Incidence, survival, and mortality of cancer in children and young adolescents in Belgium and the Netherlands in 2004-2015: A comparative population-based study.

International comparisons of cancer surveillance measures may provide insight into inequalities in registration practices, etiological factors, and treatment strategies. This study aimed to compare incidence, survival, and mortality of cancer in children and young adolescents between Belgium and the Netherlands. All children (0-14 years) and young adolescents (15-17 years) diagnosed with cancer between 2004 and 2015 were selected from the population-based cancer registries of Belgium (N = 4739) and the Netherlands (N = 7322). Differences in incidence and mortality were expressed as standardized rate ratios (SRR; BE/NL). Five-year observed survival was calculated using the Kaplan-Meier method. During 2004-2015, the overall cancer incidence among children and young adolescents was similar in both countries. Incidence of neuroblastoma was significantly higher in Belgian children (2010-2015: SRR = 1.3, 95% CI 1.0-1.6). Five-year survival of all malignant cancers was comparable in 2010-2015, exceeding 80% in both age groups. Remarkable differences in survival existed in children for malignant central nervous system (CNS) tumors in 2004-2009 (BE = 62%, NL = 45%), for acute myeloid leukemia (BE = 68%, NL = 78%) and rhabdomyosarcomas (BE = 60%, NL = 79%) in 2010-2015, and for neuroblastoma in both periods (2004-2009: BE = 76%, NL = 64%; 2010-2015: BE = 82%, NL = 64%). Overall cancer mortality in children decreased by approximately 3 percent-points annually in both countries, but was slightly lower in Belgium in 2004-2009 (SRR = 0.9, 95% CI 0.7-1.0). Despite differences for specific cancer types, overall cancer incidence, survival, and mortality were comparable between Dutch and Belgian children and young adolescents in 2010-2015. Variability in screening, diagnosis, and registration practices probably explains the observed differences in incidence and survival of neuroblastoma and malignant CNS tumors.

International study of childhood leukemia in residences near electrical transformer rooms.

OBJECTIVES: New epidemiologic approaches are needed to reduce the scientific uncertainty surrounding the association between extremely low frequency magnetic fields (ELF-MF) and childhood leukemia. While most previous studies focused on power lines, the Transformer Exposure study sought to assess this association using a multi-country study of children who had lived in buildings with built-in electrical transformers. ELF-MF in apartments above built-in transformers can be 5 times higher than in other apartments in the same building. This novel study design aimed to maximize the inclusion of highly exposed children while minimising the potential for selection bias. METHODS: We assessed associations between residential proximity to transformers and risk of childhood leukemia using registry based matched case-control data collected in five countries. Exposure was based on the location of the subject's apartment relative to the transformer, coded as high (above or adjacent to transformer), intermediate (same floor as apartments in high category), or unexposed (other apartments). Relative risk (RR) for childhood leukemia was estimated using conditional logistic and mixed logistic regression with a random effect for case-control set. RESULTS: Data pooling across countries yielded 16 intermediate and 3 highly exposed cases. RRs were 1.0 (95% CI: 0.5, 1.9) for intermediate and 1.1 (95% CI: 0.3, 3.8) for high exposure in the conditional logistic model. In the mixed logistic model, RRs were 1.4 (95% CI: 0.8, 2.5) for intermediate and 1.3 (95% CI: 0.4, 4.4) for high. Data of the most influential country showed RRs of 1.1 (95% CI: 0.5, 2.4) and 1.7 (95% CI: 0.4, 7.2) for intermediate (8 cases) and high (2 cases) exposure. DISCUSSION: Overall, evidence for an elevated risk was weak. However, small numbers and wide confidence intervals preclude strong conclusions and a risk of the magnitude observed in power line studies cannot be excluded.

Increased survival disparities among children and adolescents & young adults with acute myeloid leukemia: A Dutch population-based study.

For many cancers, adolescents and young adults (AYAs) have a poorer prognosis than pediatric patients. Our study evaluates survival outcomes of children (0-17 years) and AYAs (18-39 years) diagnosed with acute myeloid leukemia (AML) in the Netherlands between 1990 and 2015 (N = 2058) utilizing the population-based Netherlands Cancer Registry, which includes information on therapy and site of primary treatment. Five- and 10-year relative (disease-specific) survival were estimated for all patients, children and AYAs. Multivariable analyses were performed using generalized linear models (excess mortality) and logistic regression (early mortality). AYAs with AML had a substantially lower 5- and 10-year relative survival than children (5-year: 43% vs 58%; 10-year: 37% vs 51%). The gap in 5-year relative survival was largest (nearly 20 percent-points) in 2010 to 2015, despite survival improvements over time across all ages. The multivariable-adjusted excess risk of dying was 60% higher in AYAs (95% CI: 37%-86%). Early mortality (death within 30 days of diagnosis) declined over time, and did not differ between children and AYAs. In conclusion, AYAs diagnosed with AML in the Netherlands had a worse prognosis than pediatric patients. The survival gap seemed most pronounced in recent years, suggesting that improvements in care resulting in better outcome for children have not led to equal benefits for AYAs.

Improved survival for adolescents and young adults with Hodgkin lymphoma and continued high survival for children in the Netherlands: a population-based study during 1990-2015.

Population-based studies that assess long-term patterns of incidence, major aspects of treatment and survival are virtually lacking for Hodgkin lymphoma (HL) at a younger age. This study assessed the progress made for young patients with HL (<25 years at diagnosis) in the Netherlands during 1990-2015. Patient and tumour characteristics were extracted from the population-based Netherlands Cancer Registry. Time trends in incidence and mortality rates were evaluated with average annual percentage change (AAPC) analyses. Stage at diagnosis, initial treatments and site of treatment were studied in relation to observed overall survival (OS). A total of 2619 patients with HL were diagnosed between 1990 and 2015. Incidence rates increased for 18-24-year-old patients (AAPC + 1%, P = 0·01) only. Treatment regimens changed into less radiotherapy and more 'chemotherapy only', different for age group and stage. Patients aged 15-17 years were increasingly treated at a paediatric oncology centre. The 5-year OS for children was already high in the early 1990s (93%). For patients aged 15-17 and 18-24 years the 5-year OS improved from 84% and 90% in 1990-1994 to 96% and 97% in 2010-2015, respectively. Survival for patients aged 15-17 years was not affected by site of treatment. Our present data demonstrate that significant progress in HL treatment has been made in the Netherlands since 1990.

Epidemiology of childhood and adolescent cancer in Bangladesh, 2001-2014.

BACKGROUND: Cancer burden among children and adolescents is largely unknown in Bangladesh. This study aims to provide a comprehensive overview on childhood and adolescent cancers and to contribute to the future strategies to deal with these diseases in Bangladesh. METHODS: Data on malignant neoplasms in patients aged less than 20 years diagnosed between 2001 and 2014 (N = 3143) in Bangladesh was collected by the National Institute of Cancer Research and Hospital and ASHIC Foundation. The age pattern and distribution of cancer types were analysed and the incidence rates were calculated. RESULTS: The age-standardised incidence rate was 7.8 per million person-years for children (0-14 years) in the last time period (2011-2014). Retinoblastoma (25%) and leukaemia (18%) were the most common childhood cancers. For adolescents (15-19 years), the age-specific incidence rate was 2.1 per million person-years in the same time period. Most common adolescent cancers were malignant bone tumours (38%), germ cell and gonadal tumours (17%), and epithelial tumours (16%). There were more boys affected (M: F ratio 2.0 in children and 1.4 in adolescents) than girls. CONCLUSION: Cancer incidences were lower than expected most likely due to a low level of awareness about cancer among clinicians and the population, inadequate access to health care, lack of diagnostic equipment and incomplete recording of cases. Improvements on different levels should be made to get a better epidemiologic insight and to detect cancer earlier resulting in a better outcome for affected children and adolescents.

Trends in incidence, treatment and survival of aggressive B-cell lymphoma in the Netherlands 1989-2010.

Only a small number of patients with aggressive B-cell lymphoma take part in clinical trials, and elderly patients in particular are under-represented. Therefore, we studied data of the population-based nationwide Netherlands Cancer Registry to determine trends in incidence, treatment and survival in an unselected patient population. We included all patients aged 15 years and older with newly diagnosed diffuse large B-cell lymphoma or Burkitt lymphoma in the period 1989-2010 and mantle cell lymphoma in the period 2001-2010, with follow up until February 2013. We examined incidence, first-line treatment and survival. We calculated annual percentage of change in incidence and carried out relative survival analyses. Incidence remained stable for diffuse large B-cell lymphoma (n=23,527), while for mantle cell lymphoma (n=1,634) and Burkitt lymphoma (n=724) incidence increased for men and remained stable for women. No increase in survival for patients with aggressive B-cell lymphoma was observed during the period 1989-1993 and the period 1994-1998 [5-year relative survival 42% (95%CI: 39%-45%) and 41% (38%-44%), respectively], but increased to 46% (43%-48%) in the period 1999-2004 and to 58% (56%-61%) in the period 2005-2010. The increase in survival was most prominent in patients under 65 years of age, while there was a smaller increase in patients over 75 years of age. However, when untreated patients were excluded, patients over 75 years of age had a similar increase in survival to younger patients. In the Netherlands, survival for patients with aggressive B-cell lymphoma increased over time, particularly in younger patients, but also in elderly patients when treatment had been initiated. The improvement in survival coincided with the introduction of rituximab therapy and stem cell transplantation into clinical practice.

Progress against laryngeal cancer in The Netherlands between 1989 and 2010.

Cancer of the larynx is a frequently occurring head and neck cancer in The Netherlands. The main risk factors are smoking and excessive alcohol consumption. The aim of our study was to evaluate the progress against laryngeal cancer by studying trends in incidence, mortality and survival in The Netherlands. All patients in The Netherlands Cancer Registry diagnosed with invasive primary squamous cell carcinoma of the larynx during the period 1989-2010 were included for analysis. Time trends in incidence, mortality, treatment and survival were described for the total group and stratified by sex and subsite: glottis, supraglottis and subglottis. The most frequently affected subsite for men was the glottis (69%) and for women the supraglottis (55%). Glottic cancer was diagnosed at lower stages than supraglottic cancer. Incidence and mortality rates decreased for males with -2.5 and -2.8% per year, respectively, but remained stable for women, except for an increasing mortality rate in older women (EAPC: +2.5%). Five-year relative survival rates were stable for glottic (85%) and supraglottic (50%) cancer, whereas patients with high-staged cancers more often received radiotherapy. Multivariable analysis showed lower relative excess risks of dying for women, younger patients (<75 years), glottic cancer, lower stage cancer and those undergoing surgery. Changes in incidence and mortality rates are in line with changing smoking habits in The Netherlands. Declining incidence with stable survival rates gives rise to hope and worry at the same time.

Markedly increased incidence and improved survival of testicular cancer in the Netherlands.

BACKGROUND: Worldwide marked changes have been observed in the incidence and survival of testicular cancer (TC) during the last decades. We conducted a study on trends in TC incidence, treatment, survival, and mortality in the Netherlands during the period 1970-2009 with specific focus on trends according to age, histology and stage of disease. METHODS: Data from the Eindhoven cancer registry, the Netherlands cancer registry and Statistics Netherlands was used. Age-standardized incidence and mortality rates and five-year relative survival were calculated. Treatment was categorized into five major groups. RESULTS: TC incidence showed a substantial annual increase of 3.9% in the period 1989-2009. The incidence increased for all stages of both seminoma and non-seminoma TC. Stage distribution for the non-seminoma patients shifted towards more localized disease. Most patients received primary treatment according to the guidelines. Five-year relative survival improved (non-significantly) for most groups of stage and histology. TC mortality dropped sharply in the 1970s and 1980s and remained relatively stable thereafter. CONCLUSION: This study shows that incidence of TC has increased sharply in the Netherlands. Relative survival is high and improved in most disease stages. There is a growing demand for medical care of newly diagnosed TC patients and for the rapidly increasing number of prevalent TC patients.

The survival disparity between children and adolescents and young adults (AYAs) with Ewing sarcoma in the Netherlands did not change since the 1990s despite improved survival: A population-based study.

BACKGROUND: Adolescents and young adults (AYAs) with Ewing sarcoma have a worse prognosis than children. Population-based survival evaluations stratifying findings by important clinical factors are, however, limited. This Dutch population study comprehensively compared survival of children and AYAs with Ewing sarcoma over three decades considering diagnostic period, tissue of origin, tumor site, and disease stage. METHODS: Data on all children (0-17 years, N = 463) and AYAs (18-39 years, N = 379) diagnosed with Ewing sarcoma in the Netherlands between 1990-2018 were collected from the Netherlands Cancer Registry with follow-up until February 2023. Five-year relative survival was calculated using the cohort method. Multivariable analyses were conducted through Poisson regression. RESULTS: Children with Ewing sarcoma had a significantly higher 5-year relative survival than AYAs (65 % vs. 44 %). An increasing trend in survival was noted reaching 70 % in children and 53 % in AYAs in 2010-2018. Results were similar for Ewing bone sarcoma and extraosseous Ewing sarcoma. AYAs had a poorer prognosis than children for most tumor sites and regardless of disease stage. Survival probabilities were 60 % vs. 78 % for localized disease and 20 % vs. 33 % for metastatic disease. Multivariable-regression analysis, adjusted for follow-up time, diagnostic period, sex, disease stage, and tumor site, confirmed increased excess mortality among AYAs compared with children (excess HR: 1.7, 95 % CI: 1.3-2.1). CONCLUSIONS: Despite survival improvements since the 1990s, AYAs with Ewing sarcoma in the Netherlands continue to fare considerably worse than children. This survival disparity was present irrespective of tissue of origin, tumor site, and disease stage.

Impact of the COVID-19 pandemic on paediatric renal tumour presentation and management, a SIOP renal tumour study group study.

BACKGROUND: The COVID-19 pandemic had global catastrophic effects on the management of non-communicable diseases including paediatric cancers. Restrictions during the start of 2020 complicated timely referrals of patients to specialized centres. We aimed to evaluate the pandemic's impact on the number of new diagnoses, disease characteristics and management delay for paediatric renal tumour patients included in the SIOP-RTSG-UMBRELLA study, as compared with data from a historical SIOP-RTSG trial (2005-2009). METHODS: The number of intensive care admissions, population mobility rates and national lockdown periods/restrictions were used as proxies of the pandemic's severity and impact on societies. Clinical and tumour data were extracted from the SIOP-RTSG-UMBRELLA study and from historical SIOP-RTSG trials. RESULTS: During the first lockdown in Europe, the number of newly diagnosed patients decreased following restrictions and population immobilisation. Additionally, there was a higher proportion of advanced disease (37% vs. 17% before and after COVID-9, p < 0.001) and larger median tumour volume (559 cm3 vs. 328 and 434 cm3 before and after, p < 0.0001). Also in Brazil, the proportion of advanced disease was higher during the national decrease in mobilisation and start of restrictions (50% and 24% vs. 11% and 18% before and after, p < 0.01). Tumour volume in Brazil was also higher during the first months of COVID-19 (599 cm3 vs. 459 and 514 cm3 ), although not significant (p = 0.17). We did not observe any delays in referral time nor in time to start treatment, even though COVID-19 restrictions may have caused children to reach care later. CONCLUSION: The COVID-19 pandemic briefly changed the tumour characteristics of children presenting with renal tumours. The longer-term impact on clinical outcomes will be kept under review.

Progress against cancer in the Netherlands since the late 1980s: an epidemiological evaluation.

Progress against cancer through prevention and treatment is often measured by survival statistics only instead of analyzing trends in incidence, survival and mortality simultaneously because of interactive influences. This study combines these parameters of major cancers to provide an overview of the progress achieved in the Netherlands since 1989 and to establish in which areas action is needed. The population-based Netherlands Cancer Registry and Statistics Netherlands provided incidence, 5-year relative survival and mortality of 23 major cancer types. Incidence, survival and mortality changes were calculated as the estimated annual percentage change. Optimal progress was defined as decreasing incidence and/or improving survival accompanied by declining mortality, and deterioration as increasing incidence and/or deteriorating survival accompanied by increasing mortality rates. Optimal progress was observed in 12 of 19 cancer types among males: laryngeal, lung, stomach, gallbladder, colon, rectal, bladder, prostate and thyroid cancer, leukemia, Hodgkin and non-Hodgkin lymphoma. Among females, optimal progress was observed in 12 of 21 cancers: stomach, gallbladder, colon, rectal, breast, cervical, uterus, ovarian and thyroid cancer, leukemia, Hodgkin and non-Hodgkin lymphoma. Deterioration occurred in three cancer types among males: skin melanoma, esophageal and kidney cancer, and among females six cancer types: skin melanoma, oral cavity, pharyngeal, esophageal, pancreatic and lung cancer. Our conceptual framework limits misinterpretations from separate trends and generates a more balanced discussion on progress.

Trends in therapy and survival of advanced stage epithelial ovarian cancer patients in the Netherlands.

OBJECTIVE: The aim of this study was to describe trends in survival and therapy in advanced stage epithelial ovarian cancer (EOC) in the Netherlands and to determine if changes in therapy affected survival. METHODS: All EOC patients diagnosed in the Netherlands during 1989-2009 were selected from the Netherlands Cancer Registry. Differences in treatment over time were tested by the Cochran-Armitage trend test. Multivariable relative survival analyses were performed to test whether changes in treatment are associated with survival. RESULTS: 23,399 EOC patients were diagnosed, of whom 15,892 (67.9%) in advanced stage (stage ≥ 2b). In advanced stage patients, the proportion receiving (neo-)adjuvant chemotherapy and optimal debulking (residuals <1cm) increased over time in all age groups. In elderly patients (≥ 75 years) a stable proportion (approximately 28%) did not receive any treatment. Five-year relative survival in advanced stage patients increased from 18% in 1989-1993 to 28% in 2004-2009. In the multivariable model survival improved over time (relative excess risk (RER) of 2004-2009 was 0.71, 95% CI 0.67-0.75 compared to 1989-1993). This RER attenuated to 0.85 (95% CI 0.80-0.90) and 0.91 (95% CI 0.83-0.99) with inclusion of treatment variables in the model (surgery with chemotherapy or optimal surgery with chemotherapy, respectively). This suggests that the improvement was mainly, although not entirely, caused by changes in treatment. CONCLUSION: Treatment in advanced stage EOC patients in the Netherlands improved over the last two decades; more patients received (neo)adjuvant chemotherapy and underwent optimal debulking surgery. Changes in treatment led to partial improvement of survival in EOC patients.

Incidence and survival trends of uncommon corpus uteri malignancies in the Netherlands, 1989-2008.

INTRODUCTION: Corpus uteri cancer is the most common malignancy of the female reproductive tract in industrialized countries, and its incidence is increasing. Although most of these tumors are of the common endometrial type, there are also many uncommon tumors of the corpus uteri. We examined the incidence and survival of patients with uncommon epithelial tumors, carcinosarcomas, and sarcomas of the corpus uteri diagnosed since 1989. METHODS: All common and uncommon malignancies of the corpus uteri registered in the nationwide population-based Netherlands Cancer Registry (NCR) during 1989-2008 were included (n = 30,960). The histological subtypes were described according to the Blaustein classification system. Age-standardized incidence for 1989-2008 was calculated per 1,000,000 person-years (p-y), and relative survival was calculated according to the type of uncommon tumor. RESULTS: The incidence of corpus uteri malignancies increased from 159 to 177 per 1,000,000 p-y, mainly owing to the rise in endometrioid adenocarcinomas from 106 to 144 per 1,000,000 p-y. In contrast, the incidence of uncommon epithelial endometrial carcinomas (UEECs) decreased from 30 to 13 per 1,000,000 p-y, although carcinosarcomas increased slightly from 5.1 to 6.9 per 1,000,000 p-y. Furthermore, a remarkable shift in incidence of endometrial stromal cell sarcomas (ESS) was observed from high-grade ESSs to low-grade ESSs after 2003. Five-year relative survival for patients with UEEC decreased from 72% to 54% and for patients with serous adenocarcinoma from 73% to 51%. Coinciding with an increase in the incidence of common adenocarcinoma of the corpus uteri, there was a decline in uncommon adenocarcinomas and more or less a stable incidence of sarcomas and carcinosarcomas. CONCLUSION: The decrease in UEEC tumors consisted largely of fewer serous carcinomas, possibly and likely reflecting a more precise histopathological classification of villoglandular tumors. Unfortunately, relative survival for patients with UEEC, sarcomas, and carcinosarcomas did not improve over the study period, indicating a need for more research on treatment strategies for this group of patients.

Gallbladder cancer in the Netherlands: incidence, treatment and survival patterns since 1989.

BACKGROUND: To examine recent trends in gallbladder cancer (GBC) in the general population in the Western world, cancer registration data on GBC in the Netherlands were analyzed. METHODS: Trends in incidence, treatment and survival, according to gender, age and stage of disease, between 1989 and 2008 for 3,917 patients were studied. Rates were age-standardized to the European standard population (European Standardized Rates - ESR). RESULTS: The incidence rate for GBC in the Netherlands decreased rapidly during the period of 1989-2008, except for males younger than 60 years. Overall survival remained stable, short-term (3-month) and long-term (5-year) relative survival among surgically treated patients increased significantly. Treatment patterns for GBC changed. Surgery decreased from 55% in 1989 to 38% in 2008 (p < 0.001). Chemotherapy and/or irradiation increased from 1.0 to 5.8% (p < 0.001). Receiving best supportive care increased from 44% in 1989 to 57% in 2008 (p < 0.001). CONCLUSION: The incidence rate for GBC in the Netherlands has decreased rapidly. Treatment patterns for GBC have changed and survival among surgically treated patients has increased.

Intrahepatic cholangiocarcinoma in a low endemic area: rising incidence and improved survival.

BACKGROUND: To explore trends in the incidence and survival of patients with intrahepatic cholangiocarcinoma (ICC) an unselected population in Western Europe was studied. METHODS: Between 1989 and 2009, all patients newly diagnosed with ICC were selected from the Netherlands Cancer Registry (n= 809). Trends in incidence, treatment and relative survival were calculated according to gender and age. Follow-up for vital status was complete until 1st January 2010. RESULTS: The incidence rates of ICC increased significantly between 1999 and 2009, especially in the age group 45-59 years [estimated annual percentage change +3.0%, 95% confidence interval (CI) 0.2-5.8]. In the other age groups ICC incidence remained stable. Patients diagnosed with tumour lymph node metastasis (TNM) stage I mainly underwent surgery (68%), and the majority of the patients with stage II, III and IV received best supportive care (73%). One-year relative survival for patients with ICC increased significantly from 24% in 1989-1994 to 28% in 2005-2009 (P= 0.03), and corresponding 3-year relative survival improved from 4% to 8% (P= 0.02). Three-month and 1-year relative survival for patients with ICC receiving surgery was 91% and 71%, respectively. DISCUSSION: Between 1999 and 2009, the incidence of ICC rose, especially in the age group 45-59 years, suggesting aetiological influences. Survival rates have improved during the study period.

Survival rates of children and young adolescents with CNS tumors improved in the Netherlands since 1990: A population-based study.

Introduction: Survival of children with central nervous system (CNS) tumors varies largely between countries. For the Netherlands, detailed population-based estimation of incidence, survival, and mortality of pediatric CNS tumors are lacking but are needed to evaluate progress. Methods: All CNS tumors diagnosed in patients <18 years during 1990-2017 were selected from the Netherlands Cancer Registry. Other than pilocytic astrocytomas, nonmalignant tumors were included since 2000. Incidence and mortality trends were evaluated by average annual percentage change (AAPC). Changes over time in the five-year observed survival (5-year OS) were evaluated by Poisson regression models adjusted for follow-up time. Results: Between 1990 and 2017, 2057 children were diagnosed with a malignant CNS tumor and 885 with a pilocytic astrocytoma. During 2000-2017, 695 children were diagnosed with other nonmalignant CNS tumors. Incidence rates of malignant tumors remained stable, while pilocytic astrocytomas and other nonmalignant tumors increased by 2.0% and 2.4% per year, respectively. The 5-year OS rates improved for all groups; however, improvement for malignant tumors was not constant over time. The contribution of malignant tumors located at the optic nerve tumors was 1% in 2000-2009. However, shifting from pilocytic astrocytomas, increased to 6% in 2010-2017, impacting survival outcomes for malignant tumors. Conclusion: Survival rates of CNS tumors improved over time but were not accompanied by a decreasing mortality rate. The observed temporary survival deterioration for malignant tumors appears to be related to changes in diagnostics and registration practices. Whether differences in treatment regimens contribute to this temporary decline in survival needs to be verified.

Effect of Treatment in a Specialized Pediatric Hemato-Oncology Setting on 5-Year Survival in Acute Lymphoblastic Leukemia: A Quasi-Experimental Study.

Survival rates of adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) are inferior to those of pediatric ALL patients. In part, this may be caused by differences in treatment setting. Generally, children are treated in specialized pediatric hemato-oncology settings, whereas AYAs are treated in adult hemato-oncology settings. Since 2005, adult treatment protocols have included pediatric-inspired chemotherapy, which has been the standard of care for AYAs from 2008 onwards. This study aims to assess whether, despite protocols in both settings having become more similar, there remains an effect of treatment in specialized pediatric hemato-oncology settings on 5-year survival for ALL patients in the Netherlands. We used nationwide registry data (2004-2013) on 472 ALL patients aged between 10 and 30 years old. A fuzzy regression discontinuity design was applied to estimate the treatment effect using two-stage least squares regression with the treatment threshold at 17 years and 7 months of age, adjusting for sex, age at diagnosis, and immunophenotype. We found a risk difference of 0.419 (p = 0.092; 95% CI = -0.0686; 0.907), meaning a 41.9 percentage point greater probability of surviving five years after diagnosis for ALL patients treated in specialized pediatric hemato-oncology settings. Our results suggest that ALL patients around the threshold could benefit from increased collaboration between pediatric and adult hemato-oncology in terms of survival.

Incidence and survival of paediatric renal tumours in the Netherlands between 1990 and 2014.

BACKGROUND: This population-based study is the first to provide a detailed analysis of trends in incidence and survival of children and adolescents diagnosed with renal malignancies in the Netherlands. METHODS: Data on all renal malignancies diagnosed in paediatric patients (0-18 years) between 1990 and 2014 [N = 648, 92% Wilms tumour (WT)] were extracted from the Netherlands Cancer Registry. Five-year overall survival (OS) was estimated using the actuarial method. Time trends in incidence were assessed by calculating average annual percentage change. A parametric survival model was used to compare the multivariable-adjusted risk of dying from WT between two diagnostic periods. RESULTS: The incidence was 8 per million person-years and was constant over time (average annual percentage change -0.8%, p = 0.29). Patients with WT had a favourable outcome in both time periods; 5-year OS was 88% in 1990-2001 and 91% in 2002-2014. Multivariable analysis showed that the risk of dying from WT was not significantly decreased in the latest period (hazard ratio, 95% CI: 0.7, 0.4-1.3). Five-year OS decreased with increasing disease stage, ranging from 95 to 100% for stage I-II and about 80% for stage III-IV to 74% for bilateral disease. Five-year OS were 81% for renal cell carcinoma, 77% for clear cell sarcoma of the kidney and 20% for malignant rhabdoid tumour of the kidney. CONCLUSIONS: Incidence of paediatric renal malignancies in the Netherlands has been stable since the 1990s. Five-year OS of WT reached 91% and was similar to findings for other developed countries. Contrary to the excellent outcome for WT, the outcome of malignant rhabdoid tumour of the kidney remained inferior.

Progress against non-Hodgkin's lymphoma in children and young adolescents in the Netherlands since 1990: Stable incidence, improved survival and lower mortality.

BACKGROUND: With epidemiologic analyses of population-based trends in incidence and outcomes, we ascertained progress against non-Hodgkin's lymphoma (NHL) in children and young adolescents in the Netherlands since 1990. METHODS: Tumour characteristics were extracted from the Netherlands Cancer Registry for patients aged <18 years at diagnosis, between 1990 and 2015. Mortality data for 1980-2016 were derived from Statistics Netherlands. NHL subtypes comprised lymphoblastic lymphoma (LBL), Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL). Time trends in incidence and mortality rates and 5-year overall survival (OS) rates were evaluated by average annual percentage change (AAPC) analyses and parametric survival models, respectively. RESULTS: Overall incidence of NHL remained stable at 11 per million person-years (AAPC -0.2%, p = 0.68), with a marked decrease among children of 5-9 years (AAPC -2.6%, p < 0.01), especially among those with BL. Treatment regimens comprised less radiotherapy over time, especially for LBL and BL. Since 2004, most 15-17-year-old patients with NHL have been treated at a paediatric oncology centre. Five-year OS improved from 71% in 1990-94 to 87% in 2010-15 (p < 0.01), the most gain has been achieved in patients with DLBCL and ALCL from 60% and 73%, respectively, to both 90%. Population-based mortality from NHL decreased significantly towards 1.4 per million person-years (AAPC -4.2%, p < 0.01). CONCLUSIONS: This population-based epidemiological study exhibited significant progress against childhood and young adolescent NHL in the Netherlands since 1990, before the advent of a national paediatric oncologic centre in 2018: incidence decreased among children of 5-9 years, survival improved, and mortality steadily decreased over time.