1. Michelle Ghert, Xiaomei Yao, Tom Corbett, Abha Gupta, Joel Werier, Rita Kandel, Shail Verma, and the Sarcoma Disease Site Group of Cancer Care Ontario

2.  Program for Evidence-Based Care (PEBC)  Initiative of Cancer Care Ontario  Evidence-based and evidence-informed guidelines  Practice Guidelines Development Cycle 1,2 1. Browman GP, Levine MN, Mohide EA, Hayward RSA, Pritchard KI, Gafni A, et al. The practice guidelines development cycle: a conceptual tool for practice guidelines development and implementation. J Clin Oncol. 1995;13:502-12. 2. Browman GP, Newman TE, Mohide EA, Graham ID, Levine MN, Pritchard KI, et al. Progress of clinical oncology guidelines development using the practice guidelines development cycle: the role of practitioner feedback. J Clin Oncol. 1998;16(3):1226-31.

3. 1. Development of objectives and research questions 2. Existing guideline review 3. Systematic review 4. Initial recommendation 5. Internal review: 1. Expert panel review and approval 2. Report Approval Panel (clinical guideline specialists) 6. External review: 1. Targeted peer review 2. Professional consultation 7. Publication

4.  To provide evidence to determine the optimal treatment options among surgery, radiation therapy, systemic therapy, and/or any combinations thereof in patients with desmoid tumours for whom the decision has been made to undergo active treatment.

5.  Observation (no active treatment) is a safe option for most patients with desmoid tumours.  This guideline only focuses on patients who have made the decision to pursue active treatment

6.  Cochrane Library  National Guideline Clearinghouse  National Health and Medical Research Council (Australia)  New Zealand Guidelines Group  American Society of Clinical Oncology  National Institute for Health and Clinical Excellence  Scottish Intercollegiate guidelines Network  Society of Obstetricians and Gynaecologists of Canada  Gynecologic Oncology Group  Standards and Guidelines Evidence Directory of Cancer Guidelines

7.  No existing guidelines identified

8.  The Cochrane Clinical Trial Register  MEDLINE  EMBASE  American Society of Clinical Oncology (ASCO) Annual Meeting Abstracts  Connective Tissue Oncology Society (CTOS) Annual Meeting Abstracts

10.  Full text 1990-2012  Conference abstract 2009-2012 (RCTs only)  Systematic review, RCT, retrospective comparative study ≥ 30 patients, prospective single arm study ≥ 30 patients  At least one reported outcome: progression- free survival (RFS or PFS), local control rate, response rate, toxicity

12.  4 prospective single-arm studies  1 historical prospective comparative study  23 retrospective comparative studies  Study quality was assessed using the modified Newcastle-Ottawa Scale 3  Overall, the study quality from the included studies was poor to moderate. 3. Wells GA SB OCD, Peterson J, Welch V, Losos M, et al... The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [Internet]. Ottawa: Ottawa Hospital Research Institute; ©1996-2011 [cited 2013 February 21]. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm

13.  3 studies (306 patients) favored combined therapy  1 study (72 patients) no statistical difference 82% vs 68% local control

14.  65% vs. 78% local control in 115 patients  93% vs. 81% local control in 34 patients

15.  Positive margins  No radiation  Young age (<30 years)  Large tumor size  Recurrent tumor

16.  Variably reported  10-15% mild to severe toxicities/complications

17.  3 phase II studies  3 retrospective comparative studies, no adjustment for baseline variables

18.  MTX + vinblastine: PFS 67% in 30 patients  Imatinib: PFS 58% at 3 years in 51 patients  Imatinib: PFS 55% at 2 years in 35 patients

19.  Standard for cytotoxic regimens  Imatinib: rash, fatigue, nausea, vomiting, abdominal pain, neutropenia, myalgia

20. 1. Surgery with a wide margin with or without radiotherapy may be a reasonable treatment option for patients for whom surgical morbidity is deemed to be low. 2. The decision as to whether radiation therapy should be done with surgery should be made by clinicians and patients after consideration of the potential benefits of improved local control compared with the harms and toxicity associated with radiation therapy. 3. Radiation therapy alone, systemic therapy alone, or radiotherapy plus systemic therapy may be a treatment option in patients for whom surgical morbidity is deemed to be low, moderate, or high.

21.  Expert Panel: CCO Sarcoma DSG  Recommendations to clarify radiation dosages and toxicities  Approval vote 100% (77% response of 13 members)  Report Approval Panel (Approved)  Wording clarification  Qualifying statement (non-malignant tumor)

22.  Targeted Peer Review  Toronto, Vancouver, Calgary, Salt Lake City  9-item questionnaire, scored 1-5 in metrics of guideline quality  All scores 4 or 5, except ability to inform clinical decisions (one reviewer scored 3)  10 comments addressed  Professional consultation  4-item brief questionnaire  14 responses, similar feedback to TPR  2 comments addressed

23. 1. Surgery with a wide margin with or without radiotherapy may be a reasonable treatment option for patients for whom surgical morbidity is deemed to be low. 2. The decision as to whether radiation therapy should be done with surgery should be made by clinicians and patients after consideration of the potential benefits of improved local control compared with the harms and toxicity associated with radiation therapy. 3. Systemic therapy alone or radiation therapy alone may also be a reasonable treatment option for patients, regardless of whether or not their desmoid tumours are deemed to be resectable depending on individual patient situation.

24. https://www.cancercare.on.ca/toolbox/qualityguidelines/diseasesi te/sarcoma-ebs/

26.  Well-designed, high-quality RCTs or prospective comparative studies  Collaborative groups capable of RCTs: COG, SARC and PARITY Collaborators