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Abstract Introduction Enteropathy‐associated T‐cell lymphoma (EATL) is a peripheral T‐cell lymphoma (PTCL) with a poor prognosis. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide consolidated by autologous stem cell transplantation (ASCT) are recommended for fit PTCL patients. The role of etoposide and ASCT in EATL is unclear. Methods This study reports the incidence, treatment, and outcome of EATL patients using the Netherlands Cancer Registry, with nationwide coverage of >95%. Results All patients diagnosed in 1989–2021 (n = 351, 77% treated) were identified (median age 67 years, 56% male, 50% limited stage). Time period analysis assessed trends in primary therapy and overall survival (OS). Treatment included chemotherapy (CT) (34%), surgery (18%), surgery and CT (19%) or CT followed by ASCT (7%). The 5‐year OS for treated patients with limited versus advanced stage was 19% and 9% respectively. The 2‐year OS improved over time (21%–33%, p = 0.06). Surgery only (hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.55–3.01, p

Abstract First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice. Utilizing the Netherlands Cancer Registry, we identified 1577 adult patients diagnosed with advanced-stage DLBCL between 2014–2018 who completed either 6x R-CHOP21 (43%) or 6x R-CHOP21 + 2 R (57%). We used propensity scores to assess differences in event-free survival (EFS) and overall survival (OS). At five years, EFS (hazard ratio of 6x R-CHOP21 + 2 R versus 6x R-CHOP21 [HR] = 0.89; 95% confidence interval [CI], 0.72–1.09) and OS (HR = 0.93; 95% CI, 0.73–1.18) were not significantly different between both regimens. In exploratory risk-stratified analysis according to the International Prognostic Index (IPI), high-IPI patients (i.e., scores of 4-5) benefit most from 6x R-CHOP21 + 2 R (5-year absolute risk difference of EFS = 16.8%; 95% CI, −0.4%−34.1% and OS = 12.1%; 95% CI, −5.4–29.6%). Collectively, this analysis reveals no significant differences on average in EFS and OS between the two treatments. However, the potential benefits for high-risk patients treated with 6x R-CHOP21 + 2 R underscore the need for future research.

Abstract Chronic lymphocytic leukemia (CLL) manifests heterogeneously with varying outcomes. This population‐based study examined causes of death (CODs), as registered by the physician who established the death, among 20,588 CLL patients diagnosed in the Netherlands between 1996 and 2020. Utilizing cause‐specific flexible parametric survival models, we estimated cause‐specific hazard ratios (HRs) and cumulative incidences of death due to CLL, solid malignancies, other hematological malignancies, infections, and other causes. Our findings reveal CLL as the predominant COD, contributing to around 40% of relative mortality, with a declining 5‐year death probability from 16.8% in 1996–2002 to 7.6% in 2010–2020. Also, deaths attributed to solid malignancies, other hematological malignancies, and other COD diminished over time, as evidenced by respective HRs (95% confidence interval) of 0.68 (0.60%–0.77%), 0.45 (0.38%–0.53%), and 0.77 (0.66%–0.90%). In summary, our comprehensive, population‐based analysis underscores a noticeable reduction in CLL‐attributed deaths and other competing causes over the studied period. Nonetheless, CLL is registered as the most prevalent cause of mortality among contemporary diagnosed patients with CLL, emphasizing the continued relevance of CLL‐centric clinical strategies and research.

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This article highlights the recent and ongoing activities of European population-based cancer registries (PBCRs) in data quality and harmonisation in the framework of the collaboration between the European Network of Cancer Registries (ENCR) and the Directorate-General Joint Research Centre (JRC), the science and knowledge centre of the European Commission. The article concludes the Frontiers in Oncology’s Research Topic “Joining Efforts to Improve Data Quality and Harmonization Among European Population-Based Cancer Registries”, which has been an opportunity for several European researchers to share their experience on cancer data quality and harmonisation. Such experience will be helpful for PBCRs in view of future challenges and opportunities in cancer epidemiology, with a few examples discussed in the present article.

Objective Acute myeloid leukaemia (AML) prognosis is enhanced with intensive remission induction chemotherapy (ICT) in eligible patients. However, ICT eligibility perceptions may differ among healthcare professionals. This nationwide, population-based study aimed to explore regional variation in ICT application and its relation with overall survival (OS).Methods and analysis We compared nine Dutch regional networks using data from the Netherlands Cancer Registry. Regional variance was assessed for the entire population and age subgroups (ie, ≤60 years and >60 years) using multivariable mixed effects logistic and Cox proportional hazard regression analyses, expressed via median OR (MOR) and median HR (MHR).Results Including all adult AML patients from 2014 to 2018 (N=4060 patients; 58% males; median age, 70 years), 1761 (43%) received ICT. ICT application varied from 36% to 57% (MOR 1.36 (95% CI 1.11 to 1.58)) across regions, with minor variations for patients aged ≤60 years (MOR 1.16 (95% CI 1.00 to 1.40)) and more extensive differences for those aged >60 years (MOR 1.43 (95% CI 1.16 to 1.63)). Median OS spanned 4.9–8.4 months across regions (MHR 1.11 (95% CI 1.00 to 1.15)), with pronounced differences in older patients (MHR 1.12 (95% CI 1.08 to 1.20)) but negligible differences in the younger group (MHR 1.02 (95% CI 1.00 to 1.14)). Survival differences for the total population and the older patients decreased to respectively, MHR 1.09 (95% CI 1.00 to 1.13) and 1.10 (95% CI 1.04 to 1.18), after additional adjustment for the probability of receiving ICT within a region, indicating approximately 10% unexplained differences.Conclusion Regional disparities in ICT application and survival exist, especially in older AML patients. However, ICT application differences partially explain survival disparities, indicating the need for more standardised ICT eligibility criteria and a better understanding of underlying causes of outcome disparities.

Background: Population-based studies assessing long-term patterns of incidence and disease characteristics of germ cell tumors (GCTs) in children are scarce. We investigated incidence and survival trends of malignant extracranial GCTs in children using population-based nationwide data from the Netherlands. Methods: All malignant extracranial GCTs diagnosed in patients aged 0–18 years between 1990 and 2018 were selected from the Netherlands Cancer Registry. Incidence rates were calculated as the average annual number of cases per 1 million person-years. Five-year overall survival (OS) was calculated. Results: A total of 815 cases were identified. Gonadal GCTs (n=665, testis n=485, ovarian n=180) were more common than extragonadal GCTs (n=149). Stage distribution for testicular and extragonadal GCTs shifted between 1990 and 2004 and 2005–2018 towards more localized disease. The overall incidence remained stable over time, but a significant increase was noted for extragonadal GCTs in the 0–9 years age group. Survival of extragonadal GCTs (5-year OS 84.1%, 95% CI 77.1–89.1), in particular mediastinal GCTs (5-year OS 66.7%, 95% CI 45.7–81.1), was lower than that of gonadal GCTs (5-year OS testis 95.0%, 95% CI 92.7–96.7;ovary 97.8%, 95% CI 94.2–99.2). The 5-year OS of our entire cohort was 93.6% (95% CI 91.7–95.1). Five-year OS significantly increased from 89.5% (95% CI 86.1–92.2) in 1990–2004–97.4% (95% CI 95.3–98.5) in 2005–2018. Conclusions: Although the incidence of all malignant pediatric extracranial GCTs remained stable during 1990–2018, an increase was observed for extragonadal GCTs in younger children (0–9 years). There was a shift towards more localized disease for testicular and extragonadal GCTs. Five-year OS increased over time exceeding 90% (91.4%, 95% CI 82.7–95.8) in the most recent diagnostic period. Mediastinal GCTs had the lowest OS, supporting the need for future research.

Abstract Background The COVID-19 pandemic was managed in Aotearoa New Zealand (NZ) by a COVID-19 elimination policy, involving border closure and an initial national lockdown. This was different to most other countries including Northern Ireland (NI) and the Netherlands (NED). We quantify the effect of these policies on the diagnosis of three major cancers, comparing NZ with these two European countries. Method Data from NED, NZ and NI population-based cancer registries were used to assess trends in all pathologically diagnosed (PD) lung, breast, and colorectal cancers from March to December 2020 (pandemic period) and compared to the similar pre-pandemic period (2017–2019). Trend data were also collated on COVID-19 cases and deaths per 100,000 in each population. Results Comparing the pre-pandemic period to the pandemic period there were statistically significant reductions in numbers of lung (↓23%) and colorectal (↓15%) PD cancers in NI and numbers of breast (↓18%) and colorectal cancer (↓18.5%) diagnosed in the NED. In NZ there was no significant change in the number of lung (↑10%) or breast cancers (↑0.2%) but a statistically significant increase in numbers of colorectal cancer diagnosed (↑5%). Conclusion The impact of COVID-19 on cancer services was mitigated in NZ as services continued as usual reflecting minimal healthcare disruption and protected cancer services linked with the elimination approach adopted. The reduction in PD cases diagnosed in NED and NI were linked with higher COVID-19 rates and reflect societal restrictions which resulted in delayed patient presentation to primary and secondary care, disruption to screening and healthcare services as a result of COVID-19 infections on staff and the need to shift intensive care to COVID-19 patients. Reductions in PD cancers in NI and the NED and in particularly lung cancers in NI, highlight the need for targeted public health campaigns to identify and treat ‘missing’ patients. Protecting cancer services should be a priority in any future pandemic or systemic healthcare system disruption.

Summary: Cancer registry data on pediatric gliomas come with inherent limitations as inclusion criteria and registration practices of these tumors differ between registries due to specific guidelines that are lacking. These limitations can lead to biased estimates in incidence and survival outcomes. Here, we present a protocol to investigate data quality and comparability for retrospective population-based pediatric glioma studies. We describe steps for obtaining institutional permissions, dealing with data quality issues, regrouping tumors, and reporting tumors in a clinically relevant manner.For complete details on the use and execution of this protocol, please refer to Hoogendijk et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract The longevity of patients with chronic lymphocytic leukemia (CLL) has improved progressively over the past decades, making it essential to understand long-term health outcomes, such as second primary malignancies (SPMs). Therefore, this nationwide, population-based study assessed the risk of SPM development in CLL patients diagnosed during 1989-2019 in the Netherlands compared to the expected number of malignancies in an age-, sex-, and period-matched group from the general Dutch population. In 24,815 CLL patients followed for 162,698.49 person-years, 4369 SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.63 (95% confidence interval [CI] 1.59–1.68). This elevated risk was observed for solid (SIR, 1.67; 95% CI, 1.65–1.75) and hematological SPMs (SIR 1.42; 95% CI, 1.24–1.62). The highest risk for SPMs was noted beyond five years post-diagnosis (SIR, 1.70; 95% CI, 1.62–1.77), for male individuals (SIR, 1.70; 95% CI, 1.64–1.77), and patients aged 18–69 years (SIR, 1.92; 95% CI, 1.79–2.05). The risk of SPMs was higher in CLL patients who received anti-neoplastic therapy (SIR, 2.12; 95% CI, 1.96–2.28), as compared with those who did not (SIR, 1.58; 95% CI, 1.53–1.63). Routine surveillance activities and tailored interventions to counteract the increased morbidity and excess mortality associated with SPMs are essential for improving long-term outcomes in CLL patients.

The basis of diagnosis recommendations for population-based cancer registries aim to provide a standardized coding tool that reflects the certainty of cancer diagnosis, especially when pathological confirmation is lacking. The proportion of clinical diagnoses serves as an indicator of data quality. Given the evolving nature of diagnostic techniques, regular revision of the basis of diagnosis rules is crucial. To address this, a working group comprising representatives from the steering committee and member registries of the European Network of Cancer Registries was established. The original 1999 recommendations were comprehensively reviewed, resulting in the publication of an updated version. These new recommendations came into effect for incident cancer cases starting from January 1, 2023. The updated recommendations comprise an adapted code list for the basis of diagnosis, optional codes for histology cases, revisions related to flow cytometry, liquid biopsy, and cytogenetic/molecular testing, consolidation of histology codes 6 and 7, introduction of a new code 8 for cytogenetic/molecular confirmation, and establishment of new criteria for registering specific morphology codes in cancers lacking pathological confirmation.

Peripheral T-cell lymphomas (PTCL) comprise a heterogeneous group of mature T-cell neoplasms with an unfavorable prognosis; presentation with stage I(E) disease is uncommon. In clinical practice, an abbreviated chemotherapy treatment regimen combined with radiotherapy (combined modality treatment [CMT]) is commonly used, although evidence from clinical trials is lacking. The aim of this nationwide population-based cohort study is to describe first-line treatment and outcome of patients with stage I(E) PTCL. All newly diagnosed patients ≥18 years with stage I(E) anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma NOS (PTCL not otherise specified [NOS]) in 1989-2020 were identified in the Netherlands Cancer Registry. Patients were categorized according to treatment regimen, i.e., chemotherapy (CT), radiotherapy (RT), CMT, other therapy and no treatment. The primary endpoint was overall survival (OS). Patients with stage I(E) ALCL, AITL and PTCL NOS (n=576) were most commonly treated with CMT (28%) or CT (29%), 2% underwent SCT. RT only was given in 18%, and 8% received other therapy and 16% no treatment. Overall, the 5-year OS was 59%. According to subtype, 5-year OS was superior for ALCL as compared to PTCL NOS and AITL (68% vs. 55% and 52%, respectively; P=0.03). For patients treated with CMT, 5-year OS was significantly higher (72%) as compared to patients treated with either CT or RT alone (55% and 55%, respectively; P

Population-based Cancer Registries (PBCRs) are tasked with collecting high-quality data, important for monitoring cancer burden and its trends, planning and evaluating cancer control activities, clinical and epidemiological research and development of health policies. The main indicators to measure data quality are validity, completeness, comparability and timeliness. The aim of this article is to evaluate the quality of PBCRs data collected in the first ENCR-JRC data call, dated 2015.MethodsAll malignant tumours, except skin non-melanoma, and in situ and uncertain behaviour of bladder were obtained from 130 European general PBCRs for patients older than 19 years. Proportion of cases with death certificate only (DCO%), proportion of cases with unknown primary site (PSU%), proportion of microscopically verified cases (MV%), mortality to incidence (M:I) ratio, proportion of cases with unspecified morphology (UM%) and the median of the difference between the registration date and the incidence date were computed by sex, age group, cancer site, period and PBCR.ResultsA total of 28,776,562 cases from 130 PBCRs, operating in 30 European countries were included in the analysis. The quality of incidence data reported by PBCRs has been improving across the study period. Data quality is worse for the oldest age groups and for cancer sites with poor survival. No differences were found between males and females. High variability in data quality was detected across European PBCRs.Conclusionthe results reported in this paper are to be interpreted as the baseline for monitoring PBCRs data quality indicators in Europe along time.

Summary: Background: Loss of life expectancy (LOLE) may provide more intuitive information on the impact of cancer than relative survival over a fixed time horizon (e.g., 5-year relative survival). We aimed to assess the evolution of the LOLE using a nationwide, population-based cohort including patients diagnosed with one of 17 most frequent solid malignancies. Methods: From the Netherlands Cancer Registry, we selected adult patients diagnosed with one of the 17 most frequent solid malignancies in the Netherlands during 1989–2019, with survival follow-up until 2022. We used flexible parametric survival models to estimate the LOLE at diagnosis and the LOLE after surviving several years post-diagnosis (conditional LOLE; CLOLE) by cancer type, calendar year, age, sex, and disease stage. Findings: For all cancers combined, the LOLE consistently decreased from 1989 to 2019. This decrease was most pronounced for males with prostate cancer (e.g., from 6.9 [95% confidence interval [CI], 6.7–7.1] to 2.7 [95% CI, 2.5–3.0] for 65-year-olds) and females with breast cancer (e.g., from 6.6 [95% CI, 6.4–6.7] to 1.9 [95% CI, 1.8–2.0] for 65-year-olds). The LOLE among patients with cancers of the head and neck or the central nervous system remained constant over time. Overall, the CLOLE showed that the life years lost among patients with cancer decreased with each additional year survived post-diagnosis. For example, the LOLE at diagnosis for 65-year-old females diagnosed with breast cancer in 2019 was 1.9 [95% CI, 1.8–2.0] compared with 1.7 [95% CI, 1.6–1.8], 1.0 [95% CI, 0.9–1.1], and 0.5 [95% CI, 0.5–0.6] when surviving one, five, and ten years post-diagnosis, respectively. Estimates for other combinations of patient and tumour characteristics are available in a publicly available web-based application. Interpretation: Our findings suggested that the evolution of LOLE substantially varies across cancer type, age, and disease stage. LOLE estimates help patients better understand the impact of their specific cancer diagnosis on their life expectancy. Funding: None.

Key Clinical Message The prognosis of patients with relapsed or refractory (R/R) BL is poor with limited response to salvage therapy, especially for patients with early relapse (

Abstract It is unclear whether survival in diffuse large B-cell lymphoma (DLBCL) continues to increase in an era where rituximab-containing chemotherapy reigns for almost two decades. Therefore, we evaluated trends in primary therapy and relative survival (RS) among Dutch DLBCL patients diagnosed between 1989 and 2018. Analyses were performed separately according to the stage I (N = 6952) and stage II–IV disease (N = 20,676), stratified by calendar period and age (18–64, 65–74, and ≥75 years). The use of chemotherapy ± radiotherapy increased over time across all age and stage groups. As of the mid-2000s, >95% of chemotherapy-treated patients received chemoimmunotherapy, irrespective of age and stage. Overall, RS increased significantly over time across all age groups, especially after 2003 when rituximab-containing chemotherapy had become the standard of care. However, RS increased less pronounced between 2003–2010 and 2011–2018 than between 1989–2002 and 2003–2010. These findings were congruent across all studied stage groups. Five-year RS across the three age groups during 2011–2018 was 96%, 84%, and 67% for stage I DLBCL and 75%, 60%, and 46% for stage II–IV DLBCL. Collectively, survival in DLBCL increased modestly beyond the initial introduction of rituximab, with apparent survival differences across age and stage that warrant novel treatment approaches.

Abstract Studies on conditional relative survival (CRS) in chronic lymphocytic leukaemia (CLL) have hitherto been lacking in the literature. We predicted up‐to‐date estimates of 5‐year RS at diagnosis and for each additional year survived (i.e., CRS) up to 15 years post‐diagnosis among CLL patients diagnosed during 2007–2020. We showed that 5‐year CRS continues to decline gradually with each additional year survived in a contemporary era with access to novel‐based agents, irrespective of age. This finding indicates that CLL patients continue to experience substantial excess mortality compared to an age‐ and sex‐matched group from the general population.

Population-based cancer registries are responsible for collecting incidence and survival data on all reportable neoplasms within a defined geographical area. During the last decades, the role of cancer registries has evolved beyond monitoring epidemiological indicators, as they are expanding their activities to studies on cancer aetiology, prevention, and quality of care. This expansion relies also on the collection of additional clinical data, such as stage at diagnosis and cancer treatment. While the collection of data on stage, according to international reference classification, is consolidated almost everywhere, data collection on treatment is still very heterogeneous in Europe. This article combines data from a literature review and conference proceedings together with data from 125 European cancer registries contributing to the 2015 ENCR-JRC data call to provide an overview of the status of using and reporting treatment data in population-based cancer registries. The literature review shows that there is an increase in published data on cancer treatment by population-based cancer registries over the years. In addition, the review indicates that treatment data are most often collected for breast cancer, the most frequent cancer in women in Europe, followed by colorectal, prostate and lung cancers, which are also more common. Treatment data are increasingly being reported by cancer registries, though further improvements are required to ensure their complete and harmonised collection. Sufficient financial and human resources are needed to collect and analyse treatment data. Clear registration guidelines are to be made available to increase the availability of real-world treatment data in a harmonised way across Europe.

An updated European Network of Cancer registries (ENCR) Recommendations on Recording and Reporting of Urothelial Tumours of the Urinary Tract had been published in 2022. After the publication by the ENCR of the “Recommendations for coding bladder cancers” in 1995, knowledge about the biology and pathology of urinary tract tumors and their classification has varied and increased substantially. On the other hand, several studies have shown that cancer registries use different definitions, criteria for inclusion and coding of urothelial tumors. This great variability among registries affects not only the criteria for recording (registration, coding and classification) but also the criteria of reporting (counting in the statistics of incidence and survival) urinary tract tumors. This causes difficulties in the data comparability from different registries. Recording and reporting of urothelial tumors requires the application of standard criteria that must take into account the combination of the multiple aspects as the primary topography, the histological type, the grade, the extent of invasion, the multi-centricity, the progressions and the time interval between tumors. This led to the creation of a Working Group of the ENCR that developed these recommendations on the recording and reporting of urothelial tumors of the urinary tract. This article reports these recommendations and the rationale for each.

O artigo discute as ações afirmativas na educação superior dialogando com a perspectiva da Teoria do Reconhecimento em Nancy Fraser, segundo algumas concepções da filósofa em torno das lutas por justiça social na contemporaneidade. A autora defende que essas lutas precisam integrar as reivindicações por reconhecimento e redistribuição num modelo amplo que dê conta das demandas do nosso tempo. Fraser defende o modelo de status, no qual o que requer reconhecimento não é a identidade subalternizada dos grupos discriminados, mas a condição de serem parceiros em potencial na interação social em condições de igualdade. Realiza-se crítica ao modelo de status de Fraser, mas concorda-se com a importância da integração entre as exigências por reconhecimento e redistribuição, porque isoladamente cada uma não é capaz de dar conta da luta por justiça social.

Abstract Oncological care was largely derailed due to the reprioritisation of health care services to handle the initial surge of COVID-19 patients adequately. Cancer screening programmes were no exception in this reprioritisation. They were temporarily halted in the Netherlands (1) to alleviate the pressure on health care services overwhelmed by the upsurge of COVID-19 patients, (2) to reallocate staff and personal protective equipment to support critical COVID-19 care, and (3) to mitigate the spread of COVID-19. Utilising data from the Netherlands Cancer Registry on provisional cancer diagnoses between 6 January 2020 and 4 October 2020, we assessed the impact of the temporary halt of national population screening programmes on the diagnosis of breast and colorectal cancer in the Netherlands. A dynamic harmonic regression model with ARIMA error components was applied to assess the observed versus expected number of cancer diagnoses per calendar week. Fewer diagnoses of breast and colorectal cancer were objectified amid the early stages of the initial COVID-19 outbreak in the Netherlands. This effect was most pronounced among the age groups eligible for cancer screening programmes, especially in breast cancer (age group 50–74 years). Encouragingly enough, the observed number of diagnoses ultimately reached and virtually remained at the level of the expected values. This finding, which emerged earlier in age groups not invited for cancer screening programmes, comes on account of the decreased demand for critical COVID-19 care since early April 2020, which, in turn, paved the way forward to resume screening programmes and a broad range of non-critical health care services, albeit with limited operating and workforce capacity. Collectively, transient changes in health-seeking behaviour, referral practices, and cancer screening programmes amid the early stages of the initial COVID-19 epidemic in the Netherlands conjointly acted as an accelerant for fewer breast and colorectal cancer diagnoses in age groups eligible for cancer screening programmes. Forthcoming research is warranted to assess whether the decreased diagnostic scrutiny of cancer during the COVID-19 pandemic resulted in stage migration and altered clinical management, as well as poorer outcomes.

Abstract We assessed the impact of a prior malignancy diagnosis (PMD) – as a potential proxy for genetic cancer susceptibility – on the development of a second primary malignancy (SPM) and mortality in follicular lymphoma (FL) patients. From the nationwide Netherlands Cancer Registry, we selected all adult FL patients diagnosed in 1994‐2012 (n = 8028) and PMDs and SPMs relative to FL, with follow‐up until 2017. We constructed two Fine and Gray models – with death as a competing risk – to assess the association between a PMD and SPM incidence. A PMD was associated with an increased incidence of SPMs (subdistribution hazard ratio [SHR], 1.30; 95% confidence interval [CI], 1.03‐1.64) – especially carcinomas of the respiratory tract (SHR, 1.83; 95% CI, 1.10‐3.05) and cutaneous squamous cell carcinomas (SHR, 1.58; 95% CI, 1.01‐2.45) – and a higher risk of mortality in a multivariable model (HR, 1.43; 95% CI, 1.19‐1.71). However, when additionally adjusted for the receipt of systemic therapy and/or radiotherapy before FL diagnosis, only patients who received such therapies had an increased incidence of SPMs (SHR, 1.40; 95% CI, 1.02‐1.93). In conclusion, patients with a PMD had a higher rate of SPMs and mortality than those without a PMD, which might have resulted from therapy‐related carcinogenesis.

Introduction: Unambiguous data on sexual dysfunction after Hodgkin lymphoma (HL) treatment are scarce. Aims: To form a baseline in this area, we compared patient-reported sexual function in sexually active male HL survivors in complete remission with a sexually active, age-matched, male Dutch sample population. Furthermore, we explored whether sociodemographic and clinical factors were associated with sexual dysfunction in HL survivors and investigated whether reporting to perceive sexual problems was indicative for sexual dysfunction. Methods: This cross-sectional study included male patients with HL who were treated with chemotherapy and age-matched sexually active males. Main outcome measures: Outcome measures included the internationally validated International Index of Erectile Function (IIEF) and self-reported sexual problems by adding 3 items to the study-specific questionnaire. Results: Erectile dysfunction (ED) occurred in 23.3% of the HL survivors vs in 23.0% of controls: respectively 13.3% and 12.3% had moderate to severe ED. However, more HL survivors positively answered the question whether they did perceive sexual problems than controls (20.0% vs 7.0%; P = .087). More patients treated with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procabazine, and prednisone (BEACOPP) had sexual problems 33.3% vs 8.3% who were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (P = .057). Importantly, we found that the mean IIEF score for erectile function was 15.7 in HL survivors who reported to perceive sexual problems (moderate ED) vs 28.3 (normal) in those without perceiving sexual problems. Conclusion: In general, sexual function of male HL survivors is comparable to that of matched normal controls. Perceiving sexual problems was associated with lower sexual function measured by the IIEF. None of the HL survivors who were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine perceived sexual problems. However, one-third of HL survivors who were treated with BEACOPP did, including ED in one-third of the cases. This is an important consideration for daily clinical practice as BEACOPP is increasingly used as standard therapy in advanced-stage HL.Eeltink CM, Lissenberg-Witte BI, Incrocci L, et al. Self-Reported Sexual Function in Sexually Active Male Hodgkin Lymphoma Survivors. Sex Med 2020;8:428–435.

Abstract In this nationwide, population-based study, we assessed 10-year relative survival among 225,305 patients with ten early-stage cancers diagnosed in the Netherlands during 2004–2015. This study aimed to ascertain which early-stage cancer is associated with minimal or no excess mortality and likely to be diagnosed in individuals who are otherwise more healthy or health-conscious than their counterparts in the general population. Ten-year relative survival marginally exceeded 100% in patients with early-stage prostate cancer, while it was close to 100% for patients with ductal carcinoma in situ (DCIS) and stage I cancers of the breast, skin (melanoma), testis, and thyroid. In contrast, patients with early-stage oral/pharyngeal, bladder, lung, and pancreatic cancers experienced considerable excess mortality, reflected by a 10-year relative survival of 74.9%, 69.4%, 45.5%, and 33.9%, respectively. Collectively, the life expectancy of patients with DCIS and early-stage cancers of the prostate, breast, skin (melanoma), testis, and thyroid parallels the expected survival of an age-, sex-, and calendar year-matched group from the general population. Our study findings add to the controversy surrounding overdiagnosis of particular early-stage cancers that are generally not destined to metastasis or cause excess mortality.

Abstract Background Medication non-adherence is associated with poor health outcomes and increased health care costs. Depending on definitions, reported non-adherence rates in cancer patients ranges between 16 and 100%, which illustrates a serious problem. In malignancy, non-adherence reduces chances of achievement of treatment response and may thereby lead to progression or even relapse. Except for Chronic Myeloid Leukemia (CML), the extent of non-adherence has not been investigated in hematological-oncological patients in an outpatient setting. In order to explore ways to optimize cancer treatment results, this study aimed to assess the prevalence of self-administered medication non-adherence and to identify potential associated factors in hematological-oncological patients in their home situation. Methods This is an exploratory cross-sectional study, carried out at the outpatient clinic of the Department of Hematology at the VU University medical center, Amsterdam, the Netherlands between February and April 2014. Hematological-oncological outpatients were sent questionnaires retrieving information on patient characteristics, medication adherence, beliefs about medication, anxiety, depression, coping, and quality of life. We performed uni- and multivariable analysis to identify predictors for medication non-adherence. Results In total, 472 participants were approached of which 259 (55%) completed the questionnaire and met eligibility criteria. Prevalence of adherence in this group (140 male; 54,1%; median age 60 (18–91)) was 50%. In univariate analysis, (lower) age, (higher) education level, living alone, working, perception of receiving insufficient social support, use of bisphosphonates, depression, helplessness (ICQ), global health, role function, emotional function, cognitive function, social functioning, fatigue, dyspnea, diarrhea were found to be significantly related (p =

Patients with MYC-rearrangement positive large B-cell lymphoma (MYC+ LBCL) have an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) as compared to patients without MYC rearrangement. Although intensive chemotherapy regimens yield higher remission rates, toxicity remains a concern. Lenalidomide is an oral immunomodulatory drug which downregulates MYC and its target genes thereby providing support using lenalidomide as additional therapeutic option for MYC+ LBCL. A phase II trial was conducted evaluating the efficacy of lenalidomide (15 mg day 1-14) in combination with R-CHOP (R2CHOP) in newly diagnosed MYC+ LBCL patients identified through a nationwide MYC-FISH screening program. The primary endpoint was complete metabolic response (CMR) on centrally reviewed 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computer tomography (CT)-scan at end-of-treatment. Secondary endpoints were overall survival (OS), disease-free survival (DFS) and event-free survival (EFS). Eighty-two patients with stage II-IV MYC+ LBCL were treated with 6 cycles of R2CHOP. At EOT, 67% (confidence interval (CI) 58-75%) of the patients reached CMR. With a median follow-up of 25.4 months, 2-year estimates (95% CI) for OS, DFS, EFS were 73% (62-82%), 75% (63-84%) and 63% (52-73%) respectively. In this prospective trial for newly diagnosed MYC+ LBCL patients, we found that administering R2CHOP was safe, and yields comparable CMR and survival rates as in studies applying more intensive chemotherapy regimens. Hence, these findings offer new prospects for MYC+ LBCL patients and warrant comparison in prospective randomized clinical trials. This trial was registered at www.clinicaltrialsregister.eu (#2014-002654-39).

Background: Monitoring and improving quality of cancer care has become pivotal today. This is especially relevant for head and neck cancers since the disease is complex, it needs multi therapy, patients tend to be older, they tend to have comorbidities and limited social support. However, information on quality of care for head and neck cancers is scarce. In the context of the project “Information Network on Rare Cancers” we aimed to identify indicators of quality of care specific for the head and neck cancers management and to measure the quality of care for head and neck cancers in different EU Member States.Methods: We defined indicators of quality of care for head and neck cancers based on a multidisciplinary and expert-based consensus process at a European level. To test the proposed indicators, we performed an observational population-based retrospective study in four countries (Ireland, Italy, Netherlands, and Slovenia) in the years 2009–2011.Results: The main quality indicators identified are: availability of formalized multidisciplinary team, participation in clinical and translational research; timeliness of care, high quality of surgery and radiotherapy, and of pathological reporting. For head and neck cancers, the quality of care did not reach the optimal standards in most of the countries analyzed. A high proportion of patients was diagnosed at an advanced disease stage, showed delays in starting treatment (especially for radiotherapy), and there was only a very limited use of multi therapy.Conclusions: According to the achieved consensus, indicators of quality of care for head and neck cancers have to cover the patient journey (i.e., diagnosis and treatment). Our results, showed suboptimal quality of care across countries and call for solutions for ensuring good quality of care for head and neck cancer patients in all EU countries. One possible option might be to refer head and neck cancer patients to specialized centers or to networks including specialized centers.

El presente trabajo de investigación analiza la manera como se están administrando las áreas protegidas del Ecuador y cómo esto incide en el desarrollo local, para lo cual se toman como caso de estudio las áreas marinas costeras de la provincia de Santa Elena, tales como Reserva de Producción Faunística Puntilla de Santa Elena y Reserva Marina El Pelado. Estas áreas presentan ecosistemas similares y albergan una riqueza ecológica muy diversa y de gran atracción para el turismo. En este estudio se realiza una investigación empírica y descriptiva a partir de una muestra de 120 habitantes de la provincia. El objetivo principal de la investigación es determinar el nivel de participación de las comunidades locales en la administración de las áreas protegidas y su relación con el desarrollo local. Actualmente, las áreas protegidas son manejadas y administradas por el Ministerio del Ambiente.

Evaluations of the ‘real-world’ efficacy and safety of tyrosine kinase inhibitors in patients with chronic myeloid leukemia are scarce. A nationwide, population-based, chronic myeloid leukemia registry was analyzed to evaluate (deep) response rates to first and subsequent treatment lines and eligibility for a treatment cessation attempt in adults diagnosed between January 2008 and April 2013 in the Netherlands. The registry covered 457 patients; 434 in chronic phase (95%) and 15 (3%) in advanced disease phase. Seventy-five percent of the patients in chronic phase were treated with imatinib and 25% with a second-generation tyrosine kinase inhibitor. At 3 years 44% of patients had discontinued their first-line treatment, mainly due to intolerance (21%) or treatment failure (19%). At 18 months 73% of patients had achieved a complete cytogenetic response and 63% a major molecular response. Deep molecular responses (MR4.0 and MR4.5) were achieved in 69% and 56% of patients, respectively, at 48 months. All response milestones were achieved faster in patients treated upfront with a second-generation tyrosine kinase inhibitor, but ultimately patients initially treated with imatinib also reached similar levels of responses. The 6-year cumulative incidence of eligibility for a tyrosine kinase cessation attempt, according to EURO-SKI criteria, was 31%. Our findings show that in a ‘real-world’ setting the long-term outcome of patients treated with tyrosine kinase inhibitors is excellent and the conditions for an attempt to stop tyrosine kinase inhibitor therapy are met by a third of the patients.

Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19–0.68) and 0.30 (range 0.12–0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09–0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16–0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization.

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.

Population-based information on the survival of patients with myeloid malignancies is rare mainly because some entities were not recognized as malignant until the publication of the third revision of the International Classification of Diseases for Oncology and World Health Organization classification in 2000. In this study we report the survival of patients with myeloid malignancies, classified by updated criteria, in Europe. We analyzed 58,800 cases incident between 1995 to 2002 in 48 population-based cancer registries from 20 European countries, classified into HAEMACARE myeloid malignancy groupings. The period approach was used to estimate 5-year relative survival in 2000-2002. The relative overall survival rate was 37%, but varied significantly between the major groups: being 17% for acute myeloid leukemia, 20% for myelodysplastic/myeloproliferative neoplasms, 31% for myelodysplastic syndromes and 63% for myeloproliferative neoplasms. Survival of patients with individual disease entities ranged from 90% for those with essential thrombocythemia to 4% for those with acute myeloid leukemia with multilineage dysplasia. Regional European variations in survival were conspicuous for myeloproliferative neoplasms, with survival rates being lowest in Eastern Europe. This is the first paper to present large-scale, European survival data for patients with myeloid malignancies using prognosis-based groupings of entities defined by the third revision of the International Classification of Diseases for Oncology/World Health Organization classifications. Poor survival in some parts of Europe, particularly for treatable diseases such as chronic myeloid leukemia, is of concern for hematologists and public health authorities.

Cellular interactions between endothelial cells and macrophages regulate macrophage localization and phenotype, but the mechanisms underlying these interactions are poorly understood. Here we explored the role of sialoglycans on lymphatic endothelial cells (LEC) in interactions with macrophage-expressed Siglec-1 (CD169). Lectin-binding assays and mass spectrometric analyses revealed that LEC from human skin express more sialylated glycans than the corresponding blood endothelial cells. Higher amounts of sialylated and/or sulfated glycans on LEC than BEC were consistently observed in murine skin, lung and lymph nodes. The floor LEC of the subcapsular sinus (SCS) in murine lymph nodes (LN) displayed sialylated glycans at particularly high densities. The sialoglycans of LN LEC were strongly bound by Siglec-1. Such binding plays an important role in the localization of Siglec-1 + LN-SCS macrophages, as their numbers are strongly reduced in mice expressing a Siglec-1 mutant that is defective in sialoglycan binding. The residual Siglec-1 + macrophages are less proliferative and have a more anti-inflammatory phenotype. We propose that the densely clustered, sialylated glycans on the SCS floor LEC are a key component of the macrophage niche, providing anchorage for the Siglec-1 + LN-SCS macrophages., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)