Optimizing the colorectal cancer screening programme using faecal immunochemical test (FIT) in Flanders, Belgium from the "interval cancer" perspective.

BACKGROUND: Interval cancer (IC) is a critical issue in colorectal cancer (CRC) screening. We identified factors associated with ICs after faecal immunochemical test (FIT) screening and explored the impact of lowering FIT cut-off or shortening screening interval on FIT-ICs in Flanders. METHODS: FIT participants diagnosed with a CRC during 2013-2018 were included. Factors associated with FIT-ICs were identified using logistic regression. Distributions of FIT results among FIT-ICs were examined. RESULTS: In total, 10,122 screen-detected CRCs and 1534 FIT-ICs were included (FIT-IC proportion of 13%). FIT-ICs occurred more frequently in women (OR 1.58 [95% CI 1.41-1.76]) and ages 70-74 (OR 1.35 [1.14-1.59]). FIT-ICs were more often right-sided (OR 3.53 [2.98-4.20]), advanced stage (stage IV: OR 7.15 [5.76-8.88]), and high grade (poorly/undifferentiated: OR 2.57 [2.08-3.18]). The majority (83-92%) of FIT-ICs would still be missed if FIT cut-off was lowered from 15 to 10 µg Hb/g or screening interval was shortened from 2 to 1 year. CONCLUSIONS: FIT-ICs were more common in women, older age, right-sided location, advanced stage and high grade. In Flanders, lowering FIT cut-off (to 10 µg Hb/g) or shortening screening interval (to 1 year) would have a minimal impact on FIT-ICs.

Quality indicators in neuro-oncology: Review of the literature and development of a new quality indicator set for glioma care through a two-round Delphi survey.

BACKGROUND: Quality Indicators (QIs) are important tools to assess the quality and variability of oncological care. However, their application in neuro-oncology is limited so far. The objective of this study was to develop a set of QIs for glioma, covering process and outcome indicators. METHODS: A systematic review was conducted to identify both QIs in the field of adult glioma care, and guidelines or recommendations that could be translated into QIs. Also reports from national and international healthcare agencies and scientific associations ("grey literature") were taken into account. After conversion of these recommendations into QIs, merging with existing QIs found in the literature and rationalization, a two-round Delphi survey was conducted to gain consensus on relevance for the proposed QIs. RESULTS: In total 240 recommendations and 30 QIs were retrieved from the literature. After conversion, merging and rationalization, 147 QIs were evaluated in the Delphi survey and eventually consensus was gained on 47 QIs in the following 7 domains: Diagnosis and Imaging, Surgery, Pathology, Radio/Chemotherapy, Recurrence, Supportive Treatments (Epilepsy, Thromboembolism, Steroid Use and Rehabilitation) and Survival. CONCLUSION: This study defined a set of 47 QIs for assessing quality of care in adult glioma patients, distributed amongst 7 crucial phases in the patient's care trajectory. These QIs are readily applicable for use in diverse health care systems, depending on the availability of population-based health care data enabling (inter)national benchmarking.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

Risk of cardiovascular disease following gonadotropin-releasing hormone agonists vs antagonists in prostate cancer: Real-world evidence from five databases.

Observational studies in prostate cancer (PCa) have shown an increased risk of cardiovascular disease (CVD) following gonadotropin-releasing hormone (GnRH) agonists, whereas randomised-controlled trials have shown no associations. Compared to GnRH agonists, GnRH antagonists have shown less atherosclerotic effects in preclinical models. We used real-world data from five countries to investigate CVD risk following GnRH agonists and antagonists in PCa men. Data sources included cancer registries, primary and secondary healthcare databases. CVD event was defined as an incident or fatal CVD. Multivariable Cox proportional hazard models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled using random-effects meta-analysis. Stratified analyses were conducted by history of CVD and age (75 years). A total of 48 757 men were on GnRH agonists and 2144 on GnRH antagonists. There was no difference in risk of any CVD for men on GnRH antagonists and agonists (HR: 1.25; 95% CI: 0.96-1.61; I2 : 64%). Men on GnRH antagonists showed increased risk of acute myocardial infarction (HR: 1.62; 95% CI: 1.11-2.35; I2 : 0%) and arrhythmia (HR: 1.55; 95% CI: 1.11-2.15, I2 : 17%) compared to GnRH agonists. Having a history of CVD was found to be an effect modifier for the associations with some CVD subtypes. Overall, we did not observe a difference in risk of overall CVD when comparing GnRH antagonists with agonists-though for some subtypes of CVD we noted an increased risk with antagonists. Further studies are required to address potential confounding caused by unadjusted variables such as severity of CVD history and PCa stage.

Lung cancer incidence differences in migrant men in Belgium, 2004-2013: histology-specific analyses.

BACKGROUND: Immigrants make up an important share of European populations which has led to a growing interest in research on migrants' health. Many studies have assessed migrants' cancer mortality patterns, yet few have studied incidence differences. This paper will probe into histology-specific lung cancer incidence by migrant origin aiming to enhance the knowledge on lung cancer aetiology and different risk patterns among population groups. METHODS: We used data on all lung cancer diagnoses during 2004-2013 delivered by the Belgian Cancer Registry individually linked with the 2001 Belgian Census and the Crossroads Bank for Social Security. Absolute and relative inequalities in overall and histology-specific lung cancer incidence have been calculated for first-generation Italian, Turkish and Moroccan migrant men aged 50-74 years compared to native Belgian men. RESULTS: Moroccan men seemed to be the most advantaged group. Both in absolute and relative terms they consistently had lower overall and histology-specific lung cancer incidence rates compared with native Belgian men, albeit less clear for adenocarcinoma. Turkish men only showed lower overall lung cancer incidence when adjusting for education. On the contrary, Italian men had higher incidence for overall lung cancer and squamous cell carcinoma, which was explained by adjusting for education. CONCLUSIONS: Smoking habits are likely to explain the results for Moroccan men who had lower incidence for smoking-related histologies. The full aetiology for adenocarcinoma is still unknown, yet the higher incidence among Italian men could point to differences in occupational exposures, e.g. to carcinogenic radon while working in the mines.

Breast cancer by migrant background in Belgium: Lower risk, but worse survival in women of non-European origin.

Foreign and native populations differ in terms of breast cancer outcomes. Studies rarely distinguish between premenopausal and postmenopausal breast cancer, although the risk profile is different; nor between migrants of the first and second generation (FG and SG), which is crucial to examine genetic and environmental influences on breast cancer. This research fills these gaps by investigating patterns in breast cancer incidence and survival in different migrant groups by menopausal and migrant generational status, taking various risk factors into account. To this end, individually linked data from the 2001 census, the Belgian Cancer Registry and the Crossroads Bank for Social Security are used. Age-standardised incidence rates and incidence rate ratios are calculated by migrant background group, stratified according to ages 30-50 (premenopausal) and 50-70 (postmenopausal). Incidence rate ratios are examined with and without taking reproductive factors and socioeconomic position (SEP) into account. Relative survival percentages and relative excess risks of dying among premenopausal and postmenopausal patients are computed with and without controlling for the stage at diagnosis and SEP. Premenopausal breast cancer is further examined by migrant generational status. Breast cancer incidence is lower among non-European migrants compared to Belgians. Keeping SEP and known risk factors constant reduces much, but not all of the observed discrepancies. A risk convergence between SG migrants and Belgians for the development of premenopausal breast cancer is observed. Premenopausal breast cancer survival is worse among Moroccan patients due to a higher stage at diagnosis. This disadvantage is concentrated in the FG.

Thyroid cancer incidence near nuclear sites in Belgium: An ecological study at small geographical level.

In Belgium, variations in thyroid cancer incidence were observed around the major nuclear sites. The present ecological study investigates whether there is an excess incidence of thyroid cancer among people living in the vicinity of the four nuclear sites at the smallest Belgian geographical level. Rate ratios were obtained from a Bayesian hierarchical model for areas of varying sizes around the nuclear sites. Focused hypothesis tests and generalized additive models were performed to test the hypothesis of a gradient in thyroid cancer incidence with increasing levels of surrogate exposures. No evidence was found for more incident cases of thyroid cancer near the two nuclear power plants. Regarding the two industrial and research nuclear sites, no evidence for a higher incidence in the vicinity of Mol-Dessel was observed, whereas a slightly nonsignificant higher incidence was found in the close vicinity of Fleurus. In addition, significant gradients for thyroid cancer incidence were observed with the different types of surrogate exposure considered in the 20 km area around the site of Fleurus (decreasing distance, increasing wind direction frequency and increasing exposure to estimated hypothetical radioactive discharges of iodine-131). In the investigation at the smallest Belgian geographical level, variations in thyroid cancer incidence were found around the Belgian nuclear sites. Significant exposure-response relationships were also observed for the site of Fleurus. Further investigations into these findings could be useful to allow inferring causal relationships on the origin of variations in incidence and to provide information at the individual level.

Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations.

OBJECTIVE: Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation. DESIGN: Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed. Age-standardised resection rates for overall and stage I-II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models. RESULTS: A total of 153 698 records were analysed. In population-based registries in 2012-2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I-II tumours, with great international variations. During 2003-2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I-II tumours: 0.05-0.18 and 0.01-0.06 across countries) and increasing age (ORs for patients 70-79 and ≥80 versus those <60 years: 0.37-0.63 and 0.03-0.16 across countries). Patients with advanced-stage tumours (stage III-IV: 63.8%-81.2%) and at older ages (≥70 years: 52.6%-59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application. CONCLUSION: Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.

Development and validation of a prognostic model to predict the prognosis of patients who underwent chemotherapy and resection of pancreatic adenocarcinoma: a large international population-based cohort study.

BACKGROUND: Pancreatic cancer (PaC) remains extremely lethal worldwide even after resection. PaC resection rates are low, making prognostic studies in resected PaC difficult. This large international population-based study aimed at exploring factors associated with survival in patients with resected TNM stage I-II PaC receiving chemotherapy and at developing and internationally validating a survival-predicting model. METHODS: Data of stage I-II PaC patients resected and receiving chemotherapy in 2003-2014 were obtained from the national cancer registries of Belgium, the Netherlands, Slovenia, and Norway, and the US Surveillance, Epidemiology, and End Results (SEER)-18 Program. Multivariable Cox proportional hazards models were constructed to investigate the associations of patient and tumor characteristics with overall survival, and analysis was performed in each country respectively without pooling. Prognostic factors remaining after backward selection in SEER-18 were used to build a nomogram, which was subjected to bootstrap internal validation and external validation using the European datasets. RESULTS: A total of 11,837 resected PaC patients were analyzed, with median survival time of 18-23 months and 3-year survival rates of 21-31%. In the main analysis, patient age, tumor T stage, N stage, and differentiation were associated with survival across most countries, with country-specific association patterns and strengths. However, tumor location was mostly not significantly associated with survival. Resection margin, hospital type, tumor size, positive and harvested lymph node number, lymph node ratio, and comorbidity number were associated with survival in certain countries where the information was available. A median survival time- and 1-, 2-, 3-, and 5-year survival probability-predictive nomogram incorporating the backward-selected variables in the main analysis was established. It fits each European national cohort similarly well. Calibration curves showed very good agreement between nomogram-prediction and actual observation. The concordance index of the nomogram (0.60) was significantly higher than that of the T and N stage-based model (0.56) for predicting survival. CONCLUSIONS: In these large international population-based cohorts, patients with resected PaC receiving chemotherapy have distinct characteristics independently associated with survival, with country-specific patterns and strengths. A robust benchmark population-based survival-predicting model is established and internationally validated. Like previous models predicting survival in resected PaC, our nomogram performs modestly.

Statin use after diagnosis is associated with an increased survival in esophageal cancer patients: a Belgian population-based study.

PURPOSE: Preclinical studies have shown that statins reduce proliferation in esophageal cancer. Three recent observational studies have shown encouraging results but suffered from limitations. This work aimed to assess at the Belgian population level whether statin usage was associated with a decreased mortality in esophageal cancer patients. METHODS: We conducted an observational, population-based study by linking data of the Belgian Cancer Registry (BCR) with medical claims data coming from health insurance companies and mortality records collected by regional governments for patients diagnosed with esophageal cancer between 2004 and 2014. Using time-dependent Cox regression models, hazard ratios (HRs) and 95% confidence intervals (CI) for overall and cancer-specific mortality were calculated. RESULTS: Of 6,238 patients with stage I-III esophageal cancer, post-diagnostic use of statins was found in 1,628 (26%) patients. Statins use after diagnosis was associated with a reduction in overall mortality (adjusted HR = 0.84, 95% CI [0.77; 0.92]) and cancer-specific mortality (adjusted HR = 0.87, 95% CI [0.78; 0.97]). Similar association were also seen for pre-diagnostic statin use in overall (adjusted HR = 0.83, 95% CI [0.76-0.91]) and cancer-specific analysis (adjusted HR = 0.86, 95% CI [0.77-0.96]). CONCLUSIONS: In this large cohort of Belgian patients with esophageal cancer, statins use after diagnosis was associated with a decreased mortality.

Nonsurgical therapies for resected and unresected pancreatic cancer in Europe and USA in 2003-2014: a large international population-based study.

The role of chemotherapy in the treatment of pancreatic cancer (PaC) has been well-established, while radiation plays ambiguous roles. This international large-scale population-based study aimed to investigate the real-world application of chemotherapy and radiotherapy for resected and unresected PaC in Europe and USA. Population-based data from multiple European national cancer registries and the US Surveillance, Epidemiology and End Results (SEER)-18 database during 2003-2014 were analyzed. Temporal trends and geographical variations in the application rates of chemotherapy and radiotherapy were quantified using age standardization. Associations of treatment with demographic and clinical characteristics were assessed using multivariable logistic regression. A total of 141,533 PaC patients were analyzed. From 2003-2005 to 2012-2014, chemotherapy administration rates increased in most countries and more strongly among resected patients, while radiation rates were generally low with a slight decline or no obvious trend. In 2012-2014, 12.5% (Estonia) to 61.7% (Belgium) of resected and 17.1% (Slovenia) to 56.9% (Belgium) of unresected patients received chemotherapy. Radiation was administered in 2.6% (Netherlands) to 32.6% (USA) of resected and 1.0% (USA) to 6.0% (Belgium) of unresected patients. Strong temporal and geographical variations were observed. Patterns and strengths of associations of treatment administration with various demographic and clinical factors differed substantially between resected and unresected cancers and varied greatly across countries. Conclusively, administration of chemotherapy but not radiotherapy for PaC increased during the last decade in Europe and USA. Treatment rates were low and the uptake strongly varied across countries, highlighting the need for standardization in PaC treatment to improve patient care.

Stratified survival of resected and overall pancreatic cancer patients in Europe and the USA in the early twenty-first century: a large, international population-based study.

BACKGROUND: The prognosis of pancreatic cancer (PaC) strongly varies across different stages and age groups, which has unfortunately not been well recorded in the literature. This international population-based study aimed to provide tumor-node-metastasis (TNM) stage- and age-specific survival estimates and trends in resected and overall (resected and unresected) PaC in the early twenty-first century. METHODS: Using data from the US Surveillance, Epidemiology, and End Results-18 Program and the national cancer registries of the Netherlands, Belgium, Norway, and Slovenia, short-term and long-term overall survival results stratified by TNM stage and age in resected and overall primary PaC, irrespective of being microscopically confirmed or not, in 2003-2014 were computed using the Kaplan-Meier method. The temporal survival trends over three predefined periods (2003-2005, 2006-2008, and 2009-2011) were further examined using the log-rank test. RESULTS: In total, data for 125,183 patients were analyzed. Overall, age-stratified 3-year survival was 20-34% (< 60 years), 14-25% (60-69 years), and 9-13% (≥ 70 years) in stages I-II PaC; and 2-5% (< 60 years), 1-2% (60-69 years), and < 1-1% (≥ 70 years) in stages III-IV cancer. Patients who underwent operation had higher 3-year survival in each stage and age group (stages I-II: 23-39% (< 60 years), 16-31% (60-69 years), and 17-30% (≥ 70 years); stages III-IV: 5-19% (< 70 years) and 2-14% (≥ 70 years)). Perioperative survival also decreased with advancing stage and older age (stages I-II: 98-100% (< 60 years), 97-99% (60-69 years), and 94-99% (≥ 70 years); stages III-IV: 94-99% (< 70 years) and 81-96% (≥ 70 years)). Between 2003 and 2005 and 2009-2011, for overall PaC, both short-term and long-term survival improvements were observed in all countries except Belgium; for resected disease, short-term improvements were present only in the USA and Slovenia, but long-term improvements were observed in all countries except Slovenia, with stage-specific variations. CONCLUSIONS: Our large international study provides TNM stage- and age-specific population-based survival in overall and resected PaC that will facilitate clinical counseling. While the survival expectations for patients with resected PaC are substantially higher than the widely available and known dismal survival predictions for overall patients, conclusions on the benefits of resection cannot be made from this observational study. Patients with advanced-stage disease and/or older age should undergo careful risk assessment before treatment. Limited but inspiring improvement in survival is observed.

Propranolol and survival from breast cancer: a pooled analysis of European breast cancer cohorts.

BACKGROUND: Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all-cause mortality in eight European cohorts. METHODS: Incident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network. Propranolol and non-selective beta-blocker use was ascertained for each patient. Breast cancer-specific and all-cause mortality were available for five and eight cohorts, respectively. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality by propranolol and non-selective beta-blocker use. HRs were pooled across cohorts using meta-analysis techniques. Dose-response analyses by number of prescriptions were also performed. Analyses were repeated investigating propranolol use before cancer diagnosis. RESULTS: The combined study population included 55,252 and 133,251 breast cancer patients in the analysis of breast cancer-specific and all-cause mortality respectively. Overall, there was no association between propranolol use after diagnosis of breast cancer and breast cancer-specific or all-cause mortality (fully adjusted HR = 0.94, 95% CI, 0.77, 1.16 and HR = 1.09, 95% CI, 0.93, 1.28, respectively). There was little evidence of a dose-response relationship. There was also no association between propranolol use before breast cancer diagnosis and breast cancer-specific or all-cause mortality (fully adjusted HR = 1.03, 95% CI, 0.86, 1.22 and HR = 1.02, 95% CI, 0.94, 1.10, respectively). Similar null associations were observed for non-selective beta-blockers. CONCLUSIONS: In this large pooled analysis of breast cancer patients, use of propranolol or non-selective beta-blockers was not associated with improved survival.

The Impact of a Six-Year Existing Screening Programme Using the Faecal Immunochemical Test in Flanders (Belgium) on Colorectal Cancer Incidence, Mortality and Survival: A Population-Based Study.

The faecal immunochemical test (FIT) has been increasingly used for organised colorectal cancer (CRC) screening. We assessed the impact of a six-year existing FIT screening programme in Flanders (Belgium) on CRC incidence, mortality and survival. The Flemish CRC screening programme started in 2013, targeting individuals aged 50-74 years. Joinpoint regression was used to investigate trends of age-standardised CRC incidence and mortality among individuals aged 50-79 years (2004-2019). Their 5-year relative survival was calculated using the Ederer II method. We found that FIT screening significantly reduced CRC incidence, especially that of advanced-stage CRCs (69.8/100,000 in 2012 vs. 51.1/100,000 in 2019), with a greater impact in men. Mortality started to decline in men two years after organised screening implementation (annual reduction of 9.3% after 2015 vs. 2.2% before 2015). The 5-year relative survival was significantly higher in screen-detected (93.8%) and lower in FIT non-participant CRCs (61.9%) vs. FIT interval cancers and CRCs in never-invited cases (67.6% and 66.7%, respectively). Organised FIT screening in Flanders clearly reduced CRC incidence (especially advanced-stage) and mortality (in men, but not yet in women). Survival is significantly better in screen-detected cases vs. CRCs in unscreened people. Our findings support the implementation of FIT organised screening and the continued effort to increase uptake.

The effect of the Flemish breast cancer screening program on breast cancer-specific mortality: A case-referent study.

BACKGROUND: Breast cancer screening programs were introduced in many countries worldwide following randomized controlled trials in the 1980s showing a reduction in breast cancer-specific mortality. However, their effectiveness remains debated and estimates vary. A breast cancer screening program was introduced in 2001 in Flanders, Belgium where high levels of opportunistic screening practices are observed. The effectiveness of this program was estimated by measuring its effect on breast cancer-specific mortality. METHODS: We performed a case-referent study to investigate the effect of participation in the Flemish population-based mammography screening program (PMSP) on breast cancer-specific mortality from 2005 to 2017. A multiple logistic regression model assessed the association between breast cancer-specific death and screening program participation status in the four years prior to (pseudo)diagnosis (yes/no), with adjustment for potential confounders (individual socio-economic position and calendar year of diagnosis) and stratified for age. In addition, we performed different sensitivity analyses. RESULTS: We identified 1571 cases and randomly selected 6284 referents. After adjustment, women who participated in PMSP had a 51 % lower risk of breast cancer-specific mortality compared to those who did not (adjusted odds ratio [aOR] =0.49, 95 % CI: 0.44-0.55). Sensitivity analyses did not markedly change the estimated associations. Correction for self-selection bias reduced the effect size, but the estimate remained significant. CONCLUSION: Our results indicate that in a context of high opportunistic screening rates, participation in breast cancer screening program substantially reduces breast cancer-specific mortality. For policy, these results should be balanced against the potential harms of screening, including overdiagnosis and overtreatment.

Machine Learning Algorithm to Estimate Distant Breast Cancer Recurrence at the Population Level with Administrative Data.

Purpose: High-quality population-based cancer recurrence data are scarcely available, mainly due to complexity and cost of registration. For the first time in Belgium, we developed a tool to estimate distant recurrence after a breast cancer diagnosis at the population level, based on real-world cancer registration and administrative data. Methods: Data on distant cancer recurrence (including progression) from patients diagnosed with breast cancer between 2009-2014 were collected from medical files at 9 Belgian centers to train, test and externally validate an algorithm (i.e., gold standard). Distant recurrence was defined as the occurrence of distant metastases between 120 days and within 10 years after the primary diagnosis, with follow-up until December 31, 2018. Data from the gold standard were linked to population-based data from the Belgian Cancer Registry (BCR) and administrative data sources. Potential features to detect recurrences in administrative data were defined based on expert opinion from breast oncologists, and subsequently selected using bootstrap aggregation. Based on the selected features, classification and regression tree (CART) analysis was performed to construct an algorithm for classifying patients as having a distant recurrence or not. Results: A total of 2507 patients were included of whom 216 had a distant recurrence in the clinical data set. The performance of the algorithm showed sensitivity of 79.5% (95% CI 68.8-87.8%), positive predictive value (PPV) of 79.5% (95% CI 68.8-87.8%), and accuracy of 96.7% (95% CI 95.4-97.7%). The external validation resulted in a sensitivity of 84.1% (95% CI 74.4-91.3%), PPV of 84.1% (95% CI 74.4-91.3%), and an accuracy of 96.8% (95% CI 95.4-97.9%). Conclusion: Our algorithm detected distant breast cancer recurrences with an overall good accuracy of 96.8% for patients with breast cancer, as observed in the first multi-centric external validation exercise.

The Upgrade Risk of B3 Lesions to (Pre)Invasive Breast Cancer After Diagnosis on Core Needle or Vacuum Assisted Biopsy. A Belgian National Cohort Study.

INTRODUCTION: Flat epithelial atypia (FEA), lobular neoplasia (LN), papillary lesions (PL), radial scar (RS) and atypical ductal hyperplasia (ADH) are lesions of uncertain malignant potential and classified as B3 lesions by the European guidelines for quality assurance in breast cancer screening and diagnosis. Current management is usually wide local excision (WE), surveillance may be sufficient for some. We investigated the upgrade rate of B3 lesions to breast malignancy in a subsequent resection specimen after diagnosis on core needle-or vacuum assisted biopsy (CNB-VAB) in a national population-based series. METHODS: Using data from the Belgian Cancer Registry (BCR) between January 1, 2013 and December 31, 2016, inclusion criteria were new diagnosis of a B3 lesion on CNB or VAB with subsequent histological assessment on a wider excision specimen. Histological agreement between first- and follow-up investigation was analyzed to determine the upgrade risk to ductal adenocarcinoma in situ (DCIS) or invasive breast cancer (IC) according to the type of B3 lesion. RESULTS: Of 1855 diagnosed B3 lesions, 812 were included in this study: 551 after CNB-261 after VAB. After diagnosis on CNB and VAB, we found 19.0% and 14.9% upgrade to malignancy respectively. Upgrade risks after CNB and VAB were: FEA 39.5% and 17.6%; LN 40.5% and 4.3%; PL 10.4% and 12.5%; RS 25.7%and 0.0%; ADH 29.5% and 20.0%. CONCLUSION: Based on the observed upgrade rate we propose three recommendations: first, resection of ADH, and FEA with WE; second, resection of RS and classical LN with therapeutic VAB and further surveillance when radio-pathological correlation is concordant; third, surveillance of PL.

Linking clinical and population-based data in older patients with cancer in Belgium: Feasibility and clinical outcomes.

INTRODUCTION: Geriatric screening and geriatric assessment (GS/GA) have proven their benefits in the care for older patients with cancer. However, less is known about the predictive value of GS/GA for outcomes. To research this, clinical data on GS/GA can be enriched with population-based data. In this article we describe the methods and feasibility of data linkage, and first clinical outcomes (GS/GA results and overall survival). MATERIALS AND METHODS: A large cohort study consisting of patients aged ≥70 years with a new cancer diagnosis was established using linked data from clinical and population-based databases. Clinical data were derived from a previous prospective study where older patients with cancer were screened with G8, followed by GA in case of an abnormal result (GS/GA study; 2009-2015). These data were linked to cancer registration data from the Belgian Cancer Registry (BCR), reimbursement data of the health insurance companies (InterMutualistic Agency, IMA), and hospital discharge data (Technical Cell, TCT). Cox regression analyses were conducted to evaluate the prognostic value of the G8 geriatric screening tool. RESULTS: Of the 8067 eligible patients with a new cancer diagnosis, linkage of data from the GS/GA study and data from the BCR was successful for 93.7%, resulting in a cohort of 7556 patients available for the current analysis. Further linkage with the IMA and TCT database resulted in a cohort of 7314 patients (96.8%). Based on G8 geriatric screening, 67.9% of the patients had a geriatric risk profile. Malnutrition and functional dependence were the most common GA-identified risk factors. An abnormal baseline G8 score (≤14/17) was associated with lower overall survival (adjusted HR [aHR] = 1.62 [1.50-1.75], p < 0.001). DISCUSSION: Linking clinical and population-based databases for older patients with cancer has shown to be feasible. The GS/GA results at cancer diagnosis demonstrate the vulnerability of this population and the G8 score showed prognostic value for overall survival. The established cohort of almost 8000 patients with long-term follow-up will serve as a basis in the future for detailed analyses on long-term outcomes beyond survival.

End-of-Life Care in the Last Three Months before Death in Older Patients with Cancer in Belgium: A Large Retrospective Cohort Study Using Data Linkage.

This study aims to describe end-of-life (EOL) care in older patients with cancer and investigate the association between geriatric assessment (GA) results and specialized palliative care (SPC) use. Older patients with a new cancer diagnosis (2009-2015) originally included in a previous multicentric study were selected if they died before the end of follow-up (2019). At the time of cancer diagnosis, patients underwent geriatric screening with Geriatric 8 (G8) followed by GA in case of a G8 score ≤14/17. These data were linked to the cancer registry and healthcare reimbursement data for follow-up. EOL care was assessed in the last three months before death, and associations were analyzed using logistic regression. A total of 3546 deceased older patients with cancer with a median age of 79 years at diagnosis were included. Breast, colon, and lung cancer were the most common diagnoses. In the last three months of life, 76.3% were hospitalized, 49.1% had an emergency department visit, and 43.5% received SPC. In total, 55.0% died in the hospital (38.5% in a non-palliative care unit and 16.4% in a palliative care unit). In multivariable analyses, functional and cognitive impairment at cancer diagnosis was associated with less SPC. Further research on optimizing EOL healthcare utilization and broadening access to SPC is needed.

Colorectal cancer incidence and survival inequalities among labour immigrants in Belgium during 2004-2013.

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality. We aim to map out differences in CRC incidence and survival between first-generation traditional labour immigrants of Italian, Turkish and Moroccan descent and native Belgians; and assess the contribution of socioeconomic position (SEP) to these differences. Individually-linked data of the 2001 Belgian Census, the Crossroads Bank for Social Security and the Belgian Cancer Registry are used. Age-standardized incidence rates and incidence rate ratios are calculated by country of origin, with and without adjusting for SEP. For CRC patients, 5-year relative survival rates and the relative excess risk for dying within five years after diagnosis are calculated by migrant origin. Lower CRC incidence was observed among immigrants compared to native Belgians, in particular among non-Western immigrants, which could not be explained by SEP. Survival inequalities were less clear, yet, after adjusting for age and stage at diagnosis and educational attainment, we observed a survival advantage among Turkish and Italian immigrant men. Health gains can be made for the native population by adapting lifestyle. The later stage at diagnosis for immigrants is of concern. Barriers regarding screening as perceived by the vulnerable groups should be identified.