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1.
Respirology ; 29(8): 665-673, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38960450

ABSTRACT

Eligibility criteria for lung cancer screening increasingly need to consider family history of lung cancer, as well as age and smoking status. Lung cancer screening will reveal a multitude of incidental findings, of variable clinical significance, and with a need for clear pathways of management. Pulmonary nodule sampling is enhanced by intra-procedural imaging and cutting-edge robotic technology. Systematic thoracic lymph node sampling has implications for treatment efficacy. Bronchoscopic ablative techniques are feasible for peripheral lung cancers. Bronchoscopic sampling continues to have a high yield for lung cancer molecular characterization. Immunotherapy indications have expanded to include early stage and resectable lung cancer.


Subject(s)
Bronchoscopy , Early Detection of Cancer , Lung Neoplasms , Pulmonary Medicine , Humans , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Bronchoscopy/methods , Early Detection of Cancer/methods , Pulmonary Medicine/methods , Immunotherapy/methods
2.
Cell Rep Med ; 5(7): 101648, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38986624

ABSTRACT

Low migratory dendritic cell (DC) levels pose a challenge in cancer immune surveillance, yet their impact on tumor immune status and immunotherapy responses remains unclear. We present clinical evidence linking reduced migratory DC levels to immune-cold tumor status, resulting in poor patient outcomes. To address this, we develop an autologous DC-based nanovaccination strategy using patient-derived organoid or cancer cell lysate-pulsed cationic nanoparticles (cNPs) to load immunogenic DC-derived microvesicles (cNPcancer cell@MVDC). This approach transforms immune-cold tumors, increases migratory DCs, activates T cells and natural killer cells, reduces tumor growth, and enhances survival in orthotopic pancreatic and lung cancer models, surpassing conventional methods. In vivo imaging reveals superior cNPcancer cell@MVDC accumulation in tumors and lymph nodes, promoting immune cell infiltration. Mechanistically, cNPs enrich mitochondrial DNA, enhancing cGAS-STING-mediated DC activation and migration. Our strategy shifts cold tumors to a hot state, enhancing antitumor immunity for potential personalized cancer treatments.


Subject(s)
Cancer Vaccines , DNA, Mitochondrial , Dendritic Cells , Lung Neoplasms , Nanoparticles , Pancreatic Neoplasms , Dendritic Cells/immunology , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/pathology , Lung Neoplasms/immunology , Lung Neoplasms/therapy , Lung Neoplasms/pathology , Humans , Animals , DNA, Mitochondrial/genetics , DNA, Mitochondrial/immunology , Mice , Cancer Vaccines/immunology , Nanoparticles/chemistry , Cell Line, Tumor , Immunotherapy/methods , Female , Cell Movement , Mice, Inbred C57BL
3.
J Cancer Res Ther ; 20(3): 1085-1087, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-39023622

ABSTRACT

ABSTRACT: Giant cell tumor of bone (GCT) is a benign tumor of bone that is known to be locally aggressive rarely metastasizing to distant sites, most commonly to the lungs. The reported pulmonary metastasis incidence is 1 - 9%. We report a case of GCT with solitary pulmonary metastasis who had significant clinical benefit and disease control with sequential application of surgical resection of pulmonary metastasis, local external beam radiation therapy (EBRT), and systemic Denosumab. We wish to highlight that even in metastatic GCT, there is significant clinical benefit in aggressive treatment.


Subject(s)
Bone Neoplasms , Giant Cell Tumor of Bone , Lung Neoplasms , Humans , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Lung Neoplasms/therapy , Giant Cell Tumor of Bone/pathology , Giant Cell Tumor of Bone/therapy , Giant Cell Tumor of Bone/secondary , Giant Cell Tumor of Bone/diagnosis , Bone Neoplasms/secondary , Bone Neoplasms/therapy , Bone Neoplasms/pathology , Adult , Female , Femur/pathology , Femur/diagnostic imaging , Femur/surgery , Treatment Outcome , Male , Denosumab/therapeutic use , Combined Modality Therapy
4.
Front Immunol ; 15: 1349502, 2024.
Article in English | MEDLINE | ID: mdl-39015563

ABSTRACT

Non-small cell lung cancer (NSCLC) remains an unsolved challenge in oncology, signifying a substantial global health burden. While considerable progress has been made in recent years through the emergence of immunotherapy modalities, such as immune checkpoint inhibitors (ICIs), monotherapies often yield limited clinical outcomes. The rationale behind combining various immunotherapeutic or other anticancer agents, the mechanistic underpinnings, and the clinical evidence supporting their utilization is crucial in NSCLC therapy. Regarding the synergistic potential of combination immunotherapies, this study aims to provide insights to help the landscape of NSCLC treatment and improve clinical outcomes. In addition, this review article discusses the challenges and considerations of combination regimens, including toxicity management and patient selection.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Immunotherapy , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/immunology , Lung Neoplasms/therapy , Lung Neoplasms/immunology , Immunotherapy/methods , Immune Checkpoint Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Animals , Combined Modality Therapy , Treatment Outcome
5.
BMJ Open ; 14(6): e079038, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951003

ABSTRACT

BACKGROUND: Non-small cell lung cancer (NSCLC) has a poor prognosis. Transvascular intervention is an important approach for treating NSCLC. Drug-eluting bead bronchial artery chemoembolisation (DEB-BACE) is a technique of using DEBs loaded with chemotherapeutic drugs for BACE. This study aims to conduct a meta-analysis to comprehensively assess the effectiveness and safety of DEB-BACE in treating NSCLC and investigate a novel therapeutic strategy for NSCLC. METHODS AND ANALYSIS: Wanfang, China National Knowledge Infrastructure, Medline (via PubMed), Cochrane Library, Scopus and Embase databases will be searched in November 2024. A meta-analysis will be conducted to assess the effectiveness and safety of DEB-BACE in the treatment of NSCLC. The following keywords will be applied: "Carcinoma, Non-Small-Cell Lung", "Non-Small Cell Lung Cancer", "Drug-Eluting Bead Bronchial Arterial Chemoembolization" and "drug-eluting beads". Reports in Chinese or English comparing the efficacy of DEB-BACE with other NSCLC treatment options will be included. Case reports, single-arm studies, conference papers, abstracts without full text and reports published in languages other than English and Chinese will not be considered. The Cochrane Handbook for Systematic Reviews of Interventions will be used to independently assess the risk of bias for each included study. In case of significant heterogeneity between studies, possible sources of heterogeneity will be explored through subgroup and sensitivity analysis. For the statistical analysis of the data, RevMan V.5.3 will be used. ETHICS AND DISSEMINATION: This meta-analysis will seek publication in a peer-reviewed journal on completion. Ethical approval is not required for this study as it is a database-based study. PROSPERO REGISTRATION NUMBER: CRD42023411392.


Subject(s)
Bronchial Arteries , Carcinoma, Non-Small-Cell Lung , Chemoembolization, Therapeutic , Lung Neoplasms , Meta-Analysis as Topic , Humans , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Chemoembolization, Therapeutic/methods , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Research Design
6.
Pathol Oncol Res ; 30: 1611817, 2024.
Article in English | MEDLINE | ID: mdl-38957347

ABSTRACT

The delivery of neoadjuvant and perioperative therapies for non-small cell lung cancer has been radically altered by significant advances and by the incorporation of targeted therapies as well as immune checkpoint inhibitors alone or alongside conventional chemotherapy. This evolution has been particularly notable in the incorporation of immunotherapy and targeted therapy into the treatment of resectable NSCLC, where recent FDA approvals of drugs such as nivolumab and pembrolizumab, in combination with platinum doublet chemotherapy, have led to considerable improvements in pathological complete response rates and the potential for enhanced long-term survival outcomes. This review emphasizes the growing importance of biomarkers in optimizing treatment selection and explores the impact of emerging studies that challenge existing treatment paradigms and investigate novel therapeutic combinations poised to redefine standard of care practices. Furthermore, the discussion extends to the unmet needs within perioperative treatment assessment and prognostication, highlighting the prospective value of biomarkers in evaluating treatment responses and prognosis.


Subject(s)
Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Neoadjuvant Therapy , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Neoadjuvant Therapy/methods , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysis , Prognosis
7.
Front Immunol ; 15: 1386561, 2024.
Article in English | MEDLINE | ID: mdl-38957460

ABSTRACT

Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in achieving long survival of patients. MET fusion is a rare oncogenic factor, whose optimal detection and treatment are not well established. Here, we report on a 32-year-old female lung adenocarcinoma patient with positive PD-L1 and negative driver gene detected by DNA-based next-generation sequencing (NGS). A radical resection of the primary lesion after chemotherapy combined with PD-1 checkpoint inhibitor administration indicated primary immuno-resistance according to her pathological response and rapid relapse. A rare CD47-MET was detected by RNA-based NGS, which was confirmed by fluorescence in situ hybridization. Multiplex immunofluorescence revealed a PD-L1 related heterogeneous immunosuppressive microenvironment with little distribution of CD4+ T cells and CD8+ T cells. Savolitinib therapy resulted in a progression-free survival (PFS) of >12 months, until a new secondary resistance mutation in MET p.D1228H was detected by re-biopsy and joint DNA-RNA-based NGS after disease progression. In this case, CD47-MET fusion NSCLC was primarily resistant to immunotherapy, sensitive to savolitinib, and developed secondary MET p.D1228H mutation after targeted treatment. DNA-RNA-based NGS is useful in the detection of such molecular events and tracking of secondary mutations in drug resistance. To this end, DNA-RNA-based NGS may be of better value in guiding precise diagnosis and individualized treatment in this patient population.


Subject(s)
Adenocarcinoma of Lung , High-Throughput Nucleotide Sequencing , Lung Neoplasms , Proto-Oncogene Proteins c-met , Humans , Female , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/diagnosis , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/therapy , Adult , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/therapy , Proto-Oncogene Proteins c-met/genetics , Oncogene Proteins, Fusion/genetics , Drug Resistance, Neoplasm/genetics , Immune Checkpoint Inhibitors/therapeutic use
9.
BMC Pulm Med ; 24(1): 332, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987763

ABSTRACT

BACKGROUND: Real-world data regarding patient characteristics, adjuvant treatment patterns, and long-term survival outcomes are needed to better understand unmet needs among patients with completely resected early-stage non-small cell lung cancer (NSCLC). METHODS: Electronic medical records from the U.S.-based ConcertAI Patient360™ database were analyzed in patients with stage IB-IIIA NSCLC who underwent complete resection prior to March 1, 2016. Patients were followed until death or July 1, 2021. This study evaluated adjuvant chemotherapy use, and overall survival (OS) and real-world disease-free survival (rwDFS) outcomes using the Kaplan-Meier method. The correlation between OS and rwDFS was assessed using the Kendall rank test. Among patients who did not recur 5 years following surgery, landmark analyses of OS and rwDFS were conducted to understand the subsequent survival impact of remaining disease-free for at least 5 years. RESULTS: Data from 441 patients with completely resected stage IB-IIIA NSCLC were included. About 35% of patients received adjuvant chemotherapy post-resection. Median OS and rwDFS from resection were 83.1 months and 42.4 months, respectively. The 5-year OS and rwDFS rates were 65.7% and 42.1%, respectively. OS and rwDFS were positively correlated (Kendall rank correlation coefficient = 0.67; p < 0.0001). Among patients without recurrence within 5 years after resection, the subsequent 5-year OS and rwDFS survival rates were 52.9% and 36.6%, respectively. CONCLUSIONS: Use of adjuvant chemotherapy was low, and the overall 5-year OS rate remained low despite all patients having undergone complete resection. Patients who remained non-recurrent over time had favorable subsequent long-term survival.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Neoplasm Staging , Humans , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/surgery , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Female , Male , Retrospective Studies , Aged , Middle Aged , Chemotherapy, Adjuvant , Disease-Free Survival , Pneumonectomy , Kaplan-Meier Estimate , Aged, 80 and over , United States/epidemiology , Adult
10.
BMJ Open ; 14(7): e079080, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38991667

ABSTRACT

OBJECTIVE: The objective of this systematic review was to explore the evidence regarding shared decision-making (SDM) in the management of pulmonary nodules. DESIGN: Systematic review of quantitative and qualitative studies. DATA SOURCE: Studies published in English or Chinese up to April 2022 were extracted from nine databases: PubMed, PsycINFO, EMBASE, Cochrane Library, Web of Science and CINAHL, China National Knowledge Infrastructure, Wanfang Data and SinoMed Data. ELIGIBILITY CRITERIA: Studies were eligible if patients or healthcare providers are faced with pulmonary nodule management options or the interventions or experiences were focused on the patient-healthcare provider relationship or health education to make, increase or support shared decisions. All types of studies were included, including quantitative and qualitative studies. Grey literature and literature that had not been peer reviewed were excluded. Poster abstracts and non-empirical publications such as editorials, letters, opinion papers and review articles were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened abstracts and full texts, assessed quality using Joanna Briggs Institute's critical appraisal tools, and extracted data from included studies. Thematic syntheses were used to identify prominent themes emerging from the data. RESULTS: A total of 12 studies met the inclusion criteria, 11 of which were conducted in USA. These included six qualitative studies and six quantitative studies (including both survey and quasi-experimental designs). Three major themes with specific subthemes emerged: (1) Opportunity (uncertainty in the diagnosis and treatment of pulmonary nodules, willingness to participate in decision-making); (2) Ability (patient's lack of knowledge, physician's experience); and (3) Different worldview (misconception, distress among patients, preference for diagnosis and treatment). CONCLUSIONS: Uncertainty in the management of pulmonary nodules is the opportunity to implement SDM. Patients' lack of knowledge, distress, and misunderstandings between healthcare providers and patients are both the main obstacles and the causes of the application of SDM.


Subject(s)
Decision Making, Shared , Humans , Lung Neoplasms/therapy , Lung Neoplasms/psychology , Qualitative Research , Patient Participation , Multiple Pulmonary Nodules/therapy , Solitary Pulmonary Nodule/therapy , Solitary Pulmonary Nodule/psychology , Solitary Pulmonary Nodule/diagnosis , Physician-Patient Relations
11.
Sci Rep ; 14(1): 16005, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992115

ABSTRACT

Lung cancer is known for its high mortality; many patients already present with metastases at the time of diagnosis. The aim of this study is to assess the impact of new treatment strategies on the survival of primarily metastatic lung cancer patients and to analyze the differences in outcomes between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients. Population-based data, provided by the Robert-Koch Institute in Germany, was used and patients diagnosed between 2007 and 2018 were included in the study. We differentiated between NSCLC and SCLC patients and analyzed the survival over time for both sexes separately, using the Kaplan-Meier method. To evaluate survival advantages, we calculated multivariable hazard ratios. In total, 127,723 patients were considered for the study. We observed a moderate increase in survival over time. All patients showed an increased survival rate when undergoing chemotherapy. Minimal to no increase in survival was shown in NSCLC patients when receiving radiotherapy, whereas SCLC patients' survival time did benefit from it. NSCLC patients receiving immunotherapy showed an increase in survival as well. It can be concluded that advancements in radiotherapy, the application of chemotherapy, and the introduction of immunotherapies lead to an increased survival time of both NSCLC and SCLC primarily metastatic lung cancer patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Germany/epidemiology , Male , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Female , Aged , Middle Aged , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Small Cell Lung Carcinoma/mortality , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/therapy , Neoplasm Metastasis , Survival Rate , Kaplan-Meier Estimate , Aged, 80 and over , Adult , Immunotherapy/methods
12.
Cells ; 13(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38994972

ABSTRACT

Understanding tumor-host immune interactions and the mechanisms of lung cancer response to immunotherapy is crucial. Current preclinical models used to study this often fall short of capturing the complexities of human lung cancer and lead to inconclusive results. To bridge the gap, we introduce two new murine monoclonal lung cancer cell lines for use in immunocompetent orthotopic models. We demonstrate how our cell lines exhibit immunohistochemical protein expression (TTF-1, NapA, PD-L1) and common driver mutations (KRAS, p53, and p110α) seen in human lung adenocarcinoma patients, and how our orthotopic models respond to combination immunotherapy in vivo in a way that closely mirrors current clinical outcomes. These new lung adenocarcinoma cell lines provide an invaluable, clinically relevant platform for investigating the intricate dynamics between tumor and the immune system, and thus potentially contributes to a deeper understanding of immunotherapeutic approaches to lung cancer treatment.


Subject(s)
Adenocarcinoma of Lung , Carcinoma, Non-Small-Cell Lung , Immunotherapy , Lung Neoplasms , Animals , Immunotherapy/methods , Humans , Cell Line, Tumor , Mice , Lung Neoplasms/immunology , Lung Neoplasms/therapy , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/therapy , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/genetics , Disease Models, Animal , Female
13.
Oncoimmunology ; 13(1): 2377830, 2024.
Article in English | MEDLINE | ID: mdl-39005546

ABSTRACT

Attenuated measles virus (MV) exerts its oncolytic activity in malignant pleural mesothelioma (MPM) cells that lack type-I interferon (IFN-I) production or responsiveness. However, other cells in the tumor microenvironment (TME), such as myeloid cells, possess functional antiviral pathways. In this study, we aimed to characterize the interplay between MV and the myeloid cells in human MPM. We cocultured MPM cell lines with monocytes or macrophages and infected them with MV. We analyzed the transcriptome of each cell type and studied their secretion and phenotypes by high-dimensional flow cytometry. We also measured transgene expression using an MV encoding GFP (MV-GFP). We show that MPM cells drive the differentiation of monocytes into M2-like macrophages. These macrophages inhibit GFP expression in tumor cells harboring a defect in IFN-I production and a functional signaling downstream of the IFN-I receptor, while having minimal effects on GFP expression in tumor cells with defect of responsiveness to IFN-I. Interestingly, inhibition of the IFN-I signaling by ruxolitinib restores GFP expression in tumor cells. Upon MV infection, cocultured macrophages express antiviral pro-inflammatory genes and induce the expression of IFN-stimulated genes in tumor cells. MV also increases the expression of HLA and costimulatory molecules on macrophages and their phagocytic activity. Finally, MV induces the secretion of inflammatory cytokines, especially IFN-I, and PD-L1 expression in tumor cells and macrophages. These results show that macrophages reduce viral proteins expression in some MPM cell lines through their IFN-I production and generate a pro-inflammatory interplay that may stimulate the patient's anti-tumor immune response.


Subject(s)
Coculture Techniques , Macrophages , Measles virus , Oncolytic Virotherapy , Oncolytic Viruses , Tumor Microenvironment , Humans , Measles virus/genetics , Measles virus/physiology , Tumor Microenvironment/immunology , Macrophages/metabolism , Macrophages/immunology , Macrophages/virology , Oncolytic Viruses/genetics , Oncolytic Virotherapy/methods , Cell Line, Tumor , Mesothelioma, Malignant/pathology , Mesothelioma, Malignant/therapy , Interferon Type I/metabolism , Monocytes/immunology , Monocytes/metabolism , Monocytes/virology , Lung Neoplasms/pathology , Lung Neoplasms/immunology , Lung Neoplasms/therapy , Lung Neoplasms/virology , Cell Differentiation
14.
Gan To Kagaku Ryoho ; 51(6): 597-602, 2024 Jun.
Article in Japanese | MEDLINE | ID: mdl-39009513

ABSTRACT

In recent years, the human microbiota, especially the gut microbiota, has been attracting attention in various fields, and it is one of the topics in the field of oncology. The human microbiota is known to act directly or indirectly on host immunity, and the gut and lung microbiota influence each other through the"gut-lung axis". It has been suggested that dysbiosis, a condition in which the symbiosis of the human microbiota is disrupted, induces lung inflammation and various respiratory diseases, and is also implicated in the immune microenvironment of lung cancer. It is also widely known that the gut microbiota modulates the efficacy of cancer immunotherapy, a major pillar of lung cancer treatment, and many clinical trials targeting the gut microbiota, such as fecal microbiome transplantation and biotics intervention, are currently being conducted. In the future, research on lung carcinogenesis mechanisms and lung cancer treatment focusing on the human microbiota will become increasingly active.


Subject(s)
Gastrointestinal Microbiome , Immunotherapy , Lung Neoplasms , Animals , Humans , Carcinogenesis/immunology , Dysbiosis/immunology , Dysbiosis/therapy , Dysbiosis/microbiology , Gastrointestinal Microbiome/immunology , Immunotherapy/methods , Lung Neoplasms/immunology , Lung Neoplasms/therapy , Lung Neoplasms/microbiology
15.
BMC Pulm Med ; 24(1): 320, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965500

ABSTRACT

BACKGROUND: The COVID-19 pandemic has had negative drawbacks on the healthcare system worldwide and on individuals other than those directly affected by the virus. Delays in cancer therapy and diagnosis have been reported in the literature. We hypothesized similar effects on patients with lung cancer at our center. METHODS: We retrospectively analyzed data of patients referred to our center with newly diagnosed lung cancer from 2018 to 2022. We considered distribution of UICC Stages and time from case presentation in our multidisciplinary tumor board or from therapeutic indication from treating physician to therapy initiation (surgery, systemic therapies and radiation) to define delays in diagnosis and treatment. RESULTS: 1020 patients with newly diagnosed lung cancer were referred to our center from 2018 to 2022, with a median of 206 cases yearly (range: 200-208). Cases with Stage IV in 2020-2022 were significantly higher than in 2018-2019 (57% vs. 46%, p = 0,001). 228 operative resections took place between 2018 and 2022, 100 from January 2018 to February 2020 and 128 from March 2020 to December 2022. Median time from presentation in our tumor board to resection was also significantly longer after the beginning of the pandemic than before (22 days vs. 15,5 days, p = 0,013). No significant delays were observed for administration of systemic treatment and initiation of radiation. CONCLUSIONS: During the pandemic higher disease stages were reported for patients with lung cancer, yet there were no clinically relevant delays in treatment. In the context of the post-covid era new diagnostic strategies are necessary to facilitate early diagnosis of lung cancer. Despite the pandemic, for patients with suspicious symptoms prompt access to healthcare facilities is essential for early diagnosis.


Subject(s)
COVID-19 , Lung Neoplasms , Time-to-Treatment , Humans , COVID-19/epidemiology , Lung Neoplasms/therapy , Lung Neoplasms/diagnosis , Retrospective Studies , Time-to-Treatment/statistics & numerical data , Male , Female , Aged , Middle Aged , Germany/epidemiology , Aged, 80 and over , Delayed Diagnosis , SARS-CoV-2 , Adult , Cancer Care Facilities , Neoplasm Staging
16.
Cancer Immunol Immunother ; 73(9): 172, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954019

ABSTRACT

PURPOSE: In advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI) monotherapy is often preferred over intensive ICI treatment for frail patients and those with poor performance status (PS). Among those with poor PS, the additional effect of frailty on treatment selection and mortality is unknown. METHODS: Patients in the veterans affairs national precision oncology program from 1/2019-12/2021 who received first-line ICI for advanced NSCLC were followed until death or study end 6/2022. Association of an electronic frailty index with treatment selection was examined using logistic regression stratified by PS. We also examined overall survival (OS) on intensive treatment using Cox regression stratified by PS. Intensive treatment was defined as concurrent use of platinum-doublet chemotherapy and/or dual checkpoint blockade and non-intensive as ICI monotherapy. RESULTS: Of 1547 patients receiving any ICI, 66.2% were frail, 33.8% had poor PS (≥ 2), and 25.8% were both. Frail patients received less intensive treatment than non-frail patients in both PS subgroups (Good PS: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.51 - 0.88; Poor PS: OR 0.69, 95% CI 0.44 - 1.10). Among 731 patients receiving intensive treatment, frailty was associated with lower OS for those with good PS (hazard ratio [HR] 1.53, 95% CI 1.2 - 1.96), but no association was observed with poor PS (HR 1.03, 95% CI 0.67 - 1.58). CONCLUSION: Frail patients with both good and poor PS received less intensive treatment. However, frailty has a limited effect on survival among those with poor PS. These findings suggest that PS, not frailty, drives survival on intensive treatment.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Immunotherapy , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Lung Neoplasms/therapy , Male , Female , Aged , Immunotherapy/methods , Immune Checkpoint Inhibitors/therapeutic use , Middle Aged , Frailty , Aged, 80 and over
17.
Can Respir J ; 2024: 2803044, 2024.
Article in English | MEDLINE | ID: mdl-38975012

ABSTRACT

Objectives: We explored the prognostic utility of the unique combination of C-reactive-protein-to-albumin ratio (CAR) and significant weight loss (WL > 5%) over the preceding 6 months, namely, the CARWL score, in stage IIIC non-small-cell lung cancer (NSCLC) patients who underwent concurrent chemoradiotherapy (CCRT). Methods: For each patient, the CAR was calculated using C-reactive protein and albumin measurements obtained on the first day of CCRT: CAR = C-reactive protein ÷ albumin. The availability of an ideal CAR cutoff that may categorize patients into two distinct progression-free (PFS) and overall survival (OS) outcomes was explored by employing receiver operating characteristic (ROC) curve analysis. Patients were additionally divided into two groups based on their status of significant WL according to the well-recognized Delphi criteria. Then, the CARWL score was created by combining all feasible combinations of the CAR and significant WL groupings. The potential links between pretreatment CARWL groups and the post-CCRT OS and PFS outcomes were determined as the primary and secondary endpoints. Results: This retrospective cohort study comprised a total of 651 stage IIIC NSCLC patients. ROC curve analysis indicated that rounded 3.0 was the ideal CAR cutoff (area under the curve (AUC): 70.1%; sensitivity: 67.8%; specificity: 65.9%), which categorized the patients into CAR < 3.0 (N = 324) and CAR ≥ 3.0 (N = 327) groups. There were 308 (47.3%) and 343 (52.7%) patients without and with significant WL, respectively. The created CARWL groups were CARWL-0: CAR < 3.0 and WL ≤ 5.0%; CARWL-1: CAR < 3.0 and WL > 5.0%, or CAR ≥ 3.0 and WL ≤ 5.0%; and CARWL-2: CAR > 3.0 and WL > 5.0%. The Kaplan-Meier curves showed that the PFS (14.2 vs. 11.4 vs. 7.5 months; P < 0.001) and OS (37.3 vs. 23.6 vs. 12.8 months; P < 0.001) durations were gradually and significantly lowered from the CARWL-0 to CARWL-2 groups. The CARWL score's significant impacts on PFS and OS outcomes were found to be independent of the other variables in the multivariate analysis (P < 0.001, for each). Conclusions: Our findings indicate that the novel CARWL score, which accounts for pretreatment CAR and significant WL during the preceding 6 months, can reliably stratify newly diagnosed stage IIIC NSCLC patients into three groups with significantly different PFS and OS after definitive CCRT.


Subject(s)
C-Reactive Protein , Carcinoma, Non-Small-Cell Lung , Chemoradiotherapy , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/therapy , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Chemoradiotherapy/methods , Female , Male , Middle Aged , Retrospective Studies , Aged , Prognosis , C-Reactive Protein/analysis , Neoplasm Staging , Serum Albumin/analysis , Weight Loss , Adult , ROC Curve
18.
Cochrane Database Syst Rev ; 7: CD014907, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958139

ABSTRACT

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effectiveness and safety of immune checkpoint inhibitors (ICI) as monotherapy or in combination compared to standard of care for elderly people (≥ 65 years) with non-small cell lung cancer (NSCLC).


Subject(s)
Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Aged , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Systematic Reviews as Topic , Randomized Controlled Trials as Topic , Standard of Care
19.
J Cell Mol Med ; 28(13): e18520, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38958523

ABSTRACT

Lung adenocarcinoma (LUAD) is a tumour characterized by high tumour heterogeneity. Although there are numerous prognostic and immunotherapeutic options available for LUAD, there is a dearth of precise, individualized treatment plans. We integrated mRNA, lncRNA, microRNA, methylation and mutation data from the TCGA database for LUAD. Utilizing ten clustering algorithms, we identified stable multi-omics consensus clusters (MOCs). These data were then amalgamated with ten machine learning approaches to develop a robust model capable of reliably identifying patient prognosis and predicting immunotherapy outcomes. Through ten clustering algorithms, two prognostically relevant MOCs were identified, with MOC2 showing more favourable outcomes. We subsequently constructed a MOCs-associated machine learning model (MOCM) based on eight MOCs-specific hub genes. Patients characterized by a lower MOCM score exhibited better overall survival and responses to immunotherapy. These findings were consistent across multiple datasets, and compared to many previously published LUAD biomarkers, our MOCM score demonstrated superior predictive performance. Notably, the low MOCM group was more inclined towards 'hot' tumours, characterized by higher levels of immune cell infiltration. Intriguingly, a significant positive correlation between GJB3 and the MOCM score (R = 0.77, p < 0.01) was discovered. Further experiments confirmed that GJB3 significantly enhances LUAD proliferation, invasion and migration, indicating its potential as a key target for LUAD treatment. Our developed MOCM score accurately predicts the prognosis of LUAD patients and identifies potential beneficiaries of immunotherapy, offering broad clinical applicability.


Subject(s)
Adenocarcinoma of Lung , Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Immunotherapy , Lung Neoplasms , Machine Learning , Humans , Immunotherapy/methods , Prognosis , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/therapy , Biomarkers, Tumor/genetics , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Gene Expression Profiling , MicroRNAs/genetics , Multiomics
20.
Medicine (Baltimore) ; 103(29): e39044, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39029055

ABSTRACT

BACKGROUND: Solitary fibrous tumors can manifest at various anatomical sites, predominantly occurring at extrapleural sites with a peak incidence between 40 and 70 years. SFT necessitates long-term follow-up owing to its tumor characteristics. However, comprehensive reports covering the period from initial diagnosis to the patient's demise are lacking. Herein, we present a case of a malignant SFT of the buttocks that was treated at our hospital from the time of initial diagnosis to the end of life, with a literature review. METHODS: A 54-year-old woman had a T1 low-to-isobaric and T2 isobaric-to-hyperintense mass in the psoas muscle on magnetic resonance imaging, diagnosed as an SFT. Wide excision was performed, followed by postoperative radiotherapy and chemotherapy. Multiple lung metastases were treated, while bone metastases appeared in the left femur. Multiple spinal metastases developed, causing respiratory distress due to pleural effusion. Best support care was initiated; however, a thrombus appeared in the inferior vena cava. Despite anticoagulant therapy, the patient died 11 years and 6 months after the initial surgery. Herein, marginal resection resulted in a relatively short operative time and average blood loss. The radiotherapy dose was 66 Gy; no complications occurred, and local recurrence was prevented. Tumor arthroplasty was performed to stabilize the affected limbs, and the patient required careful follow-up. RESULTS: Despite the poor prognosis, the patient survived >11 years after surgery and had a favorable outcome. CONCLUSION: Long-term monitoring for potential complications remains necessary.


Subject(s)
Hemangiopericytoma , Solitary Fibrous Tumors , Humans , Female , Middle Aged , Buttocks/pathology , Solitary Fibrous Tumors/pathology , Solitary Fibrous Tumors/surgery , Solitary Fibrous Tumors/therapy , Hemangiopericytoma/surgery , Hemangiopericytoma/pathology , Hemangiopericytoma/therapy , Fatal Outcome , Magnetic Resonance Imaging , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Lung Neoplasms/therapy , Lung Neoplasms/surgery
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