These authors have contributed equally to this work
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Lung cancer (LC) is a rapidly progressing, life-threatening disease [
Variations in cancer survival between countries of comparable affluence and health systems have prompted international efforts to better understand the root of these differences. One–if not the main–reason for poor lung cancer survival may be late diagnosis [
According to the CONCORD-3 study, LC 5-year survival rates fluctuated between 7.7 and 15.7% in East-Central Europe within the 2010–2014 period [
This nationwide, retrospective study used the claim database of the National Health Insurance Fund of Hungary (NHIF), which is a nationwide insurance system (covering almost 100% of the Hungarian population), as data source. The NHIF database contains medical information regarding ID and ICD-10 codes of the in- and out-patient visits and procedures involved in medical care, containing 100% of lung cancer related intervention as there is no other insurance system for Hungarian citizens for lung cancer treatment. The study was approved by the National Ethical Committee, with the 10338-5/2019/EKU ethical approval number and the I043/88/2019 study license number.
Lung cancer (ICD-10 C34) patients newly diagnosed between January 1, 2011 and December 31, 2016 and ≥20 years or older at the time of diagnosis were included in our study. In order to identify newly diagnosed LC patients from 2011, we set a reference screening period for 2009–2010. Potential miscoding of lung cancer was prevented by only including patients with a minimum of two records of the C34 ICD-10 code within an interval of over 30 but less than 365 days following the first coding. Patients with only one recorded C34 code who died within 60 days after coding, were also included. If patients had ICD-10 codes related to other cancers or if they were administered oncological treatment other than the lung cancer-specific treatment protocol 6 months prior to or 12 months following the first recorded lung cancer code, then these patients were excluded.
Newly diagnosed LC patients were followed up until December 31, 2016 or alternatively until their dates of death, which were also obtained from the NHIF database. Since the immediate cause of death was not available from this data source, all-cause mortality data were accessed. During data collection, data were anonymized and only non-identifiable data were used in the investigation. The total number of newly diagnosed lung cancer patients per year is shown as crude numbers (
As shown in
Patient characteristics.
2011–2012 | 2013–2014 | 2015–2016 | Total | ||||||||||||||
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Patients with new LC diagnosis ( |
14,080 | 13,803 | 13,977 | 41,860 | |||||||||||||
Male ( |
8,830 | 62.71% | 8,351 | 60.50% | 8,314 | 59.48% |
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Female ( |
5,250 | 37.29% | 5,452 | 39.50% | 5,663 | 40.52% |
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Mean age at diagnosis (y, mean ± SD) | 64.88 | ±10.38 | 65.28 | ±10.29 | 65.76 | ±9.87 |
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Male (y, mean ± SD) | 64.67 | ±9.84 | 65.11 | ±9.981 | 65.69 | ±9.44 |
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Female (y, mean ± SD) | 65.22 | ±11.21 | 65.55 | ±10.97 | 65.86 | ±10.47 |
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Age groups | |||||||||||||||||
20–49 | 958 | 6.80% | 890 | 6.45% | 724 | 5.18% |
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50–59 | 4,070 | 28.91% | 3,766 | 27.28% | 3,396 | 24.30% |
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60–69 | 4,966 | 35.27% | 4,985 | 36.12% | 5,617 | 40.19% |
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70–79 | 2,983 | 21.19% | 3,035 | 21.99% | 3,165 | 22.64% |
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80–89 | 1,027 | 7.29% | 1,038 | 7.52% | 960 | 6.87% |
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90≤ | 75 | 0.53% | 89 | 0.64% | 115 | 0.82% |
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Morphology | |||||||||||||||||
Squamous cell carcinoma | 2,778 | 19.73% | 2,508 | 18.17% | 2,598 | 18.59% |
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Adenocarcinoma | 4,152 | 29.49% | 4,073 | 29.51% | 4,128 | 29.53% |
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Small cell carcinoma | 1,069 | 7.59% | 1,179 | 8.54% | 1,064 | 7.61% |
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Primary malignancy not specified | 6,081 | 43.19% | 6,043 | 43.78% | 6,187 | 44.27% |
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First line treatment | |||||||||||||||||
Systemic therapy | 3,757 | 26.68% | 3,959 | 28.68% | 4,064 | 29.08% |
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Surgery (including adjuvant therapy) | 2,480 | 17.61% | 1,860 | 13.48% | 1,582 | 11.32% |
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CI, confidence interval; LC, lung cancer; SD, standard deviation.
The bold values indicate Patient characteristics.
The highest numbers of patients were recorded in the 60–69 age group (
42.2% of the total lung cancer population (
Estimated overall survival of Hungarian lung cancer patients diagnosed between 2011 and 2016.
Females had 22.88% better lung cancer survival compare to males (HR: 0.77; 95% CI: 0.75–0.79,
Difference of estimated overall lung cancer survival between female and male in different age groups.
One-year survival rates were highest in the 20–49 age group, reaching 55.1%, while the largest 50–59 and 60–69 age cohorts had 48.3 and 44.1% survival rates by the end of the first follow-up year. The long-term survival rates decreased to 31.3, 22.5, 17.7, 10.2% in the 20–49, 50–59, 60–69 and 70–79 age cohorts, respectively (
Lung cancer patients diagnosed between 2015 and 2016 had a 5.3% lower risk of mortality compared to patients in the 2011–2012 study period (HR 0.95 95% CI 0.92–0.97;
Age, sex, histology type and treatment dependent difference in estimated overall lung cancer survival between patients diagnosed in 2015–2016 and in 2011–2012.
The improvement of survival was higher by younger age, where
Improvement of survival was found to be higher at females (HR:0.89; 95%CI:0.85–0.93;
When we compared the 2015–16 and 2011–2012 period by histology type of lung cancer, we found the highest improvement at adenocarcinoma, where hazard ratio was 0.89 (95%CI: 0.85–0.93;
We also analyzed those lung cancer patients having systemic treatment in late stage or surgery in early stage. At those, whom had surgery in first line treatment, improvement were not detected (HR:1.00; 95%CI: 0.91–1.11;
Based on the morphological report of the NHIF, the histological type of lung cancer was recorded in 56.3% of all LC patients. Adenocarcinoma was more common in females, with 33.4% vs. 27.0% in male patients, while squamous-cell carcinoma was more frequently found in the male patient population, 22.7% in males vs. 12.9% in females (
Estimated survival of Hungarian lung cancer patients depending on histological characteristics.
We could record the 1st line treatment as systemic therapy at 28.14% of all patients (including chemo and targeted therapy), and surgery (including those having adjuvant treatment) at 14.15%. The share of systemic therapy increased from 26.68 onto 29.08%, while share of those having surgery in early stage, decreased from 17.60 onto 11.32%.
Our retrospective, longitudinal analysis provides long-term LC overall survival data from Hungary based on a comprehensive, nationwide data source. This study is also the first to report an improvement in LC survival during the 2011–2016 period in Hungary. The main findings of this large-scale evaluation can be summarized as follows: 1. Hungarian LC patients had a 5-year overall survival rate of 17.9% between 2011 and 2016, with a 5.3% improvement in survival during the 6 year-study period. 2. The survival of LC depends on age and sex, as well as on cancer type. Females had a 23% lower mortality risk than male LC patients, and the highest crude survival rates were found in patients with adenocarcinoma.
Despite several recently published analyses on lung cancer in Europe [
Studies involving patients diagnosed with lung cancer before 2014 were the only data source which could provide 5-year survival data in 2019. Hence, a number of international publications and data sources were of limited comparability with regard to our study encompassing the 6 year period of 2010–2016. In the CONCORD-3 study, the age-standardized 5-year survival rates varied between 7.7 and 15.7% for East-Central Europe in the 2010–2014 diagnostic period [
We demonstrated a 5.3% improvement in survival (9.0% adjusted) between 2015–2016 and 2010–2011 periods, which was an increase expressed by hazard ratio, hence not the change of the fifth year survival rates as 2015–2016 period did not have such a long follow-up period. Nevertheless, the change is close to a yearly 1% improvement. If we compare the trends of lung cancer survival in other study, we can find a 18.9% vs 12.4% in Denmark, 14.7% vs 10.0% in United Kingdom, 20.4% vs 15.4% in Norway and 21.7% vs 18.5% in Canada by comparing the 2010–2014 and 2005–2009 periods based on the ICBP SURVMARK-2 study [
We found 23% better survival rates for female LC patients than for males, and survival differences tended to be larger (up to 37%) in the younger age groups. Gender differences have been investigated in several studies during the past decades, like in the analysis from the US lung cancer database [
On the other hand, though the improvement in survival was higher at females, especially at younger age, the interaction analysis was not significant for sex, therefore we could conclude that sex did not play role in the time dependent improvement of lung cancer.
Older lung cancer patients had poorer survival than younger patients [
Lung cancer survival is known to vary depending on the histological type of the cancer. Patients with adenocarcinoma have been shown to have higher survival rates compared to those with squamous cell carcinoma, while patients with small-cell carcinoma have been found to have the lowest 5-year survival rates compared to the previous two LC subtypes [
We found the highest improvement of survival in case of adenocarcinoma (11%), especially those, having age below 60 years at time of diagnosis. On the other hand, we did not find any change in case of small cell carcinoma, while relevant, 5%, but not significant at squamous cell carcinoma. This result is parallel with the historic changes in the treatment of different types of lung cancer. The aera of personalized treatment, the introduction of targeted therapy was most frequent at adenocarcinoma, especially at young patients (ALK inhibitors), while in older women, the possibility of EGFR inhibition resulted in visible improvement [
Strength of our study is the large number of diagnosed lung cancer patients, the carefully cleaned data, the 6-year-long follow-up period and the nationwide nature of the NHIF database, which all provide a solid foundation for drawing conclusions from our analysis. However, our study is not free from limitations. The applied exclusion criteria may have led to the exclusion of patients who had other cancer types besides lung cancer. According to our estimations however, this patient population is negligible. Moreover, the NHIF database contained data on the pathomorphology of lung cancer in only 52% of the cases. Staging, ECOG status and laboratory tests of patients were not recorded in the NHIF database. Consequently, we were not able to provide specific survival data based on these characteristics. Other limitation of our study is that we were able to provide only overall survival of lung cancer patients, and we did not estimate net survival, hence, we could not adjust the age related survival analysis to the natural survival rates of the general population. Nevertheless, as lung cancer patients have much higher mortality than the reference general population, and the vast majority of their mortality is caused by the cancer itself, this does not have a severe effect on the results and interpretation. Beside, we were able to detect the type of first treatment only certain part of lung cancer population. Those, having first line treatment as part of a study or received radiotherapy or palliative care, were not recorded in the NHIF database, hence we evaluated those, whom 1st line treatment was unambiguous, like systemic therapy or surgery and only from the perspective of survival improvement analysis.
To summarize, our study is the first to provide long-term survival data on Hungarian lung cancer patients and to report a 9.2% adjusted improvement in survival during the 6-year study period. The 5-year crude survival rate of 17.8% is comparable with neighboring countries’ data from the same period. Female lung cancer patients had a 23% better survival rate than males, which could be attributed to a higher incidence rate of adenocarcinoma in women. Survival rates were comparable to–and at the higher end of–rates registered in other East-Central European countries.
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
The study was approved by the National Ethical Committee, with the 10338-5/2019/EKU ethical approval number and the I043/88/2019 study license number.
KB and ZK equally contributed to this work.
MSD Pharma Hungary sponsored the data and statistical analysis as well as medical writer review for manuscript and will secure the publication fee if manuscript will be published. The authors declare that this study received funding from MSD Pharma Hungary Ltd. The funder had the following involvement with the study:in the study design, collection, analysis, interpretation of data, the writing of this article but was not involved in the decision to submit it for publication. JM was supported by the Hungarian Brain research Program (grant 2017-1.2.1-NKP-2017-00002), and the Hungarian NRDI Office (grant K-129065).
ZK, AV, ZN-E, and AD are employees of MSD Pharma Hungary Ltd. KH is a research fellow at Eötvös Loránd University. BN and ZV are employees of Eötvös Loránd University where their contribution to this project was financially compensated. KB and GO are employees of National Korányi Institute of Pulmonology and have received speaker honorarium from MSD Hungary. GG is employee of Oncology Center of Törökbálint and has received speaker honorarium from MSD Hungary. LT and VM are employees of Semmelweis University. LU is employee of Mátra Gyógyintézet. NB is employee of University of Debrecen. VS is employee of University of Pécs. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. ZB is employee of Syntesia Ltd. and her contribution to this project was financially compensated.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We would like to thank the NHIF for providing a comprehensive dataset for our analysis, and ZB of Syntesia Medical Communications for medical writing support.
The Supplementary Material for this article can be found online at: