INTRODUCTION:This study aimed to estimate the NHS costs of managing patients with anaplastic lymphoma kinase positive (ALK+) advanced non-small-cell lung cancer (aNSCLC), with and without brain metastases. Patients were treated with first-line (1 L) ALK tyrosine kinase inhibitors (TKIs). METHODS:We built an economic model to estimate the annual costs of managing ALK+ aNSCLC patients with and without brain metastases using estimated NHS health care resource use (HCRU) consumption. The ALK TKIs included in our model were lorlatinib, crizotinib, alectinib and brigatinib. We based our estimates on the cumulative incidence of brain metastases in four clinical trials - CROWN, ALEX, ALESIA and ALTA-1L. RESULTS:For the first year of treatment, our model estimated the annual cost of managing patients with brain metastases to be £14,870. Patients without brain metastases cost £4,133. The NHS HCRU cost savings generated by treating patients with lorlatinib increased significantly over time and were greater in patients without brain metastases at the start of their treatment (at baseline) with lorlatinib. This reflects the prevention of brain metastases with 1 L lorlatinib. CONCLUSION:The longitudinal cost data demonstrate that lorlatinib leads to potentially lower NHS management costs of brain metastases in patients with ALK+ aNSCLC.
Lung cancer and cardiovascular diseases (CVDs) frequently coexist due to shared risk factors such as aging, smoking, and chronic inflammation. The growing prevalence of elderly surgical candidates with concomitant lung cancer and CVDs presents unique diagnostic and therapeutic challenges. This review explores current strategies for managing such patients, emphasizing the importance of individualized, multidisciplinary treatment planning. Advances in minimally invasive pulmonary resection and parenchymal -sparing surgery-such as segmentectomy-have expanded surgical options, especially in frail patients. Simultaneously, improvements in cardiovascular therapies, including transcatheter aortic valve implantation (TAVI), thoracic endovascular aortic repair (TEVAR), and off-pump coronary artery bypass grafting (OPCAB), have enabled safer, staged approaches. Guideline-directed preoperative risk assessment from Japanese, American, and European societies underscores the need for tailored sequencing of cardiac and oncologic interventions. In general, a staged approach with initial cardiac stabilization followed by pulmonary resection is preferred. However, simultaneous surgery, especially OPCAB combined with pulmonary resection, may be feasible in carefully selected patients. Additionally, the cardiac toxicity of immune checkpoint inhibitors and EGFR-TKIs must be considered when planning neoadjuvant treatment. Integrating cardiovascular expertise into thoracic oncology is crucial to optimizing outcomes in this complex population.
BACKGROUND:This study evaluated the cost-effectiveness of Tepotinib versus Capmatinib in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with MET Exon 14 Skipping Mutations in China. METHODS:An economic evaluation using a 3-state partitioned survival model assessed the cost-effectiveness of Tepotinib versus Capmatinib. The Kaplan-Meier (KM) curves for overall survival (OS) and progression-free survival (PFS) from two clinical trials were digitally extracted. The Exponential model with matching-adjusted indirect comparison (MAIC) was employed at the end of the trials to extrapolate the long-term survivals. RESULTS:The estimated cost and utility of Tepotinib treatment were higher than those of Capmatinib treatment, respectively (95,392.54 USD vs. 51,003.63 USD; 2.11 QALYs vs 1.38 QALYs). The incremental cost-effectiveness ratio (ICER) of Capmatinib treatment vs. Tepotinib treatment was calculated at 60,977.28 USD/QALY. CONCLUSIONS:Tepotinib was not cost-effective compared to Capmatinib as the second-line treatment for advanced or metastatic NSCLC patients with MET exon 14 skipping mutations in China.
The utilization of pathological assessment to evaluate tumor response in patients with early-stage non-small cell lung cancer (NSCLC) has not been documented in the extant literature. A 64-year-old male patient with lung adenocarcinoma was treated with CyberKnife. A subsequent review of the images suggested that the mass in the area of radiotherapy had increased in size compared to the previous one, suggesting tumor recurrence. Consequently, surgery was performed to remove the enlarged mass. Postoperative histopathology showed no tumor tissue. This case underscores the potential efficacy of CyberKnife in the treatment of early-stage non-small cell lung cancer (NSCLC) tumors and confirms its effectiveness as a radical treatment modality, as validated by the gold standard of postoperative pathology.
AIM:To estimate brain metastases (BM) management costs in Chinese ALK+ advanced non-small-cell lung cancer (NSCLC) patients receiving first-line (1 L) ALK tyrosine kinase inhibitors (TKIs). METHODS:A survey of 105 clinical experts across 23 Chinese regions evaluated healthcare resource utilization (HCRU). Total annual costs with TKIs were calculated by weighting the management costs of patients with and without BM using the cumulative incidence rate (CIR) of BM from ALK-TKI clinical trials. RESULTS:First-year management cost averaged ¥24,974 per-patient without BM versus ¥89,859 per-patient with BM, saving ¥64,885. Subsequent years saved ¥33,231. Applying 12-month CIR of BM, the annual costs per-patient were ¥26,791 for 1 L lorlatinib versus ¥46,516 for crizotinib in the intention-to-treat (ITT) population. Subgroup analysis showed annual costs of ¥25,623 per-patient with lorlatinib in those without BM and ¥29,775 in those with BM. Alectinib's and brigatinib's costs were ¥31,073 and ¥32,760 respectively, using the 12-month CIR of BM. Lorlatinib's cost savings increased progressively over 1-4 years. Limited CIR beyond 12 months existed for brigatinib and ensartinib. Results from the Asian group's CIR aligned with global trials. CONCLUSION:Due to lower BM CIR, lorlatinib showed higher BM management cost savings compared to crizotinib and alectinib in Chinese 1 L patients.
AIMS:This study aimed to predict post-transplant malignancy risks at multiple levels among lung transplant recipients using machine learning (ML) and to identify key clinical and immunogenetic predictors. MATERIALS AND METHODS:A dataset of 30,917 lung transplant recipients with no prior cancer history was analyzed using pre-, peri-, and post-transplant variables. Multiple ML algorithms-gradient boosting, random forest, neural networks, and logistic regression-were applied to predict: (1) overall de novo malignancies (DNM), (2) skin versus non-skin cancers, and (3) skin cancer subtypes, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). RESULTS:Gradient boosting achieved the highest AUC for overall malignancies (0.746) and skin versus non-skin cancers (0.642), while random forest performed best for BCC versus SCC classification (AUC = 0.726). Significant predictors included HLA-DR alleles (DR52, DR1, DR53), A locus mismatch, recipient ethnicity, BMI, serum albumin, CMV/EBV serostatus, and cardiac-related measures (LV remodeling, cardiac output, prior cardiac surgery). Additional subtype predictors included peak PRA Class I sensitization, insulin signaling, donor-derived transfusions, and waiting list duration. CONCLUSIONS:ML-driven predictive modeling enables personalized assessment of post-transplant malignancy risk, supporting early detection, targeted surveillance, and optimized long-term care for lung transplant recipients.
INTRODUCTION:Treatment indications for oligometastatic/oligoprogressive lung tumors are growing. Safety and lack of detrimental effect on patients' quality of life are critical for novel local therapies. METHODS:We tested that the additive effect of pulsed electric field (PEF) ablation with lower-dose stereotactic body radiation therapy (SBRT) on health-related quality of life (HRQoL) as a secondary endpoint in a prospective clinical trial. FACT-Lung Cancer Subscale (FACT-LCS) and FACT-General domain surveys were collected at screening, 3 months, and 12 months. Functional clinical data included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and diffusing capacity of the lung for carbon monoxide (DLCO). RESULTS:Six patients with eight tumors were enrolled. Baseline well-being domain scores were: Physical 25.9 (Std Dev 2.3), Social 21.0 (Std Dev 6.9), Emotional 17.3 (Std Dev 4.7), Functional 21.2 (Std Dev 5.8), and LCS 19.4 (Std Dev 5.3). There were no significant changes following combined modality treatment in HRQoL domain scores or pulmonary function metrics after treatment. Lower EWB and SWB were associated with worse FVC and FEV1. CONCLUSION:In this small pilot study, no clinically meaningful declines in pulmonary function or patient-reported quality of life were observed at 3 months following combination therapy.
BACKGROUND:Metabolic reprogramming, particularly toward oxidative phosphorylation (OXPHOS), is a hallmark of lung squamous cell carcinoma (LUSC) and contributes to its aggressive phenotype and immunosuppressive microenvironment. While OXPHOS activation is increasingly recognized as a key metabolic feature in LUSC, its prognostic implications and associated gene signatures remain underexplored. This study aimed to identify OXPHOS-related differentially expressed genes (DEGs) and construct a robust prognostic signature for LUSC. METHODS:Using GEO datasets, we developed an OXPHOS-related prognostic signature via ssGSEA, differential analysis, and LASSO-Cox regression. RESULTS:An 8-gene OXPHOS-related signature (LTBP1, MFGE8, ACTN1, CD59, CDC25C, SAAL1, SFXN4, PTTG1) was identified. High-risk patients exhibited significantly shorter overall survival than low-risk patients across all cohorts. The model demonstrated strong predictive accuracy for 1-, 3-, and 5-year survival. Notably, the high-risk group showed enriched pathways related to tumor stemness and immunosuppression. CONCLUSION:We developed and validated a novel OXPHOS-based gene signature that effectively stratifies LUSC patients by risk. This signature highlights the clinical relevance of OXPHOS in LUSC prognosis and may guide personalized therapeutic strategies targeting metabolic vulnerabilities. Study limitations include its retrospective design and lack of experimental validation.
INTRODUCTION:This study aimed to examine the association between social determinants of health (SDOH) and lung cancer screening (LCS) utilization. METHODS:We analyzed data from 15,957 LCS-eligible individuals in the 2022 Behavioral Risk Factor Surveillance System survey. Primary outcomes included ever having (lifetime) LCS and meeting LCS recommendations (i.e., annual LCS). Multivariable logistic regression models examined associations between LCS outcomes and 12 adverse SDOH factors, controlling for covariates (i.e., demographics, diagnosis of asthma/COPD, and perceived general health status). RESULTS:LCS-eligible individuals with more adverse SDOH had lower odds of ever having LCS and being up to date. Those with ≥5 adverse SDOH had the lowest odds of having lifetime LCS (AOR = 0.58, 95%CI: 0.45-0.74) and meeting LCS recommendations (AOR = 0.49, 95%CI: 0.36-0.65) compared to those with none. Life dissatisfaction, lack of social and emotional support, housing insecurity, lack of health insurance, and cost as a barrier for needed medical care were independently associated with lower LCS uptake. CONCLUSIONS:Having more adverse SDOH was associated with a lower likelihood of having lifetime LCS and meeting the recommendation, with life dissatisfaction, lack of social and emotional support, housing insecurity, lack of health insurance, and medical care cost being independently associated factors.
AIMS:To describe tomographic findings in a high-risk lung cancer population in resource-limited Brazilian areas, quantify pulmonary nodules and lung cancer frequency, analyze challenges in lung cancer screening within the Brazilian public health system, assess lung function in individuals with moderate or severe emphysema, and evaluate the role of community health agents in recruiting high-risk populations. METHODS:This is a prospective, single-arm, longitudinal observational study involving individuals aged 50-80 years, current or former smokers with a smoking history of at least 20 pack-years, undergoing low-dose computed tomography (LDCT) with a 12-month follow-up. Screening results are classified according to Lung-RADS v2022 standards, with those rated as 3 or 4 undergoing further diagnostic assessments. The study aims to demonstrate the feasibility and effectiveness of lung cancer screening in socially vulnerable populations within resource-limited settings, providing essential insights to reduce mortality and improve health outcomes. CONCLUSIONS:The findings will assist the development of policies on lung cancer screening in the public health system. The study's dissemination plan includes a website, social media, and participation in scientific conferences.
BACKGROUND:Blood-based DNA methylation biomarkers have great potential for the early detection of lung cancer (LC). Here, we investigated the association between HYAL2 methylation in peripheral blood and LC. METHODS:Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was performed to measure the methylation levels of 4 CpG sites in HYAL2 gene in two independent case-control studies (168 LC cases and 167 controls in Study I, 677 LC cases and 833 controls in Study II). Logistic regression adjusted for covariates was conducted for odds ratios (ORs) and 95% confidence intervals (CIs). Non-parametric tests were applied for the comparisons of stratified groups. RESULTS:Hypomethylation of all 4 CpG sites in HYAL2 was associated with early-stage LC in the two studies (ORs range from 1.91 to 3.07 in Study I, ORs range from 1.39 to 1.86 in Study II, p < 0.05 for all). The associations were still significant for the very early-stage LC patients (stage I). Subgroup analysis indicated that the associations could be enhanced by male gender and older age. Moreover, decreased HYAL2 methylation was correlated with increased tumor size, tumor length and stage. CONCLUSIONS:Our results suggested blood-based HYAL2 hypomethylation as a potential biomarker for LC early detection.
OBJECTIVES:This was a pooled analysis of data from weekly vinorelbine (VNR) treatment arms of four individual open-label, phase II studies to assess and refine the efficacy and tolerance of weekly oral VNR in a larger cohort of patients with advanced NSCLC. MATERIALS AND METHODS:All patients included in this pooled analysis received oral VNR at the dose of 60 mg/m2 weekly at cycle 1 (3-week cycle), followed by an increase to 80 mg/m2 weekly for subsequent cycles until disease progression or toxicity. Efficacy was based on objective response rate (ORR), progression-free survival (PFS), and disease control rate (DCR). RESULTS:A total of 247 patients were included. The ORR and DCR were 8.9% and 57.5% respectively, median PFS and OS were 3.3 and 8.5 months, respectively. Less than half (40.7%) of patients reported ≥1 serious AE (regardless of causality), with 12.3% reporting ≥1 treatment-related serious AE (grade ≥3: 11.1%). The most reported grade ≥3 AEs were neutropenia (17.6%), fatigue (5.8%), and decreased appetite (4.9%). CONCLUSION:This pooled analysis showed that weekly oral VRN is a valid option, with an acceptable safety profile, in this population of patients with advanced NSCLC, confirming results from previous individual studies.
We present the case of a 66-year-old male patient who was found to have a lung nodule during the perioperative period for poorly differentiated carcinoma of the ileocecal region. Subsequent surgical procedures were performed to remove the intestinal and lung masses. Next-generation sequencing (NGS) testing demonstrated that the intestinal and lung lesions exhibited the same ALK pathogenic fusion. Following 7 months of Alectinib treatment, the patient's clinical evaluation showed stable disease. This is the first report of intestinal metastases from lung cancer with ALK fusion. Our findings indicate that a comprehensive approach, including histopathological examination and genetic testing, is necessary to diagnose and treat intestinal metastases from lung cancer accurately.
Pleural mesothelioma is a rare disease with few therapeutic options, especially in the first line refractory setting. Targeted agents did not demonstrate a significant clinical benefit in mesothelioma treatment, nevertheless a small group of patients might harbor potentially actionable somatic mutations, as in homologous repair recombination genes. In this paper we report two cases of patients with heavily pretreated pleural mesothelioma that had a relevant clinical benefit with rucaparib treatment based on somatic BRCA 1 and BRCA 2 mutations detected through next generation sequencing.
Introduction: Lung cancer is still diagnosed at an advanced stage due to lack of early disease symptoms. Areas covered: We have techniques and equipment for rapid on site evaluation of pulmonary lesions. However, with new technology or a combination of technologies in the diagnostic suite the cost of biopsy is rising. Expert opinion: The cost of diagnostic equipment and tools differ between the national health system and private sector. This is due to the economic crisis that our country entered in 2008. The costs for every procedure for lung cancer has not been updated for more than 15 years, and therefore in several cases the reimbursement for the hospitals is lower for both national and private sector.
Aim/objectives: Single-fraction stereotactic body radiation therapy (SF-SBRT) for peripheral lung tumors was reviewed. Materials & methods: Medically inoperable peripheral lung tumors eligible for SF-SBRT 34 Gray were treated. Patient characteristics, treatment and toxicity parameters were retrospectively collected, and toxicities were evaluated. Results: A total of 26 patients were assessed with median age of 74 years. Ninety-six percent had early-stage cancer and 35% were treated as per the SABR-BRIDGE protocol. Twenty-six peripheral lesions were treated (median maximal dimension 1.7 cm). Sixty-five percent had grade <= 2 toxicities with radiation pneumonitis (42.3%) and chest wall pain (35%). Radiation pneumonitis and chest wall pain rates were higher in patients with tumor diameters more than 1.5 cm. Conclusion: SF-SBRT is practical and effective treatment technique.
Aim: The aim of this meta-analysis was to investigate the relationship between the baseline systemic immune inflammatory index (SII) and prognosis in patients with NSCLC. Materials & methods: The relation between pretreatment SII and overall survival, disease-free survival, cancer-specific survival, progression-free survival and recurrence-free survival in NSCLC patients was analyzed combined with hazard ratio and 95% CI. Results: The results showed that high SII was significantly correlated with overall survival and progression-free survival of NSCLC patients, but not with disease-free survival, cancer-specific survival and recurrence-free survival. Conclusion: The study suggests that a higher SII has association with worse prognosis in NSCLC patients.PROSPERO registration number: CRD42022336270.
Aim: The main purpose of the present study was to investigate the labor market affiliation of ALK+ NSCLC patients in long-term treatment as well as overall survival and incidence/prevalence. Materials & methods: Nationwide retrospective study of all patients with ALK+ NSCLC in Denmark diagnosed between 2012 and 2018. Results: During the study period ALK+ NSCLC patients had a median overall survival of 44.0 months and a 7.8-fold increase in disease prevalence. Six months prior to diagnosis, 81% of ALK+ NSCLC patients ≤60 years of age were employed. At the end of the 18-month follow-up period, 36% were employed. Conclusion: ALK+ NSCLC patients have prolonged survival following diagnosis, but a large fraction of patients lose affiliation with the labor market.
Aim: The tumor microenvironment of NSCLC with driver mutations, such as EGFR, ALK and ROS, is less inflammatory. Materials & methods: This retrospective study included 38 patients with NSCLC driver mutations. The relationship between clinical and inflammatory markers concerning progression-free survival and overall survival was analyzed based on Kaplan-Meier curves. Results: The mean age of the patients was 59.8 ± 11.9. Progression-free survival and overall survival were significantly longer in patients under 65 years of age and with low neutrophil–lymphocyte ratio, low systemic immune-inflammation index and high lymphocyte count (p < 0.05). Conclusion: Unlike tumor biology, peripheral inflammatory parameters, such as neutrophil–lymphocyte ratio, systemic immune-inflammation index and lymphocyte count may be associated with survival in NSCLC patients with driver mutations.
Managing extensive-stage SCLC (ES-SCLC) has long been challenging for clinicians and oncologists due to its aggressive nature and poor prognosis. We report a case of a 41-year-old female with ES-SCLC who survived for six years, defying the disease's typically poor prognosis. Through a heavy treatment strategy involving chemotherapy, targeted therapy, and immunotherapy, the patient experienced robust responses and avoided distant metastasis, including brain involvement. The long-term survival case in SCLC highlights the need for further research into personalized strategies and prognostic biomarkers. This case holds significant value for both clinicians and researchers as it challenges the conventional strategies for ES-SCLC and sets the stage for future evidence-based studies aimed at extending survival in SCLC.
