Pre-operative RadiothErapy for Soft Tissue SarcOmas

Study Overview
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Brief Summary
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Soft tissue sarcomas (STSs) are malignant tumours that arise in any of the mesodermal tissues in the body including muscles, fibrous tissues, bone and cartilage, adipose tissue, and blood vessels, most frequently in the extremities (40%), trunk and retroperitoneum (40%). Traditionally, the prescription schedule for conventional preoperative RT is a regimen of 50 Gy in fractions of 1.8-2 Gy per day. Concerns regarding this regimen include the delay to definitive surgery and the higher rate of wound complications compared to post-operative radiotherapy. Hypofractionated RT is a prescription schedule in which the total dose of radiation is delivered in larger doses per fraction in fewer fractions allowing the delivery of a higher biologically effective dose (BED) to the tumour than with conventional RT [7] during a shorter period of time.

Detailed Description
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This will be a phase I/II study of hypofractionation delivering five fractions (one fraction delivered every 2nd day) of 7 Gy of external beam radiotherapy over 5 fractions (one and half week period) in patients with localized STSs who are planned to receive pre-operative radiotherapy. Patients will undergo surgery 4-6 weeks after completion of RT. Pre-treatment evaluation will be according to standard practice: History and Physical Exam height, weight history (diabetes, vascular disease) Radiology MRI of primary site or CT if MRI not tolerated CT chest Quality of Life Musculoskeletal Tumour Society Rating Scale Toronto Extremity Salvage Score (TESS) Follow-up assessment will be done as follows: History and Physical Exam Acute radiation toxicity During RT and 2 weeks after end of RT Acute surgical toxicity - wound assessment At hospital discharge, 2 weeks post-surgery 1 month post-surgery 3 months post-surgery 6 months post-surgery Late toxicity (skin, subcutaneous, bone, joint) & peripheral limb edema - Every 6 months thereafter Radiology Chest CT-scan Within 1 month pre-surgery Standard thereafter MRI or CT scan of primary site Prior to surgery, as standard Every 3-6 months or as needed after surgery Quality of life Questionnaires Toronto Extremity Salvage Score (TESS Musclo Tumor Rating Scale (MSTS) At months 1,3,6, 12, 18 and 24 after surgery. Yearly thereafter up to 5 years

Official Title
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Short Course Pre-operative RadiothErapy for Soft Tissue SarcOmas - a Phase I/II Trial (PRESTO)

Conditions
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Soft Tissue Sarcoma Adult

Intervention / Treatment
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* Radiation: Hypofractionation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven STS of the extremities, above the knee, or trunk following review by our pathologist Lesions smaller than 15cm in largest dimension Deemed appropriate for preoperative radiotherapy and conservative surgery following patient assessment by a radiation oncologist and surgical oncologist Lesion is primary or locally recurrent. Patients who underwent unplanned non-oncological excision (whoops procedure) at a referring hospital are NOT eligible No previous radiation therapy ECOG 0-2 (or Karnofsky Performance Status ≥ 70) within 60 days prior to registration Resectable primary lesion with or without distant metastasis Age ≥ 18 Patient must be able to provide study-specific informed consent prior to study entry Patient is available for treatment and follow-up Exclusion Criteria: Patients who underwent unplanned non-oncological excision (whoops procedure) at a referring hospital Lesions below the knee Prior or concurrent invasive malignancy (except non-melanomatous skin cancer) or lymphomatous/hematogenous malignancy, unless continually disease free for a minimum of 5 years Regional lymph node involvement Previous irradiation to the area to be treated Other major medical illness deemed to preclude safe administration of protocol treatment or required follow-up

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental : Short Course Pre-operative RadiothErapy<br>As part of the planning process, you need to undergo a CT Simulation.It is special type of CT scan used to measure and design the radiation fields to precisely target the tumor.It is done at the Radiation Oncology Department at the MUHC. Some patients may be asked to also undergo an MRI Simulation, and the CT simulation. You may asked to provide a blood sample to ensure good kidney function prior to the CT and MRI scans. Both CT and MRI simulations are considered standard of care. Once the simulation studies are done, there is about a 2 week waiting period for radiation planning prior to starting the radiation treatments. The hypofractionation technique will be delivering five fractions (one fraction delivered every 2nd day) of 7 Gy daily of external beam radiotherapy (EBRT) over a period of one and half weeks for a total of 35 Gy. The treatment should last approximately 30 minutes. Once treatments are done, there is a 4 to 6 week wait for surgery. | Radiation: Hypofractionation<br>* Shorter radiation therapy means that a higher dose will be given on a daily basis. The goal is to target microscopic disease and decrease the chances of local recurrence. Organs at risk (OAR) will receive doses following the constraints from the Timmerman tables used for reference when using 5 or more fractions of EBRT. Treatment will be delivered every 2nd day, for a maximum of 3 fractions per week. Daily pretreatment Image Guided Radiotherapy Images (IGRT) (Cone-Beam CT - CBCT) will be co-registered with the CT simulation dataset to adjust patient position before each treatment by matching the bone adjacent to the planned tumour volume (PTV). Treatment will be administered if there is <3 mm in any dimension, or rotation is <3 degrees. If the isocentre set-up exceeds 3 mm at any given treatment session, the treatment couch will be translated to restore its planned position.<br>* Other names: Hypofractionated Radiation Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute RadiationToxicity using Common Terminology Criteria for Adverse Events (CTCAE) V.5 | To assess, skin reactions and wound healing | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physicians Muscle Tumor Rating Scale | To assess the amount of difficulty performing activities, including motion, strength and stability | 1 year |