study protocol version 11 april...
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Study Protocol Version 11 April 2020
Contents Glossary of Abbreviations 3Project Summary 4CRC COVID Steering Group 51. Background 72. Aims and Objectives 83. Audit Standards 84. Methods 155. Data Collection 166. Data Management and Storage 207. Data Analysis 208. Study Management 209. Ethical approval 2010. Publication and Authorship Policy 21Appendix 1: CRC COVID Steering Committee Charter 22Bibliography 23
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Glossary of Abbreviations
APE Abdominoperineal Excision
CEA Carcinoembryonic antigen
CT Computer Tomography
CTC CT Colonography
CRC Colorectal Cancer
CRT Chemotherapy-Radiotherapy
COVID-19 Coronovirus disease 2019
CXB Contact X-ray Brachytherapy
ELAPE Extralevator APE
ERAS Enhanced Recovery After Surgery
ESD Endoscopic Submucosal Dissection
MRF Mesorectal Fascia
MRI Magnetic Resonance Imaging
NCCN National Comprehensive Cancer Network
NHS National Health Service (UK)
NICE National Institute for Health and Care Excellence
OGD Oesophago-Gastro-Duodenoscopy
REDCap Research Electronic Data Capture
SCPRT Short Course Pre-operative Radiotherapy
SSI Surgical Site Infection
TAE Transanal Excision
TAMIS Transanal Minimally Invasive Surgery
TEMS Transanal Endoscopic Microsurgery
TME Total Mesorectal Excision
VTE Venous Thromboembolism
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Project Summary
Short title CRC COVID
Methodology 4 phase audit/service evaluation:1. Phase 1 - National Colorectal Cancer Service Modification Survey2. Phase 2 - Evaluation of the Colorectal Cancer Service Provision3. Phase 3 - Cost analysis and Projections of Additional Resources 4. Phase 4 - Comparison of the NHS and the USA model of Healthcare
Research Site International - UK and USA
Aim Real time prediction of the impact on colorectal cancer services during COVID 19 pandemic
Primary Objectives
(All Phases)
1. Evaluate adherences and deviations from the best practice guidelines on colorectal cancer during COVID-19 pandemic
2. Determine the impact on CRC service provision following modifications on long-term cancer specific outcomes compared to national standards
3. Predict the costs attributable to modifications of CRC services during COVID-19 pandemic
4. Predict additional resources required to treat patients whose treatment has been affected by COVID-19
5. Compare the impact of COVID-19 on the NHS and USA model of healthcare in terms of service provision and cost
Study Duration Duration of COVID-19 pandemic plus additional 6 months after it subsides
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CRC COVID Steering Group
CRC COVID Contact: [email protected] , www.CRCcovid.org
Name Contact Details
Prof Paris Tekkis (Project PI)BMed.Sci., BM BS, MD, FRCS
Professor of Colorectal SurgeryFaculty of Medicine, Department of Surgery &
CancerImperial College [email protected]
Professor the Lord Darzi of Denham PC KBE FRS FMedSci HonFREng
Faculty of Medicine, Department of Surgery & Cancer
Co-Director of IGHIProfessor of Surgery, Imperial College London
Prof Nicos SavvaMA, MPhil, PhD
Professor of Operations ManagementLondon Business School
Professor Jonathan Edward Efron MD. The Mark M. Ravitch, M.D. Endowed
Professorship in Gastrointestinal SurgeryProfessor of Surgery
Johns Hopkins [email protected]
Christos Kontovounisios (Project PI)MD, PhD, FACS, FRCS
Clinical Senior LectureConsultant Colorectal and General Surgeon
Imperial College [email protected]
Najib Daulatzai BSc. (Hons), MBBS, Msc, MD (Res)
FRCS (Gen Surg.)
Consultant Colorectal and General SurgeonChelsea and Westminster Hospital
Oliver Warren BSc (Hons), MBBS (Hons), MD (Res),
FRCS (Gen.Surg.)
Consultant Colorectal and General SurgeonHonorary Clinical senior Lecturer
Imperial College [email protected]
Sarah Mills BSc (Hons), BMBCh, MD(Res), FRCS
(Gen Surg)
Consultant Colorectal SurgeonHonorary Clinical senior Lecturer
Imperial College London [email protected]
Shahnawaz Rasheed B Clin Sci, MBBS, DIC, PhD, FRCS
Colorectal Consultant Surgeon The Royal Marsden Hospital
Dr Bashar Safar MBBS
Chief of Colorectal SurgeryAssistant Professor of SurgeryThe Johns Hopkins Hospital
Dr Tinglong DaiBEng, MPhil. MSIA, PhD
Associate Professor of Operations Management and Business Analytics
Johns Hopkins University Carey Business [email protected]
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Matthew GardinerMA PhD FRCS(Plast)
Honorary Departmental Clinical Lecturer In Plastic And Reconstructive Surgery
The Kennedy Institute of Rheumatology Oxford University
Alona Courtney MBChB, BSc (Hons), MSc, MRCS
Academic Clinical Fellow in General SurgeryImperial College London
Ann-Marie HowellBSc (Hons), MBBS (Hons), PhD, MRCS
Surgical Registrar Chelsea and Westminster [email protected]
Goel MilindMSc. (LBS), B.Arch. (SPA Delhi)
ResearcherLondon Business School
Nicholas Tekkis BA (Hons) Medical Student University of Cambridge
Mr George Kouttoukis Patient [email protected]
Ms Hayley Slabbert Patient [email protected]
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1. Background
1.1 Relevance of this project COVID-19 pandemic has had a significant impact on the provision of healthcare worldwide. At a local level, hospitals have been forced to make a number of work-force modifications and changes to service-provision to combat the crisis and maintain standards of care for their patients. In Colorectal Surgical departments, face-to-face consultations have been dissolved or minimized in favour of telephone or virtual clinics. Provisions of investigations (including CT scans and endoscopies) have been significantly reduced and all benign surgical procedures postponed. Furthermore, the treatment algorithm for confirmed colorectal cancer cases has proved challenging. Intercollegiate General Surgery Guidance on COVID-19 has outlined general principles on provision of a safe surgical service during the pandemic. However, there has been no specific guidance to date on how to best modify colorectal cancer (CRC) service provision during the pandemic. Deviation from NICE guidelines on colorectal cancer service provision has the potential to lead to significantly poorer outcomes. However, the current model of cancer services delivery cannot be maintained during this pandemic, because of both resource limitation and the potential risks to patients and staff. There is an expected lack of High Dependency Beds, which are currently being utilized for COVID-19 patients. There is the risk of exposing colorectal cancer patients (the majority of whom are elderly and have significant comorbidities) to the virus during their treatment within the hospital. Patients requiring neo-adjuvant or adjuvant therapy are at particular risk. Finally, staff safety must also be considered, particularly around procedures such as endoscopy and laparoscopic surgery. In the absence of a national consensus, the onus is on individual hospital trusts and multidisciplinary teams to make very challenging decisions about individual patient care. Lack of a unified approach may have important consequences at patient and healthcare institution levels.Delay in cancer diagnosis, or treatment due to service modification is likely to create an increased demand in resources once the crisis has passed. Predicting the economic impact and planning for this is essential.Resource allocation and approach to theses issues may vary between the UK and USA and it is hoped that gaining insights from both perspectives will improve the problem solving.
1.2 National research collaborative This project will be conducted through a national research collaborative, with the support of the CRC COVID Steering Committee. We realise that a traditional model of trainee collaborative may not be possible in the current environment where many trainees are redeployed to support other specialties. Significant support will be sought from the consultant body and Cancer Nurse Specialists.
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2. Aims and Objectives The aim of the CRC COVID study is to describe the changes in colorectal cancer services in the UK and USA in response to a COVID-19 pandemic and to understand the long-term impact.
Phase 1 - National Colorectal Cancer Service Modification Survey Primary Objective:
1. Evaluate adherences and deviations from best practice guidelines on colorectal cancer during COVID-19 pandemic
Secondary Objectives:
2. Describe modifications to screening process for CRC3. Describe modifications to pre-operative, intra-operative and post-operative CRC service
delivery4. Demonstrate global effect of COVID-19 pandemic on CRC service provision irrespective of the
type of healthcare system 5. Outline consensus recommendations for sustainable modifications to CRC services
Phase 2 - Evaluation of the Colorectal Cancer Service Provision Primary objective:
1. Determine the impact of CRC service provision following modifications on long-term cancer specific outcomes compared to national standards
Secondary Objectives: 2. Predict the impact of modifications on the incidence and prevalence of different CRC stages in
12 months 3. Plan adjustments to CRC service provision after the end of pandemic
Phase 3 - Cost Analysis and Projections of Additional Resources Objectives:
1. Predict the costs attributable to modifications of CRC services during COVID-19 pandemic2. Predict additional resources required to treat patients whose treatment has been affected by
COVID-19
Phase 4 - Comparison of the NHS and the USA model of healthcare Objectives:
1. Compare the impact of COVID-19 on the NHS and USA model of healthcare in terms of service provision and cost
2. Propose a standardised model of delivering colorectal cancer services for future outbreaks
3. Audit Standards The following guidelines relate to the management of colorectal cancer and will be used as audit standards:1. NICE guidelines: Colorectal Cancer [NG151] (1)
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2. NICE guideline: Suspected cancer: recognition and referral [NG12](2)3. Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the
Management of Cancer of the Colon, Rectum and Anus (2017) (3-7)4. British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/
Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines (2020) (8)
5. NCCN Evidence Blocks: Colon Cancer 20206. NCCN Evidence Blocks: Rectal Cancer 2020
3.1 Suspected Colorectal Cancer Investigations
1. Review in colorectal clinic within 2 weeks the following patients: (2, 3)1.1.aged 40 and over with unexplained weight loss and abdominal pain 1.2.aged 50 and over with unexplained rectal bleeding1.3.aged 60 and over with iron‑deficiency anaemia or changes in their bowel habit1.4.tests show occult blood in their faeces1.5.aged over 75 with any of the following symptoms: change in bowel habit, rectal
bleeding, rectal mass, abdominal mass, anaemia2. Colonoscopy within 2 weeks is indicated in the following cases:(3)
2.1.Aged over 55 with looser and/or more frequent stools, persistently for more than 6 weeks without rectal bleeding
2.2.Aged over 40 with rectal bleeding and a change in bowel habit to looser and/or more frequent stools persistently for 6 weeks
3. Flexible sigmoidoscopy within 2 weeks is indicated in the following cases:(3)3.1.Aged over 55 with rectal bleeding persistently for >6 weeks without a change in bowel
habit & without anal symptoms 3.2.A definite palpable rectal (not pelvic) mass
4. CT Colonography or Colonoscopy within 2 weeks is indicated in the following cases:(3)4.1.A definite palpable abdominal mass
5. CT Colonography or Colonoscopy and OGD within 2 weeks is indicated in the following cases:(3)
5.1.Men of any age with unexplained iron deficiency and haemoglobin of 110 g/l or below5.2.Non-menstruating women with unexplained iron deficiency anaemia and haemoglobin
100 g/l or below
Pre-operative histology (3)
6. Preoperative histological confirmation of colonic cancer is desirable but not essential in cases with high probability of malignancy based on clinical presentation and optimal imaging
7. Pre-treatment histological confirmation of rectal cancer is considered essential. Exceptions should be rare and are usually large lesions not amenable to endoscopic removal and inconclusive biopsies
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Staging (3)
8. All patients with suspected colonic cancer should be staged with a CT thorax, abdomen and pelvis
9. All patients with suspected rectal cancer should be staged with a CT thorax, abdomen and pelvis. Patients being considered for curative loco-regional treatment should have MRI of the pelvis
10.Synchronous lesions should be identified using colonoscopy or CTC prior to colorectal cancer resection. If complete colonoscopy is not possible, CTC should be considered. CT of the thorax can be combined with CTC to permit staging at the same hospital visit
3.2 Surgical Treatment - General Principles Pre-operative planning (7)
1. Treatment should begin within 31 days of the decision to treat2. The management plans for all colorectal cancer patients should be reviewed by a Colorectal
MDT3. Peri-operative care in elective surgery should be based on ERAS principles4. Preoperative carbohydrate loading should be considered in all patients undergoing elective
colorectal cancer resection5. Routine use of mechanical bowel preparation prior to elective colorectal cancer resection
should be avoided 6. Patients who may require a stoma should be counselled preoperatively and marked by a stoma
care specialist7. Peri-operative measures to minimise SSI should be considered. A single dose of broad-
spectrum antibiotics prior to commencement of surgery should be administered8. Patients should be warned that there is potential significant delay in ileostomy closure following
anterior resection and up to 25% may never get reversed9. All patients with suspected large bowel obstruction should have a contrast-enhanced CT10.Decision-making in older patients should consider co-morbidities, life expectancy and the
natural history of the cancer, and performance status, rather than age alone11.Older patients being offered curative resection should be considered for laparoscopic surgery
Intra-operative (7)
12.Cytocidal washout of the rectal stump should be used prior to anastomosis 13.After low anterior resection, a temporary defunctioning stoma should be considered
Post-operative (7)
14.A combination of graduated compression stockings, intermittent compression devices and low molecular weight heparin should be used for VTE prophylaxis in patients undergoing surgery. Extended prophylaxis for 28 days postoperatively should be considered
15.Patients with a predicted mortality of >10% should be managed in a Critical Care Unit
Outcome standards
16.Colorectal units should expect to achieve an operative mortality of less than 20% for emergency surgery and less than 5% for elective surgery for colorectal cancer (7)
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17.A R0 resection should be achieved in >90% of colorectal cancers predicted to be resectable on appropriate staging (7)
18.The number of lymph nodes retrieved should be a median of at least 12 per specimen (5)
3.3 Colon Cancer Pre-operative management
1. cT4 colon cancer (1)1.1.Offer systemic anti-cancer therapy
2. Colonic stenting (1)2.1.acute left-sided large bowel obstruction and palliative intent 2.2.acute left-sided large bowel obstruction and curative surgery possible
Intra-operative management
3. Laparoscopic resection should be considered in all patients with colon cancer (7)
Post-operative management
4. stage III colon cancer (pT1-4, pN1-2, M0) (1, 7)4.1.Offer the following chemotherapy:
4.1.1.capecitabine in combination with oxaliplatin (CAPOX) for 3 months, or 4.1.2.oxaliplatin in combination with 5-fluorouracil and folinic acid (FOLFOX) for 3
to 6 months, or 4.1.3.single-agent fluoropyrimidine (for example, capecitabine) for 6 months
3.4 Rectal Cancer Pre-operative management
1. Early rectal cancer (cT1-T2, cN0, M0)1.1.Should not be offered pre-operative radiotherapy (1)1.2.Contact x-ray brachytherapy (CXB) is considered a treatment option for patients
considered not suitable for TEM surgery or for patients considered suitable for surgery, but who decline operation (4)
2. Rectal cancer (cT1-T2, cN1-N2, M0 or cT3-T4, any cN, M0)2.1.Should be offered pre-operative radiotherapy or chemotherapy (1)
3. Timing of surgery following chemotherapy-radiotherapy (CRT) (4)3.1.In patients receiving short course pre-operative radiotherapy (SCPRT), surgery should
be performed within 11 days from the first fraction of radiotherapy to minimize risk of complications. If surgery cannot be performed within this interval and the patient has already commenced radiotherapy, surgery should be delayed beyond 4 weeks
3.2.In patients receiving long course CRT, surgery should be scheduled 6–10 weeks after completion of CRT. A dose of at least 45 Gy in 25 fractions with synchronous 5FU or oral capecitabine is recommended
Operative management
4. Early rectal cancer (cT1-T2, cN0, M0, mesorectal fascia negative) should be treated with: (1, 4)
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4.1.Either Transanal excision (TAE) (transanal minimally invasive surgery (TAMIS) and transanal endoscopic microsurgery (TEMS)), or Endoscopic submucosal dissection (ESD), or Total mesorectal excision (TME)
4.2.Local excision after short course radiotherapy (SCRT) or chemo-radiotherapy (CRT) if patients are unfit or refuse standard resectional surgery and appear to have residual disease
5.Rectal cancer threatening, involving or beyond the mesorectal fascia (cT3-4 N0-2 M0, mesorectal fascia positive) (4)
5.1.Should be treated with long course CRT, followed by surgery 8–12 weeks later. A dose of at least 45 Gy in 25 fractions with synchronous 5FU or oral capecitabine is recommended.
5.2.In patients not sufficiently fit to tolerate long course CRT, should be treated with SCPRT followed by delayed surgery 8–12 weeks later, to allow time for maximal tumour shrinkage.
5.3.Should be restaged with MRI pelvis and CT chest, abdomen and pelvis towards the end of the 8–12 week interval between completion of RT and planned surgery.
6. Offer Laparoscopic surgery for resectable rectal cancer (1)6.1.Except where open surgery is clinically indicated
6.1.1.locally advanced tumours6.1.2.multiple previous abdominal operations6.1.3.previous pelvic surgery
Post-operative management
7. stage III rectal cancer (pT1-4, pN1-2, M0) (1)7.1.Offer the following chemotherapy:
7.1.1.capecitabine in combination with oxaliplatin (CAPOX) for 3 months, or 7.1.2.oxaliplatin in combination with 5-fluorouracil and folinic acid (FOLFOX) for 3
to 6 months, or 7.1.3.single-agent fluoropyrimidine (for example, capecitabine) for 6 months
8. Patients with high-risk stage II colorectal cancer should be considered for adjuvant chemotherapy (4)
3.5 Low rectal cancer Operative management (4)
1. For a low rectal cancer lying above the level of the anal sphincter, which is not threatening (>1 mm) the levator muscle or MRF, the mesorectal plane can be used. A TME and coloanal anastomosis may be feasible. If this is not feasible, an APE (conventional or intersphincteric) should be performed.
2. For a low rectal cancer lying above the level of the anal sphincter, which is ≤1 mm from the levator muscle or MRF or invading the levator, an ELAPE should be performed. This is generally preceded by long course CRT and an 8– 12 week gap.
3. For a low rectal cancer lying at the level of the sphincter, which is involving the submucosa only or the inner layer of the muscularis propria, the mesorectal plane can be used, continuing inferiorly into the intersphincteric plane as an APE (conventional or intersphincteric).
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4. For a low rectal cancer lying at the level of the sphincter, which involves the full thickness of the muscularis propria or extends into or beyond the intersphincteric plane to involve the external sphincter, an ELAPE should be performed. This is generally preceded by long course CRT and an 8– 12 week gap.
3.6 Metastatic colorectal cancer 1. Test for RAS and BRAF V600E mutations if suitable for systemic anti-cancer treatment (1)2. Surgery
2.1.Consider surgical resection of the primary tumour in patients with incurable metastatic colorectal cancer (1)
2.2.Patients with locally advanced and locally recurrent rectal cancer should be referred to a specialist centre for consideration for exenterative surgery (1, 7)
3. Chemotherapy (1)3.1.Oral capecitabine is recommended the first-line treatment
4. Biological therapy (1)4.1.Cetuximab is recommended for previously untreated EGFR-expressing, RAS wild-
type metastatic colorectal cancer in adults in combination with FOLFOX or FOLFIRI4.2.Panitumumab is recommended for previously untreated RAS wild-type metastatic
colorectal cancer in adults in combination with FOLFOX or FOLFIRI
Liver Metastases (1)
5. If suitable for liver resection 5.1.Consider resection 5.2.Consider systemic anti-cancer therapy
6. If unsuitable for liver resection 6.1.Consider chemotherapy with local ablative techniques 6.2.Do not offer selective internal radiation therapy (SIRT) as first-line treatment
Lung Metastases (1)
7. Consider metastasectomy, ablation or stereotactic body radiation therapy for people with lung metastases suitable for local treatment
8. Consider biopsy for a single lung lesion to exclude primary lung cancer
Peritoneal Metastases (1)
9. offer systemic anti-cancer therapy 10.Consider referring for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
(HIPEC)
Management of advanced disease (7)
11.Patients with colorectal cancer and localized peritoneal disease at primary presentation or as localized recurrence may benefit from discussion with a peritoneal malignancy unit.
12.Patients with a perforated mucinous appendiceal tumour or pseudomyxoma peritonei should be discussed with a peritoneal malignancy unit.
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13.Patients diagnosed with neuroendocrine neoplasms may benefit from referral to a regional centre specializing in neuroendocrine tumours, for confirmation of histological diagnosis and advice on subsequent management.
3.7 Follow-up 1. Detection of treatable recurrent disease (1, 6)
1.1.CT of the chest, abdomen and pelvis every 6 months for 2 years, then annually for 3 years, or
1.2.Serum CEA screening every 3 months for 2 years, then every 6 months for 3 years 2. Detection of Metachronous Colorectal Tumours and Polyps
2.1.A minimum of 2 CT scans of the chest, abdomen and pelvis in the first 3 years (6)2.2.Regular serum CEA (at least every 6 months in the first 3 years) (6)2.3.Surveillance colonoscopy 1 year after initial treatment and subsequently surveillance
colonoscopy in 3 years (8)3. After local excision of early rectal cancer, patients should be followed up with 3–6 monthly MRI,
CEA and flexible sigmoidoscopy (4)
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4. Methods This service evaluation will be carried out in 4 phases.
4.1 Phase 1 - National Colorectal Cancer Service Modification Survey The survey will be distributed nationally (UK and USA) to surgical units performing colorectal surgery. Data will be collected using REDCap. All data must be submitted within the data collection period. The results will be used to provide consensus recommendations for modifications to colorectal cancer service provision during COVID-19 pandemic across the UK. Data collection will be repeated subsequently to monitor changes in service provision.
4.2 Phase 2 - Evaluation of the Colorectal Cancer Service Provision The impact of modifications to CRC service provision will be reviewed in Phase 2.
4.2.1 Centre inclusion criteria and clinical governance
Surgical units continuing to provide colorectal cancer services will be included in this service evaluation. All participating centres will be required to register this service evaluation as per local protocol; this will be the responsibility of the local lead. Confirmation of registration and local clinical audit department approval will be required prior to issuing of REDCap access and commencement of data collection.
4.2.2 Data Collection
All surveys and data collection will follow GDPR requirements. Individual patient identifiable data will not be collected in this study. The aim of this phase is to collect data on service delivery and compare it to the national performance indicators for patients with colorectal cancer. All included centres will need to submit data initially. A selection of centres will be invited to submit subsequent data on a rotational basis and in line with the predictive model designed by the London Business School and John Hopkins Carey Business School for the duration of the pandemic.
4.2.3. Missing Data and Data Validation
After the close of the data collection period, all data sets will be checked for missing data. Where possible, centres will be given an opportunity to rectify missing data. Centres where >5% of data is missing will be excluded from data analysis and local leads will be notified. A nominated data validator will need to ensure data accuracy prior to submission. If during this process major discrepancy is identified within the data set, the centre’s data will be excluded completely from the analysis.
4.3 Phase 3 - Cost Analysis and Projections for additional resources A prediction model of the economic burden of the modifications in cancer service delivery will be designed by the London Business School and John Hopkins Carey Business School, based on previous publications and national statistics.
4.4 Phase 4 - Comparison of the NHS and the USA model of healthcare The impact of COVID-19 on the NHS and USA model of healthcare will be compared in terms of specific differences in modifications of CRC service. Data collected during Phase 2 will be used and addition to the predictive mode utilized in Phase 3.
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5. Data Collection The following data set will be collected by the local lead / collaboratives using REDCap database facility.
5.1 Phase 1 - National Colorectal Cancer Service Modification Survey Pre-operative modifications
1. Patients referred for a 2-week wait colorectal appointment is Seen face-to-faceTelephone triage and only selected patient seen face-to-face All clinics cancelled during COVID-19 pandemic
2. Colonoscopy for suspected cancer is performed In ALL patients meeting guidelines criteriaOnly in SELECTED patients with change in bowel habit for >6 weeks Only in SELECTED patients with rectal bleeding Only in SELECTED patients with iron deficiency anaemia NO endoscopy available during COVID-19 pandemic
3. Flexible sigmoidoscopy for suspected cancer is performed In ALL patients meeting guidelines criteriaOnly in SELECTED patients with with rectal bleeding persistently for >6 weeks without a change in bowel habit & without anal symptoms
Only in SELECTED patients with definite palpable rectal (not pelvic) mass NO endoscopy available during COVID-19 pandemic
4. CT Colonography for suspected cancer is performedIn ALL patients meeting guidelines criteriaIn ALL patients instead of colonoscopy Only in SELECTED patients with iron deficiency anaemiaOnly in SELECTED patients with abdominal mass NO CT Colonography available during COVID-19 pandemic
5. Where CT Colonography and Colonoscopy are suspended, patients with suspected cancer are assessed using
CT chest, abdomen and pelvisCT abdomen and pelvisTumour markers Barium enema PET CT
6. Pre-operative histology Is obtained for ALL colorectal cancer patients as per usual practice Is obtained for rectal cancer patient only
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Is NOT available for any colorectal cancer patients during COVID-19 pandemic 7. Staging of colorectal cancer
CT chest, abdomen and pelvis is performed in ALL colorectal cancer patients MRI pelvis is performed in ALL rectal cancer patients Synchronous lesions are identified using colonoscopy prior to colorectal cancer resectionSynchronous lesions are identified using CT Colonography prior to colorectal cancer resection
Synchronous lesions are NOT assessed as both CT Colonography and Colonoscopy will be suspended during COVID-19 pandemic
8. Pre-operative (neoadjuvant) radiotherapy Is offered to patient with RECTAL cancer (cT1-T2, cN1-N2, M0 or cT3-T4, any cN, M0)Is offered to patient with early RECTAL cancer (cT1-T2, cN0, M0)Is NOT offered to any patients during COVID-19 pandemicIs offered to ALL RECTAL cancer patients as a bridge to definitive surgery
9. Pre-operative (neoadjuvant) radiotherapy Is offered as short course onlyIs offered as short course with a boostIs offered as standard CRT long course
10. Pre-operative (neoadjuvant) chemotherapy Is offered to ALL cT4 colon cancer patients as usual Is offered to SELECTED cT4 colon cancer patientsIs offered to ALL patient with rectal cancer (cT1-T2, cN1-N2, M0 or cT3-T4, any cN, M0) as usual
Is offered to SELECTED patient with rectal cancer (cT1-T2, cN1-N2, M0 or cT3-T4, any cN, M0)
Is NOT offered to any patients during COVID-19 pandemic 11. COVID-19 testing is performed
Using throat / nose swabUsing CT chest Prior to commencement of colorectal cancer treatment in all patients on the day of procedure
Only in symptomatic patients or patients with infected family member on the day of procedure
12. Colorectal cancer treatment should be delayed following COVID-19 diagnosis for 7 days14 days21 daysUntil asymptomatic and completely recovered
13. Operating priority modelPrioritise early cancers
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Prioritise advanced cancerDelay ALL cancersDelay cancer treatment ONLY for patients of ASA 3 and above Aim to begin all treatments within 31 days of the decision to treat as per standard guidelines (NO change)
Intra-operative modifications
14. Laparoscopic surgery is usedIn ALL suitable patients, except where open surgery is clinically indicated (e.g. locally advanced tumours, multiple previous abdominal operations, previous pelvic surgery), as per standard practice
In ALL suitable patients using air seal devicesOnly in patients confirmed to be COVID-19 negative In exceptional casesAll colorectal cancer cases are performed as open surgery during COVID-19 pandemic because of the risks associated with laparoscopic surgery
15. Patients with Early rectal cancer (cT1-T2, cN0, M0) are offeredTAMIS or TEMS or ESD TAMIS or TEMS or ESD ONLY in confirmed COVID-19 negative patientsTAMIS or TEMS or ESD are not available during COVID-19 pandemic
16. Patients with large bowel obstruction are treated with endoluminal stentingIn emergency setting only as a bridge to curative surgeryIn an elective setting where curative surgery is delayed due to COVID-19 pandemicIn palliative setting only This procedure will not be performed during pandemic because of the risk of COVID-19 transmission
Post-operative modifications
17. HDU / ICU post-op care Is available to SELECTED patientsIs NOT available to any patients during COVID-19 pandemic
18. Adjuvant chemotherapy Is offered to ALL stage III colon cancer (pT1-4, pN1-2, M0) patients as usual Is offered to SELECTED stage III colon cancer (pT1-4, pN1-2, M0) patientsIs offered to ALL stage III rectal cancer (pT1-4, pN1-2, M0)Is offered to SELECTED stage III rectal cancer (pT1-4, pN1-2, M0)Is offered to ALL patients with metastatic colorectal cancer Is offered to SELECTED patients with metastatic colorectal cancerIs NOT offered to any patients during COVID-19 pandemic
19. Biological therapy (Cetuximab, Panitumumab) will be used In SELECTED patients with metastatic colorectal cancer
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Is NOT offered to any patients during COVID-19 pandemic 20. Follow-up with CEA and CT chest, abdomen and pelvis
Is continued as per usual protocolIs postponed in all patients to reduce the risk of exposing vulnerable patients to hospital environment
Is postponed in all patients to reduce strain on resources 21. Follow-up with Colonoscopy / Flexible sigmoidoscopy
Is continued as per usual protocolIs postponed in all patients to reduce the risk of exposing vulnerable patients to hospital environment
Is postponed in all patients because of the risk of COVID-19 transmission associated with endoscopic procedures
5.2 Phase 2 - Service Evaluation Data collection in Phase 2 will be aligned with the National Bowel Cancer Audit (NBOCA) dataset. The following performance indicators will be collected. 1. Number of patients operated with colorectal cancer 2. Patients with complete pre-treatment staging (%)3. Number of patients presenting electively with T2-T4, M0 disease4. Patients with distant metastases at time of surgery (%)5. Major surgery carried out as urgent or emergency (%)6. Laparoscopic surgery attempted (%)7. Number of colon cancer patients having major surgery8. No. patients with stage III colon cancer having major resection9. Proportion of stage III patients receiving adjuvant chemo-therapy (%)10. No. of patients with rectal cancer undergoing major surgery11. Proportion of patients reported to have negative margins (%)12. Proportion of patients receiving pre-operative radiotherapy13. Number of screening patients referred for Colorectal Cancer14. Number of detected Colorectal Cancer patient from screening
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6. Data Management and Storage Data collection practice will comply with Caldicott principles. No patient identifiable information will be collected in this audit and all data will be anonymised. Study data will be collected and managed using REDCap electronic data capture tool hosted at The Kennedy Institute of Rheumatology at the University of Oxford (9, 10). REDCap (Research Electronic Data Capture) is a secure, web-based software platform designed to support data capture for research studies, providing 1) an intuitive interface for validated data capture; 2) audit trails for tracking data manipulation and export procedures; 3) automated export procedures for seamless data downloads to common statistical packages; and 4) procedures for data integration and interoperability with external sources ( 9, 10).
7. Data Analysis All data analysis will be performed by the Study Management Group with the assistance and support of the statisticians and methodologists.
7.1 Phase 1 - National Colorectal Cancer Service Modification Survey Data will be summarized using appropriate statistical methodology and a consensus report will be produced to reflect current national service modification. We will seek approval of the ACPGBI, NICE, RCS to make these recommendations acceptable best practice during COVID-19 pandemic. The data analysis from the Phase 1 of the study will guide the protocol development for the Phase 2.
7.2 Phase 2 - Prospective Audit of the Colorectal Cancer Service Provision Data will be summarized using appropriate statistical methodology and a report will be produced to illustrate the impact on modification on national and international CRC service delivery. Individual centres will be able to present their results at the local clinical governance meeting.
8. Study Management
CRC COVID Steering Committee will be convened from key stake-holders that are directly involved in the management of patients with colorectal cancer.
A small Study Management Group (SMG) will be assembled from the CRC COVID Steering Committee members and will be responsible for protocol design, study management, data analysis, dissemination of results and drafting of publications.
Local leads will be recruited from the body of colorectal consultants or cancer specialist nurses. They will be responsible for completion of the national service modification survey and the local service evaluation registration (where applicable). They will recruit and coordinate local collaboratives and ensure prompt data collection and submission within the allocated data collection period.
A data validator will be recruited for each local collaborative. Data validators should not participate in the data collection but rather check the accuracy of the collected data during the data validation period.
9. Ethical approval This study is a service evaluation and does not require HRA Approval or Ethical Approval. However, each participating centre should seek local permission from their R&D / audit department prior to commencement of data collection.
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10. Publication and Authorship Policy All publications and presentations will be made on behalf of the CRC COVID Study Trainee Research Collaborative. A three-tier authorship policy will be used based on the level of participation.
10.1 Named Author It is anticipated that there will be a small group of individuals that will meet the International Committee of Medical Journal Editors (ICMJE) criteria for named authorship, including:
• “Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND
• Drafting the work or revising it critically for important intellectual content; AND
• Final approval of the version to be published; AND
• Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.”(11)
Named authors will be followed by the following statement: ‘on behalf of CRC COVID Steering Committee and CRC COVID National Research Collaborative’. The names and roles of all citable collaborators will be listed at the end of the paper.
10.2 Citable collaborators Collaborators who contribute substantially to this study, but whose contribution does not meet the ICMJE standard, will be included in the list of citable collaborators as part of CRC COVID National Research Collaborative. Substantial contribution includes submitting Phase 1 survey and collecting and submitting data for Phase 2. Prior to publication, local leads will be consulted on the list of collaborators that should be cited or acknowledged.
10.3 Acknowledged collaborators Collaborators, whose contribution to this study does not meet the citable collaborator criteria, will be acknowledged and will receive a certificate of participation. The individual centre data will be owned by the local collaboratives and the individual Trusts, and can be presented as part of the local clinical governance meeting.
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Appendix 1: CRC COVID Steering Committee Charter
Roles and responsibilities The roles of the CRC COVID Steering Committee members include:• Review and approval of the study protocol and statistical analysis plan • Advising the Study Management Group (SMG) on all aspects of the study and overall
supervision• Ensuring that the study adheres to Good Clinical Practice principles • Monitor progress of the study• Attendance of planned meetings • Opportunity to comment on the study reports and publications
Benefits All members of the CRC COVID Steering Committee will be citable collaborators on all publications that ensue from this work. Steering Committee members will be invited to join the Study Management Group if they wish to become involved in the day-to-day delivery and conduct of the study.
Meetings There will be an initial meeting to approve the study protocol and set targets and deadlines for recruitment, data collection and analysis. All the relevant information will be circulated in advance of the meeting and an accurate minute of the meetings will be prepared and disseminated by the Principal Investigator. The format of the meetings may be face-to-face or teleconference, depending on the availability of the members. Reasonable travel, accommodation and other costs will be reimbursed.
Confidentiality All materials and discussions of the CRC COVID Steering Committee should be treated as strictly confidential, unless advised otherwise.
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Bibliography
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