Routes to Diagnosis in Danish Lung Cancer Patients: Emergency Presentation, Age and Smoking History-A Population-Based Cohort Study.

BACKGROUND: The fast-track cancer pathway aims to expedite diagnosis of lung cancer and treatment and is the preferred route to diagnosis. Diagnosis following an unplanned admission (unplanned route) has been associated with poor outcomes. OBJECTIVE: This study explores factors associated with lung cancer diagnosis following unplanned admissions, focusing on the elderly population. METHODS: A retrospective cohort study using population-based data from Danish registries. Factors such as age, comorbidity, performance status, smoking history, socioeconomic parameters and treatment modality were analyzed in relation to route to diagnosis and prognosis. RESULTS: Among 17,835 patients, 16% were elderly (≥ 80 years). The unplanned route constituted 28% of diagnostic routes, with higher proportion among the elderly (33%). Poor performance status and advanced disease stage were associated with the unplanned route. Married patients were less likely to undergo an unplanned route to diagnosis. Smoking did not significantly influence diagnostic route. The adjusted odds ratio for curative treatment and dying 12 months after diagnosis, following unplanned route to diagnosis were 0.68 (95% CI, 0.61-0.76) and 1.48 (95% CI, 1.36-1.61), respectively. CONCLUSION: Frailty (poor performance status and high burden of comorbidity) in addition to unfavorable socioeconomic factors, which all were more prevalent among elderly patients, were associated with undergoing an unplanned route to diagnosis. However, age itself was not. Diagnosis following unplanned admission correlated with reduced likelihood of curative treatment and poorer prognosis. Expanding screening initiatives to include frail elderly individuals living alone, along with alertness by primary care clinicians, is warranted to improve outcomes for these patients.

Outcome of Incidental Pulmonary Nodules in a Real-World Setting.

OBJECTIVES: Early diagnosis of lung cancer is imperative to improve survival. Incidental pulmonary nodules (IPN) may represent early stages of lung cancer and appropriate follow-up and management of these nodules is important, but also very resource demanding. We aim to describe the results of the CT-based follow-up on a cohort of patients with IPN in terms of detected malignancies, the proportion undergoing invasive procedures, and the subsequent outcome. MATERIALS AND METHODS: Retrospective cohort study of patients in a CT IPN follow-up program who underwent a needle biopsy of the lung from 2018 to 2021 at Aarhus University Hospital. RESULTS: A total of 4181 patients with IPN were followed with CT control scans. Out of these 249 (6%) were diagnosed with lung cancer of which 224 (90%) were diagnosed as a result of the IPN follow-up. Seventy-five percent of the patients were diagnosed in stages I to II and curable treatment was possible in 77.9% of the patients. In the CT IPN follow-up program 449 patients underwent a CT guided needle biopsy. Out of these 190 patients underwent biopsy without the detection of malignancy, corresponding to 4.5% of the entire IPN population. CONCLUSION: The cumulated incidence of lung cancer in our population in the IPN follow-up program was 6%. The probability of malignancy when undergoing an invasive procedure on an IPN was 55.7% of which lung cancer was vastly predominant. The majority of lung cancers were diagnosed in an early and potentially curable stage.

A Validated Register-Based Algorithm to Identify Patients Diagnosed with Recurrence of Surgically Treated Stage I Lung Cancer in Denmark.

Introduction: Recurrence of cancer is not routinely registered in Danish national health registers. This study aimed to develop and validate a register-based algorithm to identify patients diagnosed with recurrent lung cancer and to estimate the accuracy of the identified diagnosis date. Material and Methods: Patients with early-stage lung cancer treated with surgery were included in the study. Recurrence indicators were diagnosis and procedure codes recorded in the Danish National Patient Register and pathology results recorded in the Danish National Pathology Register. Information from CT scans and medical records served as the gold standard to assess the accuracy of the algorithm. Results: The final population consisted of 217 patients; 72 (33%) had recurrence according to the gold standard. The median follow-up time since primary lung cancer diagnosis was 29 months (interquartile interval: 18-46). The algorithm for identifying a recurrence reached a sensitivity of 83.3% (95% CI: 72.7-91.1), a specificity of 93.8% (95% CI: 88.5-97.1), and a positive predictive value of 87.0% (95% CI: 76.7-93.9). The algorithm identified 70% of the recurrences within 60 days of the recurrence date registered by the gold standard method. The positive predictive value of the algorithm decreased to 70% when the algorithm was simulated in a population with a recurrence rate of 15%. Conclusion: The proposed algorithm demonstrated good performance in a population with 33% recurrences over a median of 29 months. It can be used to identify patients diagnosed with recurrent lung cancer, and it may be a valuable tool for future research in this field. However, a lower positive predictive value is seen when applying the algorithm in populations with low recurrence rates.

[Cocaine-induced asthma exacerbation].

Asthma is one of the most common chronic diseases in children and adults. Cocaine is associated with asthma exacerbations. In Denmark, the prevalence of cocaine use has been increasing in recent years. This is a case report of a 47-year-old male with acute asthma exacerbation after cocaine use. Cocaine use is probably an underestimated reason for acute asthma exacerbations.

[Rational use of systemic corticosteroid in the treatment of obstructive lung disease, asthma, and allergic rhinitis].

The anti-inflammatory effect of systemic corticosteroid (CS) on obstructive lung diseases and seasonal allergic rhinitis is well known. So are the physiological side-effects of CS. A major development in inhalation and biologic treatment as well as hyposensibilisation has taken place in recent years and evidence of personalized use of CS in acute exacerbations increases. We review the side effects of CS and the rationale for use of systemic CS in treatment of obstructive lung diseases as asthma and COPD, as well as seasonal allergic rhinitis.

Direct and indirect economic burden of lung cancer in Denmark a nationwide study.

Background: Lung cancer is the leading cause of cancer death worldwide, but the additional economic burden regarding direct and indirect costs is largely unknown. This study provides information on the economic consequences of lung cancer on a national level. Methods: From the Danish National Patient Registry (NPR) and the Danish Civil Registration System (CPR), 53,749 patients with lung cancer were identified and matched with 214,304 controls on age, gender, region of residence and marital status in the period 1998-2010. Direct and indirect costs, health care contacts and frequency, medication and social transfer payments were extracted from national databases. Results: Direct health care cost were higher for lung cancer patients than controls both before and after being diagnosed with lung cancer. At the year of diagnosis, health care cost peaked with cost of €21,497 compared to €2,880 for controls. Average difference in income from employment was €+3,118 in years prior to diagnosis and €+748 after diagnosis in favor of controls. Average difference in total public transfer income was €+1,288 before and €+441 after diagnosis, with higher public transfer income for lung cancer patients. Conclusion: For both genders, lung cancer was associated with significantly higher rates of health-related costs, medication costs, public transfer income, social transfer payments and significantly lower income from employment until retirement (age 65).

Routes to diagnosis and the association with the prognosis in patients with cancer - A nationwide register-based cohort study in Denmark.

BACKGROUND: The prognosis of cancer is related to how the cancer is identified, and where in the healthcare system the patient presents, i.e. routes to diagnosis (RtD). We aimed to describe the RtD for patients diagnosed with cancer in Denmark by using routinely collected register-based data and to investigate the association between RtD and prognosis measured as one-year all-cause mortality. METHODS: We conducted a population-based national cohort study by linking routinely collected Danish registry data. We categorised each patient into one of eight specified RtD based on an algorithm using a stepwise logic decision process. We described the proportions of patients with cancer diagnosed by different RtD. We examined associations between RtD and one-year all-cause mortality using logistic regression models adjusting for sex, age, cancer type, year of diagnosis, region of residence, and comorbidity. RESULTS: We included 144,635 cancers diagnosed in 139,023 patients in 2014-2017. The most common RtD were cancer patient pathway from primary care (45.9 %), cancer patient pathway from secondary care (20.0 %), unplanned hospital admission (15.8 %), and population-based screening (7.5 %). The one-year mortality ranged from 1.4 % in screened patients to 53.0 % in patients diagnosed through unplanned hospital admission. Patients with an unplanned admission were more likely to die within the first year after diagnosis (OR = 3.38 (95 %CI: 3.24-3.52)) compared to patients diagnosed through the cancer patient pathway from primary care. CONCLUSION: The majority of cancer patients were diagnosed through a cancer patient pathway. The RtD were associated with the prognosis, and the prognosis was worst in patients diagnosed through unplanned admission. The study suggests that linking routinely collected registry data could enable a national framework for RtD, which could serve to identify variations across patient-, health-, and system-related and healthcare factors. This information could be used in future research investigating markers for monitoring purposes.

Comorbidity and early death in Danish stage I lung cancer patients - an individualised approach.

Background: Comorbidity is an important prognostic marker and a treatment indicator for lung cancer patients. Register-based studies often describe the burden of comorbidity by the Charlson comorbidity index (CCI) based on hospital discharge data. We assessed the association between somatic and psychiatric comorbidity and death within one year in early lung cancer and, furthermore, the burden of comorbidity according to treatment type.Material and methods: We conducted a population-based matched case-control study of stage I lung cancer identifying all treated patients who died (all-cause) within one year after diagnosis (early death group, cases). On the basis of data from the Danish Lung Cancer Registry these patients were then matched with two controls who survived more than one year (survivors). Through a review of the medical records, we validated inclusion criteria and collected data on somatic and psychiatric comorbidity. We assessed the association between comorbidity and early death with multivariate conditional logistic regression.Results: We included 221 cases and 410 controls. The mean CCI score in the early death group was 2.3 vs. 1.3 in the survivor group (p < .001). Still, 22% vs. 30% had a CCI score of zero (p = .04) with an average number of comorbidities among these patients of 1.63 vs. 1.06 respectively (p = .006). Among women, 23% in the early death group had depression vs. 13% in the survivor group, corresponding to an unadjusted odds ratio (OR) of 2.0 (CI 95% 1.0-3.7). However, in an adjusted analysis (incl. somatic comorbidities) the OR was 1.7 (CI 95% 0.8-3.5). Patients undergoing oncological therapy were older and tended to have more somatic comorbidities than the surgically treated patients.Conclusion: Comorbidity remains a significant prognostic marker even for stage I lung cancer patients with a CCI score of zero. The suggested association between early death and depression among women needs to be studied further.

Comorbidity among Danish lung cancer patients before and after initial cancer diagnosis.

Objective: Lung cancer is the leading cause of cancer-related death worldwide. This population-based longitudinal study investigates survival rates and the burden of comorbidity before and after being diagnosed with lung cancer in Denmark. Methods: From the Danish National Patient Registry (NPR) and the Danish Civil Registration System (CPR), 53,749 patients with lung cancer were identified and matched with 214,304 controls on age, gender, region of residence and marital status in the period 1998-2010. From the NPR, data on survival and comorbidity, registered as ICD-10 diagnoses, were extracted. Comorbidity was assessed using the Deyo-Charlson comorbidity score (DCcs) and mortality using Kaplan-Meier survival curves. Results: 1-year survival rate for Danish lung cancer patients was 51.7 % (CI 51.3-52.1) and 5-year survival rate was 14.7 % (CI 14.3-15.0) compared to 96.8 % (CI 96.7-96.8) and 84.0 % (CI 83.9-84.2) for controls respectively. Overall, cases had significantly more comorbidity compared to controls before being diagnosed with lung cancer. Prior to being diagnosed with lung cancer, more cases than controls had been diagnosed with other malignancies (11.4 % vs 6.0 % p<0.005), diseases of the circulatory system (16.4 % vs 13.0 % p<0.005) and respiratory diseases (12.2 % vs 4.8 % p<0.005). Among lung cancer patients 21.8 % had a DCcs ≥ 1 compared to 13.3 % among controls (P<0.005). The 1-year survival for DCcs =0 was 54.8 % (CI 54.3-55.3) for lung cancer patients and 97.8 % (CI 97.7-97.9) for controls. Decreasing survival with increasing DCcs was found in both groups. Conclusion: This study provides unique nationwide comorbidity data on patients before and after being diagnosed with lung cancer. We found increased mortality with increasing comorbidity, however more pronounced among controls compared to patients with lung cancer.

Treatment, no treatment and early death in Danish stage I lung cancer patients.

BACKGROUND: Stage I lung cancer is curable with surgery as the treatment of choice. Other effective and curative treatments exist. Nevertheless, some patients only receive palliative treatment and some receive no treatment at all. MATERIALS AND METHODS: Using the Danish Lung Cancer Registry (DLCR), we assessed treatment distribution for a population-based Danish cohort of stage I lung cancer patients diagnosed from 2011 to 2014. We assessed one-year mortality according to treatment. Furthermore, in a nested case-control study based on data from medical records, we assessed the reason for not undergoing treatment among patients in favourable performance status (PS) with no treatment registration in the DLCR. RESULTS: We identified 2985 patients, 68% (n = 2021) were treated surgically and 17% (n = 508) were managed with curative oncological therapy. The unadjusted odds ratio (OR) for death within one year was 2.5 (95% CI, 1.8-3.3) for the oncologically managed vs. the surgically treated. After adjusting for age, lung function and PS, the OR was 1.2 (95% CI, 0.8-1.9). Among 129 patients with a PS of 0-1 and no treatment registration, we established the reason for not undergoing treatment in 122 (95%). The majority (70%) were misclassified and did either not have lung cancer, had more advanced disease or were curatively treated. The 36 (30%) patients that did not undergo treatment, had a lower prevalence of adenocarcinomas (17 vs. 51%, p = 0.003), more comorbidites (median Charlson comorbidity index score 2 vs. 1, p < 0.001) and high alcohol intake (19 vs. 7%, p = 0.04) as compared to surgically treated controls. The primary reasons for no treatment were; comorbidity, patient decision and disease progression. CONCLUSION: Difference in outcome between the two major treatment groups was confounded by age, lung function and PS. Comorbidity, high alcohol intake and histology were associated with not undergoing curative treatment in spite of a favourable PS.

Smoking, alcohol, and nutritional status in relation to one-year mortality in Danish stage I lung cancer patients.

INTRODUCTION: In addition to the highest incidence rate of lung cancer among the Nordic countries, Denmark has the highest mortality rate. Moreover, rates of tobacco and alcohol consumption are among the highest in these countries. METHOD: In a population-based matched case/control study, we aimed to assess the association between one-year all-cause mortality and a number of smoking-related parameters, high-risk alcohol intake, and nutritional status in clinical stage I lung cancer patients. RESULTS: We included 221 patients who died within one year after diagnosis (early death) and 410 matched controls who survived more than one year (survivor). The odds ratio (OR) for early death among never-smokers was 0.3 (CI 95%: 0.1-0.9). There was no significant difference between patients who died early and survivors in proportions of current smokers (49 vs. 45%), number of cumulated pack-years (45 vs. 46), daily tobacco consumption (15 vs. 14 cigarettes/day), patients who quit smoking after diagnosis (25 vs. 40%) and the prevalence of chronic obstructive pulmonary disease (COPD) (43 vs. 38%). Patients that died early received more medications for COPD (p = 0.03) and smoked more after diagnosis, 14 vs. 10 cigarettes per day (p = 0.03). The unadjusted OR for high-risk alcohol intake was 2.2 (CI 95% 1.3-3.7) in the early death group vs. the survivors. However, in a treatment-stratified analysis this was observed only for surgically treated patients (OR, 3.2; CI 95% 1.7-6.1). Low nutritional status was associated with early death, unadjusted (OR 2.3; CI 95% 1.4-3.7), while OR was 1.8 (95% CI 1.0-2.3) adjusted for high-risk alcohol intake and COPD. Treatment selection according to and interventions against these factors before and after lung cancer diagnosis may improve outcomes.

[Smoking cessation and lung cancer treatment].

Many resources have been spent to successfully improve the outcome and prognosis of lung cancer during the last decade. However, surprisingly few studies and real-life settings deal with smoking cessation as an integrated part of screening and treatment for lung cancer even though the evidence is compelling - these events offer a window of opportunity, as smokers are motivated to quit. Furthermore, the effect of smoking cessation with respect to survival, prognosis and quality of life equals the established treatment: surgery, chemotherapy and radiation.

Early death in Danish stage I lung cancer patients: a population-based case study.

OBJECTIVE: Clinical stage (c-stage) at diagnosis is the most significant prognostic marker for patients with cancer, where 1- and 5-year survival rates as main landmarks when assessing outcomes. This is a population-based case study of Danish c-stage I lung cancer patients who were considered candidates for curative therapy and then died within 1 year after diagnosis (cases). Cases were identified in the Danish Lung Cancer Register (DLCR), and medical records were used to retrieve treatment details and cause of death (CoD). Our aims were, if possible, to identify and describe clusters of patients, in terms of CoD and treatment modality at risk for an adverse short-term outcome. RESULTS: Patients who died early were more frequently male, older, had squamous-cell histology, were less frequently surgically treated and generally had a higher burden of comorbidity. In terms of CoD, 29% died of lung cancer with distant recurrence (DR) as the most common type of recurrence (55%). Death from co-morbidity occurred for 23%, where the largest proportion (36%) died from another cancer. Nineteen percentage died from treatment complications, with the majority being male (p < .001). The remainder died of unknown or other causes. CONCLUSIONS: Lung cancer with DR remains the most common CoD. Identifying and accordingly treating patients at risk for DR could potentially improve outcomes. Further studies of the predominantly male subgroup of patients who die of treatment complications are needed. Death from co-morbidity especially in patients with another cancer is a significant CoD and when assessing the quality of lung cancer care a competing event.

Assessing the pattern of recurrence in Danish stage I lung cancer patients in relation to the follow-up program: are we failing to identify patients with cerebral recurrence?

BACKGROUND: There is paucity of evidence regarding the optimal follow-up (FU) regimen for lung cancer. Consequently, FU is organized differently across countries. The Danish FU regimen has short FU intervals with a computed tomography (CT) scan of the chest and upper abdomen every three months in the early phase (first 2 years), then every six months in the late phase of FU (3rd, 5th year). Characterizing recurrences missed by the FU program in terms of site, tumor histology, department, and phase of FU, could improve the FU program. MATERIAL AND METHOD: A case-control study of curatively treated stage I lung cancer patients who attended the Danish FU-program and had recurrence identified through the follow-up program (controls, FU group) or outside FU program (cases, symptomatic group). RESULTS: Of 233 included patients with recurrence, the FU group constituted 85% (n = 197). Among the 15% (n = 36) in the symptomatic group, 53% had involvement of the central nervous system compared with 3% in the FU group. The unadjusted odds ratio (OR) for having an isolated brain recurrence (IBR) in the symptomatic group was 52.3 (95%CI: 15.1-181.4) as compared with the FU group. The OR for having a symptomatic recurrence in the early phase of FU was 2.5 (95%CI: 0.7-8.7) compared with the late phase. CONCLUSIONS: The FU program did not identify the majority of patients with IBR. Including cerebral imaging in the FU program may result in an earlier detection of brain metastases. These matters should be studied in a prospective setting.

Lung cancer guidelines in Sweden, Denmark, Norway and Finland: a comparison.

BACKGROUND: The Nordic countries are similar in terms of demographics and health care organization. Yet there are marked differences in lung cancer mortality, for which Denmark historically has had the poorest outcome. One of several possible reasons for these differences could have to do with how lung cancer is diagnosed and treated in the different Nordic countries. However, among the four most populous Nordic countries: Sweden, Denmark, Norway and Finland, there is a paucity of knowledge about differences and similarities in recommendations in the national guidelines for non-small cell lung cancer (NSCLC) and the methodology by which the guidelines are developed. METHODS: We identified and evaluated the development and content of the available clinical care guidelines for NSCLC in the four countries. Moreover, we compared the integrated cancer pathways in these countries. We have used case examples to illustrate areas with clear differences in clinical care recommendations. RESULTS: There are notable differences in the methodology by which the guidelines are developed, published and updated to comply with international recommendations. The Norwegian guidelines are developed and updated according to the most rigorous methodology and have so far been updated most frequently. We found that on the basis of recommendations patients with NSCLC are treated differently with regard to bevacizumab therapy and radiation dosing regimens. Cerebral imaging practices in patients with locally advanced NSCLC also differ. There is, moreover, a marked difference with regard to efforts to help patients to quit smoking. All except Finland have integrated cancer pathways for fast track diagnosis and treatment. Guidelines for follow-up of lung cancer patients also differ, with the Danish follow-up regimen as the most comprehensive. To obtain consensus on optimal clinical care, areas with differences in recommendations or where recommendations are based on a low level of evidence should be subjected to further studies.

Treatment of acute ulcerative colitis with infliximab, a retrospective study from three Danish hospitals.

BACKGROUND: In acute steroid-refractory ulcerative colitis, rescue therapy with infliximab has become a therapeutic option in patients facing colectomy. Data on efficacy and safety in this setting are sparse. METHODS: Patients with ulcerative colitis and acute and severe steroid-refractory disease, who were given infliximab as rescue therapy, were identified by a review of patients' records and databases of infliximab-treated patients. Data on patient background, concomitant medication, endoscopic and laboratory results, clinical activity and adverse events were collected. RESULTS: Fifty-six patients, all admitted because of high disease activity of short duration, and failing high-dose glucocorticoid treatment, received infliximab treatment and were followed up for a median of 538 days (range 2-1769). Colectomy was avoided in 61% of cases. No fatalities were observed. Concomitant medication at the end of follow-up indicated a low number of relapses in patients without colectomies. CONCLUSIONS: Our results show a lasting benefit of infliximab rescue therapy in 61% of patients with acute, steroid-refractory ulcerative colitis, a low incidence of late colectomies, and low frequency of steroid use in patients who avoided colectomy. High levels of C-reactive protein on admittance and at the first infliximab infusion were associated with colectomy. Our study adds to the growing experience of infliximab treatment of patients with acute, steroid-refractory ulcerative colitis.