Variation in diagnosis, treatment and outcome in colon and rectal cancer

Large variation between hospitals and pathology laboratories was demonstrated in adherence to the guidelines. This is associated with type and volume of hospitals and pathology laboratories. However, not all variation could be explained by these characteristics. The aim of this thesis was to identify factors influencing quality of care by investigating the variation in guidelines adherence of patients with colon and rectal cancer in the Netherlands. Considerable variation in lymph node evaluation between hospitals and pathology laboratories was revealed leading to suboptimal staging and potentially inaccurate treatment plans. Furthermore, large differences between hospitals were found in treatment according tot the guidelines. Based on the results of this thesis, it can be conclude that a part of the variation is associated with type and volume of hospitals and pathology laboratories. However, the large differences between individual hospitals suggests that these characteristics do not account for all variation. Therefore, further research is necessary to identify best practices and analyse factors which influence quality of care and outcome.UBL - phd migration 201

Nationwide evaluation of mutation-tailored anti-EGFR therapy selection in patients with colorectal cancer in daily clinical practice

For a nationwide real-word data study on the application of predictive mutation testing of patients with colorectal cancer (CRC) for anti-epidermal growth factor receptor (EGFR) therapy stratification, pathology data were collected from the Dutch Pathology Registry from October 2017 until June 2019 (N=4060) and linked with the Netherlands Cancer Registry. Mutation testing rates increased from 24% at diagnosis of stage IV disease to 60% after 20-23 months of follow-up (p<0.001). Application of anti-EGFR therapy in KRAS/NRAS wild-type patients was mainly observed from the third treatment line onwards (65% vs 17% in first/second treatment line (p<0.001)). The national average KRAS/NRAS/BRAF mutation rate was 63.9%, being similar for next-generation sequencing (NGS)-based approaches and single gene tests (64.4% vs 61.2%, p=ns). NGS-based approaches detected more additional potential biomarkers, for example, ERBB2 amplifications (p<0.05). Therefore, single gene tests are suitable to stratify patients with mCRC for anti-EGFR therapy, but NGS is superior enabling upfront identification of therapy resistance or facilitate enrolment into clinical trials.Molecular tumour pathology - and tumour geneticsMTG2 - Moleculaire genetica van gastrointestinale tumore

Incidence of Interval Colorectal Cancer After Negative Results From First-Round Fecal Immunochemical Screening Tests, by Cutoff Value and Participant Sex and Age

Background & Aims: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and the effects of different cutoff values and patient sex and age. Methods: We collected data from participants in a population-based

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

Spatial variation in stage distribution in colorectal cancer in the Netherlands

Background: In the Netherlands the incidence of colorectal cancer has increased, mainly in the eastern part of the country. Patient delay due to unawareness or ignorance of symptoms and differences in use of diagnostic tools could have influence on the stage distribution. The aim of this study was to evaluate geographical differences in stage-specific incidence rates of colon and rectal cancer in the Netherlands.\ud \ud Methods: Age-adjusted incidence rates for cancers of the colon and rectum diagnosed in 2001–2005 and registered in the Netherlands Cancer Registry were calculated for each municipality and stage. The incidence for each 500 m by 500 m grid was estimated as a weighted average of the incidence rates of the neighbouring municipalities. The incidence rates and the stage distribution are both presented as maps. Geographic variation in stage-specific incidence was evaluated using spatial scan statistic.\ud \ud Results: In both colon and rectal cancer, significant spatial variation in stage-specific incidences was found, except for colon cancer of stages III and IV. The regions with a higher stage-specific incidence were almost all in the south eastern part of the Netherlands, however, these differences were not seen in the stage distribution. There were no differences in stage distribution between large cities and the rest of the country.\ud \ud Conclusions: These maps give insight into differences in stage-specific incidences of colon and rectal cancer in the Netherlands. Educational interventions to increase the awareness of symptoms of colorectal cancer may be especially useful for the population in regions with high incidence of advanced stages

Variation in treatment and outcome in patients with non-small cell lung cancer by region, hospital type and volume in the Netherlands

Background: Care processes for patients with NSCLC can vary by provider, which may lead to unwanted variation in outcomes. Therefore, in modern health care an increased focus on guideline development and implementation is seen. It is expected that more guideline adherence leads to a higher number of patients receiving optimal treatment for their cancer which could improve overall survival. Objective: The aim of this study was to evaluate variations in treatment patterns and outcomes of patients with NSCLC treated in different (types of) hospitals and regions in the Netherlands. Especially, variation in the percentage of patients receiving the optimal treatment for the stage of their disease, according to the Dutch national guideline of 2004, was analyzed. Methods: All patients with a histological confirmed primary NSCLC diagnosed in the period 2001–2006 in all Dutch hospitals (N = 97) were selected from the population-based Netherlands Cancer Registry. Hospitals were divided in groups based on their region (N = 9), annual volume of NSCLC patients, teaching status and presence of radiotherapy facilities. Stage-specific differences in optimal treatment rates between (groups of) hospitals and regions were evaluated. Results: In the study period 43 544 patients were diagnosed with NSCLC. The resection rates for stage I/II NSCLC patients increased during the study period, but resection rates varied by region and were higher in teaching hospitals for thoracic surgeons (OR 1.5; 95%CI 1.2–1.9, p = 0.001) and in hospitals with a diagnostic volume of more than 50/year (OR 1.3; 95%CI 1.1–1.5, p = 0.001). Also the use of chemoradiation in stage III patients increased, though marked differences between hospitals in the use of chemoradiation for stage III patients were revealed. Differences in optimal treatment rates between hospitals led to differences in survival. Conclusion: Treatment patterns and outcome of NSCLC patients in the Netherlands varied by region and the hospital their cancer was diagnosed in. Though resection rates were higher in hospitals training thoracic surgeons, variation between individual hospitals was much more distinct. Hospital characteristics like a high diagnostic volume, teaching status or availability of radiotherapy facilities proved no guarantee for optimal treatment rates