Is the porcine RN locus a pleiotropic QTL? A Bayesian marker assisted segregation analysis

International audienc

Colorectal Cancer Stage Distribution at First and Repeat Fecal Immunochemical Test Screening

Background &amp; Aims: For colorectal cancer (CRC) screening to be effective, it is important that screen-detected cancers are found at an early stage. Studies on stage distribution of screen-detected CRC at repeat screening of large population-based fecal immunochemical test (FIT)-based screening programs and the impact of FIT cut-off values on staging currently are lacking. Methods: We obtained data for FIT-positive participants (FIT cut-off, 47 μg hemoglobin/g feces) at their first or second (ie, repeat) screening from the Dutch National Screening Database from 2014 to 2018. Tumor characteristics were acquired through linkage with The Netherlands Cancer Registry. We compared stage at diagnosis (I–II vs III–IV) of CRCs detected at a first or second screening. In addition, we analyzed the hypothetical yield and stage distribution of CRC for different FIT cut-off values up to 250 μg hemoglobin/g feces.Results: At the first and second screenings, respectively, 15,755 and 3304 CRCs were detected. CRCs detected at the first or second screening were equally likely to be stages I to II (66.5% vs 67.7%; relative risk, 1.02; 95% CI, 1.00–1.05). A hypothetical increase of the FIT cut-off value from 47 μg to 250 μg resulted in a reduction of detected CRCs by 88.3% and 79.0% at the first or second screening, respectively. Even then, the majority of detected CRCs (63%–64%) still would be diagnosed at stages I to II. Conclusions: FIT-based screening is effective in downstaging CRC, and also at repeat screening. Increasingly, the FIT cut-off level has a limited impact on the stage distribution of detected CRCs, although it greatly affects CRC detection and thus is important to keep low.</p

Medical and health economic assessment of radiosurgery for the treatment of brain metastasis

Background: Radiotherapy for patients suffering from malignant neoplasms has developed greatly during the past decades. Stereotactic radiosurgery (SRS) is one important radiotherapeutic option which is defined by a single and highly focussed application of radiation during a specified time interval. One of its important indications is the treatment of brain metastases. Objectives: The objective of this HTA is to summarise the current literature concerning the treatment of brain metastasis and to compare SRS as a single or additional treatment option to alternative treatment options with regard to their medical effectiveness/efficacy, safety and cost-effectiveness as well as their ethical, social and legal implications. Methods: A structured search and hand search of identified literature are performed from January 2002 through August 2007 to identify relevant publications published in English or German. Studies targeting patients with single or multiple brain metastases are included. The methodological quality of included studies is assessed according to quality criteria, based on the criteria of evidence based medicine. Results: Of 1,495 publications 15 medical studies meet the inclusion criteria. Overall study quality is limited and with the exception of two randomized controlleed trials (RCT) and two meta-analyses only historical cohort studies are identified. Reported outcome measures are highly variable between studies. Studies with high methodological quality provide evidence, that whole-brain radiotherapy (WBRT) in addition to SRS and SRS in addition to WBRT is associated with improved local tumour control rates and neurological function. However, only in patients with single brain metastasis, RPA-class 1 (RPA = Recursive partitioning analysis) and certain primary tumour entities, this combination of SRS and WBRT is associated with superior survival compared to WBRT alone. Studies report no significant differences in adverse events between treatment groups. Methodologically less rigorous studies provide no conclusive evidence with regard to medical effectiveness and safety, comparing SRS to WBRT, neurosurgery (NS) or hypofractionated radiotherapy (HCSRT). The quality of life is not investigated in any of the studies. Within the searched databases a total of 320 economic publications are identified. Five publications are eligible for this report. The five reports have a quiet variable quality. Concerning the economic efficiency of alternative equipment, while assuming equal effectiveness, the calculations show, that economic efficiency depends to a large extend on the number of patients treated. In case the two alternative equipments are used solely for SRS, the Gamma Knife might be more cost-efficient. Otherwise an adapted linear accelerator is most likely to be beneficial because of its flexibility. One Health Technology Assessment (HTA) states, that the cost for a Gamma Knife and a dedicated linear accelerator are comparable, while an adapted version is cheaper. No reports concerning ethical, legal and social aspects are identified. Discussion: Overall, quantity and quality of identified studies is limited. However, the identified studies indicate that the prognosis of patients with brain metastases is despite highly developed and modern treatment regimes still limited. Conclusive evidence with regard to the effectiveness of identified interventions is only available for the combined treatment of SRS and WBRT compared to SRS or WBRT alone. Furthermore, there is insufficient evidence to compare SRS with WBRT, NS or HCSRT. The efficiency of the different equipments depends to a great extent on the number and the indications of the patients treated. If dedicated systems are used to their full capacity, there is some evidence for superior cost-effectiveness. If more treatment flexibility is required, adapted systems seem to be advantageous. However, equal treatment effectiveness is a necessary assumption for these conclusions. The need for a treatment precision can influence the purchase decision. No reports concerning more recent therapeutic alternatives are currently available. Conclusion: Combination of SRS and WBRT is associated with improved local tumour control and neurological function compared to SRS or WBRT alone. However, only for patients with single metastasis there is strong evidence that this results in improved survival compared to WBRT alone. Methodologically rigorous studies are warranted to investigate SRS compared to WBRT and NS and to investigate the quality of life in patients undergoing these treatment regimes.Concerning the type of equipment used, economic efficiency depends to a great extend on the capacity at which the system can be used. Dedicated systems might be favourable for a high number of patients, while lower patient counts probably favour adapted systems with their superior treatment flexibility. Using the equipment at its full capacity may result in a limited number of machines, what in turn may give rise to the question of an equal and easy access to this technology. Studies focusing on the comparative effectiveness and cost-effectiveness of different treatment options and their combinations, especially for the German setting, are warranted

Evaluation of a new approach for semi-automatic segmentation of the cerebellum in patients with multiple sclerosis

Cerebellar dysfunction is an important contributor to disability in patients with multiple sclerosis (MS), however, few in vivo studies focused on cerebellar volume loss so far. This relates to technical challenges regarding the segmentation of the cerebellum. In this study, we evaluated the semi-automatic ECCET software for performing cerebellar volumetry using high-resolution 3D T1-MR scans in patients with MS and healthy volunteers. We performed test-retest as well as inter-observer reliability testing of cerebellar segmentation and compared the ECCET results with a fully automatic cerebellar segmentation using the FreeSurfer software pipeline in 15 MS patients. In a pilot matched-pair analysis with another data set from 15 relapsing-remitting MS patients and 15 age- and sex-matched healthy controls (HC), we assessed the feasibility of the ECCET approach to detect MS-related cerebellar volume differences. For total normalized cerebellar volume as well as grey and white matter volumes, intrarater (intraclass correlation coefficient (ICC)=0.99, 95% CI=0.98-0.99) and interobserver agreement (ICC=0.98, 95% CI=0.74-0.99) were strong. Comparison between ECCET and FreeSurfer results likewise yielded a good intraclass correlation (ICC=0.86, 95% CI=0.58-0.95). Compared to HC, MS patients had significantly reduced normalized total brain, total cerebellar, and grey matter volumes (p≤0.05). ECCET is a suitable tool for cerebellar segmentation showing excellent test-retest and inter-observer reliability. Our matched-pair analysis between MS patients and healthy volunteers suggests that the method is sensitive and reliable in detecting cerebellar atrophy in M