Colorectal Cancer Screening among Government Servants in Brunei Darussalam

Background: This study concerns uptake and results of colorectal cancer (CRC) screening of governmentservant as part of the Health Screening Program that was conducted in Brunei Darussalam in 2009. Materialsand Methods: Government servants above the age of 40 or with family history of CRC were screened with a singlefecal occult blood test (FIT, immunohistochemistry). Among 11,576 eligible subjects, 7,360 (66.9%) returned theirspecimen. Subjects with positive family history of CRC (n=329) or polyps (n=135) were advised to attend clinicsto arrange screening. All the subjects with positive FIT (n=142, 1.9%) were referred to the endoscopy unit forcounselling for screening colonoscopy. Results: Overall only 17.7% of eligible subjects attended for screening;54.9% (n=79/142) of positive FIT, 8.8% (n=29/329) of positive family history of CRC and none with history ofpolyps (n=0/135). Of these, only 54 patients (50.5%) agreed for colonoscopy, 52 (48.6%) declined as they wereasymptomatic, and one was not offered (0.9%) due to his very young age. On screening colonoscopy, 12.9% (n=7)had advanced lesions including a sigmoid carcinoma in situ and six advanced polyps. The other findings includednon advanced polyps (n=21), diverticular (n=11) and hemorrhoids (n=26). One patient who missed his screeningcolonoscopy appointment re-presented two years later and was diagnosed with advanced right sided CRC. Allthe advanced lesions were detected in patients with positive FIT, giving a yield of 20.5% for advanced lesionsincluding cancers in the 5.1% FIT positive subjects. Conclusions: Our study showed screening for CRC evenwith a single FIT was effective. However, the uptake rate was poor with just over half of the patients agreeing toscreening colonoscopy. Measures to increase public awareness are important. Since one limitation of our studywas the relatively small sample size, larger studies should be conduced in future.     

A willingness-to-pay study of oral epidermal growth factor tyrosine kinase inhibitors in advanced non-small cell lung cancer

PURPOSE: Oral epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are new agents in the treatment of advanced non-small cell lung cancer (NSCLC). Phase II studies demonstrate objective tumor responses and symptom improvement, combined with minimal toxicity and the convenience of an oral agent. We evaluated patient utility through willingness-to-pay (WTP) for these agents in the treatment of advanced NSCLC in Canada. METHODS: Advanced NSCLC patients and healthy subjects participated in a structured interview and bidding exercise, reviewing current evidence supporting EGFR TKI therapy in advanced NSCLC and patient willingness-to-pay for treatment. RESULTS: Fifty-seven patients and 54 healthy subjects participated. The median amount both groups were willing to pay for a month of oral EGFR TKI therapy was $100 CAD (range $0-5000 per month). A minority of NSCLC patients received employment income, the majority relying on disability, pension income, and social assistance for financial support. Affordability of these agents was a key concern for both advanced NSCLC patients and healthy subjects. Univariate predictors of WTP included marital status, prior chemotherapy treatment, receiving pension income or financial social assistance. In multivariate analysis, only prior chemotherapy remained a significant predictor of WTP (p=0.049). CONCLUSION: Both advanced NSCLC patients and healthy subjects feel oral EGFR TKIs are worth paying for in the treatment of advanced NSCLC, but are willing to pay only a fraction of the market price. As many advanced NSCLC patients are financially disadvantaged, the potential for restricted access to newer therapies is of concern.     

Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas

Given the current increase in colorectal cancer screening, information on performance of screening tests is needed, especially in groups with a presumed lower test performance. We compared test performance of immunologic fecal occult blood testing (FIT) and pseudosigmoidoscopy with colonoscopy for detection of advanced adenomas in an average risk screening population. In addition, we explored the influence of gender, age, and location on test performance. FIT was collected prior to colonoscopy with a 50 ng/mL cutoff point. FIT results and complete colonoscopy findings were available from 329 subjects (mean age: 54.6 ± 3.7 years, 58.4% women). Advanced adenomas were detected in 38 (11.6%) of 329 subjects. Sensitivity for advanced adenomas of FIT and sigmoidoscopy were 15.8% (95% CI: 6.0-31.3) and 73.7% (95% CI: 56.9-86.6), respectively. No sensitivity improvement was obtained using the combination of sigmoidoscopy and FIT. Mean fecal hemoglobin in FIT positives was significantly lower for participants with only proximal adenomas versus those with distal ones (P = 0.008), for women versus men (P = 0.023), and for younger (<55 years) versus older (≥55 years) subjects (P = 0.029). Sensitivities of FIT were 0.0% (95% CI: 0.0-30.9) in subjects with only proximal versus 21.4% (95% CI: 8.3-41.0) in those with distal nonadvanced adenomas; 5.3% (95% CI: 0.0-26.0) in women versus 26.3% (95% CI: 9.2-51.2) in men; 9.5% (95% CI: 1.2-30.4) in younger versus 23.5% (95% CI: 6.8-49.9) in older subjects. Sigmoidoscopy had a significantly higher sensitivity for advanced adenomas than FIT. A single FIT showed very low sensitivity, especially in subjects with only proximal nonadvanced adenomas, in women, and in younger subjects. This points to the existence of "low" FIT performance in subgroups and the need for more tailored screening strategies.     

Understanding How Out‐of‐Pocket Expenses,Treatment Value,and Patient Characteristics Influence Treatment Choices

Purpose.

Cost sharing, intended to control the “overuse” of health care resources, may also reduce use of necessary services. The influence of cost on the treatment choices of patients with life-threatening illness, such as cancer, is unknown.

Methods.

A convenience sample of patients undergoing surveillance following curative treatment for localized cancer completed a paper survey that included three scenarios to elicit the maximum copayment they would be willing to pay for better treatment outcomes. Scenario A described a treatment for a curable cancer in terms of recurrence risk. Scenarios B and C described treatments for noncurable cancer in terms of the 2-year survival probability and median life expectancy.

Results.

The sample (n = 60) was 78% female, 83% aged <65 years, and 58% college graduates. Thirteen percent reported making financial sacrifices to pay for treatment. Patients were willing to pay higher copayments for more effective treatments (p < .05 for all three scenarios). In scenario B, patients who were employed demonstrated a greater willingness to pay (WTP) (odds ratio [OR], 12.6; 95% confidence interval [CI], 2.0–80.4), when controlling for efficacy. In scenario C, college graduates showed greater WTP (OR, 5.0; 95% CI, 1.2–20.9) and patients who reported previous financial sacrifices showed lower WTP (OR, 0.2; 95% CI, 0.04–0.6).

Conclusion.

This pilot study suggests that patients may be less willing to pay high copayments for treatments with modest benefit. Even among this relatively young, affluent, and educated population, demographic variables were related to WTP. Larger studies in more diverse populations should be conducted to better understand how cost may influence treatment decisions and cancer treatment outcomes.     

Pioneering Annual Colorectal Cancer Screening and Treatment Targeting Low Income Communities in Malaysia (20102015)

The aim of this study was to assess the rate of uptake of a customised annual Colorectal Cancer Awareness, Screening and Treatment Project (CCASTP) using faecal immunohistochemical test (FIT) kits in low income communities in Malaysia. The immediate objectives were (1) to evaluate the level of adherence of CRC screening among lowincome groups, (2) to assess the knowledge and awareness of the screened population and (3) to assess the accuracy of FIT kits. A total of 1,581 FIT kits were distributed between years 2010 to 2015 to healthy asymptomatic participants of the annual CCASTP organized by Empowered the Cancer Advocacy Society of Malaysia. Data for sociodemographic characteristics, critical health and lifestyle information of the registered subjects were collected. Findings for use of the FIT kits were collected when they were returned for stool analyses. Those testingd positive were invited to undergo a colonoscopy examination. A total of 1,436 (90.8%) of the subjects retuned the FITkits, showing high compliance. Among the 129 subjects with positive FIT results, 92 (71.3%) underwent colonoscopy. Six cases (6.5%) of CRC were found. Based on the data collected, the level of awareness of stool examination and knowledge about CRC was poor amongst the participants. Gender, age group, ethnicity and risk factors (i.e. smoking, lack of exercise and low consumption of fresh fruits) were associated with positive FITkit results. In conclusion, CRC screening can be performed in the community with a single FITkit. Although CRC knowledge and awareness is poor in lowincome communities, the average return rate of the FIT kits and rate of colonoscopy examination were 91.2% and 70.3%, respectively.     

Preferences and Acceptance of Colorectal Cancer Screening in Thailand

Colorectal cancer (CRC) is now common in Thailand with an increase in incidence over time. Health authoritiesare planning to implement a nationwide CRC screening program using fecal immunochemical test (FIT) as aprimary screening tool. This study aimed to estimate preferences and acceptance of FIT and colonoscopy, explorefactors influencing the acceptance, and investigate reasons behind choosing and rejecting to screen before theprogram was implemented. Patients aged 50-69, visiting the primary care unit during the study period, wereinvited to join this study. Patients with a history of cancer or past CRC screening were excluded. Face-to-faceinterviews were conducted. Subjects were informed about CRC and the screening tests: FIT and colonoscopy.Then, they were asked for their opinions regarding the screening. The total number of subjects was 437 (86.7%response rate). Fifty-eight percent were females. The median age was 58 years. FIT was accepted by 74.1% ofsubjects compared to 55.6% for colonoscopy. The acceptance of colonoscopy was associated with perceivedsusceptibility to CRC and family history of cancer. No symptoms, unwilling to screen, healthy, too busy and anxiousabout diagnosis were reasons for refusing to screen. FIT was preferred for its simplicity and non-invasivenesscompared with colonoscopy. Those rejecting FIT expressed a strong preference for colonoscopy. Subjects chosecolonoscopy because of its accuracy; it was refused for the process and complications. If the screening programis implemented for the entire target population in Thailand, we estimate that 106,546 will have a positive FIT,between 8,618 and 12,749 identified with advanced adenoma and between 2,645 and 3,912 identified with CRCin the first round of the program.     

Awareness of cervical cancer and HPV vaccination and its affordability among rural folks in Penang Malaysia

Introduction: As the second most common cancer in women worldwide, cervical cancer causes major health and economic burdens. Recent introduction of HPV immunization program locally has been encouraging but vaccine uptake remains poor. In addition, no study has been conducted to explore the people’s awareness and knowledge on cervical cancer, HPV and its vaccine in a rural setting in Malaysia after the inception of the HPV vaccination program. Objective: This study was conducted to determine the awareness of cervical cancer, HPV vaccination and its affordability among people in a rural area in Malaysia. Method: A cross-sectional study was conducted among 116 participants in a village in Penang. All consenting female villagers aged 13 years and above, and males who were married were interviewed using a questionnaire. Results: Most participants (88.8%) had heard of cervical cancer, however only 29.3% and 42.2% of them had heard of HPV and HPV vaccination respectively. Only 5.2% knew the actual market price for the vaccine. They were willing to pay an average of RM 96.7 (USD $27.7) for the full course of vaccination if it is not given to them for free, whereas the market price is RM1200 (USD $342.85). Conclusion: Awareness among the Malaysian population in a rural setting on HPV and HPV vaccination is low. Educating the public on the infection can help control the illness. Cost of the HPV vaccine is a serious barrier to the success of the vaccination program in Malaysia.     

The Optimal Cut-Off Level of The Fecal Immunochemical Test For Colorectal Cancer Screening in a Country with Limited Colonoscopy Resources: A Multi-Center Study from Thailand

Background: Selecting the cut-off point for the fecal immunochemical test (FIT) for colorectal cancer (CRC) screening programs is of prime importance. The balance between the test performance for detecting advanced neoplasia and the available colonoscopy resources should be considered. We aimed to identify the optimal cut-off of FIT for advanced neoplasia in order to minimize colonoscopy burden. Methods: We conducted a multi-center study in 6 hospitals from diverse regions of Thailand. Asymptomatic participants, aged 50-75 years, were tested with one-time quantitative FIT (OC-SENSOR, Eiken Chemical Co.,Ltd., Tokyo, Japan) and all participants underwent colonoscopy. We assessed test performance in detecting advanced neoplasia (advanced adenoma and CRC) and measured the burden of colonoscopy with different cut-offs [25 (FIT25), 50 (FIT50), 100 (FIT100), 150 (FIT150), and 200 (FIT200)ng/ml]. Results: Among 1,479 participants, advanced neoplasia and CRC were found in 137 (9.3%) and 14 (0.9%), respectively. From FIT25 to FIT200, the positivity rate decreased from 18% to 4.9%. For advanced neoplasia, an increased cut-off decreased sensitivity from 42.3% to 16.8% but increased specificity from 84.2% to 96.3%. The increased cut-off increased the positive predictive value (PPV) from 21.5% to 31.5%. However, all cut-off points provided a high negative predictive value (NPV) (>90%). For CRC, the miss rate for FIT25 to FIT 150 was the same (n=3, 21%), whereas that with FIT200 increased to 35% (n=5). Conclusions: In a country with limited-colonoscopy resources, using FIT150 may be preferred because it offers both high PPV and NPV for advanced neoplasia detection. It could also decrease colonoscopy workload, while maintaining a CRC miss rate similar to those with lower cut-offs.     

Uptake of faecal immunochemical test screening among nonparticipants in a flexible sigmoidoscopy screening programme

Screening programmes based on single modality testing may prevent individuals with a preference for a different test from participating. We conducted a population-based trial to determine whether nonparticipants in flexible sigmoidoscopy (FS) screening were willing to attend faecal immunochemical test (FIT) screening. In total, 8,407 subjects were invited in a primary FS screening programme. Invitees did not know at the time of FS invitation that nonparticipants would be offered FIT screening. A total of 4,407 nonparticipants of FS screening were invited for FIT screening (cut-off 50 ng haemoglobin/ml). The participation rate to FS screening was 31% [95% confidence interval (CI): 30-32%]. Among the FS nonparticipants 25% (CI: 24-26%) did attended FIT screening. The participation rate of the two-stage recruitment for FS and FIT screening was 45% (CI: 44-46%). FIT screenees were older (p = 0.02), more often women (p < 0.001) and had a lower social economic status (p = 0.01) than FS screenees. The detection rate (DR) for advanced adenoma was 3.5% (CI: 2.5-4.8%), and for colorectal cancer (CRC) it was 0.3% (CI: 0.1-0.8%) among participants to FIT screening. The DR of the two-stage recruitment was 6.1% (n = 202) for an advanced adenoma and 0.5% (n = 16) for a CRC. In conclusion, offering FIT screening to nonparticipants in a FS screening programme increases the overall participation rate considerably, as a quarter of nonparticipants of FS screening was willing to attend FIT screening. The participation rate remains lower for primary FIT screening in the same population (62%). Women in the target population were more likely to refuse FS than FIT screening. Countries introducing FS screening should be aware of these preferences.     

Optimizing Screening for Colorectal Cancer: An Algorithm Combining Fecal Immunochemical Test,Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden

BackgroundFecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT⁺) screening population and thereby reduce the colonoscopy burden.Materials and methodsFrom the Danish National Colorectal Cancer Screening Program, 4048 FIT⁺ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling.ResultsThe discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs.ConclusionA screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.     

2015—2019年广州市结直肠癌筛查不同初筛方式阳性人群肠镜结果分析

[目的]分析2015—2019年广东省广州市结直肠癌筛查的数据,比较不同初筛方式阳性人群肠镜结果,以期更好地动员居民参与肠镜检查。[方法]整理2015—2019年广州市结直肠癌筛查数据,将初筛阳性人群分为5组:仅高危因素问卷评估阳性(免疫化学法粪便隐血试验阴性)[high risk factor questionnaire (HRFQ) positive and fecal immunochemical test(FIT)negative,HRFQ+&Double-FIT-]、HRFQ阳性和1次FIT阳性(HRFQ+&Single-FIT+)、HRFQ阴性和1次FIT阳性(HRFQ-&Single-FIT+)、HRFQ阴性和2次FIT阳性(HRFQ-&DoubleFIT+)、HRFQ阳性和2次FIT阳性(HRFQ+&Double-FIT+)。采用多元Logistic回归比较不同初筛方式阳性人群肠镜结果。[结果]广州市共完成初筛403 585人,初筛阳性69 619人,初筛阳性率为17.25%,肠镜检查依从性为28.53%;HRFQ+&Double-FIT+、HRFQ-&DoubleFIT+、HRFQ-&Single-FIT+、HRFQ+&Single-FIT+组检出异常风险分别是HRFQ+&DoubleFIT-组的1.638、1.642、1.174和1.515倍,HRFQ-&Double-FIT+和HRFQ+&Single-FIT+组检出腺瘤风险分别是HRFQ+&Double-FIT-组的1.306和1.214倍,HRFQ+&Double-FIT+、HRFQ-&Double-FIT+、HRFQ-&Single-FIT+、HRFQ+&Single-FIT+检出进展性腺瘤风险分别是HRFQ+&Double-FIT-组的4.823、5.870、2.571和2.463倍,HRFQ+&Double-FIT+、HRFQ-&Double-FIT+、HRFQ-&Single-FIT+、HRFQ+&Single-FIT+检出肠癌风险分别是HRFQ+&Double-FIT-组的33.532、31.345、5.353和6.627倍。[结论]广州市结直肠癌筛查肠镜检查依从性较低,应加大对结直肠癌初筛阳性人群的动员,尤其是FIT 2次阳性的人群。     

定量粪便免疫化学试验筛查阈值对结直肠肿瘤早筛价值的影响

目的:分析定量粪便免疫化学试验（fecal immunochemistry test，FIT）筛查阈值对体检人群结直肠肿瘤早筛价值的影响。方法:以2017年07月至2021年06月在我院接受定量FIT检测并行肠镜检查的1 267例人群为研究对象，比较不同性质肿瘤的定量FIT数值和阳性率。通过Logistic 回归和受试者工作特征（receiver operating characteristic，ROC）曲线分析比较不同性别、年龄和不同阳性阈值下定量FIT对进展期肿瘤的筛检效能。结果:定量 FIT筛查阳性率为4.7%，阳性人群肠镜依从性为22.2%。结直肠癌患者的定量FIT数值高于进展期腺瘤和其他肠镜结果。当定量FIT水平为100~199 μg/L、200~299 μg/L、300~499 μg/L和500 μg/L以上时，患进展期肿瘤的风险分别是<100 μg/L时的4.296倍、4.121倍、6.506倍和10.474倍。不同阳性阈值下，FIT阳性组进展期肿瘤检出率均高于阴性组，且在男性和50~75岁人群中均有统计学差异。在100 μg/L时的比值比（odds ratio，OR）最大（总体OR=6.817，95%CI:2.727~17.040；男性OR=5.570，95%CI:2.198~14.115；50~75岁OR=10.178，95%CI:3.158~32.803）。此时，定量FIT对进展期肿瘤的灵敏度分别为94.7%、93.0%、96.2%，特异度分别为27.6%、29.6%、28.7%。当阳性阈值由100 μg/L升高至500 μg/L时，FIT诊断进展期肿瘤的灵敏度下降，特异度升高，但阳性预测值和阴性预测值变化不大。结论:定量FIT阳性阈值在100 μg/L时筛查进展期结直肠肿瘤的灵敏度较好，但特异度较低，是应用在体检人群伺机性筛查中较好的结直肠肿瘤早筛参考指标。     

Impact of adenoma detection on the benefit of faecal testing vs. colonoscopy for colorectal cancer

Colonoscopy quality, as measured by adenoma detection rates, varies widely across providers and is inversely related to patients' post‐colonoscopy cancer risk. This has unknown consequences for the benefits of faecal immunochemical testing (FIT) vs. primary colonoscopy screening for colorectal cancer. Using an established microsimulation model, we predicted the lifetime colorectal cancer incidence and mortality benefits of annual FIT vs. 10‐yearly colonoscopy screening at differing ADR levels (quintiles; averages 15.3–38.7%), with colonoscopy performance assumptions estimated from community‐based data on physician ADRs and patients' post‐colonoscopy risk of cancer. For patients receiving FIT screening with follow‐up colonoscopy by physicians from the highest ADR quintile, simulated lifetime cancer incidence and mortality were 28.8 and 5.4 per 1,000, respectively, vs. 20.6 and 4.4 for primary colonoscopy screening (risk ratios, RR = 1.40; 95% probability interval (PI), 1.19–1.71 for incidence, and RR = 1.22; 95%PI, 1.02–1.54 for mortality). With every 5% point ADR decrease, lifetime cancer incidence was predicted to increase on average 9.0% for FIT vs. 12.3% for colonoscopy, and mortality increased 9.9% vs. 13.3%. In ADR quintile 1, simulated mortality was lower for FIT than colonoscopy screening (10.1 vs. 11.8; RR = 0.85; 95%PI, 0.83–0.90), while incidences were more similar. This suggests that relative cancer incidence and mortality reductions for FIT vs. colonoscopy screening may differ by ADR, with fewer predicted deaths with colonoscopy screening in higher ADR settings and fewer deaths with annual FIT screening in lower ADR settings.     

Lack of Association between Red Meat Consumption and a Positive Fecal Immunochemical Colorectal Cancer Screening Test in Khon Kaen,Thailand: a Population- Based Randomized Controlled Trial

Background: There is convincing evidence from epidemiological studies that meat consumption increases colorectal cancer (CRC) risk. However, assessment of any association with a positive fecal immunochemical test (FIT) in CRC screening has been limited. If a link could be shown this might be helpful for establishing a risk group for colonoscopy. Objective: This study aimed to assess any association between meat consumption and other lifestyle factors and a positive FIT result in a Thai population. Methods: A cross-sectional analytical study was conducted with 1,167 participants in a population-based randomized controlled trial. CRC was screened from May 2016 - February 2017. Subjects aged 45-74 years who met the eligibility criteria were randomly allocated to the study arm. A positive FIT was determined with cut-off 100 ng/mL. Multiple logistic regression was used to analyze any relationship between lifestyle factors and a positive FIT. Result: The total number of subjects was 1,060 (90.8% return rate of FIT). With FIT100, FIT150, and FIT200, positive tests were found in 92 (8.68%), 74 (6.98%), and 60 (5.66%), respectively. No significant associations were noted with any of the variables, except for being aged 60-74 years (ORadj = 1.62, 95% CI: 1.03-2.54) Borderline significance was observed for high consumption of vegetables (ORadj = 0.62, 95% CI: 0.36-1.07) and being male (ORadj = 1.39, 95% CI: 0.87-2.22). Conclusion: Despite the evidence from the literature, no association was here found between a positive FIT result and meat consumption or other well-established lifestyle parameters. Being aged 60-74 years was a risk factor which should be taken into account in CRC screening strategy in countries like Thailand with limited access to endoscopy.     

Plasma miRNA-based signatures in CRC screening programs

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.     

Screening strategies for colorectal cancer among patients with nonalcoholic fatty liver disease and family history

Patients with nonalcoholic fatty liver disease (NAFLD) and family history of colorectal cancer (CRC) are at higher risks but how they should be screened remains uncertain. Hence, we evaluated the cost‐effectiveness of CRC screening among patients with NAFLD and family history by different strategies. A hypothetical population of 100,000 subjects aged 40–75 years receive: (i) yearly fecal immunochemical test (FIT) at 50 years; (ii) flexible sigmoidoscopy (FS) every 5 years at 50 years; (iii) colonoscopy 10 yearly at 50 years; (iv) colonoscopy 10 yearly at 50 years among those with family history/NAFLD and yearly FIT at 50 years among those without; (v) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and yearly FIT at 50 years among those without and (vi) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and colonoscopy 10 yearly at 50 years among those without. The incremental cost‐effectiveness ratio (ICER) was studied by Markov modeling. It was found that colonoscopy, FS and FIT reduced incidence of CRC by 49.5, 26.3 and 23.6%, respectively. Using strategies 4, 5 and 6, the corresponding reduction in CRC incidence was 29.9, 30.9 and 69.3% for family history, and 33.2, 34.7 and 69.8% for NAFLD. Compared with no screening, strategies 4 (US$1,018/life‐year saved) and 5 (US$7,485) for family history offered the lowest ICER, whilst strategy 4 (US$5,877) for NAFLD was the most cost‐effective. These findings were robust when assessed with a wide range of deterministic sensitivity analyses around the base case. These indicated that screening patients with family history or NAFLD by colonoscopy at 50 years was economically favorable.     

Strong subsite‐specific variation in detecting advanced adenomas by fecal immunochemical testing for hemoglobin

Fecal immunochemical tests (FITs) for hemoglobin are increasingly recommended and used in colorectal cancer (CRC) screening. We aimed to provide a detailed assessment of the sensitivity of FIT according to type and subsite of neoplasms in a true screening setting. A quantitative FIT (FOB Gold, Sentinel Diagnostics, Milano, Italy) was applied prior to colonoscopy by 3,466 participants of the German screening colonoscopy program. Subsite specific sensitivity for various types of colorectal neoplasms was derived by comparing FIT results with findings at screening colonoscopy. The most advanced finding at colonoscopy was CRC, advanced adenoma, and nonadvanced adenoma in 29, 354 and 686 cases, respectively. Per‐adenoma sensitivity for large advanced adenomas (>1 cm) strongly varied by location (p < 0.001): cecum: 0/14 (0%), ascending colon and right flexure: 11/43 (26%), transverse colon and left flexure: 2/14 (14%), descending colon: 7/12 (58%), sigmoid colon: 47/92 (51%), rectum: 14/39 (36%). By contrast, the FIT detected all of 5 proximal CRC and 23 out of 24 (96%) distal CRCs, whereas per‐adenoma sensitivity of both proximal (17/259, 7%) and distal nonadvanced adenomas (20/237, 8%) essentially equaled the false positivity rate among those without neoplasms (152/2,397, 6%). In conclusion, we found a very large gradient of subsite specific FIT sensitivity for detecting large advanced adenomas ranging from 0% for advanced adenomas located in the cecum to >50% for those located in the descending or sigmoid colon. By contrast, FIT sensitivity was uniformly excellent for CRC and uniformly poor for nonadvanced adenomas, regardless of their location.