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ObjectivesAdvanced ovarian cancer has a poor prognosis, with a 5 year survival probability of MethodsPopulation based data from the Belgian Cancer Registry were coupled with administrative reimbursement data from the compulsory health insurance organizations and the national database where date of death is registered, based on the patient's unique national number. Patients with epithelial ovarian cancer stage IV diagnosed in 2004–17 were included. The proportion of patients who underwent debulking surgery and received bevacizumab was calculated per incidence year. Survival was compared for the three incidence periods (2004–08, 2009–13, 2014–17) and before and after the introduction of bevacizumab.Results2034 patients with stage IV epitheial ovarian cancer were included. From 2012 onwards, uptake of bevacizumab increased, with 50% of patients with stage IV ovarian cancer diagnosed in 2017 receiving bevacizumab. The proportion of stage IV patients who underwent debulking surgery also increased over time, from 21.1% in 2004–08 to 50.4% and 45.4% in 2009–13 and 2014–17, respectively. The 3 year observed survival probability fluctuated between 27% and 42% without a trend over time. The increase in debulking surgery was associated with improved survival (hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.79 to 0.98) but the introduction of bevacizumab was not (HR 0.94, 95% CI 0.85 to 1.03). For patients diagnosed in 2004, the mean cost per patient treated with oncological drugs was about €12 500, which doubled to about €25 000 for patients diagnosed in 2014 or later.ConclusionsDespite a rise in the use of debulking surgery and the introduction of bevacizumab into clinical practice, no improvement in 3 year survival probability was observed for patients with advanced ovarian cancer in Belgium.

Background: The effects of recently implemented colorectal cancer screening programmes in Europe on colorectal cancer mortality will take several years to be fully known. We aimed to analyse the characteristics and parameters of screening programmes, proportions of colorectal cancers detected through screening, and stage distribution in screen-detected and non-screen-detected colorectal cancers to provide a timely assessment of the potential effects of screening programmes in several European countries. Methods: We conducted this population-based study in nine European countries for which data on mode of detection were available (Belgium, Denmark, England, France, Italy, Ireland, the Netherlands, Slovenia, and Spain). Data from 16 population-based cancer registries were included. Patients were included if they were diagnosed with colorectal cancer from the year that organised colorectal cancer screening programmes were implemented in each country until the latest year with available data at the time of analysis, and if their age at diagnosis fell within the age groups targeted by the programmes. Data collected included sex, age at diagnosis, date of diagnosis, topography, morphology, clinical and pathological TNM information based on the edition in place at time of diagnosis, and mode of detection (ie, screen detected or non-screen detected). If stage information was not available, patients were not included in stage-specific analyses. The primary outcome was proportion and stage distribution of screen-detected versus non-screen detected colorectal cancers. Findings: 228 667 colorectal cancer cases were included in the analyses. Proportions of screen-detected cancers varied widely across countries and regions. The highest proportions (40–60%) were found in Slovenia and the Basque Country in Spain, where FIT-based programmes were fully rolled out, and participation rates were higher than 50%. A similar proportion of screen-detected cancers was also found for the Netherlands in 2015, where participation was over 70%, even though the programme had not yet been fully rolled out to all age groups. In most other countries and regions, proportions of screen-detected cancers were below 30%. Compared with non-screen-detected cancers, screen-detected cancers were much more often found in the distal colon (range 34·5–51·1% screen detected vs 26·4–35·7% non-screen detected) and less often in the proximal colon (19·5–29·9% screen detected vs 24·9–32·8% non-screen detected) p≤0·02 for each country, more often at stage I (35·7–52·7% screen detected vs 13·2–24·9% non-screen detected), and less often at stage IV (5·8–12·5% screen detected vs 22·5–31·9% non-screen detected) p

Background Increased awareness of gastric cancer risk, easy access to upper endoscopy, and high definition endoscopes with virtual chromoendoscopy may have led to the increase in early diagnosis of gastric cancer observed in recent years in Europe, which may be associated with improved survival. Currently, no data exist on the impact of early diagnosis on survival at a populational level in Europe. Our aim was to assess gastric cancer incidence, early diagnosis, and survival in northwestern and southern European countries with a low-to-moderate incidence of gastric cancer. Methods Data on 41 138 gastric cancers diagnosed in 2007–2016 were retrieved from national cancer registries of Belgium, the Netherlands, and northern Portugal. Age-standardized incidence and mortality rates were assessed and expressed per 100 000 person-years. Early diagnosis was defined as T1 tumors. Net survival estimates for 2007–2011 vs. 2012–2016 were compared. Results Age-standardized incidence and mortality decreased over time in Belgium, northern Portugal, and the Netherlands (relative incidence decrease 8.6 %, 4.5 %, and 46.8 %, respectively; relative mortality decrease 22.0 %, 30.9 %, and 50.0 %, respectively). Early gastric cancer diagnosis increased over time for all countries. Net 1-year survival improved significantly between the two time periods in all countries, and at 5 years in Belgium and Portugal. Conclusions This is the first study comparing trends (2007–2016) in gastric cancer incidence and mortality in some European countries. We found an increasing proportion of T1 gastric cancers and a decrease in age-standardized mortality over time, supporting the use of secondary prevention strategies.

Background Patients with left-sided colorectal cancer (L-CRC) are known to have a significantly better prognosis than those with right-sided CRC (R-CRC). It has been hypothesized that RAS, BRAF mutations, or deficient mismatch repair status (MMR) might be responsible for the prognostic effect of primary tumor location (PTL). This study aims to evaluate the prognostic effect of PTL in the Belgian population and to determine the role of biomarkers (MMR, BRAF, and RAS status) in this effect. Patients and Methods We performed a retrospective analysis of Belgian Cancer Registry data. First, we studied the prognostic effect of PTL on 5-year relative survival of 91 946 patients diagnosed with CRC (all stages) from 2004-2015. Second, we investigated the interaction between biomarkers and the prognostic effect of PTL in 1818 patients diagnosed with stage IV CRC in 2014-2015. Results L-CRC was associated with a significantly better 5-year relative survival compared to R-CRC in all stages and ages combined (68.4%, 95% CI, 67.7-69.1% vs 65.6%, 95% CI, 64.7-66.4%). Also, when stratified by age, sex, and stage, the prognosis of L-CRC was better compared to R-CRC in most subgroups. Only in stage II and certain subgroups of elderly patients, the opposite was observed. Furthermore, our data showed that none of the biomarkers had a significant interaction with the effect of PTL on survival. Conclusion This population-based study confirms that L-CRC is associated with significantly better relative survival compared to R-CRC, in all stages and ages combined. Furthermore, in stage IV L-CRC is associated with a longer survival than R-CRC, regardless of MMR, RAS, and BRAF status.

The objective is to investigate tumour prognostic factors versus breast density in screen-detected cancers and interval cancers. The results may highlight the need for more personalised screening protocols based on breast density in organized screening programmes.A retrospective study was performed of tumour characteristics of screen-detected cancers (n=468) and interval cancers (n=515) of 983 women who participated in the Flemish Breast Cancer Screening Programme in 2009-2010. Breast density was obtained from the screening programme data. Information on nodal invasion and histological grading was taken from the Belgian Cancer Registry. Tumour size and proliferation and receptor expression status were retrieved from pathology reports. The differences in tumour characteristics between screen-detected and interval cancers as well as the variation in these variables with breast density in both groups were studied by logistic regression.A comparison of tumour characteristics between screen-detected cancers and interval cancers systematically showed features of more aggressive tumours in interval cancers: larger tumour size, nodal invasion, grade 3 tumours, and hormone receptor negative phenotype (p0.05). The analysis of tumour characteristics versus breast density in screen-detected cancers showed higher numbers of aggressive grade 3 tumours in low-density breasts and of the luminal A subtype with good prognosis in high-density breasts (p0.05). This analysis for interval cancers highlights a high proportion of the difficult-to-treat triple-negative subtype in low-density breasts compared with high-density breasts. In conclusion, the study data support arguments against changes in breast cancer screening programmes with prolongation of screening intervals in low-density breasts.

The PHIRI Federated Research Infrastructure (FRI) is supported by a containerized reproducible solution for data analysis (i.e. use cases) to be deployed on-premises by each participant partner (a.k.a PHIRI-app) to generate a set of local results (outputs) to be further analysed and interpreted generating relevant insight for health policy. This use case will seek to elicit whether there has been an increase in time to treatment in women diagnosed with breast cancer in the month previous to the lockdown measures, as compared with the woman diagnosed with breast cancer before that period and whether the distribution of this delay could be influenced by the healthcare reorganisation measures due to the COVID pandemic. Health Systems across Europe had to reorganise healthcare services reallocating resources towards providing complex assistance to COVID-19 patients. COVID-19 surge of cases during the different epidemic waves requiring intensive care has led countries to cancel or postpone non-urgent care (i.e. elective surgery). The present outputs correspond to the analyses of four nodes that completed the deployment of the analytical pipeline in their premises (Belgium (BE), Wales (UK), Marche (IT), and Aragon (ES)). Others are still ongoing; so, Latvia is reviewing some errors in their dataset; in turn, Croatia, Estonia and Slovenia showed availability for the deployment of the use case. The outputs from the local analyses in those countries include: - Interactive joint report of the trends in diagnosis and delayed treatment for breast cancer (HTLM) - Compilation of the local reports for each country (ZIP file containing HTML documents) - Compilation of the Data Quality Analysis reports for the original data in each country (ZIP file containing HTML documents), Note: All HTML documents are auto-contained and can be downloaded and opened using a regular web browser. Caution: The results of the current outputs reporting observations from the local analyses should be interpreted within the context of the purposes of Use Case B and the PHIRI project., {"references":["Enrique Bernal-Delgado, & Marc Van den Bulcke. (2022). PHIRI - WP6 - Use Case B Common Data Model (2.0.0). Zenodo. https://doi.org/10.5281/zenodo.6357891","Francisco Estupiñán-Romero, Javier González-Galindo, Natalia Martínez-Lizaga, & Enrique Bernal-Delgado. (2022). PHIRI - WP6 - Use Case B scripts for local analyses (R Markdown) (4.0.0). Zenodo. https://doi.org/10.5281/zenodo.6359893","Javier González-Galindo, Francisco Estupiñán-Romero, David Chichell-Ruíz, Juan González-García, Carlos Tellería-Orriols, & Enrique Bernal-Delgado. (2022). PHIRI APP - WP7 - PHIRI Federated Research Infrastructure (FRI) - D7.1 Small-scale prototype of PHIRI federated infrastructure (2.2.2). Zenodo. https://doi.org/10.5281/zenodo.6483177"]}

Introduction: Flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL), radial scars (RS) and atypical ductal hyperplasia (ADH) are lesions of uncertain malignant potential in the breast, which are described as B3 lesions in the B classification system of the European Working Group for Breast Cancer Screening Pathology. Current standard for management of B3 lesions on core needle biopsy (CNB) or vacuum assisted biopsy (VAB), is wide local excision (WE). However, recent consensus-based guidelines no longer recommend WE for all such lesions, but propose surveillance following CNB or VAB to be sufficient in some cases. In the absence of a Belgian guideline on the treatment of B3 lesions, this study was conducted to identify which B3 lesions have the lowest likelihood for breast malignancy and could therefore be spared from WE. Methods: Using data from the Belgian Cancer Registry (BCR), all patients with a new diagnosis of a B3 lesion on CNB or VAB between 2013-2016 and who had a histological follow up with VAB or WE after CNB or WE after VAB were included. Histological follow-up was retrieved from BCR and limited to 12 months following diagnosis. Histology was compared between the first- and follow-up investigation to determine the upgrade risk to ductal carcinoma in situ (DCIS) or invasive breast cancer (IC) according to the type of B3 lesion. Patients with synchronous (pre-) invasive lesions were excluded. Results: Between 2013-2016 there were 812 B3 lesions available for upgrade analysis after initial diagnosis. After CNB 551 lesions had WE or VAB as follow up and after VAB 261 lesions had WE. After primary diagnosis on CNB, the total upgrade risk was 19,0%. There was histological agreement in 57,9% and no B3 lesion or upgrade was reported in 21,8%. Per B3 lesion subtype the upgrade risk to DCIS - IC after diagnosis on CNB was: ADH 17,1%-12,4%, FEA 21,1% - 18,4%, LN 18,9% -21,6%, RS 14,3% - 11,4%, and PL 7,2% - 3,2%. After initial diagnosis on VAB the total upgrade risk was 14,9%. There was histological agreement in 52,9% and no B3 lesion or upgrade was found in 31,4%. Per B3 subtype the upgrade risk to DCIS - IC after diagnosis on VAB was: ADH 17,3%- 2,7%, FEA 11,7%- 5,9%, LN 0,0% - 4,3%, PL 10,4% - 2,1%. We found no upgrade for RS. (Table 1). Conclusions: In a series of B3 lesions with a histological follow-up, we notice that overall upgrade risk is higher for lesions detected on CNB than on VAB: 19,0% vs. 14,9%. The majority of lesions showed histological agreement between initial B3 diagnosis and histological follow-up: 57,9% after CNB and 53,5% after VAB. More investigation is needed to make a proper risk assessment as to which B3 lesions can be followed with regular surveillance. Also, further prospective research is needed to get a better understanding of associated risk factors for upgrade, upgrade risk and lifetime risk of developing breast cancer after diagnosis of a B3 lesion. Table 1: Upgrade risk per B3 subtype after diagnosis on CNB or VABSubtypeNumberCNB followed by VAB or WEDCISICTotal Upgrade riskCNBNumberVAB followed by WEDCISICUpgrade riskVAB followed by WEADH10517,1%12,4%29,5%11017,3%2,7%20,0%FEA3821,1%18,4%39,5%5111,7%5,9%17,6%LN3718,9%21,6%40,5%460%4,3%4,3%PL3367,2%3,2%10,4%4810,4%2,1%12,5%RS3514,3%11,4%25,7%60%0%0%Total551261Upgrade105/55119,0%39/26114,9%B3 lesion319/55157,9%138/26152,9%No B3 lesion120/55121,8%82/26131,4%Result not available7/5511,3%2/2610,8% Citation Format: Nynke Willers, Patrick Neven, Giuseppe Floris, Cecile Colpaert, Eva Oldenburger, Sileny Han, Chantal Van Ongeval, Ann Smeets, Francois Duhoux, Hans Wildiers, Petra Denolf, Isabel De Brabander, Nancy Van Damme, Harlinde De Schutter. The upgrade risk to (pre-)invasive breast cancer for B3 lesions diagnosed on core needle or vacuum assisted biopsy. A Belgian retrospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-52.

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.

The incidence of neuroendocrine neoplasms (NEN) in the rectum is rising since the introduction of colonoscopy screening programs. Guidelines, such as the European NeuroEndocrine Tumor Society (ENETS) algorithm, are mainly based on expert opinion. The goal of this nationwide study is to gain a better insight into the evolution in pathology reporting and adherence to the ENETS guidelines in Belgium. In Belgium, all NENs have to be reported to the Belgian Cancer Registry. We thoroughly reviewed all available pathology reports, coded as rectal NEN between 2004 and 2015, and reclassified according to World Health Organisation (WHO) classification 2019. To evaluate the adherence to the ENETS guidelines, population-based cancer registry data were linked with the medical procedures of the Belgian Health Insurance database. A total of 670 rectal NEN were retained and 16% of the cases needed reclassification. Annual incidence between 2004 and 2015 tripled from 0,20 to 0,61 per 100.000 inhabitants. Reporting of Ki67 proliferation index ameliorated most, while reporting of tumor size, lymphovascular and perineural invasion remained disappointing. Endoscopic ultrasound was performed in only 36.6% of the cases, while the mostly recommended mode of treatment (endoscopic/surgical/no resection) was followed in the majority of the cases. Incidence of rectal NEN in Belgium increased throughout the years and quality of pathology reporting improved especially after the WHO classification update in 2010. The growing awareness and knowledge among clinicians and pathologists in the community counters the need for centralization.

As part of its core business of gathering population-based information on new cancer diagnoses, the Belgian Cancer Registry receives free-text pathology reports, describing results of (pre-)malignant specimens. These reports are provided by 82 laboratories and written in 2 national languages, Dutch or French. For breast cancer, the reports characterize the status of estrogen receptor, progesterone receptor, and Erb-b2 receptor tyrosine kinase 2. These biomarkers are related with tumor growth and prognosis and are essential to define therapeutic management. The availability of population-scale information about their status in breast cancer patients can therefore be considered crucial to enrich real-world scientific studies and to guide public health policies regarding personalized medicine. The main objective of this study is to expand the data available at the Belgian Cancer Registry by automatically extracting the status of these biomarkers from the pathology reports. Various types of numeric features are computed from over 1,300 manually annotated reports linked to breast tumors diagnosed in 2014. A range of popular machine learning classifiers, such as support vector machines, random forests and logistic regressions, are trained on this data and compared using their F1 scores on a separate validation set. On a held-out test set, the best performing classifiers achieve F1 scores ranging from 0.89 to 0.92 for the four classification tasks. The extraction is thus reliable and allows to significantly increase the availability of this valuable information on breast cancer receptor status at a population level.

Background: Most studies investigating the impact of coronavirus infectious disease-19 (COVID-19) on mortality among patients with cancer were performed in a hospital setting, and the evidence is thus based on a selected and frail subset of patients. This study evaluates the excess mortality during the first wave of COVID-19 in a nationwide, prevalent cancer cohort in Belgium. Methods: Mortality was studied among almost 240,000 patients with cancer diagnosed between 2013 and 2018 and alive on January 1, 2020. The observed number of deaths in the months January to June 2020 was compared with the expected number of deaths applying the monthly mortality rates observed in the cancer cohort during the previous years. A comparison using the excess mortality rates from the general population was performed. Results: An excess number of deaths of about 400 was observed in the month of April, coinciding with a peak of COVID-19 diagnoses in Belgium and corresponding to a 33% rise in mortality. A comparable number of excess deaths was estimated if the COVID-19 excess mortality rates from the general Belgian population were applied to the cancer cohort, stratified by age and sex. Conclusions: A considerable excess mortality in the Belgian cancer cohort was observed during the initial peak of COVID-19 in Belgium. The pattern of excess mortality was, however, not markedly different from that observed in the general population. Impact: These results suggest that the susceptibility of prevalent cancer patients to COVID-19–induced mortality during the first wave of the pandemic was comparable with the general population.

Purpose: The primary aim of the study was to assess the association between having a radiotherapy (RT) department on-site at the surgical centre and the performed postoperative treatment strategy for prostate cancer (PCa) patients. According to the current international guidelines, adjuvant radiotherapy (ART) or a regular prostate-specific antigen (PSA)-based follow-up with (early) salvage radiotherapy ((e)SRT) if needed is recommended in case of adverse pathological characteristics. Material and methods: Prospective data on consecutive robot-assisted radical prostatectomy (RARP) patients in Belgium from 2009 to 2016 were identified in the Belgian Robotic-Assisted-Laparoscopic-Prostatectomy (Be-RALP) database. Multivariable regression was used to evaluate patient- and facilityrelated factors associated with postoperative radiation treatment. Results: 2072 patients undergoing a RARP, suffering at least one of the following adverse pathological features, i.e., extracapsular extension (ECE), seminal vesicle invasion (SVI) or positive section margins (PSM), and with registered follow-up until 24months were enrolled. After RARP, ART was applied to 9.1% and (e)SRT to 12.6% of the patients. Multivariable analysis demonstrated that patients were more likely to receive ART or (e)SRT if they were operated in a hospital with a RT department on-site (odds ratio, ART: 1.49 [1.07-2.07]; (e)SRT: 1.55 [1.16-2.06]). Furthermore, the presence of higher tumour category (T-category) and/or PSM on final pathology was associated with a higher chance of getting ART and (e)SRT (p

Nearest Neighbour (NN) propensity score (PS) matching methods are commonly used in pharmacoepidemiology to estimate treatment response using observational data. Unfortunately, there is limited evidence on the optimal approach for accurately estimating binary treatment response and, more so, to estimate its variance. Bootstrapping, although commonly used to accurately estimate variance, is rarely used together with PS matching. In this Monte Carlo simulation-based study, we examined the performance of bootstrapping used in conjunction with PS matching, as opposed to different NN matching techniques, on a simulated dataset exhibiting varying levels of real world complexity. Thus, an experimental design was set up that independently varied the proportion of patients treated, the proportion of outcomes censored and the amount of PS matches used. Simulation results were externally validated on a real observational dataset obtained from the Belgian Cancer Registry. We found all investigated PS methods to be stable and concordant, with k-NN matching to be optimally dealing with the censoring problem, typically present in chronic cancer-related datasets, whilst being the least computationally expensive. In contrast, bootstrapping used in conjunction with PS matching, being the most computationally expensive, only showed superior results in small patient populations with long-term largely unobserved treatment effects. ispartof: SCIENTIFIC REPORTS vol:10 issue:1 ispartof: location:England status: published

Background: A previous investigation of the occurrence of childhood acute leukemia around the Belgian nuclear sites has shown positive associations around one nuclear site (Mol-Dessel). In the following years, the Belgian Cancer Registry has made data available at the smallest administrative unit for which demographic information exists in Belgium, i.e. the statistical sector. This offers the advantage to reduce the potential misclassification due to large geographical scales.Methods: The current study performed for the period 2006-2016 uses Poisson models to investigate (i) the incidence of childhood acute leukemia within 20 km around the four Belgian nuclear sites, (ii) exposure-response relationships between cancer incidence and surrogate exposures from the nuclear sites (distance, wind direction frequency and exposure by hypothetical radioactive discharges taking into account historical meteorological conditions). All analyses are carried out at statistical sector level.Results: Higher incidence rate ratios were found for children

INTRODUCTION AND OBJECTIVE:Different international guideline organisations offer tools to categorise prostate cancer patients into risk groups. These risk groups have great implications on the furt...

Introduction There is a steady rise in Stereotactic Body RadioTherapy (SBRT) utilization in oligometastatic disease (OMD). This may generate important financial consequences for radiotherapy budgets. The National Institute for Health and Disability Insurance of Belgium (NIHDI) initiated a coverage with evidence development (CED) project for innovative radiotherapy, including SBRT, in 2011. A cost calculation and budget estimation for SBRT in the OMD setting was carried out. Materials and methods Predictive growth scenarios for future uptake of SBRT for OMD in Belgium were developed using demographics and CED data. The provider cost of SBRT for OMD in Belgium was calculated using the Time-Driven Activity-Based Costing (TD-ABC) model developed by ESTRO-HERO, alimented with national data on resources, treatments and operational parameters, and compared to the new reimbursement. Combining these, the future financial impact of this novel treatment indication for healthcare providers and payers in Belgium was evaluated. Results The number of 428 OMDs treated with SBRT in Belgium in 2017 is expected to increase between 484 and 2073 courses annually by 2025. A provider cost of €4360 per SBRT was calculated (range: €3488–€5654), whereas the reimbursement covers between €4139 and €4654. Large variations in potential extra provider costs by 2025 ensue from the different scenarios, ranging between €1,765,993 and €9,038,754. Provider costs and reimbursement show good agreement. Conclusion Although the financial impact of SBRT for OMD in Belgium is forecasted to remain acceptable, even in extreme scenarios, further clinical trials and real-life clinical and financial monitoring with prospective data gathering are necessary to refine the data.

Background: Biobanks play a critical role in cancer research by providing high quality biological samples for research. However, the availability of tumor samples in single research institutions is often limited, especially for rare cancers. In order to facilitate the search for samples scattered among different Belgian institutions, a nationwide virtual tumorbank project was launched and is operational since February 2012. The Belgian Virtual Tumorbank (BVT) network encompasses the tumor biobanks from eleven Belgian university hospitals that collect and store residual human tumor samples locally and is coordinated by the Belgian Cancer Registry. Materials and Methods: A web application was developed and consists of two modules. The registration module (BVTr) centralizes the tumor sample data from the local partner biobanks. The catalog module (BVTc) allows researchers to trace the tumor samples in the 11 tumor biobanks. The BVTc contains patient, medical and technical data, but excludes identifying information to ensure privacy of individuals. Automatic and manual controls guarantee high quality data on the samples requested by scientists for research purposes in oncology. A major advantage of the BVT network is that the available data can be linked to the data of the Belgian Cancer Registry for quality control purposes. Results: Currently, more than 92,000 registrations are available in the catalog. Twenty-seven percent of the residual primary tumor samples originate from breast tissue, but also less frequent localisations such as head and neck (4%), male genital organs (1.7%), and urinary tract (1%) are available. In addition to the residual tumor tissue samples, also other available material can be stored and registered by the local biobanks. The most common type is corresponding normal tissue (19%).Other frequently available materials are plasma, blood, serum, DNA, and buffy coat. Even PBMCs, RNA, cytology, and urine are available in some cases. Discussion and Conclusion: The BVT catalog is a valuable source of information for oncology research and the ultimate goal is to promote multidisciplinary cancer research (i.e., pathogenesis, disease prediction, prevention, diagnosis, treatment, and prognosis) for the benefit of all cancer patients.

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., What's new? Potential cancer risk associated with living near nuclear installations has long been a public concern. In Belgium, a previous study found a higher incidence around the two nuclear sites with research and industrial activities, but not around the two nuclear power plants. Exposure misclassification due to the large geographical scale could not be excluded, however. The present study, which uses data available at the smallest Belgian geographical level, confirms the previously‐described incidence patterns around the nuclear power plants and for one of the research and industrial sites. There was a significant exposure‐response relationship for the latter. This finding is valuable for thyroid cancer etiology.

BACKGROUND: Prediction of lymph node invasion (LNI) after radical prostatectomy has been rarely assessed in robotically assisted laparoscopic radical prostatectomy (RALP) series. We aimed to develop and externally validate a pretreatment nomogram for the prediction of LNI following RALP in patients with high- and intermediate-risk prostate cancer. METHODS: 1654 RALP patients were prospectively collected between 2009 and 2016 from academic and community hospitals. We included patients with intermediate- and high-risk prostate cancer who underwent pelvic lymph node dissection (e-PLND). Logistic regression analysis was applied to construct a nomogram to predict LNI. Centers were randomly assigned to the training cohort (80%) and validation cohort (20%). The discriminative accuracies were evaluated by the areas under the curve and by the calibration plot. The net benefit of the nomogram to predict LNI was assessed by decision curve analysis and a cut-off was proposed. RESULTS: In total, 14% of the patients in our cohort had pN1 disease. Applying logistic regression analysis, the following covariates were chosen to develop the nomogram: initial PSA, clinical T stage, biopsy Gleason sum, and proportion of positive biopsy cores. The nomogram showed a median discriminative accuracy of 73% and excellent calibration. The net benefit of the model ranged between 7% and 51% predicted risk of LNI. A cut-off to perform e-PLND was set at 7%. This would permit a 29% of avoidable e-PLND, missing 9.4% of patients with LNI. CONCLUSIONS: We developed and externally validated a nomogram to predict LNI in patients treated with RALP from a prospective, multi-institutional, nationwide series. A risk of LNI > 7% is proposed as cut-off above which e-PLND is recommended. ispartof: UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS vol:38 issue:2 ispartof: location:United States status: published

Background Robot-assisted radical prostatectomy (RALP) in high-risk and locally advanced prostate cancer (PCa) is gaining increasing traction. The optimal use of additional treatments for PCa with seminal vesicle invasion (pT3b) after RALP remains ill explored. Objective To evaluate the management of pT3b PCa after RALP in current clinical practice. Design, setting, and participants As part of the prospective Belgian RALP Consortium project (October 2009–March 2016), 796 patients with pT3b disease were evaluated. Intervention Robot-assisted radical prostatectomy. Outcome measurements and statistical analysis Population and perioperative characteristics were described to assess surgical outcome. Multivariable regression analyses were used to identify independent predictors of lymph node invasion (pN1), positive surgical margins (R+), postoperative morbidity, and additional treatments. Results and limitations In this prospective population-based registry, 85% of patients with clinical high-risk locally advanced PCa received pelvic lymph node dissection (PLND). Early postoperative complications (0–30 d) were observed in 68 patients (8.5%). During oncologic follow-up (median 12 mo), 63% of pN1 patients and 56% of R+ patients received additional therapy. Performing PLND (necessary for assessing pN1 status) was a specific predictor for androgen deprivation therapy only, whereas R+ and younger age were independent predictors for radiotherapy only. Limitations include the nonstandardized policy on additional treatments among hospitals. Conclusions In current practice, RALP is performed with acceptable morbidity for PCa with seminal vesicle invasion and the use of postoperative additional treatments is influenced by different patient, tumor, and surgical variables. Despite the recommendations, 15–21% of patients do not receive adequate pelvic lymph node staging and adjuvant therapy is given in 38% of patients. Full and correct staging of the real disease extent remains important in the management of these patients. Patient summary This study on prostate cancer with seminal vesicle invasion after robot-assisted prostatectomy evaluates the use of additional treatments in current clinical practice. Additional treatments for advanced prostate cancer should be patient-adjusted according to the disease extent.

This study evaluates the surgical stress response following laparoscopic and open liver resection for colorectal liver metastasis (CRLM).Patients with CRLM were prospectively randomized to receive open or laparoscopic liver resection (NCT03131778). Blood samples were drawn preoperatively and 24 h after resection. The serum interleukin-6 (IL-6) and IL-8 levels were measured. Furthermore, the mRNA levels of angiogenesis-related factors (vascular endothelial growth factor [VEGF] and HIF-1) and inflammation-related factors (COX-2 and MMP-9) in both tumor tissue and normal liver parenchyma were detected.Twenty patients for each arm were included. Size of metastasis, type of resection, and neoadjuvant therapy were comparable between groups. Postoperative stay was shorter in the laparoscopic group. Higher levels of IL-6 were observed after the operation in both open and laparoscopic groups, although no differences in the post-operative levels between the groups was noted. Similarly, there were no significant differences in the mRNA expression of VEGF, HIF-1, MMP-9, and COX-2 between the treatment groups. No differences were observed in terms of overall survival and disease free survival.The immunological effects of treatment were similar between the groups. Thus, the laparoscopic approach does not seem to significantly influence the surgical stress and tumor related factors in patients suffering from colorectal liver metastases.

The present study investigates whether there is an excess incidence of thyroid cancer among people living in the vicinity of the nuclear sites in Belgium. Adjusted Rate Ratios were obtained from Poisson regressions for proximity areas of varying sizes. In addition, 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. Residential proximity to the nuclear site, prevailing dominant winds frequency from the site, and simulated radioactive discharges were used as surrogate exposures. No excess incidence of thyroid cancer was observed around the nuclear power plants of Doel or Tihange. In contrast, increases in thyroid cancer incidence were found around the nuclear sites of Mol-Dessel and Fleurus; risk ratios were borderline not significant. For Mol-Dessel, there was evidence for a gradient in thyroid cancer incidence with increased proximity, prevailing winds, and simulated radioactive discharges. For Fleurus, a gradient was observed with increasing prevailing winds and, to a lesser extent, with increasing simulated radioactive discharges. This study strengthens earlier findings and suggests increased incidences in thyroid cancer around two of the four Belgian nuclear sites. Further analyses will be performed at a more detailed geographical level. This study is carried out in the framework of the tasks of the Scientific Institute of Public Health (WIV-ISP). As a scientific institute, costs for open access publications are foreseen in the WIV-ISP policy.

Background: Rare cancers pose challenges for diagnosis, treatments, and clinical decision making. Information about rare cancers is scant. The RARECARE project defined rare cancers as those with an annual incidence of less than six per 100 000 people in European Union (EU). We updated the estimates of the burden of rare cancers in Europe, their time trends in incidence and survival, and provide information about centralisation of treatments in seven European countries. Methods: We analysed data from 94 cancer registries for more than 2 million rare cancer diagnoses, to estimate European incidence and survival in 2000–07 and the corresponding time trends during 1995–2007. Incidence was calculated as the number of new cases divided by the corresponding total person-years in the population. 5-year relative survival was calculated by the Ederer-2 method. Seven registries (Belgium, Bulgaria, Finland, Ireland, the Netherlands, Slovenia, and the Navarra region in Spain) provided additional data for hospitals treating about 220 000 cases diagnosed in 2000–07. We also calculated hospital volume admission as the number of treatments provided by each hospital rare cancer group sharing the same referral pattern. Findings: Rare cancers accounted for 24% of all cancers diagnosed in the EU during 2000–07. The overall incidence rose annually by 0.5% (99·8% CI 0·3–0·8). 5-year relative survival for all rare cancers was 48·5% (95% CI 48·4 to 48·6), compared with 63·4% (95% CI 63·3 to 63·4) for all common cancers. 5-year relative survival increased (overall 2·9%, 95% CI 2·7 to 3·2), from 1999–2001 to 2007–09, and for most rare cancers, with the largest increases for haematological tumours and sarcomas. The amount of centralisation of rare cancer treatment varied widely between cancers and between countries. The Netherlands and Slovenia had the highest treatment volumes. Interpretation: Our study benefits from the largest pool of population-based registries to estimate incidence and survival of about 200 rare cancers. Incidence trends can be explained by changes in known risk factors, improved diagnosis, and registration problems. Survival could be improved by early diagnosis, new treatments, and improved case management. The centralisation of treatment could be improved in the seven European countries we studied., peer-reviewed

Given the importance of angiogenesis for a tumor's survival and growth, several therapeutic strategies rely on the selective inhibition of angiogenesis and the destruction of existing tumor vasculature. These strategies raise the need for a noninvasive tool to evaluate tumor vasculature. We describe the radiosynthesis and evaluation of an imaging tracer that specifically binds tumor subendothelial collagen and thereby images tumor vasculature. Methods: Tc-99m-tricarbonyl was prepared and labeled with His-collagen-binding adhesion protein 35 (CNA35). After in vitro specificity testing, in vivo biodistribution and dosimetric studies were performed in healthy nude mice via planar imaging. Tc-99m-(CO)(3) His-CNA35 was evaluated for in vivo imaging of tumor vasculature in a HT29 colorectal carcinoma xenograft. Results: The labeling procedure yielded a compound with 95%-99% radiochemical purity and good in vitro stability. An in vitro binding test confirmed specificity and functionality. Tc-99m-(CO)(3) His-CNA35 rapidly cleared from the blood and pre-dominantly accumulated in the kidneys and liver. The effective dose for a proposed single injection of 500 MBq of Tc-99m-(CO)(3) His-CNA35 is 3.70 mSv per organ or 2.01 mSv/g of tissue. Tumors were successfully visualized, and uptake correlated with ex vivo immunohistochemical staining of tumor vasculature. Conclusion: Tc-99m-(CO)(3) His-CNA35 may be a useful radioligand for the in vivo detection of tumor vasculature through subendothelial collagen binding. A noninvasive method of imaging tumor vasculature that could provide a reliable assessment of tumor vasculature would allow evaluation of the effectiveness of commonly used antiangiogenic therapies and determination of their optimal dosing and scheduling.

As apoptosis occurs over an interval of time after administration of apoptosis-inducing therapy in tumors, the changes in technetium 99m (99mTc)-tricarbonyl (CO)3 His-annexin A5 (His-ann A5) accumulation over time were examined. Colo205-bearing mice were divided into six treatment groups: (1) control, (2) 5-fluorouracil (5-FU; 250 mg/kg), (3) irinotecan (100 mg/kg), (4) oxaliplatin (30 mg/kg), (5) bevacizumab (5 mg/kg), and (6) panitumumab (6 mg/kg). 99mTc-(CO)3 His-ann A5 was injected 4, 8, 12, 24, and 48 hours posttreatment, and micro–single-photon emission computed tomography was performed. Immunostaining of caspase-3 (apoptosis), survivin (antiapoptosis), and LC3-II (autophagy marker) was also performed. Different dynamics of 99mTc-(CO)3 His-ann A5 uptake were observed in this colorectal cancer xenograft model, in response to a single dose of three different chemotherapeutics (5-FU, irinotecan, and oxaliplatin). Bevacizumab-treated mice showed no increased uptake of the radiotracer, and a peak of 99mTc-(CO)3 His-ann A5 uptake in panitumumab-treated mice was observed 24 hours posttreatment, as confirmed by caspase-3 immunostaining. For irinotecan-, oxaliplatin-, and bevacizumab-treated tumors, a significant correlation was established between the radiotracer uptake and caspase-3 immunostaining ( r = .8, p < .05; r = .9, p < .001; r = .9, p < .001, respectively). For 5-FU- and panitumumabtreated mice, the correlation coefficients were r = .7 ( p = .18) and r = .7 ( p = .19), respectively. Optimal timing of annexin A5 imaging after the start of different treatments in the Colo205 model was determined.

We evaluated the relationship of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-derived pharmacokinetic parameters and contrast agents with different molecular weights (MW) in a pancreatic tumor mouse model.Panc02 tumors were induced in mice at the hind leg. DCE-MRI was performed using Gadolinium (Gd)-based contrast agents with different MW: Gd-DOTA (0.5 kDa), P846 (3.5 kDa), and P792 (6.47 kDa). Quantitative vascular parameters (AUC, K(trans), V(e), and V(p)) were calculated according to a modified Tofts two-compartment model. Values for all contrast groups were compared for tumor and control (muscle) tissues.Values for K(trans) and V(e) were significantly higher in tumor tissue than in muscle tissue. When comparing contrast agents, lowest absolute K(trans) values were observed using P792. The relative increase in K(trans) in tumor tissue compared with normal tissue was highest after the use of P792. In both tumor and normal tissues, K(trans) decreased with increasing molecular weight of the contrast agent used.It was demonstrated that values for the different DCE-MRI vascular (permeability) parameters are highly dependent on the contrast agent used. Due to their potential to better differentiate tumor from muscle tissue, higher molecular weight contrast agents show promise when evaluating tumors using DCE-MRI.

Purpose To evaluate the tumour growth delay of a peritoneal carcinomatosis (PC) of colorectal origin after intraperitoneal chemotherapy with paclitaxel/randomly-methylated-β-cyclodextrin (Pac/RAME-β-CD) versus Taxol® at normo- and hyperthermic conditions in rats. Methods Hyperthermic intraperitoneal chemotherapy (HIPEC) was performed 7 days post implantation of the tumour with both formulations at a Pac concentration of 0.24 mg/ml. Tumour evaluation was performed via positron emission tomography (PET) and magnetic resonance imaging (MRI) imaging, measuring tumour activity and tumour volume, respectively. Scans were taken at 2 and 7 days post treatment. Results PET and MRI data showed a significant reduction in tumour activity and tumour volume for rats treated with Pac/RAME-β-CD (at normo- and hyperthermic conditions), compared to the control group. Treatment with Taxol® did not result in a significant reduction of tumour activity and tumour volume. No significant differences between the normo- and hyperthermic conditions were observed for both formulations, indicating that hyperthermia and paclitaxel were not synergistic despite the direct cytotoxic effect of hyperthermia. Conclusion Monitoring tumour growth via PET and MRI indicated that Pac/RAME-β-CD inclusion complexes had a significantly higher efficacy compared to Taxol® in a rat model for peritoneal carcinomatosis.

A predictive technique in the management of patients with cancer could improve the therapeutic index by allowing better individualization of treatment. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique that can provide anatomical and physiological information on the tumor and its microenvironment. We studied the effect of chemotherapy (gemcitabine), anti-angiogenesis therapy (sunitinib) and radiotherapy on the kinetics of DCE-MRI parameters in a preclinical model of pancreatic cancer using P846, a new low-diffusible contrast agent. Mice underwent DCE-MRI before treatment (MRI1), after 1 week of treatment (MRI2), and after 1 additional week (MRI3). Combined treatment with radiotherapy and sunitinib had a synergistic effect on tumor growth. In radiotherapy/sunitinib-treated mice, a decrease in K(trans) at MRI2 predicted its superior antivascular and antitumor effect at an early time. An increased K(trans) at MRI2, as seen in gemcitabine- and gemcitabine/sunitinib-treated mice, reflects increased permeability for P846 and might predict a smaller therapeutic effect at this early time. This study shows that the kinetics of DCE-MRI parameters depends on the contrast agent used. P846 appears to be a promising low-diffusible agent to monitor therapeutic effects in this preclinical cancer model, but further studies are needed to compare its behavior with Gd-DTPA and macromolecular-weight contrast agents. Sunitinib as a radiosensitizer is promising for future clinical trials in human pancreatic cancer.

Colorectal malignancies demonstrating microsatellite instability (MSI) have a very heterogeneous histological appearance, better prognosis, and altered response to therapy. Consequently, identification of the MSI phenotype is both relevant and interesting as a screening and prognostic tool and as a potential predictive factor of chemotherapeutic response. Several groups have argued for the exclusive use of mononucleotide markers for MSI analysis. In this study, an alternative MSI typing multiplex system of mononucleotide microsatellite repeats was developed. This system obviates the need to compare allelic profiles between tumor and matching normal DNA, rendering MSI analysis amenable to high throughput. The quasi-monomorphic allelic distribution of five alternative mononucleotide markers was evaluated in genomic DNA. Only SEC63 and CAT25 were found to be quasi-monomorphic and were thus combined with BAT25 and BAT26 from the Bethesda panel. Consequently, 177 colorectal cancer samples previously analyzed by the Bethesda panel were tested for MSI using this alternative mononucleotide panel. In an attempt to resolve discordant cases, immunohistochemistry of MLH1, MSH2, and MSH6 was performed. The concordance between both panels reached 99.4% when microsatellite stability and MSI-L were grouped together. These new markers were subsequently multiplexed in a single polymerase chain reaction assay. The resulting mononucleotide fluorescent multiplex MSI assay has high accuracy, reliability, and throughput, thus reducing the time and cost involved in MSI testing.

Increased expression of glucose transporters has been reported in many cancers. It is not known whether Sodium dependent GLucose Transporter 1 (SGLT1) is up-regulated in pancreatic cancer. We studied the expression of SGLT1, Bcl-2 and p53 in primary pancreatic adenocarcinomas related to survival. In primary tumors, mean SGLT1-Hscore (n = 83) was 4.24 (median 3.0, range 0.5-15.0). Patients with positive staining for Bcl-2 had higher mean SGLT1-Hscores than those without Bcl-2 expression: 5.87 vs. 3.07 (P = 0.025). No correlation was found between expression of p53 and SGLT1 (P = 0.881). On multivariate analysis TNM stage (P = 0.015) and SGLT1 (P = 0.030) showed prognostic value for disease free survival (DFS). For overall survival (OS), TNM stage (P0.001) and chemotherapy (P = 0.048) were prognostic and SGLT1 showed a trend (P = 0.071). In a subgroup of younger patients (ageor = median, 63.9 y) who did not receive chemotherapy, SGLT1 was a very strong predictor of DFS (P = 0.005). We conclude that high SGLT1 expression (H scoremedian, 3.0) in pancreatic adenocarcinomas was significantly correlated with DFS and a trend was found for OS, especially in younger patients. High SGLT1 expression in primary tumors was correlated with high Bcl-2 expression, not with p53 expression. This supports our hypothesis that SGLT1 and Bcl-2 expression could serve as prognostic markers in pancreatic cancer.

Because it spares many normal tissues and reduces the integral dose, proton therapy (PT) is the preferred tumor irradiation technique for treating childhood cancer. However, to the best of our knowledge, no systematic review of the clinical effectiveness of PT in children has been reported in the scientific literature. A systematic search for clinical outcome studies on PT published between 2007 and 2015 was performed in Medline (through OVID), EMBASE, and the Cochrane Library. Twenty-three primary studies were identified, including approximately 650 patients overall. The median/mean follow-up times were limited (range, 19-91 months). None of the studies were randomized, 2 were comparative, and 20 were retrospective. Most suffered from serious methodologic limitations, yielding a very low level of clinical evidence for the outcomes in all indications. For example, for retinoblastoma, very low-level evidence was found that PT might decrease the incidence of second malignancies. For chondrosarcoma, chordoma, craniopharyngioma, ependymoma, esthesioneuroblastoma, Ewing sarcoma, central nervous system germinoma, glioma, medulloblastoma, osteosarcoma, and rhabdomyosarcoma, there was insufficient evidence to either support or refute PT in children. For pelvic sarcoma (ie, nonrhabdomyosarcoma and non-Ewing sarcoma), pineal parenchymal tumor, primitive neuroectodermal tumor, and "adult-type" soft tissue sarcoma, no studies were identified that fulfilled the inclusion criteria. Although there is no doubt that PT reduces the radiation dose to normal tissues and organs, to date the critical clinical data on the long-term effectiveness and harm associated with the use of PT in the 15 pediatric cancers under investigation are lacking. High-quality clinical research in this area is needed.

INTRODUCTION AND OBJECTIVES: Bladder outlet obstruction (BOO) after prostate cancer treatment (PCT) includes urethral strictures, bladder neck contractures and stenosis of the prostatic urethra. We have shown that by 10 years post-PCT, BOO occurs in 20-38% of men, varying by PCT type. BOO recurrence is common and the need for retreatment may burden the cancer survivor. We sought to describe the burden of BOO in a population-based cohort by detailing the types and numbers of BOO procedures performed per patient. METHODS: From a SEER-Medicare cohort of men aged 66 years diagnosed with non-metastatic prostate cancer (1992-2007), we identified 12,676 men who underwent at least one surgery for BOO after radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy (BT), EBRTþBT, RPþEBRT or cryotherapy. To describe the risk of multiple treatments, we report the incidence rate per personyear and incidence rate ratios of BOO treatment. Cox proportional hazards regression with repeated events analysis was used to adjust for demographic, clinical and cancer characteristics. RESULTS: Median follow-up was 8.8 years. 45% underwent more than one treatment; mean number of treatments was 2.5 (range 1 to 7). Men who received EBRTþBT were most likely to receive seven or more treatments (9.2%), and those receiving RP were least likely (4.5%). Incidence rate ratio and Cox proportional hazards of BOO for each treatment group are shown in the Table. Direct vision internal urethrotomy or transurethral incision of bladder neck contracture was the most common type of stricture treatment across all cancer treatment groups (43.0-51.1%). In RP (35.0%) and RPþEBRT (34.7%), dilation was the second most common treatment of BOO. In EBRT (41.2%), BT (37.0%) and BTþEBRT (28.9%), transurethral resection was the second most common surgery treatment. CONCLUSIONS: When BOO occurs after PCT, nearly half of patients undergo multiple treatments. Men with BOO after radiation or cryotherapy undergo treatments that are more invasive and they have a higher retreatment rate than men with BOO after RP. The need for BOO retreatment and the burden it creates for the cancer survivor deserves more investigation.

Neoadjuvant therapy is increasingly used in resectable locally advanced rectal cancer. The exact role of the addition of chemotherapy is not established. We compared neoadjuvant therapy using chemoradiation (CRT) or hyperfractionated accelerated radiotherapy (HART).Clinical, pathological, and survival data were obtained from patients with resectable stage II or III rectal cancer within 7 cm from the anal verge. A group of 50 patients was treated with a preoperative dose of 41.6 Gy of radiotherapy (RT) in two daily fractions of 1.6 Gy over 13 days immediately followed by surgery (HART). A second group of 96 patients received 45 Gy of conventionally fractionated RT in 25 daily fractions of 1.8 Gy combined with 5-fluorouracil-based chemotherapy followed by surgery within 4 to 6 weeks (CRT). Both groups were compared in terms of morbidity, pathological downstaging, local recurrence, and survival.Both groups were comparable in terms of preoperative clinicopathological variables. The mean distance from the anal verge was 5.8 cm (HART) versus 4.9 cm (CRT). Sphincter preservation was possible in 74% (HART) versus 83.5% (CRT) of patients (P = .013). The clinical anastomotic leak rate was 2% (HART) versus 2.2% (CRT). Pathological complete response was observed in 4% (HART) versus 18% (CRT) of the resected specimens (P = .002). A pelvic recurrence developed in 6% (HART) versus 4.4% (CRT) of patients (P = .98). Overall 5-year survival was 58% (HART) versus 66% (CRT) (P = .19); disease-free 5-year survival was 51% (HART) versus 62% (CRT) (P = .037).Compared with preoperative HART followed by immediate surgery, preoperative CRT followed by a 6-week waiting period enhances pathological response and increases sphincter preservation rate. This could be explained by the addition of chemotherapy or the longer interval between neoadjuvant therapy and surgery. No statistically significant difference was observed in local control or overall survival.

Objective To investigate the effect of infliximab treatment on antinuclear antibodies (ANAs), anti–double-stranded DNA (anti-dsDNA), antinucleosome, antihistone, and anti–extractable nuclear antigen (anti-ENA) antibodies in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients. Methods Sera from 62 RA and 35 SpA patients treated with infliximab were tested at baseline and week 30 (RA group) or week 34 (SpA group). ANAs were tested by indirect immunofluorescence (IIF) on HEp-2 cells. Anti-dsDNA antibodies were detected by IIF on Crithidia luciliae and by enzyme-linked immunosorbent assay (ELISA) and were further isotyped with γ, μ, and α chain–specific conjugates at various time points. Antinucleosome antibodies were tested by ELISA. Antihistone and anti-ENA antibodies were detected by line immunoassay. Results Initially, 32 of 62 RA patients and 6 of 35 SpA patients tested positive for ANAs. After infliximab treatment, these numbers shifted to 51 of 62 (P < 0.001) and 31 of 35 (P < 0.001), respectively. At baseline, none of the RA or SpA patients had anti-dsDNA antibodies. After infliximab treatment, 7 RA patients (P = 0.016) and 6 SpA patients (P = 0.031) became positive for anti-dsDNA antibodies. All 7 anti-dsDNA–positive RA patients had IgM and IgA anti-dsDNA antibodies. Three of the 6 anti-dsDNA–positive SpA patients had IgM and IgA anti-dsDNA antibodies, and 2 had IgM anti-dsDNA antibodies alone. In both diseases, the IgM anti-dsDNA antibodies appeared before the IgA anti-dsDNA antibodies. During the observation period, no IgG anti-dsDNA antibodies or lupus symptoms were observed. The development of antinucleosome, antihistone, or anti-ENA antibodies following infliximab treatment was observed in some patients, but the numbers were not statistically significant. Conclusion Infliximab treatment may induce ANAs, and especially IgM and IgA anti-dsDNA antibodies, in RA and SpA patients. However, no anti-dsDNA IgG antibodies or lupus symptoms were observed during the period of observation in this study, and the development of antinucleosome, antihistone, or anti-ENA antibodies was not statistically significant. These observations do not exclude potential induction of clinically significant lupus in the long term, and further followup is therefore mandatory.

4126 Background: Concerns have been raised on the risk of pancreatic cancer associated with specific anti-diabetic therapies. We have examined the risk of pancreatic cancer among patients with diabetes prescribed with an oral anti-diabetic drug (OAD) or an incretin drug (DPP4i and GLP-1 RA) or insulin. Methods: The public health insurance databases of Belgium and of Lombardy Region, Italy include nearly 100% of the population living in these countries. We created within these databases two cohorts that included adult patients who were first prescribed an incretin drug or another noninsulin antidiabetic drug (NIAD) during 01/07/2008-31/12/2013 in Belgium and during 01/01/2008-31/12/2012 in Lombardy Region. The risk of pancreatic cancer after prescription of an anti-diabetic drug was evaluated using multivariate adjusted Cox models including time-dependent variables. Adjusted hazard ratios (aHRs) from Belgium and Italy were pooled using fixed effects meta-analyses. Results: Results in both cohorts were similar. Among those patients prescribed an OAD, 45% of pancreatic cancers occurred within the 6 months following first prescription, 20% in months 7 to 12 after first prescription and proportions decreased progressively during follow-up. The aHR of pancreatic cancer among subjects prescribed an incretin compared to an OAD was 2.14 [95% CI, 1.71 to 2.67]. The aHR decreased from 3.35 [CI, 2.32 to 4.84] in the first 3 months after first incretin prescription, 2.12 [CI, 1.22 to 3.66] in months 3 to 5.9, 1.95 [CI, 1.20 to 3.16] in months 6 to 11.9, to 1.69 [CI, 1.12 to 2.55] after 12 months. The risk of pancreatic cancer among subjects who were subsequently prescribed insulin was 6.89 [CI, 6.05 to 7.85]. The time from OAD prescription to a shift to incretins or to insulin was significantly lower in patients who were subsequently diagnosed with a pancreatic cancer. Conclusions: The increased risk of pancreatic cancer associated with anti-diabetic therapies could be the consequence of an occult pancreatic cancer that provokes diabetes (reverse causation bias). The search for an occult pancreatic cancer in subjects with newly diagnosed diabetes or patients shifting to more potent anti-diabetic therapy may lead to earlier detection of this cancer.