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Background: Lung cancer, once rare, has evolved into the global leading cause of cancer-related mortality, primarily driven by widespread cigarette smoking in the 20th century. This study explores the historical trends of lung cancer incidence in Denmark over four decades, emphasizing the impact of smoking prevalence, age, and gender on the observed patterns., Materials and Methods: Drawing upon data from the Danish National Patient Register and information on smoking habits provided by the Danish Health Authority, this study investigates lung cancer incidence rates, demographic shifts, and smoking prevalence from 1980 to 2022., Results: Smoking prevalence exhibited a consistent decline in males from 1950 to 2022, whereas female smoking prevalence maintained a stable level from 1950 to 1987, followed by a subsequent decline from 1987 to 2022. A peak in lung cancer crude incidence rates was identified during 2014-2017, with no significant difference observed before and after this period. Over the period, the gender distribution transitioned from a male majority to an equal male-female ratio, and age-specific disparities indicated declines in patients aged 50-59 and increases in those above 80 years., Interpretation: The certainty of a decline in lung cancer incidence in the coming years remains unclear. Based on smoking prevalence, it might still be a decade away. To ensure a sustained decline in lung cancer incidence, targeted interventions are imperative, including customized smoking cessation programs that could be designed favorably for females. Given the modest decline in smoking prevalence over the last decade, legislation aimed at discouraging young individuals from smoking is pivotal. As of now, these efforts have not been implemented in Denmark.

Background: This study evaluates the validity of the information in the Danish Lung Cancer Registry (DLCR). Since 2000, the DLCR has been a tool for monitoring interventions and outcome of all Danish lung cancer patients with the intent to streamline and improve treatment and survival. The DLCR receives information from the Danish Patient Registries in addition to clinical information from the treating physicians. In the year 2022, more than 50 papers have been published using DLCR as a data source. However, the DLCR has not previously been validated., Methods: A random sample of 1000 patients diagnosed with non-small cell lung cancer from 2014 to 2016 and recorded in the DLCR were included for validation. Medical records were reviewed and were considered as the "gold standard" to which data listed in the DLCR were compared., Results: Information was retrieved from medical charts for all patients. Agreement on stage at diagnosis was 90.1 % (95 % CI 88.0-91.9) and on date of diagnoses was 93.8 (95 % CI 92.1-93.2). Agreement on smoking status in pack years (+/- 10 pack years) was 91.2 % (95 % CI 88.6-93.2). The positive predictive value of treatment intent was 87.4 (95 % CI 85.1-89.6)., Conclusion: The data in the DLCR are complete, detailed and accurate. The comparison of data from the DLCR with the medical records revealed overall high validity of the data in the registry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The majority of lung cancer cases are diagnosed late, resulting in poor prognosis and high mortality rates. Early detection and management of lung cancer can improve patient outcomes and reduce mortality rates. Pulmonary nodules are key factors in the early detection of lung cancer, they are common in high-risk populations and require correct classification to determine whether they are benign or malignant. Over the last decade a steep increase in the number of thoracic CT scans has been seen in Denmark, resulting in substantial resources allocated to CT follow-up of incidentally detected pulmonary nodules. The implementation of a nationwide Danish prospective pulmonary nodule registry is to methodically record pulmonary nodules and thereby evaluate the scope of pulmonary nodule follow-up, the nature of the nodules, and the clinical progression of patients with pulmonary nodules., Methods: A prospective pulmonary nodule registry (Danish Lung Nodule Registry) will be a natural appendix to the Danish Lung Cancer Registry. Three new ICD-10 classification codes will be introduced, defining the type of nodule: /DR91.1/ Solid nodule /DR91.2/ Part-solid nodule; /DR91.3/ Non-solid nodule. Furthermore, an additional letter will describe whether the imaging exam is performed on suspicion of lung cancer (A), or the finding is incidental (B). Registration of the nodules will be performed by the departments of respiratory medicine who manage follow-up of pulmonary nodules. It is estimated that around 7000 nodules will be registered annually., Discussion: The registration of patients in the lung nodule registry complies with current Danish legislation. The registry will be seamlessly integrated with other nationwide Danish registries, including the Danish Lung Cancer Registry, to collect additional patient data and improve the quality and scope of the data acquired. The results from these comprehensive epidemiological studies will be of significant interest and offer valuable research opportunities., Competing Interests: Declaration of Competing Interest The authors declare they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Lung cancer is the leading cause of cancer-related death globally. Incidental pulmonary nodules represent a golden opportunity for early diagnosis, which is critical for improving survival rates. This study explores the impact of missed pulmonary nodules on the progression of lung cancer., Methods: A total of 4,066 stage IV lung cancer cases from 2019 to 2021 in Danish hospitals were investigated to determine whether a chest computed tomography (CT) had been performed within 2 years before diagnosis. CT reports and images were reviewed to identify nodules that had been missed by radiologists or were not appropriately monitored, despite being mentioned by the radiologist, and to assess whether these nodules had progressed to stage IV lung cancer., Results: Among stage IV lung cancer patients, 13.6% had undergone a chest CT scan before their diagnosis; of these, 44.4% had nodules mentioned. Radiologists missed a nodule in 7.6% of cases. In total, 45.3% of nodules were not appropriately monitored. An estimated 2.5% of stage IV cases could have been detected earlier with proper surveillance., Conclusion: This study underlines the significance of monitoring pulmonary nodules and proposes strategies for enhancing detection and surveillance. These strategies include centralized monitoring and the implementation of automated registries to prevent gaps in follow-up., (© 2024 S. Karger AG, Basel.)

Competing Interests: Competing interests: None declared.

Background: To identify non-small-cell lung cancer (NSCLC) patients in need of comprehensive support, we examined the association between patient and disease-related factors of vulnerability related to not receiving guideline-recommended treatment., Material and Methods: We identified 14,597 non-small-cell lung cancer (NSCLC) patients with performance status <3 during 2013-2018 in the Danish Lung Cancer Registry. Multivariate logistic regression models were used to estimate Odds Ratios (ORs) and 95% confidence intervals (CIs) for receiving guideline-recommended treatment according to stage, comorbidities, age, performance status, long distance to hospital, cohabitation status, education and alcohol abuse., Results: 21% of stage I-IIIA NSCLC patients did not receive curative treatment while 10% with stage IIIB-IV did not receive any oncological therapy. Factors associated with reduced likelihood of receiving curative treatment included: advanced stage (OR = 0.45; 95% CI = 0.42-0.49), somatic comorbidity (OR = 0.72; 95% CI = 0.63-0.83), age ≥ 80 years (OR = 0.59; 95% CI = 0.55-0.64), performance status = 2 (OR = 0.33; 95% CI = 0.28-0.39) and living alone (OR = 0.79; 95% CI = 0.69-0.90). Results were similar for stage IIIB-IV NSCLC patients, although a statistically significant association was also seen for long distances to the hospital (OR = 0.71; 95% CI = 0.58-0.86)., Conclusions: Several factors are associated with not receiving guideline-recommended NSCLC treatment with age, performance status, comorbidity and stage being most predictive of no treatment receipt. Efforts should be made to develop support for vulnerable lung cancer patients to improve adherence to optimal first-line therapy.

Background: We examined the number of lung cancers diagnosed, the quality of care and the socio-economic and clinical characteristics among patients with lung cancer during the COVID-19 pandemic compared to previous years., Methods: We included all patients ≥ 18 years old diagnosed with lung cancer from 01 January 2018 to 31 August 2021 as registered in the Danish Lung Cancer Registry. Using a generalised linear model, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) of the associations between the pandemic and socioeconomic and clinical factors, and indicators of quality., Results: We included 18,113 patients with lung cancer (82.0% non-small cell lung cancer (NSCLC)), which was similar to the preceding years, although a decline in NSCLC cases occurred during the first lockdown period in 2020. No difference in distribution of income or educational level was observed. No difference was observed in the quality of treatment - as measured by curative intent, proportion of patients resected or who died within 90 days of diagnosis., Conclusion: Using nationwide population-based data, our study reassuringly shows no adverse effects of the COVID-19 pandemic on the diagnosis, socio-economic characteristics nor quality of treatment of lung cancer, as compared to the preceding years., Competing Interests: Declaration of Competing Interest The authors report that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: PD-1/PD-L1 inhibitors have improved survival for patients with non-small cell lung cancer (NSCLC). We evaluated natural killer cell activity (NKA) and methylated HOXA9 circulating tumor DNA (ctDNA) as prognostic biomarkers in NSCLC patients treated with PD-1/PD-L1 inhibitors., Methods: Plasma was prospectively collected from 71 NSCLC patients before treatment with PD-1/PD-L1 inhibitors and before cycles 2-4. We used the NK Vue ® assay to measure the level of interferon gamma (IFNγ) as a surrogate for NKA. Methylated HOXA9 was measured by droplet digital PCR., Results: A score combining NKA and ctDNA status measured after one treatment cycle had a strong prognostic impact. Group 1 had IFNγ < 250 pg/ml and detectable ctDNA (n = 27), group 2 consisted of patients with either low levels of IFNγ and undetectable ctDNA or high levels of IFNγ and detectable ctDNA (n = 29), group 3 had IFNγ ≥250 pg/ml and undetectable ctDNA (n = 15). Median OS was 221 days (95% CI 121-539 days), 419 days (95% CI 235-650 days), and 1158 days (95% CI 250 days-not reached), respectively (P = 0.002). Group 1 had a poor prognosis with a hazard ratio of 5.560 (95% CI 2.359-13.101, n = 71, P < 0.001) adjusting for PD-L1 status, histology, and performance status., Conclusions: Combining NKA and ctDNA status after one cycle of treatment was prognostic in patients with NSCLC treated with PD-1/PD-L1 inhibitors., (© 2023. The Author(s).)

Background: There is an urgent need for early detection of lung cancer. Screening with low-dose computed tomography (LDCT) is now implemented in the US. Supplementary use of a lung cancer biomarker with high specificity is desirable., Objective: To assess the diagnostic properties of a biomarker panel consisting of cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125)., Methods: A cohort of 250 high-risk patients was investigated on suspicion of lung cancer. Ahead of diagnostic work-up, blood samples taken. Cross-validated prediction models were computed to assess lung cancer detection properties., Results: In total 32% (79/250) of patients were diagnosed with lung cancer. Area under the curve (AUC) for the three biomarkers was of 0.795, with sensitivity/specificity of 57%/93% and negative predictive value of 83%. When combining the biomarkers with US screening criteria, the AUC was 0.809, while applying only US screening criteria on the cohort, yielded an AUC of 0.62. The ability of the biomarkers to detect stage I-II lung cancer was substantially lower; AUC 0.54., Conclusions: In a high-risk cohort, the detection properties of the three biomarkers were acceptable compared to current LDCT screening criteria. However, the ability to detect early stage lung cancer was low.

Background: Computed tomography (CT) examinations are increasingly used worldwide and incidental findings are growing likewise. Lung cancer stage at diagnosis is pivotal to survival. The earliest stage of lung cancer, stage IA is in most cases asymptomatic. Potentially, increased use of clinical CTs could induce a stage shift toward earlier lung cancer diagnosis., Materials and Methods: Data on the number of CT thorax in Denmark and the stage distribution of Danish lung cancer patients 2013-2020 were acquired from, respectively, the Danish Health Data Authority and the Danish Lung Cancer Registry. Clinical auditing of stage IA lung cancer patients was performed in the period 2019-2021 in a Danish region to assess the reasons for referral. Auditing of stage IV lung cancer patients was done to see whether a CT thorax was performed in a two-year period before diagnosis., Results: All regions showed an increase in CTs per 1000 inhabitants. However, the number of CTs performed in 2013 differed by more than 50% among regions, and the increase per year also differed, from an increase of 1.9 to 3.4 more examinations per year. A significant correlation between CTs and fraction of stage IA lung cancers was seen in four out of the five regions. The audit of stage IA lung cancer cases revealed that 86.8% were incidental findings. Audit of stage IV lung cancer found that 4.3% had a nodule/infiltrate on a previous CT within a 2-year period prior to the diagnosis of lung cancer that was the probable origin of stage IV lung cancer., Conclusion: The study found that the vast majority of early-stage lung cancers were incidental findings. It highlights that follow-up algorithms of incidental findings should be used in accordance with guidelines and it should be unequivocally how the CT follow-up of pulmonary infiltrates is managed.

Objective: Natural killer (NK) cells play an essential role in the immune response against cancer. However, immune escape mechanisms may cause inferior NK cell activity (NKA) in patients with cancer. This prospective study examined the relationship between NKA and lung cancer in a high-risk cohort., Methods: In a cohort study, 250 participants referred by their general practitioner for suspicion of lung cancer were included. Before clinical investigation, blood was collected into NK Vue tubes, and the level of interferon gamma after 24 hours served as a surrogate marker for NKA., Results: Among 250 patients, 79 were diagnosed with lung cancer. No difference in NKA was found between patients with lung cancer and control participants in which lung cancer was ruled out (median 226 pg/mL vs. 450 pg/mL). However, there was a significant difference in NKA between patients with late-stage lung cancer and controls (median 161 pg/mL vs. 450 pg/mL). A linear regression model showed that NKA was not influenced by age, sex or smoking status., Conclusions: The significantly lower NKA in patients with late-stage lung cancer warrants further investigation combining NKA with other biomarkers and examining the potential role of NKA as a marker of disseminated disease.

Objectives: Early detection of lung cancer is pivotal for an optimal prognosis. CT screening is currently implemented in USA. To decrease the amount of CT scans, the application of a blood-based biomarker as part of screening criteria is desirable., Materials and Methods: The EarlyCDT® Lung test was performed in a high-risk cohort composed 246 patients referred from their GP on suspicion of lung cancer. Blood samples were taken at first visit and patients underwent diagnostic workup on suspicion of lung cancer resulting in either a malignant diagnosis or ruled out cancer. Sensitivity and specificity of the EarlyCDT® Lung were calculated in the cohort and subgroups based on age, smoking history, sex and lung cancer stage., Results: Overall sensitivity in the cohort was 33 % for lung cancer and 31 % for primary lung cancer and lung metastases combined. Sensitivity in age groups was 11 % (60 years or below), 31 % (61-75 years) and 55 % (>75 years). In patients with at least 10 tobacco pack years, sensitivity was 33 % while the sensitivity in patients with at least 50 tobacco pack years was 44 %. The assay sensitivity in stage I-II lung cancer patients was 21 %, while this was 40 % in stage III-IV lung cancer patients. In a subgroup of patients that met current CT screening criteria (age 55-80 years and minimum 30 tobacco pack years) the sensitivity was 37 %., Conclusion: The rationale of screening for lung cancer is to find patients in an early and resectable stage. However, the EarlyCDT® Lung test performed best in elderly, late stage lung cancer patients with a heavy smoking history. Based on these results, the current study finds insufficient sensitivity of the EarlyCDT® Lung test to be used as part of inclusion criteria in a low-dose CT program for detection of lung cancer., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to describe the impact on patient-reported outcomes of introducing Shared Decision Making (SDM) and a Patient Decision Aid (PtDA) in the initial process of lung cancer diagnostics., Methods: We conducted a prospective cohort study, where a control cohort was consulted according to usual clinical practice. After introducing SDM through a PtDA and training of the staff, the SDM cohort was enrolled in the study. All patients completed four questionnaires: the Decisional Conflict Scale (DCS) before and after the consultation, the CollaboRATE scale after the consultation, and the Decision Regret Scale (DRS)., Results: Patients exposed to SDM and a PtDA had significantly improved DCS scores after the consultation compared to the control group (a difference of 10.26, p = 0.0128) and significantly lower DRS scores (a difference of 8.98, p = 0.0197). Of the 82 control patients and 52 SDM patients 29% and 54%, respectively, gave the maximum score on the CollaboRATE scale (Pearson's chi 2 8.0946, p = 0.004)., Conclusion: The use of SDM and a PtDA had significant positive impact on patient-reported outcomes., Practice Implications: Our results may encourage the increased uptake of SDM in the initial process of lung cancer diagnostics., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: This Danish study evaluated the association between psychiatric comorbidity and the course of chronic obstructive pulmonary disease (COPD), lung cancer and tuberculosis (TB) of an entire nation., Methods: Data from the Danish National Patient Registry (1998-2009), material status, gender, educational level, comorbidities, age at diagnosis and death, medication, and causes of death were extracted from national databases. We identified 71,874 patients with COPD and found 32,282 with a pre-index psychiatric comorbidity, 20,787 patients with lung cancer and found 8406 with a pre-index psychiatric comorbidity, and 3495 patients with TB and found 797 with a pre-index psychiatric morbidity. Within the three groups we compared the patients with/without a pre-index psychiatric comorbidity., Results: We found a reduced survival in patients with COPD or TB and a pre-existing psychiatric comorbidity. For all three pulmonary diseases, we found significantly higher age (p < .001) at time of diagnosis, higher Deyo-Charlson Comorbidity Index (p < .001), and an overrepresentation of singles (p < .001) in patients with a psychiatric comorbidity. COPD and lung cancer patients with a psychiatric comorbidity were significantly overrepresented by women (p < .001). Patients with COPD and a psychiatric comorbidity died most frequently of lung cancer (24%). Advancing age and Deyo-Charlson index were associated with a higher mortality rate whereas being a woman and married/co-habiting yielded a lower mortality rate for patients with a psychiatric comorbidity., Conclusion: To our knowledge, this is the first epidemiological study investigating the influence of a psychiatric comorbidity on the course of COPD, lung cancer and TB at a national level. Our results emphasize the importance of detecting these major respiratory diseases in patients with psychiatric comorbidities and intensifying the treatment and follow up of these patients., (Copyright © 2017. Published by Elsevier Ltd.)

Idiopathic pulmonary fibrosis (IPF) is a complex disease that is associated with various respiratory and non-respiratory comorbidities. The most common comorbidity is cardiovascular disease (CVD), which increases in incidence with increasing duration of IPF and is associated with a higher risk of mortality. The direction of causality between CVD and IPF is unclear. There is evidence that IPF is associated with a prothrombotic state; however, warfarin is not beneficial in IPF patients. Lung cancer is another common comorbidity, being present in more than 50% of IPF patients at 10 years after diagnosis. IPF and lung cancer share several risk factors and pathogenic pathways and also show a similar anatomic distribution; this can make radiological diagnosis difficult. As with CVD, lung cancer in IPF patients is associated with a significantly worse prognosis and treatment options are limited. Surgery, chemotherapy, and radiotherapy have all been associated with an increased risk of morbidity and mortality. However, treatment may be considered in selected patients with less advanced cancer and less advanced IPF. Emphysema may occur in patients with IPF and is believed to represent a distinct clinical syndrome, known as the combined pulmonary fibrosis and emphysema (CPFE) syndrome. CPFE has a strong male predominance, is strongly linked with smoking, and has distinct radiographic features. CPFE is also associated with a very high frequency of pulmonary hypertension, which is associated with a poor prognosis. There are no specific treatments for CPFE and evaluation of IPF therapies in CPFE patients is urgently needed.