Developing a Pan-European Technical Standard for a Comprehensive High-quality Lung Cancer CT Screening Program. An ERS Technical Standard.

Screening for lung cancer with low radiation dose computed tomography (LDCT) has a strong evidence base. The European Council adopted a recommendation in November 2022 that lung cancer screening be implemented using a stepwise approach. The imperative now is to ensure that implementation follows an evidence-based process that delivers clinical and cost effectiveness. This ERS Taskforce was formed to provide a technical standard for a high-quality lung cancer screening program. METHOD: A collaborative group was convened to include members of multiple European societies (see below). Topics were identified during a scoping review and a systematic review of the literature was conducted. Full text was provided to members of the group for each topic. The final document was approved by all members and the ERS Scientific Advisory Committee. RESULTS: Ten topics were identified representing key components of a screening program. The action on findings from the LDCT were not included as they are addressed by separate international guidelines (nodule management and clinical management of lung cancer) and by a linked taskforce (incidental findings). Other than smoking cessation, other interventions that are not part of the core screening process were not included (e.g. pulmonary function measurement). Fifty-three statements were produced and areas for further research identified. CONCLUSION: This European collaborative group has produced a technical standard that is a timely contribution to implementation of LCS. It will serve as a standard that can be used, as recommended by the European Council, to ensure a high quality and effective program.

ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.

BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.

HUNCHEST-II contributes to a shift to earlier-stage lung cancer detection: final results of a nationwide screening program.

OBJECTIVES: The introduction of low-dose CT (LDCT) altered the landscape of lung cancer (LC) screening and contributed to the reduction of mortality rates worldwide. Here we report the final results of HUNCHEST-II, the largest population-based LDCT screening program in Hungary, including the screening and diagnostic outcomes, and the characteristics of the LC cases. METHODS: A total of 4215 high-risk individuals aged between 50 and 75 years with a smoking history of at least 25 pack-years were assigned to undergo LDCT screening. Screening outcomes were determined based on the volume, growth, and volume doubling time of pulmonary nodules or masses. The clinical stage distribution of screen-detected cancers was compared with two independent practice-based databases consisting of unscreened LC patients. RESULTS: The percentage of negative and indeterminate tests at baseline were 74.2% and 21.7%, respectively, whereas the prevalence of positive LDCT results was 4.1%. Overall, 76 LC patients were diagnosed throughout the screening rounds (1.8% of total participants), out of which 62 (1.5%) patients were already identified in the first screening round. The overall positive predictive value of a positive test was 58%. Most screen-detected malignancies were stage I LCs (60.7%), and only 16.4% of all cases could be classified as stage IV disease. The percentage of early-stage malignancies was significantly higher among HUNCHEST-II screen-detected individuals than among the LC patients in the National Koranyi Institute of Pulmonology's archive or the Hungarian Cancer Registry (p < 0.001). CONCLUSIONS: HUNCHEST-II demonstrates that LDCT screening for LC facilitates early diagnosis, thus arguing in favor of introducing systematic LC screening in Hungary. CLINICAL RELEVANCE STATEMENT: HUNCHEST-II is the so-far largest population-based low-dose CT screening program in Hungary. A positive test's overall positive predictive value was 58%, and most screen-detected malignancies were early-stage lesions. These results pave the way for expansive systematic screening in the region. KEY POINTS: • Conducted in 18 medical facilities, HUNCHEST-II is the so far largest population-based low-dose CT screening program in Hungary. • The vast majority of screen-detected malignancies were early-stage lung cancers, and the overall positive predictive value of a positive test was 58%. • HUNCHEST-II facilitates early diagnosis, thus arguing in favor of introducing systematic lung cancer screening in Hungary.

Nationwide lung cancer screening with low-dose computed tomography: implementation and first results of the HUNCHEST screening program.

OBJECTIVES: Lung cancer (LC) kills more people than any other cancer in Hungary. Hence, there is a clear rationale for considering a national screening program. The HUNCHEST pilot program primarily aimed to investigate the feasibility of a population-based LC screening in Hungary, and determine the incidence and LC probability of solitary pulmonary nodules. METHODS: A total of 1890 participants were assigned to undergo low-dose CT (LDCT) screening, with intervals of 1 year between procedures. Depending on the volume, growth, and volume doubling time (VDT), screenings were defined as negative, indeterminate, or positive. Non-calcified lung nodules with a volume > 500 mm3 and/or a VDT < 400 days were considered positive. LC diagnosis was based on histology. RESULTS: At baseline, the percentage of negative, indeterminate, and positive tests was 81.2%, 15.1%, and 3.7%, respectively. The frequency of positive and indeterminate LDCT results was significantly higher in current smokers (vs. non-smokers or former smokers; p < 0.0001) and in individuals with COPD (vs. those without COPD, p < 0.001). In the first screening round, 1.2% (n = 23) of the participants had a malignant lesion, whereas altogether 1.5% (n = 29) of the individuals were diagnosed with LC. The overall positive predictive value of the positive tests was 31.6%. Most lung malignancies were diagnosed at an early stage (86.2% of all cases). CONCLUSIONS: In terms of key characteristics, our prospective cohort study appears consistent to that of comparable studies. Altogether, the results of the HUNCHEST pilot program suggest that LDCT screening may facilitate early diagnosis and thus curative-intent treatment in LC. KEY POINTS: • The HUNCHEST pilot study is the first nationwide low-dose CT screening program in Hungary. • In the first screening round, 1.2% of the participants had a malignant lesion, whereas altogether 1.5% of the individuals were diagnosed with lung cancer. • The overall positive predictive value of the positive tests in the HUNCHEST screening program was 31.6%.

[First experiences with HUNCHEST - low-dose CT lung cancer screening programme]. / Kezdeti tapasztalatok a HUNCHEST ­ alacsony dózisú CT-tüdorákszurési pilotprogrammal.

INTRODUCTION: Lung cancer is the cause of death of around 8000 Hungarians each year. AIM: International studies have proved that low-dose CT (LDCT) screening lowers the lung cancer mortality of high risk patients. The HUNCHEST pilot study launched in 2014 studies the possibilities of a lung cancer screening programme in Hungary. The study is also aimed at showing whether there is an increased number of detected lung cancer in the subgroup with chronic obstructive pulmonary disease (COPD). METHOD: COPD and nonCOPD subjects, smokers and non-smokers are screened with low-dose CT in the 50-79 age group. RESULTS AND CONCLUSION: The study is still undergoing recruitement, but in the light of the first results, the principles of the screening programme at the National Korányi Institute of Pulmonology are also presented. Orv Hetil. 2018; 159(43): 1741-1746.

[Model concept of the health economic evaluation of low-dose CT lung cancer screening in Hungary]. / Az alacsony dózisú CT-vel végzett tüdorákszurés magyarországi egészség-gazdaságtani elemzésének koncepcionális terve.

INTRODUCTION: Lung cancer is a rapidly progressing, often life-threatening disease that constitutes a huge societal burden. Because of the scarce resources of the Hungarian health care system, the cost-effectiveness of introducing low-dose computed tomography screening is a relevant health policy matter. AIM: The aim of this study is to design a model concept for assessing the cost-effectiveness of low-dose computed tomography lung cancer screening in Hungary, and to define the required steps for performing the analysis. METHOD: A targeted literature review was conducted to identify and synthesize the evidence on efficacy and effectiveness of screening, and results were evaluated based on adaptability to Hungarian settings. We also summarized the available Hungarian scientific evidence and reconstructed the potential patient pathways. RESULTS: In accordance with these findings, we recommend to perform the full health-economic evaluation of low-dose computed tomography lung cancer screening using a complex model structure that consists of several sub-models and is capable to follow the population at risk on life-time horizon. CONCLUSIONS: The proposed cost-effectiveness model will be suitable to provide data for further analyses that support decision-making on introducing low-dose computed tomography lung cancer screening as public health program. Orv Hetil. 2017; 158(25): 963-975.

HUNCHEST projects-advancing low-dose CT lung cancer screening in Hungary.

Lung cancer, the leading cause of malignancy-related deaths worldwide, demands proactive measures to mitigate its impact. Low-dose computer tomography (LDCT) has emerged as a promising tool for secondary prevention through lung cancer screening (LCS). The HUNCHEST study, inspired by the success of international trials, including the National Lung Cancer Screening Trial and the Dutch NELSON study, embarked on the first LDCT-based LCS program in Hungary. The initiative assessed the screening efficiency, incorporating lung function tests and exploring the interplay between lung cancer and chronic obstructive pulmonary disease (COPD). Building upon this foundation, an implementation trial involving 18 Hungarian centers supported by the Ministry of Human Capacities demonstrated the feasibility of LCS within a multicentric framework. These centers, equipped with radiology capabilities, collaborated with multidisciplinary oncology teams, ensuring optimal patient pathways. However, a critical challenge remained the patient recruitment. To address this, the HUNCHEST 3 project, initiated in 2023, seeks to engage general practitioners (GPs) to reach out to eligible patients within a municipality collective of 60 thousand inhabitants. The project's ultimate success is contingent upon the willingness of eligible individuals to undergo LDCT scans. In conclusion, the HUNCHEST program represents a crucial step in advancing lung cancer screening in Hungary. With a focus on efficiency, multidisciplinary collaboration, and innovative patient recruitment strategies, it endeavors to contribute to the reduction of lung cancer mortality and serve as a blueprint for potential nationwide LCS programs.

From the IASLC Early Detection and Screening Committee Terminology Issues in Screening and Early Detection of Lung Cancer - IASLC Early Detection and Screening Committee Expert Group Recommendations.

INTRODUCTION: To facilitate global implementation of lung cancer (LC) screening and early detection in a quality assured and consistent manner, common terminology is needed. Researchers and clinicians within different specialties may use the same terms but with different meanings, or different terms for the same intended meanings. METHODS: The Diagnostics Working Group of the International Association for the Study of Lung Cancer Early Detection and Screening Committee has analyzed and discussed relevant terms used on a regular basis and suggests recommendations for consensus definitions of terminology applicable in this setting. We explored how to reach consensus to define relevant and unambiguous terminology for use by health care providers, researchers, patients, screening participants and family. RESULTS: Terms and definitions for epidemiological and health-economical purposes included: Standardized incidence and mortality rates, LC specific survival, long-term survival and cure rates, and overdiagnosis, overtreatment, undertreatment. Terms and definitions for defining screening findings included: Positive, false positive, negative, false negative and indeterminate findings and additional and incidental findings. Terms and definitions for describing parameters in screening programmes included: Opportunistic vs programmatic screening, screening rounds, interval/interim diagnoses, invasive and minimally invasive procedures. Terms and definitions for shared decision making included: LC screening - possible harms and risks and LC risk and modifiers prior and posterior to a measure. CONCLUSIONS: A common set of terminology with standard definitions is recommended for describing clinical LC screening programmes, the discussion about effectiveness and outcomes, or the clinical setting. The use of the terms should be clearly defined and explained.

Decreasing incidence and mortality of lung cancer in Hungary between 2011 and 2021 revealed by robust estimates reconciling multiple data sources.

Objective: Hungary has repeatedly been shown to have the highest cancer-related mortality and incidence in Europe. Despite lung cancer being the most abundant malignant diagnosis in Hungary, numerous concerns have been raised recently regarding the bias inherent to reported incidence estimates. Re-analysis of reimbursement claims has been suggested previously by our group as an alternative approach, offering revised figures of lung cancer incidence between 2011 and 2016. Leveraging on this methodology, we aimed at updating Hungarian lung cancer incidence estimates with an additional 5 years (2017-2021), including years affected by the COVID-19 pandemic. Additionally, we also attempted to improve the robustness of estimates by taking additional characteristics of the patient pathway into account. Methods: Lung cancer patients between 2011 and 2021 were identified based on reimbursement-associated ICD-10 codes, histology codes and time patterns. Multiple query architectures were tested for sensitivity and compared to official estimates of the Hungarian National Cancer Registry (HNCR). Epidemiological trends were estimated by Poisson-regression, corrected for age and sex. Results: A total of 89,948 lung cancer patients diagnosed in Hungary between 2011 and 2021 have been identified by our study. In 2019 alone, 7,887 patients were diagnosed according to our optimized query. ESP2013 standardized rate was estimated between 92.5/100,000 (2011) and 78.4/100,000 (2019). In 2019, standardized incidence was 106.8/100,000 for men and 59.7/100,000 for women. Up until the COVID-19 pandemic, lung cancer incidence was decreasing by 3.18% (2.1%-4.3%) yearly in men, while there was no significant decrease in women. Young age groups (40-49 and 50-59) featured the largest improvement, but women aged 60-79 are at an increasing risk for developing lung cancer. The COVID-19 pandemic resulted in a statistically significant decrease in lung cancer incidence, especially in the 50-59 age group (both sexes). Conclusion: Our results show that using an optimized approach, re-analysis of reimbursement claims yields robust estimates of lung cancer incidence. According to this approach, the incidence rate of male lung cancer is declining in Hungary, in concordance with the trend observed for lung cancer mortality. Among women aged 60-79, the incidence of lung cancer has risen, requiring more attention in the near future.

Shall We Screen Lung Cancer With Low-Dose Computed Tomography? Cost-Effectiveness in Hungary.

OBJECTIVES: Clinical data and cost-effectiveness analyses from several countries support the use of low-dose computed tomography (LDCT) to screen patients with high risk of lung cancer (LC). This study aimed to explore the economic value of screening LC with LDCT in Hungary. METHODS: Cohorts of screened and nonscreened subjects were simulated in a decision analytic model over their lifetime. Five steps in the patient trajectory were distinguished: no LC, nondiagnosed LC, screening, diagnosed LC, and post-treatment. Patient pathways were populated based on the Hungarian pilot study of screening, the Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) LC screening trial, and local incidence and prevalence data. Healthcare costs were obtained from the National Health Insurance Fund. Utility data were obtained from international sources and adjusted to local tariffs. Scenarios according to screening frequency, age bands (50-74, 55-74 years), and smoking status were analyzed. RESULTS: Annual LDCT-based screening compared with no screening for 55- to 74-year-old current smokers showed 0.031 quality-adjusted life-year (QALY) gains for an additional €137, which yields €5707 per QALY. Biennial screening for the same target population showed that purchasing 1 QALY would cost €10 203. The least cost-effective case was biennial screening of the general population aged 50 to 74 years, which yielded €37 931 per QALY. CONCLUSIONS: Screening LC with LDCT for a high-risk population could be cost-effective in Hungary. For the introduction of screening with LDCT, targeting the most vulnerable groups while having a long-term approach on costs and benefits is essential.

Computed Tomography-Based Quantitative Texture Analysis and Gut Microbial Community Signatures Predict Survival in Non-Small Cell Lung Cancer.

This study aims to combine computed tomography (CT)-based texture analysis (QTA) and a microbiome-based biomarker signature to predict the overall survival (OS) of immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients by analyzing their CT scans (n = 129) and fecal microbiome (n = 58). One hundred and five continuous CT parameters were obtained, where principal component analysis (PCA) identified seven major components that explained 80% of the data variation. Shotgun metagenomics (MG) and ITS analysis were performed to reveal the abundance of bacterial and fungal species. The relative abundance of Bacteroides dorei and Parabacteroides distasonis was associated with long OS (>6 mo), whereas the bacteria Clostridium perfringens and Enterococcus faecium and the fungal taxa Cortinarius davemallochii, Helotiales, Chaetosphaeriales, and Tremellomycetes were associated with short OS (≤6 mo). Hymenoscyphus immutabilis and Clavulinopsis fusiformis were more abundant in patients with high (≥50%) PD-L1-expressing tumors, whereas Thelephoraceae and Lachnospiraceae bacterium were enriched in patients with ICI-related toxicities. An artificial intelligence (AI) approach based on extreme gradient boosting evaluated the associations between the outcomes and various clinicopathological parameters. AI identified MG signatures for patients with a favorable ICI response and high PD-L1 expression, with 84% and 79% accuracy, respectively. The combination of QTA parameters and MG had a positive predictive value of 90% for both therapeutic response and OS. According to our hypothesis, the QTA parameters and gut microbiome signatures can predict OS, the response to therapy, the PD-L1 expression, and toxicity in NSCLC patients treated with ICI, and a machine learning approach can combine these variables to create a reliable predictive model, as we suggest in this research.

Air Pollution and Lung Cancer: A Review by International Association for the Study of Lung Cancer Early Detection and Screening Committee.

INTRODUCTION: The second leading cause of lung cancer is air pollution. Air pollution and smoking are synergistic. Air pollution can worsen lung cancer survival. METHODS: The Early Detection and Screening Committee of the International Association for the Study of Lung Cancer formed a working group to better understand issues in air pollution and lung cancer. These included identification of air pollutants, their measurement, and proposed mechanisms of carcinogenesis. The burden of disease and the underlying epidemiologic evidence linking air pollution to lung cancer in individuals who never and ever smoked were summarized to quantify the problem, assess risk prediction models, and develop recommended actions. RESULTS: The number of estimated attributable lung cancer deaths has increased by nearly 30% since 2007 as smoking has decreased and air pollution has increased. In 2013, the International Agency for Research on Cancer classified outdoor air pollution and particulate matter with aerodynamic diameter less than 2.5 microns in outdoor air pollution as carcinogenic to humans (International Agency for Research on Cancer group 1) and as a cause of lung cancer. Lung cancer risk models reviewed do not include air pollution. Estimation of cumulative exposure to air pollution exposure is complex which poses major challenges with accurately collecting long-term exposure to ambient air pollution for incorporation into risk prediction models in clinical practice. CONCLUSIONS: Worldwide air pollution levels vary widely, and the exposed populations also differ. Advocacy to lower sources of exposure is important. Health care can lower its environmental footprint, becoming more sustainable and resilient. The International Association for the Study of Lung Cancer community can engage broadly on this topic.

Significant changes in advanced lung cancer survival during the past decade in Hungary: impact of modern immunotherapy and the COVID-19 pandemic.

Objective: The approval of immunotherapy (I-O) for the treatment of late-stage non-small cell lung cancer (NSCLC) opened new perspectives in improving survival outcomes. However, survival data have not yet been provided from the period of the Covid-19 pandemic. The aims of our study were to assess and compare survival outcomes of patients with advanced LC receiving systemic anticancer treatment (SACT) before and after the approval of immunotherapy in Hungary, and to examine the impact of pandemic on survival outcomes using data from the Hungarian National Health Insurance Fund (NHIF) database. Methods: This retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with advanced stage lung cancer (LC) (ICD-10 C34) between 1 January 2011 and 31 December 2021 and received SACT treatment without LC-related surgery. Survival rates were evaluated by year of diagnosis, sex, age, and LC histology. Results: In total, 35,416 patients were newly diagnosed with advanced LC and received SACT during the study period (mean age at diagnosis: 62.1-66.3 years). In patients with non-squamous cell carcinoma, 3-year survival was significantly higher among those diagnosed in 2019 vs. 2011-2012 (28.7% [95% CI: 26.4%-30.9%] vs. 14.45% [95% CI: 13.21%-15.69%], respectively). In patients with squamous cell carcinoma, 3-year survival rates were 22.3% (95% CI: 19.4%-25.2%) and 13.37% (95% CI: 11.8%-15.0%) in 2019 and 2011-2012, respectively, the change was statistically significant. Compared to 2011-2012, the hazard ratio of survival change for non-squamous cell carcinoma patients was 0.91, 0.82, and 0.62 in 2015-2016, 2017-2018, and 2019, respectively (p<0.001 for all cases). In the squamous cell carcinoma group, corresponding hazard ratios were 0.93, 0.87, and 0.78, respectively (p<0.001 for all cases). Survival improvements remained significant in both patient populations during the Covid-19 pandemic (2020-2021). No significant improvements were found in the survival of patients with small cell carcinoma. Platinum-based chemotherapy was the most common first-line treatment in all diagnostic periods, however, the proportion of patients receiving first- or second-line immunotherapy significantly increased during the study period. Conclusion: 3-year survival rates of NSCLC almost doubled among patients with non-squamous cell carcinoma and significantly improved at squamous cell carcinoma over the past decade in Hungary. Improvements could potentially be attributable by the introduction of immunotherapy and were not offset by the Covid-19 pandemic.

ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.

BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.

[Low-dose lung cancer screening programs - European outlook]. / Alacsony dózisú tüdorákszuro programok ­ európai kitekintés, 2022.

Lung cancer has a high incidence and mortality throughout the world. For a long time no screening methods were available that could detect early, operable lung cancers, and could significantly lower mortality. The NLST trial, published in 2013, and the NELSON trial in 2019 both proved that low-dose CT lung cancer screening in a targeted group of at-risk people lowers long-term mortality significantly. In parallel to, or following these studies pilot programs were started in several European countries, including Hungary. In this article different European approaches are presented, when available including the results thereof.

Screening for Lung Cancer in Individuals Who Never Smoked: An International Association for the Study of Lung Cancer Early Detection and Screening Committee Report.

Screening with low-dose computed tomography of high-risk individuals with a smoking history reduces lung cancer mortality. Current screening guidelines and eligibility criteria can miss more than 50% of lung cancers, and in some geographic areas, such as East Asia, a large proportion of the missed lung cancers are in never-smokers. Although randomized trials revealed the benefits of screening for people who smoke, these trials generally excluded never-smokers. Thus, the feasibility and effectiveness of lung cancer screening of individuals who never smoked are uncertain. Several known and suspected risk factors for lung cancers in never-smokers such as exposure to secondhand smoke, occupational carcinogens, radon, air pollution, and pulmonary diseases, such as chronic obstructive pulmonary disease and interstitial lung diseases, and intrinsic factors, such as age, are well noted. In this regard, knowledge of risk factors may make possible quantification and prediction of lung cancer risk in never smokers. It is worth considering if and how never smokers could be included in population-based screening programs. As the implementation of these programs is challenging in many countries owing to multiple factors and the epidemiologic differences by global regions, these issues will need to be evaluated in each country taking into account various factors, including accuracy of risk assessment and cost-effectiveness of screening in never smokers. This report aims to outline current knowledge on risk factors for lung cancer in never smokers to propose research strategies for this topic and initiate a broader discussion on lung cancer screening of never smokers. Similar considerations can be made in current and ex-smokers, which do not fulfill the current screening inclusion criteria, but otherwise are at increased risk. Although screening of never smokers may in the future be effectively conducted, current evidence to support widespread implementation of this practice is lacking.

Lung Cancer Screening Considerations During Respiratory Infection Outbreaks, Epidemics or Pandemics: An International Association for the Study of Lung Cancer Early Detection and Screening Committee Report.

After the results of two large, randomized trials, the global implementation of lung cancer screening is of utmost importance. However, coronavirus disease 2019 infections occurring at heightened levels during the current global pandemic and also other respiratory infections can influence scan interpretation and screening safety and uptake. Several respiratory infections can lead to lesions that mimic malignant nodules and other imaging changes suggesting malignancy, leading to an increased level of follow-up procedures or even invasive diagnostic procedures. In periods of increased rates of respiratory infections from severe acute respiratory syndrome coronavirus 2 and others, there is also a risk of transmission of these infections to the health care providers, the screenees, and patients. This became evident with the severe acute respiratory syndrome coronavirus 2 pandemic that led to a temporary global stoppage of lung cancer and other cancer screening programs. Data on the optimal management of these situations are not available. The pandemic is still ongoing and further periods of increased respiratory infections will come, in which practical guidance would be helpful. The aims of this report were: (1) to summarize the data available for possible false-positive results owing to respiratory infections; (2) to evaluate the safety concerns for screening during times of increased respiratory infections, especially during a regional outbreak or an epidemic or pandemic event; (3) to provide guidance on these situations; and (4) to stimulate research and discussions about these scenarios.

The budget impact of lung cancer screening with low-dose computed tomography / A kis dózisú komputertomográfiával történo tüdorákszurés költségvetési hatása.

Összefoglaló. Bevezetés: Korábbi vizsgálatunk szerint a kis dózisú komputertomográfiával évente végzett tüdorákszurés 50-74 éves dohányzók körében költséghatékony, és az 55-74 évesek körében költségmegtakarító. Célkituzés: Ennek a vizsgálatnak a célja a korábbi hosszú távú költséghatékonysági elemzés kiegészítése egy finanszírozó szempontú, rövid és középtávú költségvetési hatásvizsgálattal. Módszer: Egészség-gazdaságtani modellünk az 50-74 éves, naponta dohányzó lakosság tüdorákszurésének költségét hasonlítja össze a szervezett szurésben nem részesülo, naponta dohányzó lakosság költségével. Ehhez megvizsgáljuk a célpopuláció létszámának alakulását, az eredményes elérés és felfedezés valószínuségét, továbbá a szurés nyomán felmerülo terápiás költségeket és megtakarításokat. A szurés és a kivizsgálások után diagnosztizált betegek útját az érvényben lévo hazai ellátási protokollnak megfeleloen követjük. A kezelések eredményességét a HUNCHEST-felmérés adatai alapján, a kezelésekhez tartozó beavatkozások költségét közfinanszírozási adatok alapján számoljuk. Eredmények: A kis dózisú komputertomográfiával történo tüdorákszurés az érintett lakosság 10%-ának várható részvétele mellett a kezdeti évben mintegy 3,3 milliárd, az 5. évben 1,9 milliárd Ft éves többletkiadással jár. A 3. évig szuréssel felfedezett betegek terápiája többe kerül, mint a szurés nélkülieké, ugyanakkor a 4. és 5. évben a szurés nélküli csoportban a késobbi stádiumban felismert betegek kezelési költsége már meghaladja a szurt betegek terápiás költségét. A 3. évtol folyamatosan növekvo terápiás megtakarítás a teljes szurés költségét a 10. évre az 1. év kiadásának 20%-ára csökkenti. Következtetések: A kis dózisú komputertomográfiával történo tüdorákszurés bevezetése évi 2,6 milliárd Ft többletforrást igényelne, és folyamatos kiadáscsökkenés mellett hosszú távon akár nettó megtakarítást is eredményezhet a nem szervezett szuréshez képest. A kockázati csoportok pontosítása, például kiemelt földrajzi területeken végzett célzott szurés tovább javíthatja az eredményeket. Orv Hetil. 2021; 162(24): 952-959. INTRODUCTION: Our earlier analysis indicated that screening lung cancer patients with low-dose computed tomography amongst smokers between age of 50-74 and between age of 55-74 is cost-effective and cost-saving, respectively. OBJECTIVE: This study aims to extend the long-term cost-effectiveness analysis with short- and mid-term budget impact analysis. METHOD: The health economic model compares the cost of nationwide screening amongst smokers between 50-74 years to the current occasional screening policy. The analysis determines the size of the target population, recruitment rates and market uptake. Health care finance costs associated with the patient pathways are determined by national guidelines and clinical practice. Screening and treatment effectiveness are based on the HUNCHEST survey and international scientific literature, while the cost of health states and events are determined using national tariffs. RESULTS: Assuming 10% uptake of low-dose computed tomography screening for the target population will cost an additional 3.3 billion HUF and 1.9 billion HUF in the 1st and 5th years, respectively. Until the 3rd year, new patients' treatment costs exceed costs due to late discovery and delay in treatment. This pattern is changing from the 4th year on. Due to timely care savings by the 10th year in the screened population will reduce total costs to the 20% of the first year costs. CONCLUSIONS: Introduction of national screening for lung cancer patients with low-dose computed tomography is estimated to cost around additional 2.6 billion HUF/year and could end up in net savings in the long run. Identification of risk groups according to regional or other strata could increase the effectiveness and efficiency of the program. Orv Hetil. 2021; 162(24): 952-959.

Different Trends in Excess Mortality in a Central European Country Compared to Main European Regions in the Year of the COVID-19 Pandemic (2020): a Hungarian Analysis.

Objective: This study examined cumulative excess mortality in European countries in the year of the Covid-19 pandemic and characterized the dynamics of the pandemic in different countries, focusing on Hungary and the Central and Eastern European region. Methods: Age-standardized cumulative excess mortality was calculated based on weekly mortality data from the EUROSTAT database, and was compared between 2020 and the 2016-2019 reference period in European countries. Results: Cumulate weekly excess mortality in Hungary was in the negative range until week 44. By week 52, it reached 9,998 excess deaths, corresponding to 7.73% cumulative excess mortality vs. 2016-2019 (p-value = 0.030 vs. 2016-2019). In Q1, only Spain and Italy reported excess mortality compared to the reference period. Significant increases in excess mortality were detected between weeks 13 and 26 in Spain, United Kingdom, Belgium, Netherland and Sweden. Romania and Portugal showed the largest increases in age-standardized cumulative excess mortality in the Q3. The majority of Central and Eastern European countries experienced an outstandingly high impact of the pandemic in Q4 in terms of excess deaths. Hungary ranked 11th in cumulative excess mortality based on the latest available data of from the EUROSTAT database. Conclusion: Hungary experienced a mortality deficit in the first half of 2020 compared to previous years, which was followed by an increase in mortality during the second wave of the COVID-19 pandemic, reaching 7.7% cumulative excess mortality by the end of 2020. The excess was lower than in neighboring countries with similar dynamics of the pandemic.

Assessment of the circulating klotho protein in lung cancer patients.

The anti-aging factor, klotho has been identified as a tumor suppressor in various human cancers, including lung cancer. In vitro studies provided evidence that klotho expression influences the characteristics of lung cancer cells, however, in vivo results are lacking. The aim of our study was to evaluate whether circulating klotho protein might serve as a potential biomarker of lung cancer. Blood samples were taken from 45 newly diagnosed lung cancer patients (31 NSCLC, 14 SCLC) and 43 control subjects. Plasma klotho concentration was measured using ELISA. No difference in plasma klotho values was detected between patients and control subjects (366.3 (257.9-486.8) vs. 383.5 (304.6-489.7) pg/ml respectively (median (IQR)); p > 0.05). Plasma klotho levels in patients with distant metastasis did not differ from less advanced stage disease (354.2 (306.9-433.3 vs. 328.5 (242.5-419.7) pg/ml, p > 0.05). In contrast, analyzed with one-way ANOVA, significant difference (p = 0.04) was found between the examined histological types of lung cancer: adenocarcinoma (353 (329.4-438.5) pg/ml), squamous cell carcinoma (308 (209.6-348.1) pg/ml) and small cell lung cancer (388.8 (289.9-495.4) pg/ml). However, Tukey's post hoc test did not reveal significant difference between any pairs of histological groups. There was no difference between any histological subtype and health either. Our results suggest that circulating klotho protein cannot be considered as a biomarker for lung cancer. Further studies are warranted in order to examine the relationship between klotho expression in lung tissue and circulating levels of the protein, and to explore its mechanism of action in lung cancer.