Pre-operative Hypofractionated Proton Therapy

Study Overview
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Brief Summary
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This study is being done to see if proton therapy for certain kinds of sarcomas (extremity and trunk soft tissue) is safe and effective. As part of the study, patients will have five fractions of proton therapy before the participants have surgery for the sarcoma. The study will measure wound complications and functional outcomes / quality of life after the procedures. Patients will be asked to complete questionnaires about the treatment and quality of life from the time of enrollment until about two years after surgery. Otherwise, the participants will have standard of care follow ups with the treatment team.

Official Title
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PROspective Phase II Trial of Pre-operative Hypofractionated protoN Therapy for Extremity and Truncal Soft Tissue sarcOma

Conditions
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Soft Tissue Sarcoma

Intervention / Treatment
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* Radiation: hypofractionation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (≥18 years of age) Patients with primary or locally recurrent extremity or truncal soft tissue sarcoma WHO/ECOG status ≤2 Exclusion Criteria: History of prior local radiation therapy Inability to tolerate treatment position for duration of simulation or treatment Tumor originating in retroperitoneal location Patients planned for systemic therapy including chemotherapy, targeted agents, and immunotherapy Co-existing malignancy or treated malignancy in the last 2 years expected to limit life expectancy; does not include completely resected cutaneous basal cell carcinoma, squamous cell carcinoma, in situ breast or cervical malignancies, or other pathologies at the discretion of the investigators. Confirmed pregnancy.

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: Pre-operative hypofractionated proton therapy<br>Patients will have 5 fractions of proton therapy prior to surgical resection of their sarcoma. | Radiation: hypofractionation<br>* This study is being done to see if hypofractionation in treating sarcoma, will also provide patients with a faster and safer treatment outcome.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of major wound complications | Number of major wound complications as defined by the CAN-NCIC-SR2 trial (secondary operation under general or regional anaesthesia for wound repair (debridement, operative drainage, and secondary wound closure including rotationplasty, free flaps, or skin grafts), or wound management without secondary operation…[including] an invasive procedure without general or regional anaesthesia (mainly aspiration of seroma), readmission for wound care such as intravenous antibiotics, or persistent deep packing for 120 days or longer.) | 90 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute grade ≥3 adverse events | Rate of acute grade 3 or higher adverse events (CTCAE5) | 2 years after treatment | 
| Rate of local recurrence free survival | Number of patients without local recurrence on CT and/or MRI at specified time points. | 1 and 2 years after enrollment | 
| Rate of metastasis free survival | Number of patients without metastasis on CT and/or MRI at specified time points. | 1 and 2 years after enrollment | 
| Rate of late grade ≥2 radiation toxicity | Rate of grade 2 or higher CTCAE5 adverse events associated with radiation therapy (fibrosis, lymphedema, or joint stiffness). | median two year follow up | 
| Musculoskeletal Tumor Rating Scale scores | The Musculoskeletal Tumor Rating Scale measures physical function in patients with musculoskeletal tumors. The total score for the MSTS ranges 0-30 with higher scores indicating better function. | baseline, 2-12 weeks after end of radiation therapy, after surgery (3-6 month follow up), every 3 months during follow up for 2 years | 
| Toronto Extremity Salvage Score (TESS) scores | The Toronto Extremity Salvage Score (TESS) measures physical function in patients with musculoskeletal tumors. The total score for the TESS ranges 0-100 with higher scores indicating better function. | baseline, 2-12 weeks after end of radiation therapy, after surgery (3-6 month follow up), every 3 months during follow up for 2 years | 
| Functional Assessment of Cancer Therapy-General (FACT-G) scores | The Functional Assessment of Cancer Therapy-General (FACT-G) measures quality of life for patients with cancer. The total score for the FACT-G ranges 0-108 with higher scores indicating better function. | baseline, 2-12 weeks after end of radiation therapy, after surgery (3-6 month follow up), every 3 months during follow up for 2 years | 
| Rate of pathologic complete response | Pathologic complete response rate is reported as the number of patients who achieve pathologic complete response after treatment. As per the NCCN guidelines, pathologic response is graded by the system recommended by the AJCC Cancer Staging Manual and CAP guidelines: Complete response - no remaining viable cancer cells Moderate response - only small clusters/single cancer cells remain Minimal response - residual cancer remaining, but with predominant fibrosis Poor response - minimal/no tumor kills, extensive residual cancer | through study conclusion (estimated 5 years from opening) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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proton therapy, soft tissue sarcoma, hypofractionated