression levels of MiR-34a and P53 were up-regulated significantly by hesperidin treatment, while the EGFR and P53 genes were down-regulated. The flow cytometer confirmed that cell cycle arrest occurred at the sub-G1 and G2 phases in A549 and H460, respectively. Conclusions: Our study demonstrated that hesperidin extract could significantly inhibit non-small lung cancer cell growth by induction of the apoptosis signalling pathway. Therefore, hesperidin might open novel strategies for effective and safe cancer treatment and reduce the adverse side effects of several chemotherapeutic treatments such as cisplatin. [ABSTRACT FROM AUTHOR]

Purpose:This article reviews the relevant literature on paraneoplastic neurological syndromes of small cell lung cancer and discusses the clinical presentation, pathophysiology, and diagnosis of these syndromes. It also includes a summary of the current treatment options for the management of them. Views: Paraneoplastic syndromes are a group of signs and symptoms that develop due to cancer in a remote site, mainly triggered by an autoantibody produced by the tissues involved or lymphocytes during anti-cancer defense. Among the cancers associated with paraneoplastic syndromes, lung cancers are the most common type, with small cell lung cancer being the most common subtype. The most common antibody associated with paraneoplastic syndromes is anti-Hu. Neurological and neuroendocrine syndromes comprise the majority of small cell lung cancer-related paraneoplastic syndromes. Classical paraneoplastic neurological syndromes include inappropriate antidiuretic hormone secretion, Cushing’s syndrome, myasthenia gravis, Lambert-Eaton myasthenic syndrome, limbic encephalitis, paraneoplastic cerebellar degeneration, opsoclonus myoclonus ataxia, sensory neuropathy, and chorea. Conclusions: Antibodies mediate paraneoplastic syndromes, and antibody detection is a crucial part of diagnosing these entities. Managing the underlying tumor is the best treatment approach for most paraneoplastic syndromes. Therefore, early diagnosis of small cell lung cancer may significantly improve the prognosis of paraneoplastic syndromes associated with it. [ABSTRACT FROM AUTHOR]

Background Mediastinal lymphadenopathies with high 18-fluorodeoxyglucose uptake in patients previously operated on for lung cancer are alarming for recurrence and necessitate invasive diagnostic procedures. Peroperative placement of oxidized cellulose to control minor bleeding may lead to a metastasis-like image through a foreign body reaction within the dissected mediastinal lymph node field at postoperative examinations. In this study, we investigated clinicopathological features and the frequency of foreign body reaction mimicking mediastinal lymph node metastasis. Methods Patients who underwent surgery for lung cancer between January 2016 and August 2021 and who were subsequently evaluated for mediastinal recurrence with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) were included. Patients were grouped according to the results of EBUS-TBNA as metastasis, foreign body, and reactive. Clinicopathological features of these patients were compared and characteristics of patients in the foreign body group were scrutinized. Results EBUS-TBNA was performed on a total of 34 patients during their postoperative follow-up due to suspicion of mediastinal recurrence. EBUS-TBNA pathological workup revealed metastasis in 18 (52.9%), foreign body reaction in 10 (29.4%) and reactive lymph nodes in 6 (17.6%) patients. Mean maximum standardized uptake value (SUVMax) for metastasis group and foreign body group were 9.39 ± 4.69 and 5.48 ± 2.54, respectively (p = 0.022). Time interval between the operation and EBUS-TBNA for the metastasis group was 23.72 ± 10.48 months, while it was 14.90 ± 12.51 months in the foreign body group (p = 0.015). Conclusion Foreign body reaction mimicking mediastinal lymph node metastasis is not uncommon. Iatrogenic cause of mediastinal lymphadenopathy is related to earlier presentation and lower SUVMax compared with metastatic lymphadenopathy. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the effects of ward noise reduction administration on the lung function and mental health of patients with lung cancer. Methods: A total of 195 patients who underwent lung cancer surgery in PLA Northern Theater Command Air Force Hospital from November 2020 to November 2022 were selected to be divided into a control group (routine nursing) and an observation group (routine nursing and ward noise reduction administration) in accordance with the medical record system. The general demographic data, noise level, lung function (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC)), and complications of patients in the two groups were collected. Propensity score matching (PSM) was used to balance the baseline data of the two groups, and t-test and chi-square test were used to analyze the data. Results: After PSM was conducted, 50 patients were enrolled in each group. No statistical difference was found in the baseline data, preadministration noise levels, and FEV1, FVC, FEV1/FVC, state-anxiety inventory (S-AI), and trait anxiety inventory scale (T-AI) scores between the two groups (P > 0.05). After ward noise reduction was administered, the noise level in the observation group was lower than that in the control group (P < 0.05). The FEV1, FVC, and FEV1/FVC scores of the observation group were higher than those of the control group but were not statistically significant (P > 0.05). The S-AI and T-AI scores of the observation group were lower than those of the control group (P < 0.05). No differences were found in the complications between the two groups (P > 0.05). Conclusion: Administering ward noise reduction in patients with lung cancer can alleviate their negative emotions, thus worthy of clinical adoption. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) represents the most common histological type of lung cancer, characterized by a five-year survival rate of 15% and poor prognosis. Accumulating evidence indicates a prominent role of endoplasmic reticulum (ER) stress and the protein kinase RNA-like ER kinase (PERK)-dependent pathway of the unfolded protein response (UPR) in the pathogenesis of NSCLC. Increased expression of downstream targets of PERK was observed in various subtypes of NSCLC, and it was associated with a more aggressive phenotype, high risk of recurrence, and poor prognosis. Therefore, the present study aimed to investigate the biological effect of the selective PERK inhibitor NCI 159456 on A549 NSCLC cells and Human Pulmonary Fibroblasts (HPF) in vitro. Treatment of both normal and ER-stressed A549 cells with NCI 159456 resulted in a significant increase in the mRNA expression level of pro-apoptotic genes like activating transcription factor 4 (ATF4), DNA damage inducible transcript 3 (DDIT3), and BCL2 Associated X, Apoptosis Regulator (BAX) as well as a decreased level of the anti-apoptotic gene B-cell lymphoma 2 (Bcl-2). Cytotoxicity and genotoxicity analyses revealed that NCI 159456 significantly decreased viability and increased DNA damage in A549 cells under normal and ER stress conditions. Caspase-3 and reactive oxygen species (ROS) detection assays demonstrated that NCI 159456 significantly induced apoptosis and increased the ROS level in normal and ER-stressed A549 cells. Importantly, treatment with the inhibitor did not affect substantially normal HPF cells at any used concentration. The results indicate that PERK inhibitors could potentially be applied as a targeted therapy for NSCLC. [ABSTRACT FROM AUTHOR]

Background/Aim: Recent lung cancer treatments include an immune checkpoint inhibitor (ICI) pembrolizumab, platinum-based agents, plus an additional cytotoxic anticancer agent. Nutritional indices, such as the geriatric nutritional risk index (GNRI) and the prognostic nutritional index (PNI), are known to correlate with the prognosis of cancer chemotherapy. Several previous studies have investigated the relationship between PNI and treatment response in non-small cell lung cancer patients, reporting significantly increased OS and PFS in the high PNI group before treatment. However, the relationship between the threedrug combination and GNRI/PNI is unclear. The current study aimed to investigate the association of nutritional indices with duration of treatment success and occurrence of side effects in triple therapy. Patients and Methods: Seventytwo patients with non-small cell lung cancer, treated with combination of carboplatin, pemetrexed, and pembrolizumab from November 2019 to September 30, 2022, were classified into two groups (High and Low) for GNRI and PNI, and a retrospective study was performed. Results: In terms of time-to-treatment-failure (TTF), univariate and multivariate Cox proportional hazards regression analysis showed the Low-PNI group to have significantly shorter TTF than the High-PNI group (p=0.006); multivariate analysis results also showed PNI as a factor affecting TTF (HR=2.791, 95%CI=1.362-5.721, p=0.005). On the other hand, GNRI was not shown to be a factor affecting TTF. Conclusion: PNI at the start of treatment was an independent prognostic factor affecting treatment success time (TTF) in non-small cell lung cancer patients receiving triple therapy. However, PNI was not shown to be a prognostic predictor of irAE development. [ABSTRACT FROM AUTHOR]

Introduction: Adaptive radiotherapy (ART) is an essential approach to account for anatomical and biological uncertainties. Adaptive radiotherapy is, however, time-consuming, and it is unclear which patients are eligible or when is the best time to start ART. Methods: This prospective study was conducted at Kasr El-Aini Center of Clinical Oncology and Nuclear Medicine, Cairo, Egypt from January 2019 to December 2020. Thirty patients with pathologically proven, limited-stage small cell or stage I-II non-small cell lung cancer who were either not fit for or refused surgery or had stage III disease were recruited and underwent treatment planning to receive 60 Gy on a conventional 3D conformal radiation schedule with platinum-based chemotherapy. All patients underwent computed tomography (CT) planning within 2 and 4 weeks of starting radiation therapy to assess the need for adaptation. Pulmonary function test and echocardiography findings were assessed at the end of treatment and at 3 and 6 months after treatment, and were compared to the baseline. Results: We found a significant reduction in mean value of the planning target volume (PTV) in the CT scans at the second (331 cm3) and fourth (257 cm3) weeks of treatment as compared to baseline (342 cm3) (p-value, 0.0001). Adaptation decreased the dose to the organ at risk with statistical significance and with improvement of the target coverage. At week 2 of radiotherapy, the need for adaptation was correlated to the conformity index (p = 0.0473), esophageal V35 (p = 0.0488), esophageal V50 (p = 0.0295), and its mean dose (p = 0.0087). At week 4 it was correlated to forced expiratory volume in 1 second (FEV1) (p = 0.0303), ratio between the forced expiratory volume in 1 second and the forced vital capacity (FEV1/FVC) (p = 0.0024), and echocardiography (p = 0.0183). Conclusions: Conformity index and esophageal dose constraints can predict the need for adaptation at week 2, whereas baseline pulmonary function parameters and echocardiography can predict the need for adaptation at week 4 of radiotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Discrete choice experiments (DCE) are commonly used to elicit patient preferences and to determine the relative importance of attributes but can be complex and costly to administer. Simpler methods that measure relative importance exist, such as swing weighting with direct rating (SW-DR), but there is little empirical evidence comparing the two. This study aimed to directly compare attribute relative importance rankings and weights elicited using a DCE and SW-DR. Methods: A total of 307 patients with non–small-cell lung cancer in Italy and Belgium completed an online survey assessing preferences for cancer treatment using DCE and SW-DR. The relative importance of the attributes was determined using a random parameter logit model for the DCE and rank order centroid method (ROC) for SW-DR. Differences in relative importance ranking and weights between the methods were assessed using Cohen's weighted kappa and Dirichlet regression. Feedback on ease of understanding and answering the 2 tasks was also collected. Results: Most respondents (>65%) found both tasks (very) easy to understand and answer. The same attribute, survival, was ranked most important irrespective of the methods applied. The overall ranking of the attributes on an aggregate level differed significantly between DCE and SW-ROC (P < 0.01). Greater differences in attribute weights between attributes were reported in DCE compared with SW-DR (P < 0.01). Agreement between the individual-level attribute ranking across methods was moderate (weighted Kappa 0.53–0.55). Conclusion: Significant differences in attribute importance between DCE and SW-DR were found. Respondents reported both methods being relatively easy to understand and answer. Further studies confirming these findings are warranted. Such studies will help to provide accurate guidance for methods selection when studying relative attribute importance across a wide array of preference-relevant decisions. Highlights: Both DCEs and SW tasks can be used to determine attribute relative importance rankings and weights; however, little evidence exists empirically comparing these methods in terms of outcomes or respondent usability. Most respondents found the DCE and SW tasks very easy or easy to understand and answer. A direct comparison of DCE and SW found significant differences in attribute importance rankings and weights as well as a greater spread in the DCE-derived attribute relative importance weights. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer⁃related deaths worldwide, and in the past few years, many studies have found that gut flora has an important role in the development of lung cancer. The intestinal microbiota is considered as a human microbial organ, which not only affects the human body’s functions such as digestion and anti⁃infection, but also influences the human body’s response to tumor therapy by participating in immunomodulation and metabolism. In addition, the interaction between microorganisms and host cells is crucial for regulating local and systemic physiological functions, which can influence the local microenvironment and immune system function of the host, thus affecting tumor development and anti⁃tumor therapeutic effects. In this paper, we will review the mechanisms by which intestinal flora influence lung cancer development and their clinical significance in lung cancer treatment. [ABSTRACT FROM AUTHOR]

Lung carcinoma stands as a prevalent malignancy characterized by a distressingly elevated fatality rate. Immunotherapy, administered either as a monotherapy or together with chemotherapy, represents the primary therapeutic approach for the majority of individuals grappling with advanced non-small cell lung cancer. The influence of systemic inflammation in fostering cancer dissemination and progression is a well-documented phenomenon. This literature review examines contemporary indices and scoring systems, which have emerged as informative indicators of systemic inflammation in recent years. These indices and scores are valuable prognostic and predictive elements in assessing treatment response among patients with metastatic lung cancer undergoing immunotherapeutic treatment. [ABSTRACT FROM AUTHOR]

Background: Gefitinib (GEF) is a tyrosine kinase inhibitor that has proven good efficacy against Non-small cell Lung Carcinoma (NSCLC). It has low solubility and dissolution rate and low oral bioavailability. This work aimed to improve efficacy by loading on ZSM-5 silica nanoparticles and testing the prepared delivery system on A-549 lung cancer cells. Methods: ZSM-5 was synthesized in the laboratory and different methods of loading GEF on the nanoparticles were used, then the system was characterized by X-ray diffraction, Fourier Transport Infra-Red (FTIR), and drug release and dissolution. Results and conclusion: GEF-loaded nanoparticles (NPs) showed prolonged release of GEF over 12 hours with an improved biological efficacy expressed by the decrease in IC50 compared to free GEF (P < 0.001) using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Also, there was a significant decrease in migration and colony formation ability of the GEF-loaded NPs on A-549 lung cancer cells. In conclusion, loading GEF onto ZSM-5 NPs resulted in a lower IC50 and improved biological action toward A-549 cells. [ABSTRACT FROM AUTHOR]

Objective: Malnutrition is a complication of chronic kidney disease (CKD) that contributes to poor survival. The Advanced Lung Cancer Inflammation Index (ALI) was designed to assess systemic inflammation in patients with metastatic cell lung cancer. The Geriatric Nutritional Risk Index (GNRI) was shown to predict mortality in patients undergoing dialysis. Considering the role of inflammation and malnutrition in mortality, this study aimed to investigate the relationship between a new index, ALI, in concordance with GNRI, and mortality in HD and PD patients. Methods: Patients undergoing maintenance hemodialysis (HD) and peritoneal dialysis (PD) at our institution between February 2012 and October 2022 were studied retrospectively. Advanced Lung Cancer Inflammation Index and GNRI were calculated by recommended formulas. The primary outcome was all-cause mortality. Results: A total of 176 patients (88 with HD and 88 with PD) were included in the study. The mean age was 50 ± 16 years. In receiver operating characteristic analysis for ALI, the best cutoff value was 36.9 to predict mortality with a sensitivity of 88% and specificity of 72.8%, and the area under the curve was 0.850 (95% CI, 0.763-0.937; P < .005) in HD patients and 37.2 to predict mortality with a sensitivity of 88% and specificity of 67.1 %, and the area under the curve was 0.832 (95% CI: 0.729-0.934; P < .005) in PD patients. In the Cox regression analysis, the major factors affecting mortality were age, C-reactive protein level, ALI, and GNRI. Conclusion: The nutritional risk assessment measures, GNRI and ALI, predict mortality in CKD patients. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate to usability and feasibility of perfusion computerized tomography (PCT) in differentiating small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC). Methods: Between September 2013 and February 2022, 42 patients with a detected lung mass took part in the present study. All patients went through PCT examination, and data regarding permeability (PMB), blood flow (BF), and blood volume (BV) of the tumor were acquired. These parameters along with mass diameter of the tumors were compared in both cancer types. Results: Maximum tumor diameter was measured as 48 ± 11 mm in average in the SCLC cases and 49 ± 15 mm in the NSCLC cases (P = .892). There was a correlation at a moderate level between the tumor's maximal diameter and PMB (r = .49, P = .020). Regarding tumor PMB values, there was a meaningful variation between the 2 tumor groups (SCLC: 16.4 ± 3.6 mL/100 mL/min; NSCLC: 5.1 ± 2.8 mL/100 mL/min; P = .001). No further meaningful differences were observed among the BF- and BV-related comparisons. Conclusion: Among the perfusion parameters in lung PCT, PMB can be used to distinguish the NSCLC from SCLC in patients who were diagnosed with lung cancer. [ABSTRACT FROM AUTHOR]

Background: Metastatic masses in the pancreatic head are uncommon, and consensus on their optimal management is lacking. Although renal cell carcinomas are most commonly associated with pancreatic metastases, there are also reported instances of pancreatic metastases originating from lung cancer. Case Report: A 65-year-old male presenting with jaundice underwent imaging studies, which revealed a mass in the pancreatic head. Subsequent imaging identified a 7 cm tumor in the left lung's hilar region, originating from the bronchus. A bronchoscopic biopsy of this hilar mass confirmed small-cell lung carcinoma. Biopsy results from the pancreatic head mass, obtained through endoscopic ultrasound, confirmed it as a metastasis from the primary small-cell lung carcinoma. The patient commenced systemic chemotherapy. Conclusion: In the differential diagnosis of pancreatic head masses, clinicians should consider the possibility of rare metastatic masses. The treatment for metastatic cases should be determined through a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Background: The most recommended treatment for stage IV EGFR-positive lung cancer is osimertinib monotherapy. The dosage of osimertinib is fixed at 80 mg/day regardless of body surface area (BSA), however some patients withdraw or reduce the dosage due to adverse events (AEs). Methods: We performed a retrospective cohort study of 98 patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), who received 80 mg osimertinib as the initial treatment. We investigated the impact of BSA on efficacy and safety of osimertinib. Results: The cut-off value of BSA was estimated using the receiver operating characteristics curve, and was determined to be 1.5 m2. There were 44 patients in the BSA < 1.5 group and 54 patients in the BSA ≥ 1.5 group. There was no significant difference in the incidence of AEs (hematologic toxicity of ≥grade 3 or higher, and non-hematologic toxicity of ≥grade 3) between the two groups. However, the incidence of dose reduction due to AEs was significantly higher in the BSA < 1.5 group compared with the BSA ≥ 1.5 group (16 patients vs 5 patients, p = 0.003). The main reasons were fatigue, anorexia, diarrhea, and liver disfunction. Median progression-free survival (PFS) was not significantly different (16.9 months in the BSA < 1.5 group vs 18.1 months in the BSA ≥ 1.5 group, p = 0.869). Conclusion: Differences in BSA affected the optimal dose of osimertinib. However, the PFS with osimertinib treatment was not affected by BSA. Therefore, when using osimertinib as an initial treatment for patients with EGFR-mutant NSCLC, dose reduction to control AEs should be considered, especially in the BSA

Introduction. We prospectively examined current clinical practices in patients with inoperable epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) fusion-positive (EGFR+ and ALK+, respectively) non-small cell lung cancer (NSCLC) in Nagano Prefecture, Japan. Material and methods. The study population consisted of newly diagnosed patients with inoperable EGFR+ and ALK+ NSCLC in 14 hospitals in Nagano between May 2016 and March 2019. Both initial and subsequent treatment decisions were made at the discretion of the attending physician. Results. A total of 281 patients with EGFR+ NSCLC (mean age, 74 years, 59.1% female) and 26 patients with ALK+ NSCLC (mean age, 66 years, 53.8% female) were included in the study. The study population consisted of 148/107/29/20/3 cases with performance status 0/1/2/3/4 and 6/2/31/194/75 cases with clinical stage I/II/III/IV/recurrence, respectively. First-line therapy with tyrosine kinase inhibitors was performed in 259 (92.2%) and 22 (84.6%) patients with EGFR+ and ALK+ NSCLC, respectively. The median overall survival rate was 41.2 months (95% CI 36.8-45.6 months) with EGFR+. It was not reached with ALK+. Conclusions. This observational analysis represents a valuable resource for evaluating the outcomes of treatment in patients with NSCLC. [ABSTRACT FROM AUTHOR]

Background/Aim: Targeting apoptotic pathways has been identified as a promising strategy for the treatment of lung cancer. We synthesized a new derivative of renieramycin T (RT), named DH_22, and examined its anticancer activities in human lung cancer cells. Materials and Methods: The RT derivative DH_22 was chemically modified from RT. The apoptosis-inducing effect was evaluated in A549 cells by annexin V-FITC/PI staining and nuclear staining assay (Hoechst/PI). In addition, the molecular pathway was analyzed by western blot analysis. Results: In the cell viability and nuclear staining tests, DH_22 was discovered to be cytotoxic with an IC50 of 13.27 μM; it induced apoptosis of lung cancer cells. Regarding the mechanism, DH_22 contributed to the activation of p53- dependent apoptosis and decreased the cellular level of cMyc. The p53-dependent mechanism was indicated by an increase in p53, an induction of the pro-apoptotic Bax protein, and a decrease in the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein. Conclusion: DH_22 has great potential for further development as a new anticancer drug. [ABSTRACT FROM AUTHOR]

In the course of lung cancer, normal cells are transformed into cancerous ones, and changes occur in the microenvironment, including the extracellular matrix (ECM), which is not only a scaffold for cells, but also a reservoir of cytokines, chemokines and growth factors. Metalloproteinases (MMPs) are among the elements that enable ECM remodeling. The publication focuses on the problem of changes in the gene expression of MMP2, MMP9 and tissue inhibitor of metalloproteinases (TIMP1) in the blood of NSCLC patients during therapy (one year after surgical resection of the tumor). The paper also analyzes differences in the expression of the studied genes in the tumor tissue, as well as data collected in publicly available databases. The results of blood tests showed no differences in the expression of the tested genes during therapy; however, changes were observed in cancerous tissue, which was characterized by higher expression of MMP2 and MMP9, compared to non-cancerous tissue, and unchanged expression of TIMP1. Nevertheless, higher expression of each of the studied genes was associated with shorter patient survival. Interestingly, it was not only the increased expression of metalloproteinase genes, but also the increased expression of the metalloproteinase inhibitor (TIMP1) that was unfavorable for patients. [ABSTRACT FROM AUTHOR]

This study investigated the usefulness of [18F]-3'-deoxy-3'-fluorothymidine (18F-FLT) and [18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging for predicting the therapeutic efficacy of non-small cell lung cancer (NSCLC) irradiation at an early stage after radiation treatment. Mice were xenografted with the human lung adenocarcinoma line A549 or large cell lung cancer line FT821. Tumour uptake of 18F-FLT and 18F-FDG was imaged using PET/CT before and 1 week after irradiation. In A549 tumours, 18F-FLT uptake was significantly decreased, and 18F-FDG uptake was unchanged post-irradiation compared with pre-irradiation. In FT821 tumours, uptake of both 18F-FLT and 18F-FDG uptake was substantially decreased post-irradiation compared with pre-irradiation. In both xenografts, tumour volumes in the irradiated groups were significantly decreased compared with those in the control group. 18F-FLT is expected to contribute to individual NSCLC therapy because it accurately evaluates the decrease in tumour activity that cannot be captured by 18F-FDG. 18F-FDG may be useful for evaluating surviving cells without being affected by the inflammatory reaction at an extremely early stage, approximately 1 week after irradiation. Combined use of 18F-FLT and 18F-FDG PET/CT imaging may increase the accurate prediction of radiotherapy efficacy, which may lead to improved patient outcomes and minimally invasive personalised therapy. [ABSTRACT FROM AUTHOR]

Background: Percutaneous Microwave Ablation (MWA) of lung malignancies is a procedure with many technical challenges, among them the risk of residual disease. Recently, dedicated software able to predict the volume of the ablated area was introduced. Cone-beam computed tomography (CBCT) is the imaging guidance of choice for pulmonary ablation in our institution. The volumetric prediction software (VPS) has been installed and used in combination with CBCT to check the correct position of the device. Our study aimed to compare the results of MWA of pulmonary tumours performed using CBCT with and without VPS. Methods: We retrospectively reviewed 1-month follow-up enhanced contrast-enhanced computed tomography (CECT) scans of 10 patients who underwent ablation with the assistance of VPS (group 1) and of 10 patients who were treated without the assistance of VPS (group 2). All patients were treated for curative purposes, the maximum axial diameter of lesions ranged between 5 and 22 mm in group 1 and between 5 and 25 mm in group 2. We compared the presence of residual disease between the two groups. Results: In group 1 residual disease was seen in only 1 patient (10%) in which VPS had ensured complete coverage of the tumour. In group 2 residual disease was found in 3 patients (30%). Conclusions: Using this software during MWA of lung malignancies could improve the efficacy of the treatment compared to the conventional only CBCT guidance.

Objective. The purpose of this study was to evaluate the clinical efficacy of apatinib plus concurrent radiotherapy on carcinoma embryonic antigen (CEA) and vascular endothelial growth factor (VEGF) expression in patients with non-small-cell lung cancer (NSCLC) with oligometastases. Methods. This is a prospective randomized controlled trial. Sixty-four patients with oligometastatic NSCLC who were treated in the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2017 to January 2019 were randomly assigned into the control group and the study group, with 32 cases in each group. The control group was treated with stereotactic body radiotherapy (SBRT), and the study group was treated with apatinib. Results. The overall response rate (ORR) of the study group was significantly higher than that of the control group. The carcinoma embryonic antigen (CEA) and the vascular endothelial growth factor (VEGF) in the two groups were significantly decreased, with lower results in the study group compared to the control group. The 12-month and 24-month overall survival (OS) of the study group were significantly higher than those of the control group. There was no significant difference in progression-free survival (PFS) between the two groups. The median OS in the control group was 20.0 months, and the study group had not yet reached the median OS; the OS in the study group was significantly higher than that in the control group. There was no significant difference in adverse reactions between the two groups. Conclusion. For patients with oligometastatic lung cancer, apatinib combined with chemotherapy can significantly improve clinical efficacy, reduce tumor marker expression, and extend overall survival with good safety profiles. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to investigate the function of miR‐3529‐3p in lung adenocarcinoma and MnO2‐SiO2‐APTES (MSA) as a promising multifunctional delivery agent for lung adenocarcinoma therapy. Methods: Expression levels of miR‐3529‐3p were evaluated in lung carcinoma cells and tissues by qRT‐PCR. The effects of miR‐3529‐3p on apoptosis, proliferation, metastasis and neovascularization were assessed by CCK‐8, FACS, transwell and wound healing assays, tube formation and xenografts experiments. Luciferase reporter assays, western blot, qRT‐PCR and mitochondrial complex assay were used to determine the targeting relationship between miR‐3529‐3p and hypoxia‐inducible gene domain family member 1A (HIGD1A). MSA was fabricated using MnO2 nanoflowers, and its heating curves, temperature curves, IC50, and delivery efficiency were examined. The hypoxia and reactive oxygen species (ROS) production was investigated by nitro reductase probing, DCFH‐DA staining and FACS. Results: MiR‐3529‐3p expression was reduced in lung carcinoma tissues and cells. Transfection of miR‐3529‐3p could promote apoptosis and suppress cell proliferation, migration and angiogenesis. As a target of miR‐3529‐3p, HIGD1A expression was downregulated, through which miR‐3529‐3p could disrupt the activities of complexes III and IV of the respiratory chain. The multifunctional nanoparticle MSA could not only efficiently deliver miR‐3529‐3p into cells, but also enhance the antitumor function of miR‐3529‐3p. The underlying mechanism may be that MSA alleviates hypoxia and has synergistic effects in cellular ROS promotion with miR‐3529‐3p. Conclusions: Our results establish the antioncogenic role of miR‐3529‐3p, and demonstrate that miR‐3529‐3p delivered by MSA has enhanced tumor suppressive effects, probably through elevating ROS production and thermogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: Precision medicine has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). Due to the discovery of novel predictive biomarkers, an exhaustive molecular characterization of the disease is required for adequate clinical management. In this research, we aim to evaluate the implementation of next-generation sequencing (NGS) in routine diagnostics under a quality management system. In a cohort of 350 patients, NGS studies were able to reveal a distinct molecular profile of the disease according to sex and smoking status, as well as co-occurring and mutually exclusive relationships between molecular alterations. In stage IV patients, targeted therapies were associated with longer progression-free and overall survival. NGS has expanded precision medicine in our center by increasing the percentage of patients with actionable molecular alterations. Our findings consolidate the use of NGS as a molecular diagnostic tool in the clinical routine of a public healthcare hospital. Next-generation sequencing (NGS) is a molecular approach able to provide a comprehensive molecular profile of non-small cell lung cancer (NSCLC). The broad spectrum of biomarker-guided therapies has positioned molecular diagnostic laboratories as a central component of patient clinical management. Here, we show the results of an UNE-EN ISO 15189:2022 NGS-accredited assay in a cohort of 350 patients. TP53 (51.0%), KRAS (26.6%) and EGFR (12.9%) were the most frequently mutated genes. Furthermore, we detected co-occurring and mutually exclusive alterations, as well as distinct molecular profiles according to sex and smoking habits. Actionable genetic alterations were significantly more frequent in female patients (80.5%, p < 0.001) and in never-smoker patients (87.7%, p < 0.001). When NGS was established as the main molecular testing strategy, 36.4% of patients received at least one line of targeted treatment. Among 200 patients with stage IV NSCLC, first-line treatment with targeted therapies was associated with a longer progression-free survival (PFS) (13.4 months (95% CI, 10.2–16.6) (p = 0.001)). Similarly, the overall survival (OS) of patients receiving at least one targeted drug was significantly longer (26.2 months (95% CI, 11.8–40.5) (p < 0.001)). Our results show that the implementation of NGS in the public healthcare system has provided a broader application of precision medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: In a cohort of patients diagnosed with metastatic non-small cell lung cancer (NSCLC) where chemotherapy is an integral part of the treatment, shedding light on the characteristics of patients who refuse chemotherapy provides valuable data on the possible reasons and aid in recommending strategies to narrow the gaps in survival outcomes. This original contribution extracted from data in the National Cancer Database (NCDB), one of the largest national registries on cancer patients in the United States, is intended to provide generalizable information to improve cancer care delivery. Unfortunately, to our knowledge, retrospective studies looking into reasons for refusing standard treatment modalities for NSCLC are lacking. (1) Background: Disparities in cancer treatment and outcomes have long been well-documented in the medical literature. With the eruption of advances in new treatment modalities, the long-existing disparities are now being further uncovered and brought to the attention of the medical community. While social health determinants have previously been linked to treatment disparities in lung cancer, we analyzed data from the National Cancer Database to explore sociodemographic and geographic factors related to accepting or declining physician-recommended chemotherapy. Patients diagnosed with metastatic lung cancer between 2004 and 2016 who declined chemotherapy recommended by their physicians were included in this study. Multivariate logistic regression analysis was performed. Cox Regression and Kaplan-Meier analyses were performed to look for survival characteristics. (2) Results: 316,826 patients with Stage IV lung cancer were identified. Factors related to a higher rate of refusal by patients included older age > 70, female sex, low income, lack of insurance coverage, residency in the New England region, and higher comorbidity. Patients living in areas with lower education were less likely to decline chemotherapy. (3) Conclusion: Further understanding of the factors impacting treatment decisions would be essential to improve the efficacy of care delivery in patients with cancer and reduce reversible causes of disparity. [ABSTRACT FROM AUTHOR]

Simple Summary: Aberrations in DNA methylation profiles may alter the expression of key miRNAs in non-small cell lung cancer. In this study, we focus on the analysis of the imprinted C19MC and MIR371-3 miRNA clusters due to their oncogenic role. We identified the DNA methylation status and discovered its deregulated target genes in this disease. Additionally, we found five downstream target genes that were correlated with worse overall survival in non-small cell lung cancer. We conclude that C19MC and MIR371-3 are key players in lung cancer because their polycistronic epigenetic regulation leads to differential tumor expression, affecting downstream targets with prognostic value. Epigenetic mechanisms have emerged as an important contributor to tumor development through the modulation of gene expression. Our objective was to identify the methylation profile of the imprinted C19MC and MIR371-3 clusters in patients with non-small cell lung cancer (NSCLC) and to find their potential target genes, as well as to study their prognostic role. DNA methylation status was analyzed in a NSCLC patient cohort (n = 47) and compared with a control cohort including COPD patients and non-COPD subjects (n = 23) using the Illumina Infinium Human Methylation 450 BeadChip. Hypomethylation of miRNAs located on chromosome 19q13.42 was found to be specific for tumor tissue. We then identified the target mRNA–miRNA regulatory network for the components of the C19MC and MIR371-3 clusters using the miRTargetLink 2.0 Human tool. The correlations of miRNA-target mRNA expression from primary lung tumors were analyzed using the CancerMIRNome tool. From those negative correlations identified, we found that a lower expression of 5 of the target genes (FOXF2, KLF13, MICA, TCEAL1 and TGFBR2) was significantly associated with poor overall survival. Taken together, this study demonstrates that the imprinted C19MC and MIR371-3 miRNA clusters undergo polycistronic epigenetic regulation leading to deregulation of important and common target genes with potential prognostic value in lung cancer. [ABSTRACT FROM AUTHOR]

The landmark ADAURA study recently demonstrated a significant disease-free survival benefit of adjuvant osimertinib in patients with resected EGFR -mutated lung adenocarcinoma. However, data on prevalence rates and stage distribution of EGFR mutations in non-small cell lung cancer in Western populations are limited since upfront EGFR testing in early stage lung adenocarcinoma is not common practice. Here, we present a unique, real-world, unselected cohort of lung adenocarcinoma to aid in providing a rationale for routine testing of early stage lung cancers for EGFR mutations in the West-European population. We performed routine unbiased testing of all cases, regardless of TNM stage, with targeted next-generation sequencing on 486 lung adenocarcinoma cases between 01- January 2014 and 01 February 2020. Clinical and pathological data, including co-mutations and morphology, were collected. EGFR- mutated cases were compared to KRAS- mutated cases to investigate EGFR- specific characteristics. In total, 53 of 486 lung adenocarcinomas (11%) harboured an EGFR mutation. In early stages (stage 0-IIIA), the prevalence was 13%, versus 9% in stage IIIB-IV. Nine out of 130 (7%) stage IB-IIIA patients fit the ADAURA criteria. Early stage cases harboured more L858R mutations (p = 0.02), fewer exon 20 insertions (p = 0.048), fewer TP53 co-mutations (p = 0.007), and were more frequently never smokers (p = 0.04) compared to late stage cases with EGFR mutations. The KRAS -mutated cases were distributed more evenly across TNM stages compared to the EGFR- mutated cases. As (neo-)adjuvant targeted therapy regimes enter the field of lung cancer treatment, molecular analysis of early stage non-small cell lung cancer becomes relevant. Testing for EGFR mutations in early stage lung adenocarcinoma holds a substantial yield in our population, as our number needed to test ratio for adjuvant osimertinib was 14.4. The observed differences between early and late stage disease warrant further analysis to work towards better prognostic stratification and more personalised treatment. • EGFR mutation prevalence was 9% in early stage NSCLC in our West-European cohort. • EGFR mutation prevalence is spread unevenly across TNM stages. • Number needed to test for adjuvant osimertinib was 14.4 in our population. • Early- and late stage EGFR -mutated NSCLC differs in clinicopathological features. [ABSTRACT FROM AUTHOR]

Objectives. Indoleamine 2,3-dioxygenase 1 (IDO1) acts as the key rate-limiting enzyme that converts tryptophan (Trp) to kynurenine (Kyn). Its activity was primarily induced by interferon-γ (IFN-γ), which was reported to play a role in the development of acute radiation-induced pneumonitis. In this study, we aimed to investigate the correlation between IDO1 activity and radiation-induced lung toxicity (RILT) in stage III nonsmall cell lung cancer (NSCLC) patients who were treated with chemoradiotherapy (CRT). Materials and Methods. Systemic IDO1 activity was reflected by Kyn : Trp ratio. Plasma levels of Kyn and Trp in 113 stage III NSCLC patients were measured by high-performance liquid chromatography (HPLC) before the initiation of radiotherapy. Dynamic change of IDO1 activity was followed in 23 patients before, during, and after radiotherapy. We also used RNA sequencing (RNA-seq) data from the Cancer Genome Atlas Program (TCGA) database and performed gene set enrichment analysis (GSEA) to explore how IDO1 was involved in the development of RILT. Results. 9.7% (11/113) of the whole group developed G 3 + (greater than or equal to Grade 3) RILT. Preradiation IDO1 activity was significantly higher in patients who developed G 3 + RILT than in non G 3 + RILT patients. (P = 0.029 , AUC = 0.70). Univariate and multivariate analyses showed that high IDO1 activity was independently associated with the risk of G 3 + RILT (P = 0.034). A predictive model combining both IDO1 activity and FEV1 was established for severe RILT and displayed a moderate predictive value (AUC = 0.83, P < 0.001). The incidence of G 3 + RILT was 2.6% (1/38) in patients with an IDO activity ≤0.069 and FEV1 > 59.4%, and 50.0% (6/12) in those with an IDO activity >0.069 and FEV1 ≤ 59.4%. Of 23 patients with dynamic tracking, the IDO1 activity of postradiation was significantly lower than midradiation (P = 0.021), though no significant differences among the three time points were observed (P = 0.070). Bioinformatic analysis using RNA-seq data from 1014 NSCLC patients revealed that IDO mainly functioned in the inflammatory response instead of the late fibrosis process in NSCLC patients. Conclusion. High baseline IDO1 activity combined with unfavorable baseline FEV1 was predictive of severe RILT in unresectable stage III NSCLC patients. IDO1 might play a role in the acute inflammatory response. Finding effective interventions to alleviate RILT using IDO inhibitors is warranted in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer is one of the most common human cancers and the leading cause of cancer-related mortality worldwide. The advent of immunotherapy for the treatment of non-small cell lung cancer has significantly improved progression-free survival, overall survival, and the patient's quality of life in comparison to chemotherapy. Currently, it is estimated that long-term survival can be achieved in more than 15% of patients treated with immunotherapy. Therefore, the optimal duration of immunotherapy in long survivors needs to be established to avoid overtreatment, side effects, and high costs and at the same time, protect them from potential disease relapse. The aim of this review is to discuss all the aspects related to the optimal duration of immunotherapy in long survivors with non-small cell lung cancer. Lung cancer is one of the most common human malignancies and the leading cause of cancer-related death worldwide. Novel therapeutic approaches, like targeted therapies against specific molecular alterations and immunotherapy, have revolutionized in the last decade the oncological outcomes in patients affected by non-small cell lung cancer (NSCLC). The advent of immunotherapy for the treatment of NSCLC has significantly improved overall and progression-free survival, as well as the patient's quality of life in comparison to traditional chemotherapy. Currently, it is estimated that long-term survival can be achieved in more than 15% of NSCLC patients treated with immunotherapy. Therefore, the optimal duration of immunotherapy in long survivors needs to be established to avoid overtreatment, side effects, and high costs and at the same time, protect them from potential disease relapse or progression. We performed a narrative review to discuss all the aspects related to the optimal duration of immunotherapy in long survivors with NSCLC. Data regarding the duration of immunotherapy in the most impacting clinical trials were collected, along with data regarding the impact of toxicities, side effects, and costs for healthcare providers. In addition, the two-year immunotherapy scheme in patients who benefit from first-line or subsequent treatment lines are examined, and the need for biomarkers that can predict outcomes during and after immunotherapy cessation in patients affected by NSCLC are discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor Treating Fields (TTFields) are electric fields that prevent cancer cell survival and tumor growth, without impacting healthy cells. TTFields therapy is delivered to the tumor using arrays that are placed on the patient's skin, surrounding the tumor site, without the need for invasive procedures. Taxanes are chemotherapies used to successfully treat several aggressive cancers and are associated with side effects such as neutropenia (low neutrophils) and peripheral neuropathy. Although taxanes are considered to be the standard of care for many cancers, there is a need to identify other treatments that can be used in combination, to enhance their effectiveness, without increasing the side effects. The preclinical (laboratory) and clinical (human) data summarized here suggest that TTFields therapy together with taxanes may be beneficial in the treatment of several cancers. Non-small cell lung cancer, ovarian cancer, and pancreatic cancer all present with high morbidity and mortality. Systemic chemotherapies have historically been the cornerstone of standard of care (SOC) regimens for many cancers, but are associated with systemic toxicity. Multimodal treatment combinations can help improve patient outcomes; however, implementation is limited by additive toxicities and potential drug–drug interactions. As such, there is a high unmet need to develop additional therapies to enhance the efficacy of SOC treatments without increasing toxicity. Tumor Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. The therapy is locoregional and is delivered noninvasively to the tumor site via a portable medical device that consists of field generator and arrays that are placed on the patient's skin. As a noninvasive treatment modality, TTFields therapy-related adverse events mainly consist of localized skin reactions, which are manageable with effective acute and prophylactic treatments. TTFields selectively target cancer cells through a multi-mechanistic approach without affecting healthy cells and tissues. Therefore, the application of TTFields therapy concomitant with other cancer treatments may lead to enhanced efficacy, with low risk of further systemic toxicity. In this review, we explore TTFields therapy concomitant with taxanes in both preclinical and clinical settings. The summarized data suggest that TTFields therapy concomitant with taxanes may be beneficial in the treatment of certain cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: The management of non-small cell lung cancer with a common EGFR mutation has evolved over the past decades. While frontline use of second- or third-generation EGFR tyrosine kinase inhibitors (TKIs) is preferred over first-generation EGFR-TKIs, choosing the ideal agent depends on multiple factors (drug availability, physician comfort, specific EGFR mutation, presence of brain metastasis, etc.). Furthermore, defining subsequent therapies at the time of progression will rely on numerous variables (extent of disease, frontline EGFR TKI generation used, mechanism of resistance, etc.). Consequently, defining an optimal sequencing strategy is both, crucial and challenging. In this review, we present a detailed summary of evidence supporting the use of EGFR TKIs with or without other therapeutic approaches, outline available options at the time of disease progression, summarize investigational strategies, and suggest an approach to therapeutic sequencing in patients with common EGFR mutations. The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC in the first-line setting, therapy selection after progression on EGFR TKIs remains complex. Multiple groups are investigating novel therapies and drug combinations to determine the optimal therapy and treatment sequence for these patients. In this review, we summarize the landmark trials and history of the approval of EGFR TKIs, their efficacy and tolerability, and the role of these therapies in patients with central nervous system metastasis. We also briefly discuss the mechanisms of resistance to EGFR TKIs, ongoing attempts to overcome resistance and improve outcomes, and finalize by offering treatment sequencing recommendations. [ABSTRACT FROM AUTHOR]

To assess the risk of cardiac toxicity following radical radiotherapy in advanced lung cancer patients. Patients with a diagnosis of stage III non-small cell lung cancer (NSCLC) receiving chemoradiotherapy were extracted from a population-based cohort in Ontario, Canada. The primary outcome of cardiac toxicity, defined as cardiac events or congestive heart failure, was assessed at 1 and 5 years following chemoradiotherapy. Secondary outcomes included overall survival, survival in relationship to post-treatment cardiac events and the effect of radiotherapy technique on cardiac toxicity. In total, 2031 NSCLC patients were included. The cumulative incidence of cardiac toxicity at 5 years was 20.3% (18.4–22.3). The median survival was 13.7 months in NSCLC patients who had a cardiac event post-chemoradiotherapy compared with 23.4 months in those who did not (P = 0.012). There was a trend towards increased cumulative cardiac toxicity (hazard ratio 3.37, P = 0.14) with three-dimensional conformal radiotherapy compared with intensity-modulated or volumetric arc radiotherapy techniques. The risk of cardiac events and congestive heart failure 5 years after radical thoracic radiotherapy appears high and survival is inferior at 1 year in those patients who experience a cardiac event post-treatment. More conformal radiotherapy techniques may help reduce cardiac toxicity. Further studies should investigate adaptive treatment planning and close monitoring and intervention in this high-risk group after chemoradiotherapy. • There may be an elevated risk of cardiac disease following radiotherapy for NSCLC. • The risk of death may be higher in patients who experience cardiac events after treatment for NSCLC. • Increasing age and male sex may also confer increased cardiac disease risk in NSCLC patients. • Treatment technique may have the potential to modify cardiac risk. [ABSTRACT FROM AUTHOR]

Background: Wide variation exists globally in the treatment and outcomes of stage III patients with non–small cell lung cancer (NSCLC). We conducted an up-to-date patterns of care analysis in the state of Victoria, Australia, with a particular focus on the proportion of patients receiving treatment with radical intent, treatment trends over time, and survival. Materials and Methods: Stage III patients with NSCLC were identified in the Victorian Lung Cancer Registry and categorized by treatment received and treatment intent. Logistic regression was used to explore factors predictive of receipt of radical treatment and the treatment trends over time. Cox regression was used to explore variables associated with overall survival (OS). Covariates evaluated included age, sex, ECOG performance status, smoking status, year of diagnosis, Australian born, Aboriginal or Torres Strait Islander status, socioeconomic status, rurality, public/private status of notifying institution, and multidisciplinary meeting discussion. Results: A total of 1396 patients were diagnosed between 2012 and 2019 and received treatment with radical intent 67%, palliative intent 23%, unknown intent 5% and no treatment 5%. Radical intent treatment was less likely if patients were >75 years, ECOG ≥1, had T3-4 or N3 disease or resided rurally. Surgery use decreased over time, while concurrent chemoradiotherapy and immunotherapy use increased. Median OS was 38.0, 11.1, and 4.4 months following radical treatment, palliative treatment or no treatment, respectively. Conclusion: Almost a third of stage III patients with NSCLC still do not receive radical treatment. Strategies to facilitate radical treatment and better support decision making between increasing multimodality options are required. Variations exist in the treatment and outcomes for patients with stage III non–small cell lung cancer. This article reports an up-to-date patterns of care analysis focusing on the proportion of patients receiving treatment with radical intent, treatment trends over time, and survival. [ABSTRACT FROM AUTHOR]

Background: To explore the efficacy and prognostic factors of different treatment modalities on anaplastic lymphoma kinase (ALK)+ non‐small cell lung cancer (NSCLC) patients with brain metastases (BMs). Methods: A total of 86 patients were enrolled into the study. They were divided into two cohorts based on their history of treatment with ALK tyrosine kinase inhibitors (ALK‐TKIs) prior to the incidence of BMs. ALK‐TKI‐naïve patients with BMs were included in cohort 1 (n = 59); patients who developed BMs after ALK‐TKIs treatment were enrolled in cohort 2 (n = 27). Prognostic factors related with overall survival (OS) when treated with ALK‐TKIs were assessed in multivariable analysis. Results: With a median follow‐up of 41.8 months, the median OS was 34.8 months. In cohort 1, the OS, intracranial progression‐free survival (iPFS), and progression‐free survival (PFS) were 38.7 months (95% CI: 23.3 to 54.1), 18.5 months (95% CI: 9.6 to 27.4), and 19.1 months (95% CI: 13.7 to 24.5), respectively. Significantly improved OS and iPFS were noted in those patients in which second‐generation ALK‐TKIs versus crizotinib were initiated (OS: not reached vs. 29.0 months, p = 0.040; iPFS: 22.8 vs. 11.9 months, p = 0.035). In cohort 2, patients who experienced BMs as a result of the treatment failure of ALK‐TKIs had a median OS of 27.1 months. Considerable duration of stable disease in patients with measurable BMs was observed (iPFS: 11.5 months, 95% CI: 4.4 to 18.6; PFS: 12.2 months, 95% CI: 3.2 to 21.1). Conclusion: Second‐generation ALK‐TKIs further improved the duration of intracranial response and survival in ALK+ NSCLC patients with BMs in a real‐world setting. The potent intracranial efficacy of second‐generation ALK‐TKIs might generate the lowered urgency of local treatment. [ABSTRACT FROM AUTHOR]

Background and Aims. Histone deacetylase 1 (HDAC1) codes a protein that is a component of the histone deacetylase complex. The abnormal expression of HDAC1 is strongly correlated with cell proliferation, differentiation, transcription, and translation. Through continuous screening of genes associated with changes in lung adenocarcinoma (LUAD), gene networks are formed to explore tumor pathogenesis and new therapeutic targets. Methods. We evaluated HDAC1 gene survival analysis and its expression of LUAD using relevant websites and databases (TCGA and GEO databases). Through data mining, we determined the frequency and type of HDAC1 mutation, obtained the relevant heat map of the gene interaction network, completed the analysis of gene ontology and function enrichment, and understood the pharmaceutic of HDAC1. Results. We found that HDAC1 expression was associated with the prognosis of patients with LUAD. In gene expression analysis, HDAC1 was highly expressed in LUAD, and the HDAC1 interaction gene network (MARCKSL, eIF3I) was closely related to cellular gene expression. Functional network analysis shows that the expression of HDAC1 is related to the monitoring point of the G1-S phase of the cell cycle and the activation of the Notch signaling pathway (CSL transcription factor), which is involved in the process of cell proliferation and differentiation and gene expression associated with new therapeutic targets. Conclusion. Our data revealed the expression and potential regulatory factors of HDAC1 in LUAD of data mining, which laid a foundation for the study of the occurrence, development, and treatment of HDAC1 in LUAD. [ABSTRACT FROM AUTHOR]

Introduction: To calculate the number of days patients with terminal nonsmall cell lung cancer (NSCLC) spent at home in the last 3 months of life, and to identify factors that predict a lower proportion of days at home. Material and methods: Retrospective study of 434 deceased patients with NSCLC. The number of days spent in a hospital or nursing home was identified from electronic health records. Results: Most patients received primary chemotherapy. Only 45% received palliative care provided by a dedicated palliative care team (PCT). In the last 3 months of life, only 39 patients (9%) were not hospitalized. The median number of days spent in hospital was 17, range 0-61. Hospital death occurred in 48%. Admission to a nursing home was recorded in 45%. Overall, the patients spent a median of 64 days at home. Both, older patients and females spent fewer days at home. Family network and aspects of palliative care, possibly reflecting the symptom duration or burden, also impacted days at home. Conclusions: Long-lasting need for PCT support (not just the final 3 months) and earlier necessity for opioid analgesics were predictive for a reduced number of days at home. However, modifiable factors such as sex were identified too. [ABSTRACT FROM AUTHOR]