Colorectal cancer surveillance in Hodgkin lymphoma survivors at increased risk of therapy-related colorectal cancer: Study design

Background: Second primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine have an increased risk to develop colorectal cancer. Colonoscopy surveillance plays an important role in colorectal cancer prevention by removal of the precursor lesions (adenomas) and early detection of cancer, resulting in improved survival rates. Therefore, Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine could benefit from colonoscopy, or other surveillance modalities, which are expected to reduce colorectal cancer incidence and mortality. Current knowledge on clinicopathological and molecular characteristics of therapy-related colorectal cancer is limited. The pathogenesis of such colorectal cancers might be different from the pathogenesis in the general population and therefore these patients might require a different clinical approach. We designed a study with the primary aim to assess the diagnostic yield of a first surveillance colonoscopy among Hodgkin lymphoma survivors at increased risk of colorectal cancer and to compare these results with different screening modalities in the general population. Secondary aims include assessment of the test characteristics of stool tests and evaluation of burden, acceptance and satisfaction of CRC surveillance through two questionnaires. Methods/Design: This prospective multicenter cohort study will include Hodgkin lymphoma survivors who survived =8years after treatment with infradiaphragmatic radiotherapy and/or procarbazine (planned inclusion of 259 participants). Study procedures will consist of a surveillance colonoscopy with removal of precursor lesions (adenomas) and 6-8 normal colonic tissue biopsies, a fecal immunochemical test and a stool DNA test. All neoplastic lesions encountered will be classified using relevant histomorphological, immunohistochemical and molecular analyses in order to obtain more insight into colorectal carcinogenesis in Hodgkin lymphoma survivors. The Miscan-model will be used for cost-effectiveness analyses. Discussion: Evaluation of the diagnostic performance, patient acceptance and burden of colorectal cancer surveillance is necessary for future implementation of an individualized colorectal cancer surveillance program for Hodgkin lymphoma survivors. In addition, more insight into treatment-induced colorectal carcinogenesis will provide the first step towards prevention and personalized treatment. This information may be extrapolated to other groups of cancer survivors. Trial registration: Registered at the Dutch Trial Registry (NTR): NTR4961

Anticipating implementation of colorectal cancer screening in The Netherlands: a nation wide survey on endoscopic supply and demand

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) screening requires sufficient endoscopic resources. The present study aims to determine the Dutch endoscopic production and manpower for 2009, evaluate trends since 2004, determine additional workload which would be caused by implementation of a CRC screening program, and inventory colonoscopy rates performed in other European countries.</p> <p>Methods</p> <p>All Dutch endoscopy units (N = 101) were surveyed for manpower and the numbers of endoscopy procedures performed in 2009. Based on calculations in the report issued by the Dutch Health Council, future additional workload caused by faecal immunochemical test (FIT) screening was estimated. The number of colonoscopies performed in Europe was evaluated by a literature search and an email-inquiry.</p> <p>Results</p> <p>Compared to 2004, there was a 24% increase in total endoscopies (N = 505,226 in 2009), and a 64% increase in colonoscopies (N = 191,339 in 2009) in The Netherlands. The number of endoscopists had increased by 4.6% (N = 583 in 2009). Five years after stepwise implementation of FIT-based CRC screening, endoscopic capacity needs to be increased an additional 15%. A lack of published data on the number of endoscopies performed in Europe was found. Based on our email-inquiry, the number of colonoscopies per 100,000 inhabitants ranged from 126 to 3,031 in 15 European countries.</p> <p>Conclusions</p> <p>Over the last years, endoscopic procedures increased markedly in The Netherlands without a corresponding increase in manpower. A FIT-based CRC screening program requires an estimated additional 15% increase in endoscopic procedures. It is very likely that current colonoscopy density varies widely across European countries.</p

Adherence to colorectal cancer screening: Four rounds of faecal immunochemical test-based screening

Background:The effectiveness of faecal immunochemical test (FIT)-based screening programs is highly dependent on consistent participation over multiple rounds. We evaluated adherence to FIT screening over four rounds and aimed to identify determinants of participation behaviour.Methods:A total of 23 339 randomly selected asymptomatic persons aged 50-74 years were invited for biennial FIT-based colorectal cancer screening between 2006 and 2014. All were invited for every consecutive round, except for those who had moved out of the area, passed the upper age limit, or had tested positive in a previous screening round. A reminder letter was sent to non-responders. We calculated participation rates per round, response rates to a reminder letter, and differences in participation between subgroups defined by age, sex, and socioeconomic status (SES).Results:Over the four rounds, participation rates increased significantly, from 60% (95% CI 60-61), 60% (95% CI 59-60), 62% (95% CI 61-63) to 63% (95% CI 62-64; P for trend&lt;0.001) with significantly higher participation rates in women in all rounds (P&lt;0.001). Of the 17 312 invitees eligible for at least two rounds of FIT screening, 12 455 (72%) participated at least once, whereas 4857 (28%) never participated; 8271 (48%) attended all rounds when eligible. Consistent participation was associated with older age, female sex, and higher SES. Offering a reminder letter after the initial invite in the first round increased uptake with 12%; in subsequent screening rounds this resulted in an additional uptake of up to 10%.Conclusions:In four rounds of a pilot biennial FIT-screening program, we observed a consistently high and increasing participation rate, whereas sending reminders remain effective. The substantial proportion of inconsistent participants suggests the existence of incidental barriers to participation, which, if possible, should be identified and removed

Does CT colonography have a role for population-based colorectal cancer screening?

Colorectal cancer (CRC) is the second most common cancer and second most common cause of cancer-related deaths in Europe. CRC screening has been proven to reduce disease-specific mortality and several European countries employ national screening programmes. These almost exclusively rely on stool tests, with endoscopy used as an adjunct in some countries. Computed tomographic colonography (CTC) is a potential screening test, with an estimated sensitivity of 88 % for advanced neoplasia ≥10 mm. Recent randomised studies have shown that CTC and colonoscopy have similar yields of advanced neoplasia per screened invitee, indicating that CTC is potentially viable as a primary screening test. However, the evidence is not fully elaborated. It is unclear whether CTC screening is cost-effective and the impact of extracolonic findings, both medical and economic, remains unknown. Furthermore, the effect of CTC screening on CRC-related mortality is unknown, as it is also unknown for colonoscopy. It is plausible that both techniques could lead to decreased mortality, as for sigmoidoscopy and gFOBT. Although radiation exposure is a drawback, this disadvantage may be over-emphasised. In conclusion, the detection characteristics and acceptability of CTC suggest it is a viable screening investigation. Implementation will depend on detection of extracolonic disease and health-economic impact

Screening for colorectal cancer: possible improvements by risk assessment evaluation?

Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including colono- and sigmoidoscopy, CT- and MR-colonography, capsule endoscopy, DNA and occult blood in feces, and so on. The pros and cons of the various tests, including economic issues, are debated. Although a plethora of evaluated and validated tests even with high specificities and reasonable sensitivities are available, an international consensus on screening procedures is still not established. The rather limited compliance in present screening procedures is a significant drawback. Furthermore, some of the procedures are costly and, therefore, selection methods for these procedures are needed. Current research into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a “risk assessment evaluation” (RAE) test. It is assumed that such a test may lead to higher acceptance among the screening populations, and thereby improve the compliances. Furthermore, the involvement of the media, including social media, may add even more individuals to the screening programs. Implementation of validated RAE and progressively improved screening methods may reform the cost/benefit of screening procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest

Smoking status informs about the risk of advanced serrated polyps in a screening population

Background and study aims: Evidence has accumulated that approximately 15% to 30% of colorectal cancers (CRC) arise from serrated polyps (SP). Population screening, therefore, should be designated to detect advanced SP, in addition to advanced adenomas and CRC. We aimed to evaluate whether CRC risk factors also act as risk factors for advanced SP. Patients and methods: Data were collected in the colonoscopy arm of a multicenter randomized trial comparing colonoscopy with CT-colonography for primary population screening. Information on risk factors was obtained by screening participants before colonoscopy with a validated risk questionnaire. Advanced SP were defined as SP10mm and/or with dysplasia. Endoscopists were instructed to resect all detected lesions. Odds ratios (OR) for the detection of advanced SP as most advanced lesion were calculated using multiple logistic regression analysis. Results: Of 6600 invited participants, 1426 underwent a colonoscopy and 1236 also completed the questionnaire. In 40 participants an advanced SP was the most advanced lesion detected. Multivariate analysis demonstrated a strong association between current smoking and the presence of at least one advanced SP (OR 4.50; 95% CI 2.23-8.89; P&lt;0.001). A significant association was also demonstrated for higher fiber intake (OR 1.36 per 20 gram intake; CI 1.07-1.73; P=0.01). Other clinical CRC risk factors did not show a significant association with the presence of at least one advanced SP in the univariate analyses. Fecal haemoglobin levels were also not significantly associated with the presence of advanced SPs (OR 1.00 per 10ng/mL CI 0.97-1.03, P=0.99). Conclusions: Current smoking is a strong clinical risk factor for the presence of advanced SPs. As such, smoking status could contribute to risk stratification in targeted CRC population screening. Dutch Trial Register: NTR1829 (www.trialregister.nl

Smoking status informs about the risk of advanced serrated polyps in a screening population

Background and study aims: Evidence has accumulated that approximately 15% to 30% of colorectal cancers (CRC) arise from serrated polyps (SP). Population screening, therefore, should be designated to detect advanced SP, in addition to advanced adenomas and CRC. We aimed to evaluate whether CRC risk factors also act as risk factors for advanced SP. Patients and methods: Data were collected in the colonoscopy arm of a multicenter randomized trial comparing colonoscopy with CT-colonography for primary population screening. Information on risk factors was obtained by screening participants before colonoscopy with a validated risk questionnaire. Advanced SP were defined as SP10mm and/or with dysplasia. Endoscopists were instructed to resect all detected lesions. Odds ratios (OR) for the detection of advanced SP as most advanced lesion were calculated using multiple logistic regression analysis. Results: Of 6600 invited participants, 1426 underwent a colonoscopy and 1236 also completed the questionnaire. In 40 participants an advanced SP was the most advanced lesion detected. Multivariate analysis demonstrated a strong association between current smoking and the presence of at least one advanced SP (OR 4.50; 95% CI 2.23-8.89; P&lt;0.001). A significant association was also demonstrated for higher fiber intake (OR 1.36 per 20 gram intake; CI 1.07-1.73; P=0.01). Other clinical CRC risk factors did not show a significant association with the presence of at least one advanced SP in the univariate analyses. Fecal haemoglobin levels were also not significantly associated with the presence of advanced SPs (OR 1.00 per 10ng/mL CI 0.97-1.03, P=0.99). Conclusions: Current smoking is a strong clinical risk factor for the presence of advanced SPs. As such, smoking status could contribute to risk stratification in targeted CRC population screening. Dutch Trial Register: NTR1829 (www.trialregister.nl