Head and neck cancers survival in Europe, Taiwan, and Japan : results from RARECAREnet Asia based on a privacy-preserving federated infrastructure

The Taiwan cancer registry was funded by the Health Promotion Administration, Ministry of Health and Welfare of Taiwan, grant no. A1101009: Tobacco Health and Welfare Taxation. TM and HC were supported for the present manuscript and received grants from the "Health and Labor Sciences Research Grant (20EA1026)". FM was supported for the present manuscript by the "Netherlands Comprehensive Cancer Organisation". This research was funded by the Italian Ministry of Health "Ricerca Corrente" funds. The funders had no role in study design, data collection and analysis, interpretation of data, writing of the report, and the decision to submit the paper for publication.Background: The head and neck cancers (HNCs) incidence differs between Europe and East Asia. Our objective was to determine whether survival of HNC also differs between European and Asian countries. Methods: We used population-based cancer registry data to calculate 5-year relative survival (RS) for the oral cavity, hypopharynx, larynx, nasal cavity, and major salivary gland in Europe, Taiwan, and Japan. We modeled RS with a generalized linear model adjusting for time since diagnosis, sex, age, subsite, and histological grouping. Analyses were performed using federated learning, which enables analyses without sharing sensitive data. Findings: Five-year RS for HNC varied between geographical areas. For each HNC site, Europe had a lower RS than both Japan and Taiwan. HNC subsites and histologies distribution and survival differed between the three areas. Differences between Europe and both Asian countries persisted even after adjustments for all HNC sites but nasal cavity and paranasal sinuses, when comparing Europe and Taiwan. Interpretation: Survival differences can be attributed to different factors including different period of diagnosis, more advanced stage at diagnosis, or different availability/access of treatment. Cancer registries did not have stage and treatment information to further explore the reasons of the observed survival differences. Our analyses have confirmed federated learning as a feasible approach for data analyses that addresses the challenges of data sharing and urge for further collaborative studies including relevant prognostic factors

Long-term survival for lymphoid neoplasms and national health expenditure (EUROCARE-6): a retrospective, population-based study

BACKGROUND: Management of lymphoid malignancies requires substantial health system resources. Total national health expenditure might influence population-based lymphoid malignancy survival. We studied the long-term survival of patients with 12 lymphoid malignancy types and examined whether different levels of national health expenditure might explain differences in lymphoid malignancy prognosis between European countries and regions.METHODS: For this observational, retrospective, population-based study, we analysed the EUROCARE-6 dataset of patients aged 15 or older diagnosed between 2001 and 2013 with one of 12 lymphoid malignancies defined according to International Classification of Disease for Oncology (third edition) and WHO classification, and followed up to 2014 (Jan 1, 2001-Dec 31, 2014). Countries were classified according to their mean total national health expenditure quartile in 2001-13. For each lymphoid malignancy, 5-year and 10-year age-standardised relative survival (ASRS) was calculated using the period approach. Generalised linear models indicated the effects of age at diagnosis, gender, and total national health expenditure on the relative excess risk of death (RER).FINDINGS: 82 cancer registries (61 regional and 21 national) from 27 European countries provided data eligible for 10-year survival estimates comprising 890 730 lymphoid malignancy cases diagnosed in 2001-13. Median follow-up time was 13 years (IQR 13-14). Of the 12 lymphoid malignancies, the 10-year ASRS in Europe was highest for hairy cell leukaemia (82·6% [95% CI 78·9-86·5) and Hodgkin lymphoma (79·3% [78·6-79·9]) and lowest for plasma cell neoplasms (29·5% [28·9-30·0]). RER increased with age at diagnosis, particularly from 55-64 years to 75 years or older, for all lymphoid malignancies. Women had higher ASRS than men for all lymphoid malignancies, except for precursor B, T, or natural killer cell, or not-otherwise specified lymphoblastic lymphoma or leukaemia. 10-year ASRS for each lymphoid malignancy was higher (and the RER lower) in countries in the highest national health expenditure quartile than in countries in the lowest quartile, with a decreasing pattern through quartiles for many lymphoid malignancies. 10-year ASRS for non-Hodgkin lymphoma, the most representative class for lymphoid malignancies based on the number of incident cases, was 59·3% (95% CI 58·7-60·0) in the first quartile, 57·6% (55·2-58·7) in the second quartile, 55·4% (54·3-56·5) in the third quartile, and 44·7% (43·6-45·8) in the fourth quartile; with reference to the European mean, the RER was 0·80 (95% CI 0·79-0·82) in the first, 0·91 (0·90-0·93) in the second, 0·94 (0·92-0·96) in the third, and 1·45 (1·42-1·48) in the fourth quartiles.INTERPRETATION: Total national health expenditure is associated with geographical inequalities in lymphoid malignancy prognosis. Policy decisions on allocating economic resources and implementing evidence-based models of care are needed to reduce these differences.</p

Head and neck cancers survival in Europe, Taiwan and Japan: results from RARECAREnet Asia based on a privacy-preserving federated infrastructure

The Taiwan cancer registry was funded by the Health Promotion Administration, Ministry of Health and Welfare of Taiwan, grant no. A1101009: Tobacco Health and Welfare Taxation. TM and HC were supported for the present manuscript and received grants from the "Health and Labor Sciences Research Grant (20EA1026)". FM was supported for the present manuscript by the "Netherlands Comprehensive Cancer Organisation". This research was funded by the Italian Ministry of Health "Ricerca Corrente" funds. The funders had no role in study design, data collection and analysis, interpretation of data, writing of the report, and the decision to submit the paper for publication.Background: The head and neck cancers (HNCs) incidence differs between Europe and East Asia. Our objective was to determine whether survival of HNC also differs between European and Asian countries. Methods: We used population-based cancer registry data to calculate 5-year relative survival (RS) for the oral cavity, hypopharynx, larynx, nasal cavity, and major salivary gland in Europe, Taiwan, and Japan. We modeled RS with a generalized linear model adjusting for time since diagnosis, sex, age, subsite, and histological grouping. Analyses were performed using federated learning, which enables analyses without sharing sensitive data. Findings: Five-year RS for HNC varied between geographical areas. For each HNC site, Europe had a lower RS than both Japan and Taiwan. HNC subsites and histologies distribution and survival differed between the three areas. Differences between Europe and both Asian countries persisted even after adjustments for all HNC sites but nasal cavity and paranasal sinuses, when comparing Europe and Taiwan. Interpretation: Survival differences can be attributed to different factors including different period of diagnosis, more advanced stage at diagnosis, or different availability/access of treatment. Cancer registries did not have stage and treatment information to further explore the reasons of the observed survival differences. Our analyses have confirmed federated learning as a feasible approach for data analyses that addresses the challenges of data sharing and urge for further collaborative studies including relevant prognostic factors

The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers

Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). Study design Registry-based cohort study including only people with rare head and neck cancers. Objectives 1.To help describe the natural history of rare head and neck cancers; 2.To evaluate factors that influence prognosis; 3.To assess treatment effectiveness; 4.To measure indicators of quality of care. Methods Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won t select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients and cancers variables and indicators describing the quality of care. Multivariable Cox s proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/ confounders and confounding by indication (selective prescribing) will be present. Results The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed

Long-term survival for lymphoid neoplasms and national health expenditure (EUROCARE-6): a retrospective, population-based study

Background: Management of lymphoid malignancies requires substantial health system resources. Total national health expenditure might influence population-based lymphoid malignancy survival. We studied the long-term survival of patients with 12 lymphoid malignancy types and examined whether different levels of national health expenditure might explain differences in lymphoid malignancy prognosis between European countries and regions. Methods: For this observational, retrospective, population-based study, we analysed the EUROCARE-6 dataset of patients aged 15 or older diagnosed between 2001 and 2013 with one of 12 lymphoid malignancies defined according to International Classification of Disease for Oncology (third edition) and WHO classification, and followed up to 2014 (Jan 1, 2001-Dec 31, 2014). Countries were classified according to their mean total national health expenditure quartile in 2001-13. For each lymphoid malignancy, 5-year and 10-year age-standardised relative survival (ASRS) was calculated using the period approach. Generalised linear models indicated the effects of age at diagnosis, gender, and total national health expenditure on the relative excess risk of death (RER). Findings: 82 cancer registries (61 regional and 21 national) from 27 European countries provided data eligible for 10-year survival estimates comprising 890 730 lymphoid malignancy cases diagnosed in 2001-13. Median follow-up time was 13 years (IQR 13-14). Of the 12 lymphoid malignancies, the 10-year ASRS in Europe was highest for hairy cell leukaemia (82·6% [95% CI 78·9-86·5) and Hodgkin lymphoma (79·3% [78·6-79·9]) and lowest for plasma cell neoplasms (29·5% [28·9-30·0]). RER increased with age at diagnosis, particularly from 55-64 years to 75 years or older, for all lymphoid malignancies. Women had higher ASRS than men for all lymphoid malignancies, except for precursor B, T, or natural killer cell, or not-otherwise specified lymphoblastic lymphoma or leukaemia. 10-year ASRS for each lymphoid malignancy was higher (and the RER lower) in countries in the highest national health expenditure quartile than in countries in the lowest quartile, with a decreasing pattern through quartiles for many lymphoid malignancies. 10-year ASRS for non-Hodgkin lymphoma, the most representative class for lymphoid malignancies based on the number of incident cases, was 59·3% (95% CI 58·7-60·0) in the first quartile, 57·6% (55·2-58·7) in the second quartile, 55·4% (54·3-56·5) in the third quartile, and 44·7% (43·6-45·8) in the fourth quartile; with reference to the European mean, the RER was 0·80 (95% CI 0·79-0·82) in the first, 0·91 (0·90-0·93) in the second, 0·94 (0·92-0·96) in the third, and 1·45 (1·42-1·48) in the fourth quartiles. Interpretation: Total national health expenditure is associated with geographical inequalities in lymphoid malignancy prognosis. Policy decisions on allocating economic resources and implementing evidence-based models of care are needed to reduce these differences. Funding: Italian Ministry of Health, European Commission, Estonian Research Council

Long-term survival and cure fraction estimates for childhood cancer in Europe (EUROCARE-6): results from a population-based study

Background: The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer. Methods: In this population-based study, we analysed 135 847 children (aged 0–14 years) diagnosed during 2000–13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival. Findings: 5-year survival for all childhood cancer combined in Europe in 2010–14 was 81% (95% CI 81–82), showing an increase of three percentage points compared with 2004–06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% [95% CI 60–79] to 87% [77–93]). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010–13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73–75) in 1998–2001 to 80% (79–81) in 2010–13. In the latter cohort, the cure fraction rate ranged from 99% (95% CI 74–100) for retinoblastoma to 60% (58–63) for CNS tumours and reached 90% (95% CI 87–93) for lymphoid leukaemia and 70% (67–73) for acute myeloid leukaemia. Interpretation: Childhood cancer survival is increasing over time in Europe but there are still some differences among countries. Regular monitoring of childhood cancer survival and estimation of the cure fraction through population-based registry data are crucial for evaluating advances in paediatric cancer care. Funding: European Commission

Complete cancer prevalence in Europe in 2020 by disease duration and country (EUROCARE-6): a population-based study

Background Cancer survivors-people living with and beyond cancer-are a growing population with different health needs depending on prognosis and time since diagnosis. Despite being increasingly necessary, complete information on cancer prevalence is not systematically available in all European countries. We aimed to fill this gap by analysing population-based cancer registry data from the EUROCARE-6 study. Methods In this population-based study, using incidence and follow-up data up to Jan 1, 2013, from 61 cancer registries, complete and limited-duration prevalence by cancer type, sex, and age were estimated for 29 European countries and the 27 countries in the EU (EU27; represented by 22 member states that contributed registry data) using the completeness index method. We focused on 32 malignant cancers defined according to the third edition of the International Classification of Diseases for Oncology, and only the first primary tumour was considered when estimating the prevalence. Prevalence measures are expressed in terms of absolute number of prevalent cases, crude prevalence proportion (reported as percentage or cases per 100 000 resident people), and age-standardised prevalence proportion based on the European Standard Population 2013. We made projections of cancer prevalence proportions up to Jan 1, 2020, using linear regression. Findings In 2020, 23 711 thousand (95% CI 23 565-23 857) people (5 center dot 0% of the population) were estimated to be alive after a cancer diagnosis in Europe, and 22 347 thousand (95% CI 22 210-22 483) in EU27. Cancer survivors were more frequently female (12 818 thousand [95% CI 12 720-12 917]) than male (10 892 thousand [10 785-11 000]). The five leading tumours in female survivors were breast cancer, colorectal cancer, corpus uterine cancer, skin melanoma, and thyroid cancer (crude prevalence proportion from 2270 [95%CI 2248-2292] per 100 000 to 301 [297-305] per 100 000). Prostate cancer, colorectal cancer, urinary bladder cancer, skin melanoma, and kidney cancer were the most common tumours in male survivors (from 1714 [95% CI 1686-1741] per 100 000 to 255 [249-260] per 100 000). The differences in prevalence between countries were large (from 2 to 10 times depending on cancer type), in line with the demographic structure, incidence, and survival patterns. Between 2010 and 2020, the number of prevalent cases increased by 3 center dot 5% per year (41% overall), partly due to an ageing population. In 2020, 14 850 thousand (95% CI 14 681-15 018) people were estimated to be alive more than 5 years after diagnosis and 9099 thousand (8909-9288) people were estimated to be alive more than 10 years after diagnosis, representing an increasing proportion of the cancer survivor population. Interpretation Our findings are useful at the country level in Europe to support evidence-based policies to improve the quality of life, care, and rehabilitation of patients with cancer throughout the disease pathway. Future work includes estimating time to cure by stage at diagnosis in prevalent cases. Copyright (c) 2024 Elsevier Ltd. All rights reserved