Progress against lung cancer, Denmark, 2008-2022.

BACKGROUND AND PURPOSE: There has been marked progress against lung cancer in Denmark. To gain further insight into the different aspects of the improvement, we examined the stage-specific incidence rates, stage-specific survival and mortality rates. MATERIALS AND METHODS: We used information from the Danish Lung Cancer Registry on date of diagnosis and clinical stage to calculate age-standardised incidence rates and patient survival by sex, period and stage. Information about age-standardised lung cancer-specific mortality rates by sex and period was extracted from The Danish Health Data Authority. RESULTS: Firstly, the decrease in incidence rates was due to a reduction in the rates of advanced stages. Secondly, there was a gradual increase in survival across all stages, and thirdly, the mortality rates gradually decreased over time. INTERPRETATION: The improvements in survival and mortality from lung cancer were due to decreasing incidence rates of advanced cancer and improvement in survival at all stages of the disease.

Introduction of the Danish Lung Nodule Registry: A part of the Danish Lung Cancer Registry.

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.

Use of [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography after Curative Treatment of Non-Small-Cell Lung Cancer Patients: A Nationwide Cohort Study.

[¹8F]Fluorodeoxyglucose positron emission tomography/computed tomography ([¹8F]FDG PET/CT) is a valuable imaging tool in the post-treatment management of non-small-cell lung cancer (NSCLC). This study aimed to investigate the trends in utilization and factors associated with the use of [¹8F]FDG PET/CT after curative-intent treatment. Data from 13,758 NSCLC patients diagnosed between 2007 and 2020 identified in the Danish Lung Cancer Registry, who underwent curative-intent treatment, were analyzed using multivariable regression. The results showed a significant increase in the use of [¹8F]FDG PET/CT scans, from 10.4 per 100 patients per year in 2007 to 39.6 in 2013, followed by a period of stability. Higher utilization rates were observed in patients who received radiotherapy (22% increase compared to surgical resection) and in patients with stage II-III disease (14% and 20% increase compared to stage I, respectively). Additionally, utilization was increased when other diagnostic procedures were performed, such as MRI, ultrasound, endoscopy, and biopsy. These findings highlight an increasing reliance on [¹8F]FDG PET/CT in post-treatment NSCLC, especially after radiotherapy and in patients with locally advanced disease, where treatment-induced radiographic changes and an increased risk of recurrence present a significant diagnostic challenge.

Consequences of Losing Incidental Pulmonary Nodules to Follow-Up: Unmonitored Nodules Progressing to Stage IV Lung Cancer.

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.

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.

Decision support to general practice in choice of chest imaging for patients with pulmonary symptoms.

INTRODUCTION: The choice of chest imaging for patients with respiratory problems is based on risk profile and symptoms. In 2018-2020, GPs in the catchment area of Silkeborg Regional Hospital, Denmark, were offered direct referral for either X-ray or low-dose computed tomography (LDCT) of the chest for patients with respiratory symptoms who did not meet the criteria for a contrast-enhanced CT (CECT) of the chest and upper abdomen as part of the lung cancer referral pathway. The aim of this study was 1) to estimate the percentage of patients referred for LDCT or chest X-ray who met CECT criteria based on the clinical information in the referral letters, and 2) to assess the GPs' response to standard questions regarding the active feedback provided. METHODS: The study was conducted from April to October 2019. Radiographers initially assessed all referrals for X-ray or LDCT, and contacted the GPs if they assessed that symptoms and clinical characteristics justified CECT. RESULTS: In the study period, 1,112 referrals for chest imaging from GPs were received; in 97 cases (9%), the referral information warranted CECT as part of a lung cancer referral package. In 71% (69/97) of these cases, the GP accepted the conversion to CECT; 55 of 73 LDCTs and 14 of 24 X-rays. In 15 cases, the GP adhered to the requested imaging owing to clinical assessment or their agreement with the patient, and in the remaining 13 cases no specific reason was given. CONCLUSION: The feedback provided was well received by GPs and the approach adopted may be a step towards structured decision support to facilitate the choice of chest imaging. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Diagnosis and treatment of lung cancer in Denmark during the COVID-19 pandemic.

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.

Complete Spontaneous Regression of Squamous-Cell Lung Cancer: A Case Report.

Spontaneous regression of cancer is an extremely rare phenomenon, and it has been described in only a few cases of pulmonary cancer. We report a case of complete spontaneous regression of squamous-cell lung cancer (SCLC) following a core needle biopsy in a 67-year-old female patient with two previous lung cancers and concomitant follicular lymphoma. The patient was diagnosed with SCLC after 4 core needle biopsies from a nodule in the left upper lobe and at the same time suspected of having follicular lymphoma. Treatment for the lung cancer was delayed by approximately 8 weeks because the diagnosis of lymphoma was both challenging and time-consuming. A computed tomography scan was performed in relation to the scheduled treatment for SCLC, showing that the pulmonary nodule had disappeared completely. Most other cases of spontaneous regression of lung cancer hint at the involvement of immunological factors, and this case possibly involves a combination of mechanical and local immunological factors. Genetic and immunological analysis of patients showing spontaneous regression of cancers could provide valuable information.

Does the Addition of Radial Endobronchial Ultrasound Improve the Diagnostic Yield of Electromagnetic Navigation Bronchoscopy? A Systematic Review.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Early diagnosis is crucial to increased survival rates. Radial endobronchial ultrasound (rEBUS) and electromagnetic navigation bronchoscopy (ENB) have been developed for the diagnosis of small lung lesions. The aim of this systematic review was to evaluate whether the combination of rEBUS and ENB is superior to ENB alone. METHOD: A systematic search was performed using MEDLINE, Embase, and Cochrane Library databases on "ENB," and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The project was registered with PROSPERO, number CRD42020214682. RESULTS: In total, 2,092 studies were identified through a literature search. Five studies were included in the final review. One study found that the addition of rEBUS increased diagnostic yield, while another concluded the converse. Three studies did not have significant results. Meta-analysis was not feasible due to heterogeneity and the small number of studies. CONCLUSION: As the current evidence on the topic is sparse and heterogeneous, it is not possible to conclude whether the addition of rEBUS to ENB has a significant impact on diagnostic yield. Further studies are needed to illuminate this question in order to ensure optimal choice of endoscopic technique as well as used time and resources. The project received funding from the Region of Southern Denmark's PhD fund.

Increased use of diagnostic CT imaging increases the detection of stage IA lung cancer: pathways and patient characteristics.

BACKGROUND: At Silkeborg Regional Hospital, Denmark, the number of stage IA lung cancer increased after implementation of increased use of CT investigations and a corresponding reduction in chest X-ray. The aim of the present study was to understand the changes in referral pathways, patient characteristics and imaging procedures behind the observed increase in early-stage lung cancer. METHODS: The referral and imaging pathways for all patients diagnosed with lung cancer in 2013-2018 were described based on manually curated information from the electronic health care systems and staging information from the Danish Lung Cancer Registry. We compared the clinical characteristics of patients diagnosed in 2013-2015 and in 2016-2018 after implementation of a change in the use of low dose CT scan (LDCT). For patients diagnosed in 2016-2018, stage IA lung cancer were compared to higher stages using univariable logistic regression analysis. RESULTS: Five hundred and forty-seven patients were diagnosed with lung cancer in 2013-2018. Stage IA constituted 13.8% (34/247) in 2013-2015, and 28.3% (85/300) in 2016-2018. Stage IA patients in 2016-2018 were characterised by more comorbidity, fewer packyears and tended to be older than patients with higher stages. In 2016-2018, the largest proportion of stage IA patients (55%) came from within-hospital referrals. The majority of these lung cancers were detected due to imaging procedures with other indications than suspicion of lung cancer. The proportion of stage IA increased from 12% (12/99) to 36% (47/129) (p < 0.001) for hospital referrals and from 17% (22/129) to 23% (38/165) for GP referrals (p = 0.21). The imaging procedures contributing to the increase in stage IA was contrast enhanced CT (22%¸11/51), LDCT (35%; 18/51) and X-ray followed by LDCT (25%; 13/51). CONCLUSION: The increased access to LDCT for patients referred from general practice and the increased hospital requested CT activity resulted in an increase in the number of stage IA lung cancers. Incidental findings on imaging performed for diagnostic purposes unrelated to suspicion of lung cancer contributed a large proportion of the increase.

Symptoms and lung function follow-up after lung cancer resection.

INTRODUCTION In recent decades, lung cancer is being diagnosed at ever earlier stages, leading to higher resection rates and improved survival. Therefore, more patients live with the sequelae of thoracic surgery. The standardised Danish follow-up programme after lung cancer resection includes CT and clinical evaluation at set times. METHODS An e-mail survey was conducted to evaluate local practices at lung cancer investigation sites with respect to the setup of follow-up programmes after lung cancer resection. In addition, 50 consecutive patients were seen three months after their lung cancer resection. Spirometry was performed and patients reported on their use of inhalation medicine, smoking status and quality of life. RESULTS The study revealed heterogeneous setups regarding routine spirometry (5/12 sites) and assessment by a respiratory physician (6/12). In a single-centre study including 50 patients three months after lung cancer resection, 22% of patients were using a bronchodilator even though 50% of patients were obstructive on spirometry and 48% reported shortness of breath (SOB). 17% of patients were active smokers, whereas the majority reported symptoms of a physical nature such as fatigue, SOB and cough. CONCLUSIONS It is important to establish the optimal follow-up setup with an emphasis on detection of recurrence, symptom improvement and smoking cessation. This study highlighted the importance of symptom assessment by a respiratory physician/nurse. A spirometry should be performed if patients experience SOB and the potential benefit of inhalation medicine should be assessed. FUNDING none. TRIAL REGISTRATION not relevant.

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).

Stage I lung cancer patients with or without symptoms - are the patients different and should we treat them differently?

INTRODUCTION: A large proportion of stage I cancers are found incidentally, which appears to be a prognostic factor. We investigated stage I lung cancers according to whether, or not, there had been clinical suspicion of lung cancer prior to referral and to see, if we could detect any difference regarding patient characteristics, work-up and mortality for incidental vs non-incidental findings as well as for asymptomatic vs symptomatic patients. METHODS: Medical records and referral documents for 177 patients diagnosed with stage I lung cancer were reviewed and divided based on whether the initial CT scan leading to diagnosis had been made due to suspicion of lung cancer or not. Patient characteristics and mortality between groups were compared, as well as mortality between patients with and without symptoms at the time of diagnosis. RESULTS: One-hundred-and-eight patients were diagnosed incidentally, while 69 patients were non-incidental findings. Among the incidental findings, 55% had no symptoms, whereas none in the non-incidental group were asymptomatic. Personal characteristics were comparable between the groups. Significantly more patients in the incidental group had malignant comorbidity. Non-malignant chronic co-morbidity was more prevalent in the non-incidental group, in particular lung disease. There was no difference in tumour size, histology, or survival for incidental vs non-incidental or for asymptomatic vs symptomatic patients. CONCLUSION: A large proportion of stage I lung cancers are found incidentally, especially in patients with malignant co-morbidity. We found no difference in survival to indicate that we did or should handle these patient groups differently.

Integration of cryobiopsies for interstitial lung disease diagnosis is a valid and safe diagnostic strategy-experiences based on 250 biopsy procedures.

BACKGROUND: Transbronchial cryobiopsies has become increasingly used in the diagnostic workup in patients suspected of having interstitial lung disease. The procedure is associated with less complications, morbidity and mortality compared to surgical lung biopsies although with a diagnostic yield that is not as high, but close to that of surgical lung biopsies. The aim of the present study was to describe the complications and diagnostic yield and their prognostic factors. METHODS: All patients undergoing transbronchial cryobiopsies at the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, were included in this prospective observational cohort study. RESULTS: A total of 250 patients were included [61% male, mean age 66 years (range, 22-81 years)]. Pneumothorax was detected in 70 (28%) of the patients, moderate hemorrhage in 53 (21%) and severe hemorrhage in 2 (1%) of the patients. Hemorrhage was associated with central biopsies, but not with anticoagulant therapy. None of the complications were related to lung function, exercise capacity, biopsy or probe size. Only one patient experienced an acute exacerbation. Three-month mortality was 0.4% (1 patient), caused by cancer and unrelated to the procedure. Cryobiopsies contributed to the final diagnosis in 72% of the patients and after multidisciplinary team discussion, a consensus diagnosis was obtained in 82% of the patients. The gender, the total sum of biopsy sizes, number of biopsies and presence of more than 50% alveolar tissue in biopsies increased the diagnostic yield. CONCLUSIONS: Our study confirms that using cryobiopsies in the diagnostic setup for interstitial lung diseases is safe with a limited risk of acute exacerbations and mortality. Cryobiopsies contribute to the diagnosis in the majority of patients.

Pregnancy-Associated Plasma Protein-A2 Is Associated With Mortality in Patients With Lung Cancer.

Pregnancy-associated plasma protein-A (PAPP-A) and its homolog PAPP-A2 are enzymes that modulate the availability and mitogenic activity of insulin-like growth factor-I (IGF-I). PAPP-A has been implicated in numerous cancers but reports on PAPP-A2 in malignancy are non-existent. In a prospective observational study of 689 patients under suspicion of lung cancer, we examined levels of PAPP-A and PAPP-A2 and their relationship with mortality. Serum PAPP-A and PAPP-A2 concentrations were determined in pre-diagnostic blood samples using ELISA, and immunohistochemical staining of PAPP-A and PAPP-A2 was performed in malignant tissue from five operable patients. A total of 144 patients were diagnosed with lung cancer, whereas the diagnosis was rejected in 545 subjects, who served as a control group. PAPP-A2 concentrations were higher in patients with lung cancer [median (IQR): 0.33 (0.21-0.56) ng/mL] than in controls [0.27 (0.17-0.39) ng/mL], p < 0.001, whereas PAPP-A levels did not differ. Presence of PAPP-A and PAPP-A2 were confirmed in tumor specimens, and staining occurred in a heterogeneous pattern. Patients were observed for a median (range) of 7 (6; 8) years, during which 114 patients (79.2%) died. Patient mortality differed according to PAPP-A2 tertile (p < 0.001). PAPP-A2 was associated with mortality with an unadjusted hazard ratio (95% CI) per doubling in protein concentration of 1.30 (1.12; 1.53), p = 0.001. In a multivariable model adjusted for age, sex, and BMI, PAPP-A2 remained predictive of the endpoint with a hazard ratio per doubling in protein concentration of 1.25 (1.05; 1.48), p = 0.013. Collectively, PAPP-A2, but not PAPP-A, is elevated in patients with lung cancer and associated with mortality. This novel role of PAPP-A2 in cancer warrants further functional studies as well as validation in external cohorts.

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.

Development of a novel assay for IGFBP-2 complexed with IGF-I and-II in human serum.

BACKGROUND: Insulin-like growth factor binding-protein 2 (IGFBP-2) was originally identified as an IGF-carrier, governing IGF half-life, tissue accessibility and biological effects. Later, IGFBP-2 was discovered to possess IGF-independent effects. IGFBP-2 circulates in several forms, as free protein, complexed with IGF-I or IGF-II, or as IGFBP-2 fragments. The various IGFBP-2 forms are all included when measuring serum IGFBP-2 concentrations by immunoassay (i.e., immunoreactive (ir-)IGFBP-2). In this study, we describe a novel method to measure the amount of IGF that circulates bound to IGFBP-2. METHOD: IGFBP-2 was immunoprecipitated from human serum using magnetic beads, which were subsequently eluted by acidification. After neutralization, eluates were assayed for ir-IGFBP-2, IGF-I and IGF-II and compared to serum concentrations. This allowed measurement of IGFBP-2-compexed IGF-I and IGF-II, respectively. To test the method clinically, serum from 146 patients with lung cancer, 151 patients with non-cancer pulmonary diseases and 28 healthy controls were analyzed. RESULTS: We immuno-precipitated 97 ± 3.3% of serum IGFBP-2 and recovered > 75% of IGFBP-2-complexed IGFs, with intra- and inter-assay coefficient of variations (CVs) averaging < 5% and < 13%, respectively. No co-precipitation with IGFBP-1, -3 or - 4 was detected. Serum levels of ir-IGFBP-2 (median [25;75%]) differed between groups (cancer patients vs. non-cancer patients vs. healthy controls): 342 [260;480] vs. 262 [189;388] vs. 190 [141;269] µg/l (p < .0001). In parallel with this, concentrations of IGF-II carried by IGFBP-2 averaged: 45.0 [33.3;52.5] vs. 34.2 [25.4;46.1] vs. 19.8 [14.1;26.0] µg/l (p < .0001), and concentrations of IGF-I 8.0 [5.2;11.8] vs. 5.4 [3.6;7.3] vs. 7.0 [3.8;13.0] µg/l (p < .0001). Thus, IGFBP-2 carried more IGF-II than IGF-I in all groups (p < .0001). When expressed relative to IGF-concentrations, IGFBP-2 carried 9.0 [5.3;15.5] % of the IGF-I and 4.8 [2.9;5.8] % of the IGF-II in serum from healthy subjects. Notably, in patients, IGFBP-2 carried relatively less IGF-I, but more IGF-II (p < .0001). CONCLUSION: Using our novel assay, we demonstrate: that IGFBP-2 carries ≈10% of circulating IGF-I and ≈5% of circulating IGF-II in healthy subjects; that IGF-II is the primary ligand for IGFBP-2; and that IGFBP-2 carries even more IGF-II in patients than in healthy subjects. Thus, our assay may provide information on IGFBP-2 beyond what is achievable by simply measuring ir-IGFBP-2.

Surveillance With PET/CT and Liquid Biopsies of Stage I-III Lung Cancer Patients After Completion of Definitive Therapy: A Randomized Controlled Trial (SUPER).

Despite increased focus on prevention as well as improved treatment possibilities, lung cancer remains among the most frequent and deadliest cancer diagnoses worldwide. Even lung cancer patients treated with curative intent have a high risk of relapse, leading to a dismal prognosis. More knowledge on the efficacy of surveillance with both current and new technologies as well as on the impact on patient treatment, quality of life, and survival are urgently needed. We therefore designed a randomized phase 3 trial. In one arm, every other computed tomography (CT) scan is replaced by positron emission tomography/CT, the other arm is the standard follow-up scheme with CT. The standard arm is identical to the current national Danish follow-up program. The primary endpoint is to compare the number of relapses treatable with curative intent in the 2 arms. We aim to include 750 patients over a 3-year period. Additionally, we will test the feasibility of noninvasive lung cancer diagnostics and surveillance in the form of circulating tumor DNA analysis. For this purpose, blood samples are collected before treatment and at each following control. The blood samples are stored in a biobank for later analysis and will not be used for guiding patient treatment decisions.

Vitamin B12 and its binding proteins in patients with non-small cell lung cancer referred to fast-track diagnostic work-up for lung cancer.

High cobalamin levels have previously been associated with short-term cancer risk, including lung cancer. We explored whether levels of cobalamin and/or its binding proteins are useful as a diagnostic tool in patients suspected of non-small cell lung cancer. We included 889 patients referred for fast-track diagnosis of lung cancer to Aarhus University Hospital, Denmark. We analyzed plasma concentrations of cobalamin, transcobalamin, holotranscobalamin and haptocorrin. Information on lung cancer diagnosis was retrieved from a national database. The study cohort showed levels above reference intervals for cobalamin 12%, holotranscobalamin 25%, transcobalamin 9% and haptocorrin 36% (all p-values <.05). We observed no difference in cobalamin or holotranscobalamin levels when comparing patients diagnosed with non-small cell lung cancer (n = 161, 18%) to patients without lung cancer (n = 742, 80%), while transcobalamin showed minor differences. Haptocorrin was significantly higher in those with cancer, mainly among patients with adenocarcinoma (n = 94). A comparison of patients with the highest vs. lowest quartile levels of haptocorrin yielded an adjusted odds ratio for adenocarcinoma of 2.39 (95% confidence interval: 1.26-4.55). However, ROC curve analyzes showed haptocorrin (AUC = 0.55) and total transcobalamin (AUC = 0.56) to be poor diagnostic markers for lung cancer. A high proportion of patients suspected for non-small cell lung cancer showed increased levels of cobalamin-binding proteins. We thereby confirm the association between non-small cell lung cancer and high cobalamin levels and found that haptocorrin was the major underlying factor causing high cobalamin levels. However, none of these biomarkers were of diagnostic use among patients referred for suspected lung cancer.