Preoperative Radiotherapy for Sarcomas of the Extremities With Intensity-Modulation, Image-Guidance and Small Safety-margins

Study Overview
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Brief Summary
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RATIONALE: Modern radiotherapy techniques in a neoadjuvant setting have the potential to minimize morbidity and maximize efficacy. An additional boost dose can be provided locally by HDR-brachytherapy in patients with positive margins after tumor resection. PURPOSE: This phase II trial is studying the safety and efficacy of a combination of modern radiotherapy elements applied to the tumor and small volumes of surrounding normal tissue (IMRT, IGRT; brachytherapy in case of positive resection margin) and see how well it works in treating patients with High-Risk Soft Tissue Sarcoma of the Extremities.

Official Title
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Phase II Study of Preoperative Radiotherapy for Sarcomas of the Extremities With Intensity-Modulation, Image-Guidance, Small Safety-margins and Brachytherapy Conditioned by Resection Margin

Conditions
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Soft Tissue Sarcoma of the Limb, AJCC Stage II and III

Intervention / Treatment
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* Radiation: IMRT/IGRT, Tumor resection, Brachytherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic and radiographic proof of localized high-risk soft tissue sarcoma meeting the following criteria: Lesion originates in extremity upper extremity lesions may occur from the medial border of the scapula to tumors as far distal as the finger tips lower extremity regions include hip girdle tumors commencing at the iliac crest, excluding lesions arising from within the pelvis, and extends to include lesions as far distal as the toes AJCC Stage II or III disease (except T1a-tumors or N1) Primary presentation or local recurrence after biopsy or inadequate surgery resulting in residual tumor in cross-sectional imaging Tumors must be considered resectable according to cross sectional imaging, or potentially resectable after preoperative radiotherapy ECOG Performance Status 0-2 Informed Consent Exclusion Criteria: Diagnosis of the following: Primitive neuroectodermal tumor Soft tissue Ewing's sarcoma Extraskeletal osteo- or chondrosarcoma Aggressive fibromatosis (desmoid tumors) Dermatofibrosarcoma protuberans Regional nodal disease or unequivocal distant metastasis Life expectancy < 1 year Pregnancy Major medical illness that would preclude study treatment History of major wound complication or recurrent skin infection Known HIV positivity < 2 weeks elapsed from prior surgery or cytotoxic chemotherapy persisting acute toxicities > grade 1 in tumor-bearing limb resulting from prior treatment with anti-cancer modalities Cytotoxic chemotherapy, targeted therapy or investigational agents concurrent to study treatment Prior radiotherapy to the site of present STS. Chronic requirement for treatment with immuno¬suppressive agents or steroids.

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: 1 Arm<br>Stratum A: R0, primary wound closure Stratum B: R0, secondary wound closure Stratum C: R1, tertiary wound closure | Radiation: IMRT/IGRT, Tumor resection, Brachytherapy<br>* All: Preoperative IMRT with small safety margins (GTV according to MRT plus 1.5cm laterally / 3cm proximodistally) to 50Gy total dose, 2 Gy single dose, 5 fractions per week, daily IGRT with in-room CT (Tomotherapy) Tumor resection after 4-6 weeks Stratum C: Interstitial Brachytherapy to tumor bed with 15 Gy total dose, 3 Gy single dose b.i.d. in second week after tumor resection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound Complication Rate | Wound Complication Rate up to 3 months after tumor resection | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Efficacy: Rate of margin-free resection Local control rate (LC) Metastasis-Free Survival (MFS) Disease-Free Survival (DFS) Disease-Specific Survival, Overall Survival (OS) Limb Preservation Rate (LP) | 2 years | 
| Safety | Acute toxicity as measured by CTCAE v. 4.03 Late toxicity (skin, soft tissue, joint, bone, neural toxicity) as measured by CTCAE v. 4.03 | 2 years | 
| Limb Functionality | as measured by the Musculoskeletal Tumor Society (MSTS) rating scale and the Toronto Extremity Salvage Score (TESS) | 2 years | 
| Quality of Life | as measured by QLQ C30 | 2 years | 
| Translational |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Soft tissue sarcoma, Intensity-Modulated Radiation Therapy (IMRT), Tomotherapy, Safety Margins, Image-guided Radiation Therapy, Brachytherapy, interstitial