First-Line everolimus and cisplatin in patients with advanced extrapulmonary neuroendocrine carcinoma:a nationwide phase 2 single-arm clinical trial

BACKGROUND: Extrapulmonary neuroendocrine carcinoma (EP-NEC) are an aggressive subgroup of neuroendocrine neoplasms (NEN). Advanced EP-NEC is generally treated with platinum-based cytotoxic regimens, but progressive disease occurs rapidly, resulting in a poor prognosis. Genetic alterations in the mammalian target for rapamycin (mTOR) pathway have been identified in NEN, providing a rationale for treatment with the mTOR-inhibitor everolimus. METHODS: A prospective phase 2 single-arm study included patients with advanced EP-NEC from three Dutch NEN expertise centres between March 2016 and January 2020. Treatment consisted of cisplatin 75 mg/m(2) every 3 weeks in combination with daily everolimus 7.5 mg for a maximum of six cycles, followed by maintenance everolimus until disease progression. Primary endpoint was disease control rate (DCR), defined as the sum of overall response rate (ORR) plus the rate of stable disease according to RECIST 1.1, assessed at 9-week intervals. Toxicity was evaluated according to CTCAE version 5.0. RESULTS: Thirty-nine patients, with a median age of 64 years (range: 28–74), of whom 20 (51%) were male, were enrolled. DCR was 82.1% (95% confidence interval (CI): 66.4–92.4), with an ORR of 58.9% (CI: 42.1–74.4). Median duration of response was 6.4 (CI: 5.8–7.0) months and median progression-free survival was 6.0 (CI: 4.3–7.8) months. Three patients (8%) had durable responses lasting  > 12 months. Median overall survival was 8.7 (CI: 7.8–9.6) months. Most common grade 3/4 toxicities were haematological (36%) and renal (21%). CONCLUSION: Everolimus in combination with cisplatin is an effective first-line treatment option for advanced EP-NEC, especially in highly selected patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02695459, https://clinicaltrials.gov/ct2/show/NCT02695459

Face-to-face vs telephone pre-colonoscopy consultation in colorectal cancer screening; A randomised trial

Background: A pre-colonoscopy consultation in colorectal cancer (CRC) screening is necessary to assess a screenees general health status and to explain benefits and risks of screening. The first option allows for personal attention, whereas a telephone consultation does not require travelling. We hypothesised that a telephone consultation would lead to higher response and participation in CRC screening compared with a face-to-face consultation. Methods:A total of 6600 persons (50-75 years) were 1: 1 randomised for primary colonoscopy screening with a pre-colonoscopy consultation either face-to-face or by telephone. In both arms, we counted the number of invitees who attended a pre-colonoscopy consultation (response) and the number of those who subsequently attended colonoscopy (participation), relative to the number invited for screening. A questionnaire regarding satisfaction with the consultation and expected burden of the colonoscopy (scored on five-point rating scales) was sent to invitees. Besides, a questionnaire to assess the perceived burden of colonoscopy was sent to participants, 14 days after the procedure.Results:In all, 3302 invitees were allocated to the telephone group and 3298 to the face-to-face group, of which 794 (24%) attended a telephone consultation and 822 (25%) a face-to-face consultation (P=0.41). Subsequently, 674 (20%) participants in the telephone group and 752 (23%) in the face-to-face group attended colonoscopy (P=0.018). Invitees and responders in the telephone group expected the bowel preparation to be more painful than those in the face-to-face group while perceived burden scores for the full screening procedure were comparable. More subjects in the face-to-face group than in the telephone group were satisfied by the consultation in general: (99.8% vs 98.5%, P=0.014).Conclusion:Using a telephone rather than a face-to-face consultation in a population-based CRC colonoscopy screening progr

Differences in treatment of stage I colorectal cancers:A population-based study of colorectal cancers detected within and outside of a screening program

Background:Screen-detected colorectal cancers (CRCs) are often treated less invasively than stage-matched nonscreen-detected CRCs, but the reasons for this are not fully understood. This study evaluated the treatment of stage I CRCs detected within and outside of the screening program in the Netherlands. Methods:Data from the Netherlands Cancer Registry for all stage I CRCs diagnosed between January 1, 2008 and December 31, 2020 were analyzed, comparing patient, tumor, and treatment characteristics of screen-detected and nonscreen-detected stage I CRCs. Multivariable logistic regression was used to assess the association between treatment (local excision only vs. surgical oncologic resection) and patient and tumor characteristics, stratified for T stage and tumor location. Results:Screen-detected stage I CRCs were relatively more often T1 than T2 compared with non-screen-detected stage I CRCs (66.9 % vs. 53.3 %; P 0.001). When only T1 tumors were considered, both screen-detected colon and rectal cancers were more often treated with local excision only than non-screen-detected T1 cancers (odds ratio [OR] 2.19, 95%CI 1.93 2.49; and OR 1.29, 95 %CI 1.05 1.59, respectively), adjusted for sex, tumor location, lymphovascular invasion (LVI) status, and tumor differentiation. Conclusions:Less invasive treatment of screen-detected stage I CRC is partly explained by the higher rate of T1 cancers compared with non-screen-detected stage I CRCs. T1 stage I screen-detected CRCs were also more likely to undergo less invasive treatment than non-screen-detected CRCs, adjusted for risk factors such as LVI and tumor differentiation. Future research should investigate whether the choice of local excision was related to unidentified cancerrelated factors or the expertise of the endoscopists.</p

Omineca Herald, May, 23, 1924

Background: LKB1 mutations are the underlying genetic abnormality causing Peutz-Jeghers syndrome (PJS) and are a potential target for everolimus. In this phase II study, the efficacy of everolimus on polyp and tumor growth in PJS patients was investigated. Methods: Adult patients with a proven LKB1 mutation and who were suitable for everolimus treatment were included in two different PJS cohorts: (a) patients with unresectable malignancies and (b) patients with high-risk polyps. Treatment in both groups was oral everolimus, 10 mg daily. Response rates were primary endpoints for both cohorts. Results: Between October 2011 and April 2016, only two patients were enrolled, one in each cohort. A 49-year-old patient with advanced pancreatic cancer in cohort 1 was progressive after 2 months. A 52-year-old male patient in cohort 2 experienced severe toxicity and refused treatment after 4 months, even though endoscopy suggested stabilization of polyps. Adverse

Awareness of Postpolypectomy Surveillance Guidelines: A Nationwide Survey of Colonoscopists in Canada

INTRODUCTION: Due to the increasing demand for colonoscopy, adherence to postpolypectomy surveillance guidelines is important. Suboptimal compliance can lead to unnecessary risks and ineffective use of resources. OBJECTIVE: To determine the awareness of and adherence to postpolypectomy surveillance guidelines among members of the Canadian Association of Gastroenterology (CAG). METHODS: A survey describing 14 clinical cases was mailed to all physician members (n=411) of the CAG. Respondents were required to recommend a surveillance interval and a reason for his or her choice. RESULTS: A total of 150 colonoscopists (37%) completed the survey. Adherence to the guidelines varied from 23% to 96% per clinical scenario (median 63%). Recommended surveillance intervals were too short in 0% to 60% of the different cases (median 8%). The recommended interval was most often (60%) too short for a patient with one tubular adenoma with high-grade dysplasia. Surveillance intervals were too long in 4% to 75% of the cases (median 9%). The recommended interval was most often too long in a patient with a villous adenoma 15 mm in size and removed piecemeal (75%). Most often, recommendations were reported to be based on guidelines (median 74%; range 31% to 94%). However, in nine of 14 cases, more than 10% (median 18%; range 12% to 38%) of the respondents stated that their recommendation was based on guidelines, but did not provide the appropriate surveillance interval. CONCLUSIONS: Compliance to colonoscopy surveillance guidelines is suboptimal and reflects both overuse and underuse. The results show that awareness about the content of guidelines needs to be raised and strategies implemented to increase adherence

Socio-demographic and cultural factors related to non-participation in the Dutch colorectal cancer screening programme

BackgroundHigh participation rates are essential for a screening programme to be beneficial. To reach non-participants in a targeted manner, insight in characteristics of non-participants is needed. We investigated demographic differences between participants and non-participants in the Dutch faecal immunochemical test-based colorectal cancer (CRC) screening programme.MethodsIn this population-based cohort study, we included all invitees for CRC screening in 2018 and 2019. Participation status, birth year, and sex were extracted from the Dutch national screening information system and linked to demographic characteristics from Statistics Netherlands, including migration background, level of education, socioeconomic category, household composition, and household income. A multivariable logistic regression was used to assess the association between demographic factors and participation.ResultsA total of 4,383,861 individuals were invited for CRC screening in 2018 and 2019, of which 3,170,349 (72.3%) participated. Individuals were less likely to participate when they were single and/or living with others (single with other residents versus couple: odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.31–0.38), had a migration background (e.g. Moroccan migrant versus Dutch background: OR 0.43, 95% CI: 0.42–0.44), or had a low income (lowest versus highest quintile: OR 0.45, 95% CI: 0.44–0.45). Although to a lesser extent, non-participation was also significantly associated with being male, being younger, receiving social welfare benefits and having a low level of education.ConclusionWe found that individuals who were single and/or living with others, immigrants from Morocco or individuals with low income were the least likely to participate in the Dutch CRC screening programme. Targeted interventions are needed to minimise inequities in CRC screening.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Substantial and sustained improvement of serrated polyp detection after a simple educational intervention: Results from a prospective controlled trial

Objective: Serrated polyps (SPs) are an important cause of postcolonoscopy colorectal cancers (PCCRCs), which is likely the result of suboptimal SP detection during colonoscopy. We assessed the long-term effect of a simple educational intervention focusing on optimising SP detection. Design: An educational intervention, consisting of two 45 min training sessions (held 3 years apart) on serrated polyp detection, was given to endoscopists from 9 Dutch hospitals. Hundred randomly selected and untrained endoscopists from other hospitals were selected as control group. Our primary outcome measure was the proximal SP detection rate (PSPDR) in trained versus untrained endoscopists who participated in our faecal immunochemical test (FIT)-based population screening programme. Results: Seventeen trained and 100 untrained endoscopists were included, who performed 11 305 and 51 039 colonoscopies, respectively. At baseline, PSPDR was equal between the groups (9.3% vs 9.3%). After training, the PSPDR of trained endoscopists gradually increased to 15.6% in 2018. This was significantly higher than the PSPDR of untrained endoscopists, which remained stable around 10% (p=0.018). All below-average (ie, PSPDR ≤6%) endoscopists at baseline improved their PSPDR after training session 1, as did 57% of endoscopists with average PSPDR (6%-12%) at baseline. The second training session further improved the PSPDR in 44% of endoscopists with average PSPDR after the first training. Conclusion: A simple educational intervention was associated with substantial long-term improvement of PSPDR in a prospective controlled trial within FIT-based population screening. Widespread implementation of such interventions might be an easy way to improve SP detection, which may ultimately result in fewer PCCRCs. Trial registration number: NCT03902899

Interpretation and adherence to the updated risk-stratified guideline for colonoscopy surveillance after polypectomy - a nationwide survey

Background and study aims Low adherence to the Dutch guideline for colonoscopy surveillance after polypectomy led to release of a new guideline in 2013. This new guideline was risk-stratified at a more detailed level than the previous one to achieve more efficient use of colonoscopy resources. This study assessed the feasibility of the risk-stratified guideline by evaluating correct interpretation of and adherence to this guideline. Methods Based on semi-structured interviews with 10 gastroenterologists, we developed an online survey to evaluate gastroenterologists’ recommendations for surveillance in 15 example cases of patients with polyps. If recommended intervals differed from the new guideline, respondents were asked to indicate their motives for doing so. Results Ninety-one of 592 (15.4 %) invited gastroenterologists responded to at least one case, of whom 84 (14.2 %) completed the survey. Gastroenterologists gave a correct recommendation in a median of 10 of 15 cases and adherence per case ranged from 14 % to 95 % (median case 76 %). The two cases that addressed management of serrated polyps were least often answered correctly (14 % and 28 % correct answers). Discrepancies were mainly due to misinterpretation of the guideline with respect to serrated polyps (48 %) or misreading of the questions (30 %). Conclusions Median adherence to the updated colonoscopy surveillance guideline of 76 % seems reasonable, and is higher than adherence to the previous guideline (range: 22 %-80 %, median 59 %). This shows that detailed (more complex) risk stratification for designation of a surveillance interval is feasible. Adherence could potentially be improved by clarifying correct interpretation of serrated polyps