Screening for colorectal cancer in defunctioned colons (2018)

Type of publication:
Journal article

Author(s):
*Akbar, Fayyaz; Quyn, Aaron; Steele, Robert

Citation:
Journal of medical screening; Dec 2018; vol. 25 (no. 4); p. 178-182

Abstract:
OBJECTIVES Population-based colorectal (bowel) cancer screening using faecal occult blood tests leads to a reduction in cause-specific mortality. However, in people where the colon is defunctioned, the use of standard faecal occult blood test is not appropriate. The aim of this study was to examine the current trends of clinical practice for colorectal cancer screening in people with defunctioned colons.METHODS An online survey was performed using SurveyMonkey. All members of the Association of Coloproctology of Great Britain and Ireland were invited by email to participate. Reminders were sent to non-responders and partial responders till six weeks. All responses were included in our analysis. RESULTS Of the 206 (34.59%) questionnaires completed, all questions were answered in 110 (55.8%). Among responders, 94 (85.4%) were colorectal consultant surgeons, 72% had worked in their current capacity for more than five years, and 105 (50.9%) had encountered colorectal cancer in defunctioned colons during their career. Some 72.2% of responders stated that a screening test for colorectal cancer in patients with defunctioned colons was currently not offered, or that they did not know whether or not it was offered in their area.CONCLUSIONS Bowel screening in the United Kingdom is currently not offered to 72.2% of the age appropriate population with defunctioned colons. Among responding colorectal surgeons, 50% had encountered colorectal cancer in such patients. There is considerable variability in clinical practice regarding the optimal age for onset of screening, time interval, and the optimal modality to offer for screening in such cases.

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3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial (2018)

Type of publication:
Randomised controlled trial

Author(s):
Iveson TJ, Kerr RS, Saunders MP, Cassidy J, Hollander NH, Tabernero J, Haydon A, Glimelius B, Harkin A, Allan K, McQueen J, Scudder C, Boyd KA, Briggs A, Waterston A, Medley L, Wilson C, Ellis R, Essapen S, Dhadda AS, Harrison M, Falk S, Raouf S, Rees C, Olesen RK, Propper D, Bridgewater J, Azzabi A, Farrugia D, Webb A, Cunningham D, Hickish T, Weaver A, Gollins S, Wasan HS, Paul J. [SaTH was one of the sites this trial took place at]

Citation:
Lancet Oncology 2018 Apr;19(4):562-578

Abstract:
BACKGROUND: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.
METHODS: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing.
FINDINGS: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group).
INTERPRETATION: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care.
FUNDING: Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK.

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Protein biomarkers in the rectal mucosa: a novel test for colorectal cancer? (2015)

Type of publication:
Conference abstract

Author(s):
*Lacy-Colson J., Norwood M., Murray C., Booth J.

Citation:
Gut, June 2015, vol./is. 64/(A529-A530)

Abstract:
Introduction: Earlier detection of colorectal cancer is a clinical priority. Currently very high numbers of patients are referred for colonoscopy under the 2 week rule system, with a pick up rate for cancer of 1:20 or less putting a major strain on endoscopy units investigating large numbers of the worried well. The aim of this study was to assess the correlation of protein biomarkers captured from the rectal mucosa with the presence or absence of colorectal cancer. Method We conducted a case control study of 20 patients with colorectal cancer, and 20 controls. All patients had been referred to colorectal outpatients with potentially worrying symptoms; presence or absence of cancer was determined by colonoscopy or CT virtual colonoscopy. A novel sampling device, OriColTM, was employed to collect samples of rectal mucosa for biomarker analysis. The device incorporates a nitrile membrane which, following insertion into the unprepared rectum via a standard proctoscope, is inflated to make contact with the rectal mucosa for a period of 10 s. Upon deflation and retraction of the membrane, a preservation buffer is added to preserve the sample prior to analysis. Sampling can be performed in an outpatient setting in under 2 min and has been shown to be well tolerated in >2500 patients. The levels of various antibodies, haemoglobin and carcinoembryonic antigen were analysed using conventional ELISA techniques. Statistical analysis of the trial results was performed using the Wilcoxon test for non-parametric comparisons with two sided p values. The area under the receiver operating characteristic (ROC) curve for distinguishing between the two diagnostic groups, together with its confidence interval, was calculated for each biomarker. Logistic regression analyses were used to investigate the performance of different combinations of biomarkers. This study was conducted with appropriate research ethics committee approval. Results Univariate analyses identified five candidate predictive biomarkers for colorectal cancer. All combinations of two and three predictors were investigated using logistic regression. The best performing combination of biomarkers was haemoglobin and IgA. The area under the ROC curve for this best linear combination was 0.86. Conclusion We suggest that ELISA analysis protein biomarkers collected with the OriColTM device offers a potentially useful and cost-effective pre-colonoscopy screening tool in patients referred under the 2 week rule criteria. Data from this pilot study suggests that a sensitivity of >95% can be achieved while massively reducing the number of patients requiring urgent colonoscopy to exclude a diagnosis of cancer.

Link to full-text: http://gut.bmj.com/content/64/Suppl_1/A529.2.full.pdf+html

Does compliance with the 2 week wait colorectal cancer referral system lead to a higher cancer detection rate? (2014)

Type of publication:
Conference abstract

Author(s):
*Kaur P., *Cheetham M., *McCloud J.

Citation:
Colorectal Disease, July 2014, vol./is. 16/(73), 1462-8910 (July 2014)

Abstract:
Background: Current guidelines suggest that patients with a suspected colorectal cancer are seen within 2 weeks of the referral made by general practitioners. Recent data has shown an increase in referrals with a decrease in cancer yield, with up to 25% of all referrals made not meeting referral guidelines. This study aims to determine if there is a higher cancer detection rate in referrals compliant with the referral criteria. Method: A retrospective study of patients referred to a 2-week wait colorectal clinic over a 3-month period was performed. Referral proformas and initial clinic letters were assessed to determine compliancy with the 2 week wait criteria and number of cancers diagnosed. Results: 287 patients were seen in the 3 month period. 38% of referrals were not compliant with the referral criteria. The main reasons for noncompliance were age of the patient (28%) and duration of symptoms (21%). 15 (5.2%) patients were diagnosed with cancer. Compliant referrals had higher cancer detection rate, 13/180 patients (7.2%) when compared with non-compliant referrals, 2/107 patients (1.9%). Conclusion: Compliance with the referral criteria is associated with a higher cancer detection rate. Better education for general practitioners may help to reduce the number of non-compliant referrals reducing work load on strained colorectal units.

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Incidence of metachronous colorectal tumours at one year surveillance colonoscopy (2014)

Type of publication:
Conference abstract

Author(s):
*Bajwa A., *McConnell C., *Odulaja M., *Chandra A., *Luke D., *Cheetham M.

Citation:
Colorectal Disease, September 2014, vol./is. 16/(59), 1462-8910 (September 2014)

Abstract:
Aim: The National Institution for health and care excellence (of United Kingdom) updated their guidelines for colorectal cancer follow up in 2011. This included the recommendation for a 1 year post op surveillance colonoscopy to detect metachronous malignant and premalignant colorectal tumours. The aim of this study was to assess the efficacy of this aggressive surveillance policy. Method: Seventy-five consecutive patients who had undergone colorectal resections with curative attempt over a 12 month period after the publication of the 2011 guidelines. Outcome after their 1 year surveillance colonoscopy was examined to determine the incidence of new colorectal cancers and adenomatous polyps. Results: Of 75 (male = 47) patients (median (range) 71 (34-89)) were included. No new colorectal cancers were detected at 1 year surveillance colonoscopy. New adenomatous polyps were detected in 11 of the 75 patients (15%). Conclusion: The 2011 NICE guidelines include both a recommendation for full pre operative colonoscopy to detect synchronous tumours, and one and 5 yearly post operative colonoscopies to detect metachronous lesions. The evidence for the efficacy for early surveillance is unclear. We detected no new colorectal cancers and only 15% had new adenomatous polyps at one year indicating that early surveillance may not be warranted.

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