Corrigendum: Cancer data quality and harmonization in Europe: The experience of the BENCHISTA Project - International Benchmarking of Childhood Cancer Survival by Stage.

[This corrects the article DOI: 10.3389/fonc.2023.1232451.].

Indicators of cure for women living after uterine and ovarian cancers: a population-based study.

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynaecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate Net Survival (NS), Cure Fraction, Time To Cure (5-year conditional NS>95%), Cure Prevalence (women who will not die of cancer), and Already Cured (living longer than Time to Cure). In 2018, 0.4% (121,704) of Italian women were alive after corpus uteri cancer, 0.2% (52,551) after cervical, and 0.2% (52,153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (Cure Prevalence). Women with gynaecological cancers have a residual excess risk of death <5% after 5 years since diagnosis. The Cure Fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time To Cure was ≤10 years for women with gynaecological cancers aged <55 years. 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were Already Cured. These results will contribute to improving follow-up programs for women with gynaecological cancers and supporting efforts against discrimination of already cured ones.

Protocol for investigating data quality and reporting outcomes of pediatric gliomas in population-based cancer registry research.

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.

Childhood and Adolescent Central Nervous System Tumours in Spain: Incidence and Survival over 20 Years: A Historical Baseline for Current Assessment.

BACKGROUND: Central nervous system (CNS) neoplasms are highly frequent solid tumours in children and adolescents. While some studies have shown a rise in their incidence in Europe, others have not. Survival remains limited. We addressed two questions about these tumours in Spain: (1) Is incidence increasing? and (2) Has survival improved? METHODS: This population-based study included 1635 children and 328 adolescents from 11 population-based cancer registries with International Classification of Childhood Cancer Group III tumours, incident in 1983-2007. Age-specific and age-standardised (world population) incidence rates (ASRws) were calculated. Incidence time trends were characterised using annual percent change (APC) obtained with Joinpoint. Cases from 1991 to 2005 (1171) were included in Kaplan-Meier survival analyses, and the results were evaluated with log-rank and log-rank for trend tests. Children's survival was age-standardised using: (1) the age distribution of cases and the corresponding trends assessed with Joinpoint; and (2) European weights for comparison with Europe. RESULTS: ASRw 1983-2007: children: 32.7 cases/106; adolescents: 23.5 cases/106. The overall incidence of all tumours increased across 1983-2007 in children and adolescents. Considering change points, the APCs were: (1) children: 1983-1993, 4.3%^ (1.1; 7.7); 1993-2007, -0.2% (-1.9; 1.6); (2) adolescents: 1983-2004: 2.9%^ (0.9; 4.9); 2004-2007: -7.7% (-40; 41.9). For malignant tumours, the trends were not significant. 5-year survival was 65% (1991-2005), with no significant trends (except for non-malignant tumours). CONCLUSIONS: CNS tumour incidence in Spain was found to be similar to that in Europe. Rises in incidence may be mostly attributable to changes in the registration of non-malignant tumours. The overall malignant CNS tumour trend was compatible with reports for Southern Europe. Survival was lower than in Europe, without improvement over time. We provide a baseline for assessing current paediatric oncology achievements and incidence in respect of childhood and adolescent CNS tumours.

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

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.

Current management and future challenges in salivary glands cancer.

Salivary gland cancers (SGCs) are rare, accounting for less than 5% of all malignancies of the head and neck region, and are morphologically heterogeneous. The diagnosis is mainly based on histology, with the complementary aid of molecular profiling, which is helpful in recognizing some poorly differentiated, borderline, or atypical lesions. Instrumental imaging defines the diagnosis, representing a remarkable tool in the treatment plan. Ultrasound and magnetic resonance are the most common procedures used to describe the primary tumour. The treatment of SGCs is multimodal and consists of surgery, radiotherapy, and systemic therapy; each treatment plan is, however, featured on the patient and disease's characteristics. On 24 June 2022, in the meeting "Current management and future challenges in salivary gland cancers" many experts in this field discussed the state of the art of SGCs research, the future challenges and developments. After the meeting, the same pool of experts maintained close contact to keep these data further updated in the conference proceedings presented here. This review collects the insights and suggestions that emerged from the discussion during and after the meeting per se.

Prediction of Risk of Metastatic Recurrence for Female Breast Cancer Patients in the Presence of Competing Causes of Death.

BACKGROUND: To estimate risk of recurrence for women diagnosed with nonmetastatic breast cancer considering the risks of other causes mortality. METHODS: We extend a method based on the diagnosis-metastasis-death pathway to include risks of other causes mortality. We estimate three probabilities as cumulative incidence of: (i) being alive and recurrence-free, (ii) death for other causes before a recurrence, and (iii) recurrence. We apply the method to female breast cancer relative survival from the Surveillance, Epidemiology, and End Results Program registries (2000-2018) data. RESULTS: The cumulative incidence of recurrence shows a higher increase with more advanced cancer stage and is less influenced by age at diagnosis. At 5 years from diagnosis, the cumulative incidence of recurrence is less than 3% for those diagnosed with stage I, 10% to 13% for those diagnosed with stage II, and 37% to 47% for those diagnosed with stage III breast cancer. The estimates of recurrence considering versus ignoring the risks of dying from other causes were generally consistent, except for older women with more advanced stage, and longer time since diagnosis. In these groups, the net probability of recurrence, excluding the risks of dying from other causes, were overestimated. CONCLUSIONS: For patients with cancer who are older or long-term survivors, it is important to include the risks of other cause mortality as the crude cumulative incidence of recurrence is a more appropriate measure. IMPACT: These estimates are important in clinical decision making, as higher competing mortality may preclude the benefits of aggressive treatments.

Cancer data quality and harmonization in Europe: the experience of the BENCHISTA Project - international benchmarking of childhood cancer survival by stage.

Introduction: Variation in stage at diagnosis of childhood cancers (CC) may explain differences in survival rates observed across geographical regions. The BENCHISTA project aims to understand these differences and to encourage the application of the Toronto Staging Guidelines (TG) by Population-Based Cancer Registries (PBCRs) to the most common solid paediatric cancers. Methods: PBCRs within and outside Europe were invited to participate and identify all cases of Neuroblastoma, Wilms Tumour, Medulloblastoma, Ewing Sarcoma, Rhabdomyosarcoma and Osteosarcoma diagnosed in a consecutive three-year period (2014-2017) and apply TG at diagnosis. Other non-stage prognostic factors, treatment, progression/recurrence, and cause of death information were collected as optional variables. A minimum of three-year follow-up was required. To standardise TG application by PBCRs, on-line workshops led by six tumour-specific clinical experts were held. To understand the role of data availability and quality, a survey focused on data collection/sharing processes and a quality assurance exercise were generated. To support data harmonization and query resolution a dedicated email and a question-and-answers bank were created. Results: 67 PBCRs from 28 countries participated and provided a maximally de-personalized, patient-level dataset. For 26 PBCRs, data format and ethical approval obtained by the two sponsoring institutions (UCL and INT) was sufficient for data sharing. 41 participating PBCRs required a Data Transfer Agreement (DTA) to comply with data protection regulations. Due to heterogeneity found in legal aspects, 18 months were spent on finalizing the DTA. The data collection survey was answered by 68 respondents from 63 PBCRs; 44% of them confirmed the ability to re-consult a clinician in cases where stage ascertainment was difficult/uncertain. Of the total participating PBCRs, 75% completed the staging quality assurance exercise, with a median correct answer proportion of 92% [range: 70% (rhabdomyosarcoma) to 100% (Wilms tumour)]. Conclusion: Differences in interpretation and processes required to harmonize general data protection regulations across countries were encountered causing delays in data transfer. Despite challenges, the BENCHISTA Project has established a large collaboration between PBCRs and clinicians to collect detailed and standardised TG at a population-level enhancing the understanding of the reasons for variation in overall survival rates for CC, stimulate research and improve national/regional child health plans.

Descriptive epidemiology of the head and neck cancers in old patients.

Background: In Europe, as in other high-income (HI) countries, quite half of the newly diagnosed patients with head and neck (H and N) cancers are older than 65 years of age and their proportion within the prevalent cases is even higher. Moreover, the incidence rate (IR) for all H and N cancers sites increased with age and the survival rate is lower in older patients (≥65), compared with younger patients (<65). The number of older patients affected by H and N cancers will increase because of the increase in life expectancy. The aim of the article is to provide an epidemiological description of H and N cancers in the elderly population. Material and methods: Incidence and prevalence data by time periods and continents were extracted from the Global Cancer Observatory. The survival information for Europe is obtained from the EUROCARE and RARECAREnet projects. In 2020, according to the results from these data, slightly more than 900,000 cases have been diagnosed with H and N cancers in the world, and approximately 40% were older than 65 years of age. This percentage was higher, reaching approximately 50% in the HI countries. The highest number of cases was in the Asiatic populations, while the highest crude IR was in Europe and Oceania. Among H and N cancers occurring in the elderly, laryngeal and oral cavity cancers were the most common, while nasal cavities and nasopharyngeal cancers were the rarest. This was true for all the countries, excluding some Asiatic populations, in which tumour of the nasopharynx was more common. The five-year survival rate in the European population was low in the elderly, compared with the younger for all H and N cancers, and it ranged from approximately 60% for both salivary-gland type and laryngeal to 22% for hypopharyngeal tumors. For the elderly, the conditional 5-year survival after surviving one year became more than 60% for many H and N epithelial tumors. Conclusion: The high variability in the H and N cancer incidence around the world is due to the distribution of the major risk factors which for the elderly are mainly alcohol and smoking. The reasons for low survival in the elderly are most likely due to the complexity of treatment, the late arrival of patients at diagnosis, and the difficult access to specialized centers.

Incidence Trends and Main Features of Gastro-Intestinal Stromal Tumours in a Mediterranean Region: A Population-Based Study.

Gastro-Intestinal Stromal Tumours (GISTs) are a kind of neoplasm whose diagnosis in common clinical practice just started in the current century, implying difficulties for proper registration. Staff from the Cancer Registry of Murcia, in southeastern Spain, were commissioned by the EU Joint Action on Rare Cancers into a pilot study addressing GIST registration that also yielded a population-based depiction of GISTs in the region, including survival figures. We examined reports from 2001 to 2015 from hospitals as well as cases already present in the registry. The variables collected were sex, date of diagnosis, age, vital status, primary location, presence of metastases, and risk level according to Joensuu's Classification. In total, 171 cases were found, 54.4% occurred in males, and the mean age value was 65.0 years. The most affected organ was the stomach, with 52.6% of cases. Risk level was determined as "High" for 45.0%, with an increment of lower levels in recent years. Incidence for the year 2015 doubled that of 2001. Overall, the 5-year net survival estimation was 77.0%. The rising incidence magnitude is consistent with trends in other European countries. Survival evolution lacked statistical significance. A more interventional approach in clinical management could explain the increase in the proportion of "Low Risk GISTs" and the first occurrence of "Very Low Risk" in recent years.

A new cure model that corrects for increased risk of non-cancer death: analysis of reliability and robustness, and application to real-life data.

BACKGROUND: Non-cancer mortality in cancer patients may be higher than overall mortality in the general population due to a combination of factors, such as long-term adverse effects of treatments, and genetic, environmental or lifestyle-related factors. If so, conventional indicators may underestimate net survival and cure fraction. Our aim was to propose and evaluate a mixture cure survival model that takes into account the increased risk of non-cancer death for cancer patients. METHODS: We assessed the performance of a corrected mixture cure survival model derived from a conventional mixture cure model to estimate the cure fraction, the survival of uncured patients, and the increased risk of non-cancer death in two settings of net survival estimation, grouped life-table data and individual patients' data. We measured the model's performance in terms of bias, standard deviation of the estimates and coverage rate, using an extensive simulation study. This study included reliability assessments through violation of some of the model's assumptions. We also applied the models to colon cancer data from the FRANCIM network. RESULTS: When the assumptions were satisfied, the corrected cure model provided unbiased estimates of parameters expressing the increased risk of non-cancer death, the cure fraction, and net survival in uncured patients. No major difference was found when the model was applied to individual or grouped data. The absolute bias was < 1% for all parameters, while coverage ranged from 89 to 97%. When some of the assumptions were violated, parameter estimates appeared more robust when obtained from grouped than from individual data. As expected, the uncorrected cure model performed poorly and underestimated net survival and cure fractions in the simulation study. When applied to colon cancer real-life data, cure fractions estimated using the proposed model were higher than those in the conventional model, e.g. 5% higher in males at age 60 (57% vs. 52%). CONCLUSIONS: The present analysis supports the use of the corrected mixture cure model, with the inclusion of increased risk of non-cancer death for cancer patients to provide better estimates of indicators based on cancer survival. These are important to public health decision-making; they improve patients' awareness and facilitate their return to normal life.

Cancer treatment data available in European cancer registries: Where are we and where are we going?

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.

Global survival trends for brain tumors, by histology: Analysis of individual records for 67,776 children diagnosed in 61 countries during 2000-2014 (CONCORD-3).

INTRODUCTION: Tumors of the central nervous system are among the leading causes of cancer-related death in children. Population-based cancer survival reflects the overall effectiveness of a health care system in managing cancer. Inequity in access to care world-wide may result in survival disparities. METHODS: We considered children (0-14 years) diagnosed with a brain tumor during 2000-2014, regardless of tumor behavior. Data underwent a rigorous, three-phase quality control as part of CONCORD-3. We implemented a revised version of the International Classification of Childhood Cancer (third edition) to control for under-registration of non-malignant astrocytic tumors. We estimated net survival using the unbiased nonparametric Pohar Perme estimator. RESULTS: The study included 67,776 children. We estimated survival for 12 histology groups, each based on relevant ICD-O-3 codes. Age-standardized 5-year net survival for low-grade astrocytoma ranged between 84% and 100% world-wide during 2000-2014. In most countries, 5-year survival was 90% or more during 2000-2004, 2005-2009, and 2010-2014. Global variation in survival for medulloblastoma was much wider, with age-standardized 5-year net survival between 47% and 86% for children diagnosed during 2010-2014. CONCLUSIONS: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors in children, by histology. We devised an enhanced version of ICCC-3 to account for differences in cancer registration practices world-wide. Our findings may have public health implications, because low-grade glioma is 1 of the 6 index childhood cancers included by WHO in the Global Initiative for Childhood Cancer.

Salivary gland cancers in elderly patients: challenges and therapeutic strategies.

Salivary gland carcinomas (SGCs) are the most heterogeneous subgroup of head and neck malignant tumors, accounting for more than 20 subtypes. The median age of SGC diagnosis is expected to rise in the following decades, leading to crucial clinical challenges in geriatric oncology. Elderly patients, in comparison with patients aged below 65 years, are generally considered less amenable to receiving state-of-the-art curative treatments for localized disease, such as surgery and radiation/particle therapy. In the advanced setting, chemotherapy regimens are often dampened by the consideration of cardiovascular and renal comorbidities. Nevertheless, the elderly population encompasses a broad spectrum of functionalities. In the last decades, some screening tools (e.g. the G8 questionnaire) have been developed to identify those subjects who should receive a multidimensional geriatric assessment, to answer the question about the feasibility of complex treatments. In the present article, we discuss the most frequent SGC histologies diagnosed in the elderly population and the relative 5-years survival outcomes based on the most recent data from the Surveillance, Epidemiology, and End Results (SEER) Program. Moreover, we review the therapeutic strategies currently available for locoregionally advanced and metastatic disease, taking into account the recent advances in precision oncology. The synergy between the Multidisciplinary Tumor Board and the Geriatrician aims to shape the most appropriate treatment pathway for each elderly patient, focusing on global functionality instead of the sole chronological age.

International benchmarking of childhood cancer survival by stage at diagnosis: The BENCHISTA project protocol.

BACKGROUND: Several studies have shown significant variation in overall survival rates from childhood cancer between countries, using population-based cancer registry (PBCR) data for all cancers combined and for many individual tumour types among children. Without accurate and comparable data on Tumour stage at diagnosis, it is difficult to define the reasons for these survival differences. This is because measurement systems designed for adult cancers do not apply to children's cancers and cancer registries often hold limited information on paediatric tumour stage and the data sources used to define it. AIMS: The BENCHISTA project aims to test the application of the international consensus "Toronto Staging Guidelines" (TG) for paediatric tumours by European and non-European PBCRs for six common paediatric solid tumours so that reliable comparisons of stage at diagnosis and survival rates by stage can be made to understand any differences. A secondary aim is to test the data availability and completeness of collection of several 'Toronto' consensus non-stage prognostic factors, treatment types given, occurrence of relapse/progression and cause of death as a descriptive feasibility study. METHODS: PBCRs will use their permitted data access channels to apply the Toronto staging guidelines to all incident cases of six solid childhood cancers (medulloblastoma, osteosarcoma, Ewings sarcoma, rhabdomyosarcoma, neuroblastoma and Wilms tumour) diagnosed in a consecutive three-year period within 2014-2017 in their population. Each registry will provide a de-identified patient-level dataset including tumour stage at diagnosis, with only the contributing registry holding the information that would be needed to re-identify the patients. Where available to the registry, patient-level data on 'Toronto' non-stage prognostic factors, treatments given and clinical outcomes (relapse/progression/cause of death) will be included. More than 60 PBCRs have been involved in defining the patient-level dataset items and intend to participate by contributing their population-level data. Tumour-specific on-line training workshops with clinical experts are available to cancer registry staff to assist them in applying the Toronto staging guidelines in a consistent manner. There is also a project-specific help desk for discussion of difficult cases and promotion of the CanStaging online tools, developed through the International Association of Cancer Registries, to further ensure standardisation of data collection. Country-specific stage distribution and observed survival by stage at diagnosis will be calculated for each tumour type to compare survival between countries or large geographical regions. DISCUSSION: This study will be promote and enhance the collection of standardized staging data for childhood cancer by European and non-European population-based cancer registries. Therefore, this project can be seen as a feasibility project of widespread use of Toronto Staging at a population-level by cancer registries, specifying the data sources used and testing how well standardized the processes can be. Variation in tumour stage distribution could be due to real differences, to different diagnostic practices between countries and/or to variability in how cancer registries assign Toronto stage. This work also aims to strengthen working relationships between cancer registries, clinical services and cancer-specific clinical study groups, which is important for improving patient outcomes and stimulating research.

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.

Cancer-of-Unknown-Primary-Origin: A SEER-Medicare Study of Patterns of Care and Outcomes among Elderly Patients in Clinical Practice.

Knowledge of contemporary patterns of cancer-of-unknown-primary-origin (CUP) diagnostic work-up, treatment, and outcomes in routine healthcare is limited. Thus, we examined data from elderly patients diagnosed with CUP in real-world US clinical practice. From the Surveillance, Epidemiology, and End Results-Medicare-linked database, we included patients ≥ 66 years old with CUP diagnosed between 1 January 2013 and 31 December 2015. We analyzed baseline demographics, clinical characteristics, methods of diagnostic work-up (biopsy, immunohistochemistry, imaging), treatment-related factors, and survival. CUP diagnosis was histologically confirmed in 2813/4562 patients (61.7%). Overall, 621/4562 (13.6%) patients received anticancer pharmacotherapy; among these, 97.3% had a histologically confirmed tumor and 83.1% received all three procedures. Among those with a histologically confirmed tumor, increasing age, increasing comorbidity score, not receiving all three diagnostic measures, and having a not-further specified histologic finding of only 'malignant neoplasm' were all negatively associated with receipt of anticancer pharmacotherapy. Median overall survival was 1.2 months for all patients. Median time between CUP diagnosis and treatment initiation was 41 days. Limited diagnostic work-up was common and most patients did not receive anticancer pharmacotherapy. The poor outcomes highlight a substantial unmet need for further research into improving diagnostic work-up and treatment effectiveness in CUP.

Neuroblastoma in Spain: Linking the national clinical database and epidemiological registries - A study by the Joint Action on Rare Cancers.

PURPOSE: Linkage between clinical databases and population-based cancer registries may serve to evaluate European Reference Networks' (ERNs) activity, by monitoring the proportion of patients benefiting from these and their impact on survival at a population level. To test this, a study targeting neuroblastoma (Nb) was conducted in Spain by the European Joint Action on Rare Cancers. MATERIAL AND METHODS: Subjects: Nb cases, incident 1999-2017, aged < 15 years. Linkage included: Spanish Neuroblastoma Clinical Database (NbCDB) (1217 cases); Spanish Registry of Childhood Tumours (RETI) (1514 cases); and 10 regional population-based registries (RPBCRs) which cover 33% of the childhood population (332 cases). Linkage was semiautomatic. We estimated completeness, incidence, contribution, deficit, and 5-year survival in the databases and specific subsets. RESULTS: National completeness estimates for RETI and NbCDB were 91% and 72% respectively, using the Spanish RPBCRs on International Incidence of Childhood Cancer (https://iicc.iarc.fr/) as reference. RPBCRs' specific contribution was 1.6%. Linkage required manual crossover in 54% of the semiautomatic matches. Five-year survival was 74% (0-14 years) and 90% (0-18 months). CONCLUSIONS: All three databases were incomplete as regards Spain as a whole and should therefore be combined to achieve full childhood cancer registration. A unique personal patient identifier could facilitate such linkage. Most children have access to Nb clinical trials. Consolidated interconnections between the national registry and clinical registries (including ERNs and paediatric oncology clinical groups) should be established to evaluate outcomes.

Estimating Country-Specific Incidence Rates of Rare Cancers: Comparative Performance Analysis of Modeling Approaches Using European Cancer Registry Data.

Estimating incidence of rare cancers is challenging for exceptionally rare entities and in small populations. In a previous study, investigators in the Information Network on Rare Cancers (RARECARENet) provided Bayesian estimates of expected numbers of rare cancers and 95% credible intervals for 27 European countries, using data collected by population-based cancer registries. In that study, slightly different results were found by implementing a Poisson model in integrated nested Laplace approximation/WinBUGS platforms. In this study, we assessed the performance of a Poisson modeling approach for estimating rare cancer incidence rates, oscillating around an overall European average and using small-count data in different scenarios/computational platforms. First, we compared the performance of frequentist, empirical Bayes, and Bayesian approaches for providing 95% confidence/credible intervals for the expected rates in each country. Second, we carried out an empirical study using 190 rare cancers to assess different lower/upper bounds of a uniform prior distribution for the standard deviation of the random effects. For obtaining a reliable measure of variability for country-specific incidence rates, our results suggest the suitability of using 1 as the lower bound for that prior distribution and selecting the random-effects model through an averaged indicator derived from 2 Bayesian model selection criteria: the deviance information criterion and the Watanabe-Akaike information criterion.