Clinical Trial

. 2019 Jul 1;5(7):961-966.

doi: 10.1001/jamaoncol.2019.0186.

Safety and Feasibility of Using Magnetic Resonance Imaging Criteria to Identify Patients With "Good Prognosis" Rectal Cancer Eligible for Primary Surgery: The Phase 2 Nonrandomized QuickSilver Clinical Trial

Erin D Kennedy^{1

2

3}, Marko Simunovic⁴, Kartik Jhaveri^{5

6}, Richard Kirsch⁷, Jim Brierley^{8

9}, Sébastien Drolet¹⁰, Carl Brown¹¹, Patrick M Vos¹², Wei Xiong¹³, Tony MacLean¹⁴, Selliah Kanthan¹⁵, Peter Stotland¹⁶, Simon Raphael¹⁷, Gil Chow¹⁸, Catherine A O'Brien¹⁹, Charles Cho²⁰, Cathy Streutker²¹, Raimond Wong²², Selina Schmocker¹, Sender Liberman²³, Caroline Reinhold²⁴, Neil Kopek²⁵, Victoria Marcus²⁶, Alexandre Bouchard²⁷, Caroline Lavoie²⁸, Stanislas Morin²⁹, Martine Périgny³⁰, Ann Wright¹⁰, Katerina Neumann³¹, Sharon Clarke³², Nikhilesh G Patil³³, Thomas Arnason³⁴, Lara Williams³⁵, Robin McLeod^{2

3}, Gina Brown³⁶, Alex Mathieson³⁷, Amandeep Pooni¹, Nancy N Baxter^{2

3

38

39}

Affiliations

¹ Division of General Surgery, Department of Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada.
² Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
³ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
⁴ Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
⁵ Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, Toronto, Ontario, Canada.
⁶ Women's College Hospital, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
⁸ Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
⁹ Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Department of Surgery, Centre Hospitalier Universitaire (CHU) de Quebec, Laval University, Quebec City, Quebec, Canada.
¹¹ Department of Surgery, St Paul's Hospital, Providence Health Care, Vancouver, British Columbia, Canada.
¹² Department of Radiology, St Paul's Hospital, Providence Health Care, Vancouver, British Columbia, Canada.
¹³ Department of Pathology & Laboratory Medicine, St Paul's Hospital, Vancouver, British Columbia, Canada.
¹⁴ Department of Surgery, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada.
¹⁵ Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
¹⁶ Department of Surgery, North York General Hospital, Toronto, Ontario, Canada.
¹⁷ Department of Pathology and Laboratory Medicine, North York General Hospital, Toronto, Ontario, Canada.
¹⁸ Department of Medical Imaging, North York General Hospital, Toronto, Ontario, Canada.
¹⁹ Department of Surgery, University Health Network, Toronto, Ontario, Canada.
²⁰ Department of Radiation Oncology, Southlake Regional Health Centre, Newmarket, Ontario, Canada.
²¹ Department of Pathology and Laboratory Medicine, St Michael's Hospital, Toronto, Ontario, Canada.
²² Department of Radiation Oncology, McMaster University, Juravinski Cancer Centre, Hamilton, Ontario, Canada.
²³ Department of Surgery, McGill University Health Centre (MUHC)-Montreal General Hospital, Montreal, Quebec, Canada.
²⁴ Department of Diagnostic Radiology, MUHC-Montreal General Hospital, Montreal, Quebec, Canada.
²⁵ Department of Radiation Oncology, MUHC-Montreal General Hospital, Montreal, Quebec, Canada.
²⁶ Department of Pathology and Laboratory Medicine, MUHC-Montreal General Hospital, Montreal, Quebec, Canada.
²⁷ Department of Surgery, CHU de Quebec, Laval University, Quebec City, Quebec, Canada.
²⁸ Department of Radiation Oncology, CHU de Quebec, Laval University, Quebec City, Quebec, Canada.
²⁹ Department of Medical Imaging, CHU de Quebec, Laval University, Quebec City, Quebec, Canada.
³⁰ Department of Pathology and Laboratory Medicine, CHU de Quebec, Laval University, Quebec City, Quebec, Canada.
³¹ Department of Surgery, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
³² Department of Diagnostic Radiology, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
³³ Department of Radiation Oncology, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
³⁴ Department of Pathology & Laboratory Medicine, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
³⁵ Department of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.
³⁶ Department of Radiology, The Royal Marsden Hospital National Health Service (NHS) Foundation Trust, Surrey, England, United Kingdom.
³⁷ Department of Surgery, Eastern Health Authority, Memorial University, St John's, Newfoundland, Canada.
³⁸ Division of General Surgery, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
³⁹ Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

PMID: 30973610
PMCID: PMC6583831
DOI: 10.1001/jamaoncol.2019.0186

Clinical Trial

Safety and Feasibility of Using Magnetic Resonance Imaging Criteria to Identify Patients With "Good Prognosis" Rectal Cancer Eligible for Primary Surgery: The Phase 2 Nonrandomized QuickSilver Clinical Trial

Erin D Kennedy et al. JAMA Oncol. 2019.

. 2019 Jul 1;5(7):961-966.

doi: 10.1001/jamaoncol.2019.0186.

Authors

Affiliations

¹ Division of General Surgery, Department of Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada.
² Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
³ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
⁴ Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
⁵ Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, Toronto, Ontario, Canada.
⁶ Women's College Hospital, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
⁸ Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
⁹ Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Department of Surgery, Centre Hospitalier Universitaire (CHU) de Quebec, Laval University, Quebec City, Quebec, Canada.
¹¹ Department of Surgery, St Paul's Hospital, Providence Health Care, Vancouver, British Columbia, Canada.
¹² Department of Radiology, St Paul's Hospital, Providence Health Care, Vancouver, British Columbia, Canada.
¹³ Department of Pathology & Laboratory Medicine, St Paul's Hospital, Vancouver, British Columbia, Canada.
¹⁴ Department of Surgery, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada.
¹⁵ Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
¹⁶ Department of Surgery, North York General Hospital, Toronto, Ontario, Canada.
¹⁷ Department of Pathology and Laboratory Medicine, North York General Hospital, Toronto, Ontario, Canada.
¹⁸ Department of Medical Imaging, North York General Hospital, Toronto, Ontario, Canada.
¹⁹ Department of Surgery, University Health Network, Toronto, Ontario, Canada.
²⁰ Department of Radiation Oncology, Southlake Regional Health Centre, Newmarket, Ontario, Canada.
²¹ Department of Pathology and Laboratory Medicine, St Michael's Hospital, Toronto, Ontario, Canada.
²² Department of Radiation Oncology, McMaster University, Juravinski Cancer Centre, Hamilton, Ontario, Canada.
²³ Department of Surgery, McGill University Health Centre (MUHC)-Montreal General Hospital, Montreal, Quebec, Canada.
²⁴ Department of Diagnostic Radiology, MUHC-Montreal General Hospital, Montreal, Quebec, Canada.
²⁵ Department of Radiation Oncology, MUHC-Montreal General Hospital, Montreal, Quebec, Canada.
²⁶ Department of Pathology and Laboratory Medicine, MUHC-Montreal General Hospital, Montreal, Quebec, Canada.
²⁷ Department of Surgery, CHU de Quebec, Laval University, Quebec City, Quebec, Canada.
²⁸ Department of Radiation Oncology, CHU de Quebec, Laval University, Quebec City, Quebec, Canada.
²⁹ Department of Medical Imaging, CHU de Quebec, Laval University, Quebec City, Quebec, Canada.
³⁰ Department of Pathology and Laboratory Medicine, CHU de Quebec, Laval University, Quebec City, Quebec, Canada.
³¹ Department of Surgery, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
³² Department of Diagnostic Radiology, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
³³ Department of Radiation Oncology, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
³⁴ Department of Pathology & Laboratory Medicine, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
³⁵ Department of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.
³⁶ Department of Radiology, The Royal Marsden Hospital National Health Service (NHS) Foundation Trust, Surrey, England, United Kingdom.
³⁷ Department of Surgery, Eastern Health Authority, Memorial University, St John's, Newfoundland, Canada.
³⁸ Division of General Surgery, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
³⁹ Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

PMID: 30973610
PMCID: PMC6583831
DOI: 10.1001/jamaoncol.2019.0186

Abstract

Importance: Chemoradiotherapy (CRT), followed by surgery, is the recommended approach for stage II and III rectal cancer. While CRT decreases the risk of local recurrence, it does not improve survival and leads to poorer functional outcomes than surgery alone. Therefore, new approaches to better select patients for CRT are important.

Objective: To conduct a phase 2 study to evaluate the safety and feasibility of using magnetic resonance imaging (MRI) criteria to select patients with "good prognosis" rectal tumors for primary surgery.

Design, setting, and participants: Prospective nonrandomized phase 2 study at 12 high-volume colorectal surgery centers across Canada. From September 30, 2014, to October 21, 2016, a total of 82 patients were recruited for the study. Participants were patients newly diagnosed as having rectal cancer with MRI-predicted good prognosis rectal cancer. The MRI criteria for good prognosis tumors included distance to the mesorectal fascia greater than 1 mm; definite T2, T2/early T3, or definite T3 with less than 5 mm of extramural depth of invasion; and absent or equivocal extramural venous invasion.

Interventions: Patients with rectal cancer with MRI-predicted good prognosis tumors underwent primary surgery.

Main outcomes and measures: The primary outcome was the proportion of patients with a positive circumferential resection margin (CRM) rate. Assuming a 10% baseline probability of a positive CRM, a sample size of 75 was estimated to yield a 95% CI of ±6.7%.

Results: Eighty-two patients (74% male) participated in the study. The median age at the time of surgery was 66 years (range, 37-89 years). Based on MRI, most tumors were midrectal (65% [n = 53]), T2/early T3 (60% [n = 49]), with no suspicious lymph nodes (63% [n = 52]). On final pathology, 91% (n = 75) of tumors were T2 or greater, 29% (n = 24) were node positive, and 59% (n = 48) were stage II or III. The positive CRM rate was 4 of 82 (4.9%; 95% CI, 0.2%-9.6%).

Conclusions and relevance: The use of MRI criteria to select patients with good prognosis rectal cancer for primary surgery results in a low rate of positive CRM and suggests that CRT may not be necessary for all patients with stage II and III rectal cancer.

Trial registration: ISRCTN.com identifier: ISRCTN05107772.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Ms Schmocker and Dr Pooni reported receiving grants from the Mount Sinai Hospital - University Health Network (MSH-UHN) Academic Medical Organization Innovation Fund. Dr Liberman reported receiving support from Merck and Servier. Dr Clarke reported receiving grants from GE Healthcare. No other disclosures were reported.

Figures

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Comment in

Reducing the Morbidity of Rectal Cancer Treatment.
Paty PB, Cercek A, Crane CH. Paty PB, et al. JAMA Oncol. 2019 Jul 1;5(7):940-941. doi: 10.1001/jamaoncol.2019.0181. JAMA Oncol. 2019. PMID: 30973578 No abstract available.
Gastrointestinal Cancers: Moving the Needle for Rectal, Gastroesophageal, Pancreaticobiliary, and Liver Cancers.
Kharofa J, Hallemeier CL, Huguet F, Anker CJ, Buckstein MH, Tait D, Olsen JR, Jabbour SK. Kharofa J, et al. Int J Radiat Oncol Biol Phys. 2020 Mar 15;106(4):653-662. doi: 10.1016/j.ijrobp.2019.12.011. Int J Radiat Oncol Biol Phys. 2020. PMID: 32092335 No abstract available.

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Safety and Feasibility of Using Magnetic Resonance Imaging Criteria to Identify Patients With "Good Prognosis" Rectal Cancer Eligible for Primary Surgery: The Phase 2 Nonrandomized QuickSilver Clinical Trial

Affiliations

Safety and Feasibility of Using Magnetic Resonance Imaging Criteria to Identify Patients With "Good Prognosis" Rectal Cancer Eligible for Primary Surgery: The Phase 2 Nonrandomized QuickSilver Clinical Trial

Authors

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Abstract

Conflict of interest statement

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Research Materials