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.

Opposite trends in incidence of breast cancer in young and old female cohorts in Hungary and the impact of the Covid-19 pandemic: a nationwide study between 2011-2020.

Background: This nationwide study examined breast cancer (BC) incidence and mortality rates in Hungary between 2011-2019, and the impact of the Covid-19 pandemic on the incidence and mortality rates in 2020 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Methods: Our nationwide, retrospective study included patients who were newly diagnosed with breast cancer (International Codes of Diseases ICD)-10 C50) between Jan 1, 2011 and Dec 31, 2020. Age-standardized incidence and mortality rates (ASRs) were calculated using European Standard Populations (ESP). Results: 7,729 to 8,233 new breast cancer cases were recorded in the NHIF database annually, and 3,550 to 4,909 all-cause deaths occurred within BC population per year during 2011-2019 period, while 2,096 to 2,223 breast cancer cause-specific death was recorded (CSO). Age-standardized incidence rates varied between 116.73 and 106.16/100,000 PYs, showing a mean annual change of -0.7% (95% CI: -1.21%-0.16%) and a total change of -5.41% (95% CI: -9.24 to -1.32). Age-standardized mortality rates varied between 26.65-24.97/100,000 PYs (mean annual change: -0.58%; 95% CI: -1.31-0.27%; p=0.101; total change: -5.98%; 95% CI: -13.36-2.66). Age-specific incidence rates significantly decreased between 2011 and 2019 in women aged 50-59, 60-69, 80-89, and ≥90 years (-8.22%, -14.28%, -9.14%, and -36.22%, respectively), while it increased in young females by 30.02% (95%CI 17,01%- 51,97%) during the same period. From 2019 to 2020 (in first COVID-19 pandemic year), breast cancer incidence nominally decreased by 12% (incidence rate ratio [RR]: 0.88; 95% CI: 0.69-1.13; 2020 vs. 2019), all-cause mortality nominally increased by 6% (RR: 1.06; 95% CI: 0.79-1.43) among breast cancer patients, and cause-specific mortality did not change (RR: 1.00; 95%CI: 0.86-1.15). Conclusion: The incidence of breast cancer significantly decreased in older age groups (≥50 years), oppositely increased among young females between 2011 and 2019, while cause-specific mortality in breast cancer patients showed a non-significant decrease. In 2020, the Covid-19 pandemic resulted in a nominal, but not statistically significant, 12% decrease in breast cancer incidence, with no significant increase in cause-specific breast cancer mortality observed during 2020.

Significant improvement in melanoma survival over the last decade: A Hungarian nationwide study between 2011 and 2019.

BACKGROUND: Recent real-world studies have reported significant improvements in the survival of malignant melanoma in the past few years, mainly as a result of modern therapies. However, long-term survival data from Central Eastern European countries such as Hungary are currently lacking. METHODS: This nationwide, retrospective study examined melanoma survival in Hungary between 2011-2019 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Crude overall survival and age-standardized 5-year net survival as well as the association between age, sex and survival were calculated. RESULTS: Between 2011 and 2019, 22,948 newly diagnosed malignant melanoma cases were recorded in the NHIF database (47.89% male, mean age: 60.75 years (SD: ±16.39)). Five-year overall survival was 75.40% (women: 80.78%; men: 69.52%). Patients diagnosed between 2017-2019 had a 20% lower risk of mortality compared to patients diagnosed between 2011-2012 (HR 0.80, 95% CI 0.73-0.89; p < 0.0001). Age-standardized 5-year net survival rates in 2011-2014 and 2015-2019 were 90.6% and 95.8%, respectively (women: 93.1% and 98.4%, men: 87.8% and 92.7%, respectively). The highest age-standardized 5-year net survival rates were found in the 0-39 age cohort (94.6% in the 2015-2019 period). CONCLUSION: Hungary has similar melanoma survival rates to Western European countries. Based on net survival, the risk of dying of melanoma within 5 years was cut by more than half (55%) during the study period, which coincides with the successful implementation of awareness campaigns and the wide availability of modern therapies.

Underlying reasons for post-mortem diagnosed lung cancer cases - A robust retrospective comparative study from Hungary (HULC study).

Objective: The Hungarian Undiagnosed Lung Cancer (HULC) study aimed to explore the potential reasons for missed LC (lung cancer) diagnosis by comparing healthcare and socio-economic data among patients with post-mortem diagnosed LC with those who were diagnosed with LC during their lives. Methods: This nationwide, retrospective study used the databases of the Hungarian Central Statistical Office (HCSO) and National Health Insurance Fund (NHIF) to identify patients who died between January 1, 2019 and December 31, 2019 and were diagnosed with lung cancer post-mortem (population A) or during their lifetime (population B). Patient characteristics, socio-economic factors, and healthcare resource utilization (HCRU) data were compared between the diagnosed and undiagnosed patient population. Results: During the study period, 8,435 patients were identified from the HCSO database with LC as the cause of death, of whom 1,203 (14.24%) had no LC-related ICD (International Classification of Diseases) code records in the NHIF database during their lives (post-mortem diagnosed LC population). Post-mortem diagnosed LC patients were significantly older than patients diagnosed while still alive (mean age 71.20 vs. 68.69 years, p<0.001), with a more pronounced age difference among female patients (difference: 4.57 years, p<0.001), and had significantly fewer GP (General Practitioner) and specialist visits, X-ray and CT scans within 7 to 24 months and 6 months before death, although the differences in GP and specialist visits within 7-24 months did not seem clinically relevant. Patients diagnosed with LC while still alive were more likely to be married (47.62% vs. 33.49%), had higher educational attainment, and had more children, than patients diagnosed with LC post-mortem. Conclusions: Post-mortem diagnosed lung cancer accounts for 14.24% of total lung cancer mortality in Hungary. This study provides valuable insights into patient characteristics, socio-economic factors, and HCRU data potentially associated with a high risk of lung cancer misdiagnosis.

Improving Quality Indicator of Melanoma Management - Change of Melanoma Mortality-to-Incidence Rate Ratio Based on a Hungarian Nationwide Retrospective Study.

INTRODUCTION: The incidence of melanoma has been increasing in the last decades. A retrospective Hungarian epidemiological study provided real-world data on incidence and mortality rates. There have been changing trends in incidence in Hungary in the last decade and mortality decreased, shifting mortality-to-incidence rate ratios (MIR). MIR is an indicator of cancer management quality. OBJECTIVES: Our aim is to show the changes of melanoma MIR in Hungary between 2011 and 2018 and to compare the real-world evidence-based results of our Hungarian nationwide retrospective study with other European countries. METHODS: MIR is calculated from the age-specific standardized incidence and mortality rates from our study. Annual MIR values are presented for the total population and for both sexes between 2011 and 2018, along with 95% confidence intervals. Comparison with European countries are shown for 2012 and 2018 based on the GLOBOCAN database and Eurostat health care expenditure per capita data. RESULTS: MIR decreased by 0.035 during the study years. The decrease was same in both sexes (0.031). Male had higher MIRs in all study years. In both 2012 and 2018, Hungarian MIR in both sexes was lower than the European Union average (males: 0.192 vs. 0.212 and 0.148 vs. 0.174 respectively, women: 0.107 vs. 0.129 and 0.083 vs. 0.107 respectively). DISCUSSION: Hungarian mortality-to-incidence ratio is the lowest in Central and Eastern Europe and is close to the level of Western and Northern European countries. The results are driven by the high number of new diagnosed melanoma cases.

Significant Regional Differences in Lung Cancer Incidence in Hungary: Epidemiological Study Between 2011 and 2016.

Objective: Hungary has one of the highest incidences and mortality rates of lung cancer (LC), therefore the objective of this study was to analyse and compare LC incidence and mortality rates between the main Hungarian regions. Methods: This nationwide, retrospective study used data from the National Health Insurance Fund and included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between Jan 1, 2011 and Dec 31, 2016. Age-standardized incidence and mortality rates were calculated and compared for the main regions. Results: The highest incidence rate in males was recorded in Northern Hungary (146.8/100,000 person-years [PY]), while the lowest rate was found in Western Transdanubia (94.7/100,000 PY in 2011). All rates showed a declining trend between 2011 and 2016, with the largest decrease in the Northern Great Plain (-20.0%; p = 0.008). LC incidence and mortality rates in women both showed a rising tendency in all regions of Hungary, reaching the highest in Central Hungary (59.86/100,000 PY in 2016). Lung cancer incidence and mortality rates in males correlated with the level of education and smoking prevalence (p = 0.006 and p = 0.01, respectively) in the regions. A correlation with GDP per capita and Health Development Index (HDI) index could also be observed in the Hungarian regions, although these associations were not statistically significant. No correlations could be detected between these parameters among females. Conclusion: This analysis revealed considerable differences in the epidemiology of LC between the 7 main Hungarian regions. LC incidence and mortality rates significantly correlated with smoking and certain socioeconomic factors in men, but not in women. Further research is needed to explain the regional differences.

Age and Gender Specific Lung Cancer Incidence and Mortality in Hungary: Trends from 2011 Through 2016.

Objective: No assessment was conducted describing the age and gender specific epidemiology of lung cancer (LC) prior to 2018 in Hungary, thus the objective of this study was to appraise the detailed epidemiology of lung cancer (ICD-10 C34) in Hungary based on a retrospective analysis of the National Health Insurance Fund database. Methods: This longitudinal study included patients aged ≥20 years with LC diagnosis (ICD-10 C34) between January 1, 2011 and December 31, 2016. Patients with different cancer-related codes 6 months before or 12 months after LC diagnosis or having any cancer treatment other than lung cancer protocols were excluded. Results: Lung cancer incidence and mortality increased with age, peaking in the 70-79 age group (375.0/100,000 person-years) among males, while at 60-69 age group for females (148.1/100,000 person-years). The male-to-female incidence rate ratio reached 2.46-3.01 (p < 0.0001) among the 70-79 age group. We found 2-11% decrease in male incidence rate at most age groups, while a significant 1-3% increase was observed in older females (>60) annually during the study period. Conclusion: This nationwide epidemiology study demonstrated that LC incidence and mortality in Hungary decreased in younger male and female population, however we found significant increase of incidence in older female population, similar to international trends. Incidence rates peaked in younger age-groups compared to Western countries, most likely due to higher smoking prevalence in these cohorts, while lower age LC incidence could be attributed to higher competing cardiovascular risk resulting in earlier mortality in smoking population.

Improvement in Lung Cancer Survival: 6-Year Trends of Overall Survival at Hungarian Patients Diagnosed in 2011-2016.

Objective: Lung cancer is one of the most common cancers worldwide and its survival is still poor. The objective of our study was to estimate long-term survival of Hungarian lung cancer patients at first time based on a nationwide review of the National Health Insurance Fund database. Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between January 1, 2011 and December 31, 2016. Survival rates were evaluated by year of diagnosis, patient gender and age, and morphology of lung cancer. Results: 41,854 newly diagnosed lung cancer patients were recorded. Mean age at diagnosis varied between 64.7 and 65.9 years during study period. One- and 5-year overall survival rates for the total population were 42.2 and 17.9%, respectively. Survival was statistically associated with gender, age and type of lung cancer. Female patients (n = 16,362) had 23% better survival (HR: 0.77, 95% confidence interval (CI): 0.75-0.79; p < 0.001) than males (n = 25,492). The highest survival rates were found in the 20-49 age cohort (5Y = 31.3%) and if the cancer type was adenocarcinoma (5Y = 20.5%). We measured 5.3% improvement (9.2% adjusted) in lung cancer survival comparing the period 2015-2016 to 2011-2012 (HR: 0.95 95% CI: 0.92-0.97; p = 0.003), the highest at females <60 year (0.86 (adjusted HR was 0.79), interaction analysis was significant for age and histology types. Conclusion: Our study provided long-term Lung cancer survival data in Hungary for the first time. We found a 5.3% improvement in 5-year survival in 4 years. Women and young patients had better survival. Survival rates were comparable to-and at the higher end of-rates registered in other East-Central European countries (7.7%-15.7%).

Increase in the Length of Lung Cancer Patient Pathway Before First-Line Therapy: A 6-Year Nationwide Analysis From Hungary.

Objective: This study aimed to examine the characteristics of the lung cancer (LC) patient pathway in Hungary during a 6-years period. Methods: This nationwide, retrospective study included patients newly diagnosed with LC (ICD-10 C34) between January 1, 2011, and December 31, 2016, using data from the National Health Insurance Fund (NHIF) of Hungary. The following patient pathway intervals were examined: system, diagnostic and treatment interval by age, gender, tumor type, study year and first-line LC therapy. Results: During the 6-years study period, 17,386 patients had at least one type of imaging (X-ray or CT/MRI) prior to diagnosis, and 12,063 had records of both X-ray and CT/MRI. The median system interval was 64.5 days, and it was 5 days longer among women, than in men (68.0 vs. 63.0 days). The median system interval was significantly longer in patients with adenocarcinoma compared to those with squamous cell carcinoma or small cell lung cancer (70.4 vs. 64.0 vs. 48.0 days, respectively). Patients who received surgery as first-line treatment had significantly longer median system intervals compared to those receiving chemotherapy (81.4 vs. 62.0 days). The median system interval significantly increased from 62.0 to 66.0 days during the 6-years study period. Conclusion: The LC patient pathway significantly increased in Hungary over the 6-years study period. There were no significant differences in the length of the whole LC patient pathway according to age, however, female sex, surgery as first-line treatment, and adenocarcinoma were associated with longer system intervals.

[Novel approaches to the epidemiology of lung cancer in Hungary]. / A tüdorák hazai epidemiológiai adatai új megközelítésben.

In the international publications, in the last decades, incidence and mortality of lung cancer was the highest in Hungary in the ranking of European countries and even worldwide, despite the fact that no lung cancer incidence data were reported from Hungary until 2019. In the studies published by our working group at the end of 2019 and in the first half of 2020, we were the first to publish Hungarian lung cancer incidence and mortality data based on research on the NEAK database. The results of this study showed a significant, 25-30% lower incidence of lung cancer in Hungary than the previously reported data. Based on these findings, it was determined that the previously reported Hungarian lung cancer incidence and mortality data can be compiled due to different methodological applications of inadequately calculated results, and Hungarian lung cancer incidence and mortality are equally high, but not higher than the average in Central European countries. In addition, a decrease in the incidence and mortality of male lung cancer was measured between 2011 and 2016, while increasing values were found for women.

Changing Trends in Melanoma Incidence and Decreasing Melanoma Mortality in Hungary Between 2011 and 2019: A Nationwide Epidemiological Study.

BACKGROUND: The incidence of malignant melanoma has continually increased during the past few decades, however, certain reports suggest a recent change in trends. The aim of our study was to examine the epidemiology of melanoma in Hungary. METHODS: This nationwide, retrospective, longitudinal study included melanoma patients diagnosed between 1 January 2009 and 31 December 2019 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Age-standardized incidence and cause-specific mortality rates were calculated. RESULTS: We identified 2,426 and 2,414 new melanoma cases in 2011 and in 2019. Age-standardized incidence rates were higher in males and varied between 28.28 and 34.57/100,000 person-years (PYs), and between 22.63 and 26.72/100,000 PYs in females. We found 16.14 and 18.82% increases in male and female incidence rates from 2011 to 2015 (p=0.067 and p<0.001, respectively), and 12.77 and 11.35% decreases from 2015 to 2019 (p=0.062 and p=0.004, respectively). The change of incidence trends (2011-2015 vs. 2015-2019) was significant in females (p=0.002) and in the total melanoma population (p=0.011), but not in the male population (p=0.063). A 16.55% (95% CI: -27.07 to -4.59; p=0.013) decrease in mortality rates was found in the overall melanoma population. CONCLUSIONS: We observed a significant trend change in melanoma incidence in the female and total melanoma population, and a significant decrease in mortality in the total melanoma population. These changes may be attributed to intensive melanoma awareness campaigns as well as to the increase in screening and access to modern therapies.

Revising Incidence and Mortality of Lung Cancer in Central Europe: An Epidemiology Review From Hungary.

Objective: While Hungary is often reported to have the highest incidence and mortality rates of lung cancer, until 2018 no nationwide epidemiology study was conducted to confirm these trends. The objective of this study was to estimate the occurrence of lung cancer in Hungary based on a retrospective review of the National Health Insurance Fund (NHIF) database. Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between 1 Jan 2011 and 31 Dec 2016. Age-standardized incidence and mortality rates were calculated using both the 1976 and 2013 European Standard Populations (ESP). Results: Between 2011 and 2016, 6,996 - 7,158 new lung cancer cases were recorded in the NHIF database annually, and 6,045 - 6,465 all-cause deaths occurred per year. Age-adjusted incidence rates were 115.7-101.6/100,000 person-years among men (ESP 1976: 84.7-72.6), showing a mean annual change of - 2.26% (p = 0.008). Incidence rates among women increased from 48.3 to 50.3/100,000 person-years (ESP 1976: 36.9-38.0), corresponding to a mean annual change of 1.23% (p = 0.028). Age-standardized mortality rates varied between 103.8 and 97.2/100,000 person-years (ESP 1976: 72.8-69.7) in men and between 38.3 and 42.7/100,000 person-years (ESP 1976: 27.8-29.3) in women. Conclusion: Age-standardized incidence and mortality rates of lung cancer in Hungary were found to be high compared to Western-European countries, but lower than those reported by previous publications. The incidence of lung cancer decreased in men, while there was an increase in incidence and mortality among female lung cancer patients.

Panobinostat Plus Bortezomib Versus Lenalidomide in Patients with Relapsed and/or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Treatment Comparison of Survival Outcomes using Patient-level Data.

BACKGROUND: In the UK, the standard of care for patients with multiple myeloma who received ≥2 prior treatments is lenalidomide plus dexamethasone (LEN + DEX) and pomalidomide plus DEX (POM + DEX) (in Wales only). Recently, panobinostat plus bortezomib and DEX (PAN + BTZ + DEX) was licensed in this setting. The current study assessed the progression-free survival (PFS) and overall survival (OS) outcomes with PAN + BTZ + DEX versus LEN + DEX (primary comparator) and POM + DEX (exploratory comparator). METHODS: Since an anchor-based indirect treatment comparison was not feasible, the matching-adjusted indirect treatment comparison approach was used. To compare the survival outcomes, patient-level data were generated for the comparators utilizing published Kaplan-Meier survival estimates. The use of approximated patient-level data and matched data for PAN + BTZ + DEX allowed the use of Cox proportional hazards models and the assessment of the proportional hazards assumption. In cases where there was evidence that the proportional hazards assumption was violated, time-dependent hazard ratios (HRs) were estimated. Median and mean values for PFS and OS were predicted. RESULTS: For both PFS and OS, the proportional hazards assumption was not satisfied, therefore time-dependent HRs were estimated. Using time-dependent HRs, the mean PFS was estimated to be 11.83 months for PAN + BTZ + DEX and 10.96 months for LEN + DEX. The corresponding mean OS estimates were 30.73 and 27.76 months, respectively. Comparisons with POM + DEX were affected by large uncertainty and did not allow making robust inferences. CONCLUSIONS: To our knowledge, this is the first study that combined matching-adjusted indirect treatment comparison with time-dependent HRs to address changing patterns in the HR. The results suggest that treatment with PAN + BTZ + DEX and LEN + DEX are associated with similar mean PFS and OS in the third-line treatment setting of multiple myeloma.